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Notebook - SleepNon24VLiDACMel - VLiDACMel therapy for entrainment of treatment-resistant sighted non24

SleepNon24VLiDACMel - VLiDACMel therapy for entrainment of treatment-resistant sighted non24

Man with too long a day. A metaphor of the non-24 circadian rhythm sleep-wake disorder, by Alec Gray. Reproduced with permission.


This is an experimental protocol for 24h entrainment of treatment-resistant sighted non24.

This is a work-in-progress documentation of the author's self-experiment. Hence, it will continue to evolve over time. Check out later this document for updates.

This work takes an evidence-based approach based on a mostly clinical literature review when possible and self-experimental using a combination of sleep diary, manual data logging and automatic vitals monitoring where the data is lacking in the literature (sighted non24 is pretty rare after all). The goal being to design and assess the effectiveness of therapies to manage sighted non-24.

As of July 2020, the protocol is considered mature, as it reproducibly allows for a stable (but not constant) entrainment of the author's circadian rhythm to a 24h cycle. Furthermore, all the observed effects could be elucidated by previous studies, which provides a framework to predict how this therapy works in various scenarios. This experiment is also following the new approach of radical open science, where the experiments progress is publicly accessible at nearly all stages. What remains to be explored are the following points:

  • Milestone 1 (done July 2020): Complete this document to fully describe the therapy and the theoretical physiological pathways underlying it, as well as the practical details to adjust it on an individual basis.
  • Milestone 1.5 (done August-October 2020): Reproduce the shorter than 24h circadian period with very long bright blue light therapy. This would allow to adjust backwards the circadian rhythm (ie, sleep and wake up earlier) without having to freerun forward.
  • Milestone 2 (done October 2020): Assess the necessity of each step by elimination (ie, try to keep all steps but remove one at a time, if no effect then can permanently be removed). After this milestone, the protocol will be including only the minimal set of steps necessary for entrainment of the author's circadian rhythm.
  • Milestone 2.5 (done November 2020): Update document with critical findings from side notebook. All major aspects of the therapy (such a very long light therapy being more effective than brighter light therapy) were found to be strongly supported by previous (but unpopularized) research, and adequate references were added. Added a simplified protocol (set of rules, 2 pages). The protocol is now considered mature.
  • Milestone 2.6: Update document with more findings from side notebook. (done during 2021-2022)
  • Milestone 3: Systematization of the therapy by circadian rhythm monitoring using wearable devices. Just like diabetes became medically manageable when glucose and insulin monitoring devices could be made, there needs to be a device to monitor the circadian rhythm in order to properly time the therapies on a daily basis and monitor their effects as well as chaotic biological fluctuations. (done during 2021-2022)
  • Milestone 3.5: Reproduce the shorter than 24h circadian period with very long bright blue light therapy, continuously for several weeks, while monitoring vital signs and body temperature, in order to objectively assess the phase advance produced by very long bright blue light therapy. (Failed as of 2023)
  • Milestone 4 (done 2022 - database is complete and publishable): Publication of the database of vital signs and sleep logs for this self-experiment to allow for third-party review and analyses. Database may be published in a peer-reviewed journal. See the Wearadian project on GitHub for more details on the acquisition system and access to the database.
  • Milestone 5 (partially done as of 2023 - protocol rewritten, references not rewritten but can be automatically done with custom tool): rewrite this protocol more concisely and with references in academic style instead of hyperlinks (using Zettlr) for publication in a peer-reviewed journal. — Idea: convert to a MyST Markdown or AsciiDoc document (using Pandoc?), then simply auto-extract links and move them to the end of the subsentence it was highlighting (should also take into account the "(see also here, here and here)", but likely will require some manual cleanup - but the heavy lifting would be automatically done).
  • Milestone 6 (done in March 2024): achieve one year of continuous entrainment at a stable phase. Being entrained for one year logically means that it is possible to stay forever entrained if the conditions are repeated. This is hence the ultimate n-of-1 efficacy milestone.

In addition to the therapy's protocol, there is also a TROUBLESHOOTING section towards the end of this document, which aims to answer the most common questions about the various therapies for non24 and clarify how they work and how to optimize them according to the current scientific knowledge. This section is much longer than the therapy outline, and hence it is written for the curious reader to further their knowledge and/or answer their questions about or around circadian rhythm disorders. Reading the Troubleshooting section is not mandatory, rather the reader is invited to search there in case of a specific question that is not answered in the therapy outline.

This therapy was designed to treat sighted non24. Since the tools influencing the circadian rhythm are the same for all humans (and actually most research was done on typical sleepers but are applicable for people with circadian rhythm disorders), most parts are also be applicable to DSPD with some slight changes (mostly that the goal of DSPD is to phase advance gradually, whereas non24 aims to freeze the circadian rhythm in place with a treatment-induced daily phase advance that counteracts the natural intrinsic daily phase delay). For ASPD, it should be possible to use the same tools too but timed at the opposite, under the phase delay part of the zeitgebers' PRCs (eg, being exposed to light therapy in the evening instead of at wake-up, as did Czeisler et al in a case study). Findings for individuals with a circadian rhythm disorder can also provide generalizable insights for typical sleepers as previous studies have done.

Since this protocol was written, the Circadiaware collective was founded by several developers to make open-source tools to further help with the analysis of circadian rhythm phenomena and the management of circadian rhythm disorders. You may find interesting tools there such as WebActogram, a tool to instantly screen circadian rhythm disorders, and Wearadian, a protocol design to automatically monitor 24/7 the sleep and circadian rhythm patterns out of lab.

DISCLAIMER: this protocol is not scientifically peer-reviewed and not clinically validated. It was tested on a sample size of only 2 individuals with non24 since birth and under a controlled home environment. Hence this protocol cannot be formally recommended, it should still be considered experimental and maybe risky. If you do try, it would be at your own risk (please at least ask a physician to accompany you!).

IMPORTANT HEALTH NOTE: this therapy cannot be used by individuals with epilepsy or macular degeneration or other retinal diseases or malformations (eg, aphakic people born without crystalline lens and pseudophakic who received intraocular lens implants), as these populations are at risk when using light therapy. It is also risky for people with motor disorders such as restless legs syndrome or periodic limb movement disorder as both bright light therapy and melatonin can independently increase melatonin levels which can trigger motor symptoms, however these symptoms should disappear following discontinuation of the therapy.

This document was first written and self published by Stephen Karl Larroque in June 2020, from material collected since August 2019, with substantial iterative updates over the years.
Last update: April 2024.
ORCID: https://orcid.org/0000-0002-6248-0957
Contact me on GitHub by opening an issue.

To print the document, select the text (click on the first paragraph, then SHIFT+left click at the end of the page) and right-click on the selection, then select print (ensure the option "print selected text only" is checked), in order to remove the top navigation bar that can hide text on some pages.

How to read and navigate this document

There is a button "Table of contents" at the top left corner that will show you a navigation bar with where you are in the document and allowing you to quickly jump to any section.

Each section in the document can be linked to, but there is a bug that makes the first link copy not show the correct anchor, so try to just copy the link twice and the second one should include the correct HTML anchor.

For people with sighted non-24 or DSPD who just discovered they have this disorder, I recommend first starting in the Diagnosis and sleep diary section in Troubleshooting, where you will find all the informations you need to start documenting your sleep disorder and find a sleep medicine doctor experienced with circadian rhythm disorders who can help you with getting a formal diagnosis and accommodations that are necessary for school and work, given these are extremely debilitating disorders.

Afterwards or if you have a circadian rhythm disorder but you already are diagnosed or experienced with the clinical process and are looking for a therapy protocol to entrain the circadian rhythm period or phase advance the phase, you can proceed to read the therapy's protocol. I recommend to first read the Quick protocol, to get a nice fast introduction with the big ideas clearly laid out, then if you like what you are reading and want more details, you can proceed to read the Simplified protocol or even the Full protocol.

For people who do not have a circadian rhythm disorder but are suspecting they know someone with such a disorder, for caregiver and for clinicians, you may be mo interesting in reading the Introduction to the non24 disorder (which also covers other circadian rhythm disorders, notably the effects on health). Then you can continue reading on with the section on Zeitgebers to learn more about circadian rhythm science. For clinicians or the curious minded ones, the next sections afterwards review the scientific and medical literature on sleep to explain the various choices that led to the design of this therapeutic protocol, and some insights into what may help design future circadian rhythm therapies.


My name is Stephen Karl Larroque. I am a researcher in the neuroscience of consciousness. I was born with the non-24 circadian rhythm disorder, got diagnosed the first time in my twenties, and it started to become impossible to ignore in my thirties. Facing the sparsity of knowledge and effective treatments for this disorder, this prompted the start working on my own to find evidence-based approaches to improve the management of this disorder, which ultimately led to the VLiDACMel protocol presented below. The non-24 disorder affects my lineage over at least 2 generations of direct ancestors (so I am the 3rd), which strongly suggests that it is of genetic cause, and hence will likely affect my future children.

Although I was not trained to work on this specific field of circadian rhythm science, and hence claim no authority, I found myself in the exceptional circumstances of being trained in the scientific method and specifically in biomedical science, and being afflicted by a disorder I could study with this method and by building on my predecessor's works.

This protocol as is presented in this document is publihed with no guarantee of any kind of medical use nor of safety, please regard it simply as informational content. I publish it in the hopes that such a protocol with a review of the previous evidence in the theory of circadian rhythm and circadian rhythm disorders combined with the preliminary results from my self experiment, with a clear set of rules that optimized the therapy's efficacy during this self-experiment, may help in the design of future experiments by other researchers and lead to a faster investigation and finding of new therapeutic avenues for circadian rhythm disorders.

The current document has multiple levels of reading depending on how much you want to invest time in reading its content:

  • a Simplified Protocol of VLiDACMel is presented as a set of rules for legibility. It contains the most crucial information, but lacks the subtleties of some parameters that can reduce the efficacy of the therapy.
  • a Quick 2 minutes VLiDACMel protocol which is even more concise, for those who just want a quickstart to the core elements necessary for entrainment.
  • For a more complete understanding of the protocol, the Full Protocol section outlines the entire protocol with links to the most important academic works that underlies it, as well as explain the various adjustment factors to optimize its efficacy.
  • Then, the Troubleshooting section presents an in-depth review of the science of circadian rhythm and circadian rhythm disorders, with all the links to the academic sources, this section and its subsections are primarily addressed to scientists or the very curious reader as it gets much more technical and requires the use of jargon, although the author tried to summarize in layman terms the key points in the opening paragraph of each subsection, and keeping the jargon at the minimum required for accuracy.

Although this document is primarily aimed at sighted individuals with a non-24 sleep-wake circadian rhythm disorder, it is also mostly applicable for other circadian rhythm disorders such as DSPD and night shift work disorder given the same biological pathways are involved and hence the same therapies are likely applicable, see the sections "Adaptations of this protocol for other circadian rhythm disorders (DSPD, nightshift workers)" for more specific instructions for each disorder. The information contained herein may also be partially or fully applicable to insomnia, given the strong links with circadian rhythm disorders.


This document describes a protocol for the entrainment of sighted non-24, which was designed using an evidence-based approach from a scrupulous examination of previous research, and self-experimentation to determine the factors influencing therapy's efficacy or circadian rhythm (dis)entrainment.

This section describes the starting point of this experiment and the methodology followed to derive the therapy's protocol and its results over the years. If you are interested in the reasons for its inception and some observations of its results on a single case, read on, otherwise if you just want to get started, skip to the next section.

Here are some sleep graphs of the early results from using this therapy in February to April 2020:

Zoomed out, here is my full sleep diary over 1 year, with the working therapy at the end:

The graph above shows a relatively stable entrainment over 2.5 months. As of December 2020, the author was entrained for 6 months, which is significantly much more than any published therapy protocol before. In comparison, all the author's previous attempts, most using published protocols, failed after 2 weeks to 1 month. The entrained (right part) of the graph was through the use of 1-2h of daily light therapy.

Here is the result with very long light therapy of more than 5h everyday for 10 days. This result is especially interesting as it was never observed before, with an inverse freerunning pattern: waking up 30 min earlier every day and up to 1h30 (one full ultradian cycle) earlier on the last day (which prompted the premature stopping of the self-experiment because this became uncontrollably too early):

This first experiment with very long light therapy (on the far right) was started on about the 3rd of June, after 1 more month of freerunning as can be seen during May. The very long light therapy resulted in a staggering reduction of circadian period tau under 24h at 23.5h on average and 22.5h the last day! Everything else was held constant (same melatonin intake time, same meal eating time, same daytime activities and environment), only light therapy duration was extended to reduce the circadian period under 24h. This very long light therapy experiment had to be stopped because of waking up way too early. See the Backward Cycling Therapy protocol below for more information.

Before this working therapy, the author tried: 1- melatonin only, 2- light therapy lamps + melatonin, 3- strict ketogenic diet only with timed meals (time-restricted feeding), 4- intermittent fasting (or even complete fasting for a few days), 5-carbs-only diet, and of course strict sleep hygiene, 6- chronotherapy, 7- chronotherapy with light therapy (ie, advancing light therapy 1h earlier than last target wake up time every 3 days). None of those therapies worked.

The latest working therapy protocol designed by the author, which worked for 2.5 months and reproduced for 4 months (still ongoing) at the time of this writing, is named VLiDACMel, which stands for:

  • Very long Light therapy at wake-up (after minimal core body temperature), the most important tool of this therapy,
  • Dark therapy in the evening,
  • Avoid eating Carbohydrates when Melatonin is high in the blood,
  • Take exogenous instant-release Melatonin timed before DLMO (measured via core body temperature or approximated via 3 days average of wake-up times).
  • And always curate a sleep diary to assess changes in the circadian rhythm phase and properly adapt the treatments and to assess the conditions to optimally sleep restoratively.

Concisely, this therapy is founded on the following 3 points:

  • Light exposure control: light therapy glasses Luminette at wake-up (or another light source of 500lux with optimized light angle to stimulate ipRGCs in the nasal retinal hemiregion) to phase advance and hence reduce circadian period (biological day duration). The exposure must be "very long", so use for 2-5h from wake up using relatively low intensity bright light of 500 lux. Exposure duration to light therapy can be modulated to fine-tune the wake-up time (ie, with longer exposure, the participant will wake up earlier and earlier), and this modulation is the primary way this therapy allows for flexible readjustment of the sleep schedule on a daily basis without having to freerun a full cycle again. Light therapy must always be combined with dark therapy in the evening (ie, avoidance of light exposure to avoid unwanted phase delay), by using blue light filters and dimming the brightness of any light emitting device/lamps (or use blue blocker sunglasses if environmental light sources cannot be controlled).
  • Sleep induction and consolidation by melatonin: use melatonin instant release pills, taken at a time calculated relatively to the individual's DLMO (not the bedtime), and avoidance of wakefulness inducing drugs such as caffeine. This both consolidates sleep (ie, ensures you sleep your full night and not wake up too early or in the middle of your night causing unwanted sleep deprivation) and phase advance (allow to sleep and wake up earlier). The effect of melatonin is additive with light therapy. This step can be temporary, as melatonin can be dropped later on if the user feels too drowsy during days after melatonin, but it's good to do at least for a few weeks at first to magnify the sleepiness feeling so that the user re-learns to recognize it.
  • Food timing and diet composition control: never eat after melatonin intake and reduce/minimize carbohydrates intake. In the experiment above, I was half the time under a strict ketogenic diet, and half under a balanced diet including carbs. The ketogenic diet is not necessary, but it can help at first before phasing it out.

Update on current findings of efficacy for this therapy:

The first threshold to consider any treatment potentially effective was set to 1 month of entrainment, entrainment being defined as an average wake-up time under 1 ultradian cycle (a time window of 1.5-2h), such as wake up between 9am and 11am. A secondary threshold to consider a treatment really effective is set to at least 6 months of entrainment, as evidenced by circadian rhythm measures (eg, core body temperature, not necessarily the sleep-wake patterns). A third threshold to consider a treatment effective and robust is set to at least 1 year of continuous entrainment, as to ensure the treatment allows robust entrainment despite seasonal variations in sunlight exposure and ambient temperature (ie, robustness against environmental variability).

As of April 2021, very long (5h-9h) bright light therapy plus dark therapy achieved threshold 1, and is investigated for the 2nd and 3rd thresholds. Melatonin alone passed the 1st threshold but not the 2nd.

As of August 2021, since late February 2021 the very long (5-9h) bright light therapy plus dark therapy protocol (ie, updated VLiDACMel protocol, with melatonin being optional and not used during this period) achieved thresholds 1 and 2 but failed the 3rd threshold. Indeed, the entrainment (ie, stabilized/frozen circadian phase) worked for ~7 months, whereas with no therapy entrainment (to sunlight) lasts 1 month maximum for the author. This is significantly better than no therapy, but still the entrainment is lost once or twice a year. It should be noted that the entrainment is not lost at once, but rather there is a slight remaining daily shift that accumulates over time and so the wake up time changed from 8am in late February 2021 to 4pm in late July 2021, so that the circadian phase was now akin to a DSPD pattern. The author then decided to freerun to become again more quickly in phase with the day-night cycle. This is still a failure since the entrainment couldn't be maintained fully stable. A potential improvement to this therapy may be by adjuncting a hyper photosensitizing drug, this will be explored in the future (there is a section about these drugs below in the Troubleshooting section).

In summary, the current state (as of August 2021) of efficacy of the VLiDACMel therapy is a maintenance of entrainment for 6-7 months for the author (compared to 1 month without). Anecdotal reports from other users suggest that some have obtained (much) better results, while others have reported worse (in general individuals with comorbidities that prevent the continuous use of light therapy or melatonin, such as RLS and PLMD). Elders seem to be more responsive (often, melatonin alone is sufficient for their entrainment) than younger individuals.

As of January 2022, despite more than a month (during mid October to November) without any therapy (because the light therapy glasses had to be sent back to the producer for exchange for an upgraded model), 2-4h of daily therapy allowed to drastically reduce the freerunning speed, but did not allow for a full freeze, although it is very close. Indeed, between end of September 2021 and mid-January 2022, the wake up time shifted from 1pm to 4pm, which is only a 3h phase delay under 3.5 months, in other words a (3*60)/(30*3.5) = 1.71min/day of daily freerunning delay. Compared to the author's natural daily freerunning delay of 20 to 30min/day, this is a 91% to 94% reduction in freerunning speed! And it is worth accounting for the fact that most of this phase delay happened during the period without any therapy, so this average daily freerunning delay is misleading as it was in reality mostly frozen before and after this period without therapy, as shown in the sleep diary below:

This represents the first successful significant slowdown, almost frozen, freerunning of the author's circadian rhythm during winter. Although this was still partially unsatisfactory due to the less than ideal absolute timing of the circadian night, as it was slowed down in an already delayed phase, it is still a significant improvement over having no control when there is no light therapy. This period of winter 2021 represents the first time the author could avoid a full freerunning loop. Worth noting is that this was achieved without being exposed to sunlight the vast majority of the time, with the author waking up past sunset on most days, under which conditions it is a considerable achievement to mainain a relatively entrained circadian rhythm and positive mood. Furthermore, this allowed the author to experience the mood modulation effects of light therapy (or the lack thereof), which prompted the author to modify this document to emphasize the mood modulation effect as being as important as the circadian phase shifting effect.

Here is a wide picture including all of the 2021 year, which includes a forced freerunning in August 2021 to realign the circadian night with a more favorable timing in preparation for an important personal event (and this method succeeded):

Here is the whole sleep diary over several years since the start of this whole experiment, spanning from July 2019 to January 2022, starting with no therapy at the far left, then attempting melatonin therapy with limited success, to finally end up with very long light therapy for the last three cycles (starting from 1/6/2020, at the middle of the chart):

Note that during 2021, most of the chaotic sleep that can be observed were caused by unavoidable appointments or sleep disruptors (eg, environmental noises). The effect of the latter were greatly disrupted since starting using the Hibermate earmuffs and sleep mask in December 2021, which greatly improved sleep quality and reduced sleep fragmentations.

As of August 2022, light therapy had to be mostly stopped since January 2022, being used about once every 2 weeks (or more precisely 3 weeks every 3 other weeks) due to duties and appointments. This allowed to observe that my circadian rhythm reverted under just a month or so to its original state, with a freerunning period of about 24.3h (20-30min delay per day). This allows us to infer two things:

  1. Despite use of light therapy daily over a year, effects aren't sustained over the long term: the beneficial effects of light therapy (and the other items in the VLiDACMel protocol) are only sustained as long as the therapy is used, hence, it is a maintenance therapy, not a curative therapy;
  2. VLiDACMel and light therapy are arguably safe to experiment with, as even using circadian waveform shaping (an extreme manipulation protocol) did not result in any long-term effects, discontinuation of the therapy is sufficient to recover the original circadian rhythm state after a short time (a few weeks).

(TODO: add sleep diary figure)

Hence, after 2.5 years of (self-)experimentation, we can deduce the benefits and limitations of the VLiDACMel protocol: it is likely a safe protocol, which can reduce by more than 90% the daily freerunning delay, but it cannot freeze/eliminate fully the delay, and the effects are sustained only as long as the protocol is used (although keep in mind that missing one or two days is not an issue since light therapy has an inertia period where effects are still sustained despite discontinuation, but not over weeks). Further research should test this protocol over a bigger sample to confirm these findings, as this would indeed be the first known effective maintenance therapy for the sighted non-24 disorder with the potential to significantly improve the quality of life and social integration of this population, although unfortunately not a curative treatment and not eliminating fully the impairments and handicaps caused by this disorder.

Two-minutes quickstart version of the VLiDACMel therapy protocol

A quickstart for those who don't have the time to read or don't need the details and references. Other versions with more precisions are available below.

Target populations: individuals with a circadian rhythm disorder, especially sighted non-24 for whom this protocol is optimized for, with undamaged ipRGC retinal cells as evidenced by preserved pupillary light reflex (PLR), since the ipRGC cells regulate both the PLR and circadian manipulation and the PLR was found to be a reliable discriminator to detect DSPD and especially sighted non-24, strongly suggesting that for at least some people with sighted non-24 or DSPD, one root cause is that they are less sensitive to bright light. Thus, it is arguably likely that this therapy should work for any individual with a preserved pupillary light reflex. Hence, this protocol should work for individuals with a sighted non-24 disorder, some blind non-24 (those sensitive to relative coordination to sunlight), and those with a delayed sleep-phase disorder (DSPD) with some slight modifications as indicated in the "Adaptations for DSPD" section. With further adaptations, as indicated in the relative sections, the protocol should also work for other circadian rhythm disorders (night shift work disorder, ASPD, etc). If you don't know what these disorders are or if you are unsure if you are affected, please read in the "Diagnosis" section (inside the Troubleshooting part) the instructions to monitor your sleep-wake patterns using a sleep diary or a core body temperature sensor at home, or via salivary melatonin sampling in a hospital.
Improvements you can expect: if you have sighted non-24 or blind non-24 with preserved pupillary light reflex, you can expect a drastic slowdown of your freerunning period proportional to the duration of bright light therapy. Those with a shorter circadian period, ie, closer to 24h, should see most benefits, as they can become quasi entrained to 24h, whereas it is expected to be more difficult to entrain for individuals with longer circadian periods, with those with a >26h circadian period obtaining little benefits (they will still get a slowdown, but it may not be a clinical improvement in practice for them). For DSPD, you can expect to consistently sleep and wake up a few hours earlier, proportionally to the duration of bright ligth exposure. For ASPD, you can expect to consistently sleep and wake up later. There can be minor side effects such as additional fatigue or dizziness, but no severe adverse effect, and all effects should disappear after discontinuing therapy.
Who should NOT use the therapy (contra-indications): If you have an ocular illness, ask your doctor before if you can use light therapy, otherwise melatonin can still be used. If after starting the therapy, motor dysfunctions appear or are worsened (eg, restless legs) then stop the whole therapy (both light therapy and melatonin) right now, and talk to your doctor about getting tested for a motor disoder (PLMD, RLS) or ADHD. If on the other hand you can sustain being under the sunlight, you will probably be fine. If you don't have a contra-indication to sunlight or light therapy exposure, then apriori you can safely use certified light therapy devices such as Luminette as they are medically screened and validated against FDA or european health safety norms, and the effect of light therapy on the circadian rhythm is always reversible under a few weeks of discontinuation (there is unfortunately no circadian plasticity contrary to what was presumed in the past).

Therapy's main steps, in chronological order of when to do them in the day:

  • Find your circadian night. It's when you sleep more than 6h with little to no wake ups in the middle of the night (no fragmentation). If you have non-24, freerun until your circadian night happens close to the time you want to freeze your sleep-wake schedule. Naps are allowed. Write a sleep diary all the time to monitor your sleep patterns, and bring it to a circadian rhythm disorder specialist to get diagnosed and accommodations. For diagnosis, 2-4 weeks of sleep diary data is enough, but sleep diaries are the best tool currently available to self-manage circadian rhythm disorders, hence you should continue writing them all the time. Using an electronic sleep diary can be easier over the long term (Sleepmeter Free on Android, and its widget, or a digital spreadsheet).
  • On natural (unrestricted) wake up, use light therapy glasses such as Luminette v3 for 2-8h using the lowest or medium light intensity setting. No alarm clocks, just wake up naturally. Don't use light therapy lamps, only glasses. For the first light therapy session of the day, keep your eyes closed for 30s while turning the lights on, to reduce the likelihood of headaches or dizziness due to sudden cortisol secretion caused by sudden bright light, then slowly open your eyes. Light therapy is by far the most important element of this therapy. Light therapy has two major effects: it advances earlier your circadian rhythm phase (circadian shifting effect), making you wake up earlier, and it improves your energy levels, mood and productivity (antidepressant effect). The antidepressant effect is as crucial as the phase advance effect, as it allows to remain motivated and enjoy activities, whether or not the circadian phase advance effect is sufficient for the individual to fully freeze the phase, the antidepressant effect is well worth by itself. Very long outdoors sunlight exposure is even more effective than any artificial light therapy device, but it's difficult to administer properly and constantly: on unfavorable weather (rain, snow) it is highly uncomfortable and difficult to time as sunlight must be blocked (even indoors) before your minimal core body temperature point, and sunlight cannot be used past sunset, which can be a big issue during winter in some regions of the world with particularly shorter days.
    • Side-note: Light therapy is most effective when started in the circadian morning. The above step assumes that even if you don't know when your circadian morning is, by constantly using light therapy at wake up, at some point one of your wake ups will happen in your circadian morning, and then light therapy will "freeze" your wake up time in place. This strategy has more chances to work because the wake up time (sleep offset) is much more tightly coupled with the circadian rhythm than the fall asleep time (sleep onset) (for references, see the section Seasonal variations in zeitgebers or why Bedtime and wake up time are independent (dual-oscillator model)). But you can also choose to detect your circadian morning beforehand to increase the odds the therapy works and minimize the risks of unwanted effects (ie, faster delay when exposed in the circadian evening/night). To know when is your circadian morning, try to use a sleep diary such as Sleepmeter Free, and infer approximately using the following algorithm: wait for a long sleep session, and then start light therapy at the wake up from this long sleep session just after and the following days. How to know what is a long sleep session for you? For the vast majority of adults, the average night sleep needs per 24h is 7-9h of sleep, although some adults need more (10h or more) or less (very rare, usually people who think they are short sleepers are in fact sleep deprived), but this duration can only be achieved when sleeping in phase with the circadian night or under extreme sleep pression built from severe sleep deprivation. Any sleep duration less than that should be considered an out of phase sleep, and hence not to be counted. Remember sleep works by discrete increments, called ultradian cycles, that last ~2h, hence short sleep sessions can last at most the maximum sleep you can get for your age minus one or two ultradian cycle (eg, for an adult having average sleep needs of 7-9h, they can sleep out of phase a maximum of 4-6h, these short sleep sessions should be discarded). Once you experience a sleep session long enough to fully fill your sleep needs (eg, 7-9h), start the therapy on wake up, and redo therapy at the same time the following days. You should notice your wake up time should not move or at least not as fast as before after a few days of therapy, if the timing was correct. If not, wait for another long sleep session to retry, as sometimes a long sleep session may be caused by extreme sleep pressure instead of circadian alignment, and hence be a false positive. Keep in mind that the disadvantage of the inference method is that you can wait for weeks before a long sleep session happens depending on your circumstances (especially if you restrict your sleep because of duties), whereas using a core body temperature sensor allows to know the circadian profile under just 48h. Skin temperature sensors do not work for this purpose, unless MAYBE wrist skin temperature on the radial artery with an adequately totally enclosing cotton wrist band.
    • WARNING: do NOT use bright light therapy while driving, as you need your full vision for your safety!
    • Do not use cheap light therapy lamps, such as Beurer TL30: they don't emit enough blue light and they require you to be way too close (nose on the lamp), so they are in practice ineffective. Check their manual, it should specify the distance to get the promised quantity of lux, and you will find you need to be literally the nose on the lamp for it to be effective, which is impractical and unrealistic given how long the therapy needs to be done to be effective. Expensive light therapy lamps can be effective but they are more cumbersome and much more expensive than light therapy glasses of similar melanopic intensity (ie, intensity of bright light at your eyes level), but some users with non24 report even greater efficacy with them, or better, in combination with light therapy glasses.
    • Also, bright light therapy is unnecessary when exposed to outdoors sunlight, even if cloudy or behind a glass (eg, driving), it counts as additional bright light therapy (ie, UVs filtering does NOT matter, only the quantity of Lux at eye level does). But as a rule of thumb, consider artificial bright light therapy using light therapy glasses is always necessary indoors (this is not 100% accurate as some indoors conditions can be sufficient, but it is highly variable with just head orientation, hence this rule of thumb - use a lux sensor app on your smartphone to see how much lux varies indoors), and optional or unnecessary outdoors when there is sunlight exposure (even if indirect or very cloudy).
    • If you are short on money and don't want to spend it on light therapy glasses unless you know it's going to work for you: you can try sunlight therapy instead for a few weeks, which consists in going outside (don't stay in a building, you need to get outdoors) to get exposed to sunlight at natural wake up, and stay outdoors for at least 1-2h, every single day. This is free, and you will get similar benefits to light therapy glasses (sunlight is the brightest lamp!), but it's very cumbersome: you need to do that every single day even when the weather is rainy or snowy, and even when it's cold. Hence, to make it easier, try this preferably during the warmer months, such as summer in northern countries. If your circadian rhythm stabilizes (freerunning slows down for non24 or phase advance = waking up earlier naturally for DSPD), then consider buying light therapy glasses, now that you know it works for you. This is not just for comfort, but for efficacy: during winter months, sunlight cannot be used, since it rises up too late (eg, if you want to wake up at 7-8am but dawn happens only at 9-10am then this won't work, you need artificial light therapy exposure before 7-8am to lock in your circadian phase).
    • How to assess if light therapy is safe for you? The general rule is: if you have an eye condition that makes you limit your exposure to sunlight, then you should also avoid artificial light therapy. But if you can get exposed to sunlight without any particular limit, there is no reason to expect artificial light therapy to be any more dangerous, as it is magnitudes less intense. But I'm not an ophtalmologist, so please check with a professional.
    • Tip: Keep the light therapy device on your bed table, so that you can easily reach for it first thing in the morning while still in bed.
    • During winter, should you use artificial light therapy longer than sunlight exposure (eg, if sunset is at 4pm, should you continue past that)? It depends on how long the exposure you need to be entrained. If you need 5h of exposure minimum, then this is achievable before 4pm by starting at the latest at 11am. So indeed you may use artificial light therapy longer during summer than during winter, but during winter you may have to use artificial light therapy past sunset if you need longer exposure.
  • 3h-5h before your natural fall asleep time (this should equal 12-15h before your last wake up time) is usually the start of the circadian evening, start dark therapy: dim to the minimum or switch off lamps and screens, and filter blue light using blue light filter apps and prefer red light lamps such as Yeelight 1S. Use a lux meter app on a smartphone to confirm, you should see 0 lux at best, or at least less than 10 lux. If you can't modify your environmental lights, wear orange or red tinted blue blocker glasses (use UVEX or red-tinted laser safety glasses that filter blue and green lights). Avoid eating or consuming carbohydrated meals or drinks past this time. Never consume alcohol, at any time, as it majorly disrupts the circadian rhythm. Avoid caffeine in the circadian evening, and also in the day if you are not an avid user, as effects can carry over 48h.
    • Pro tip: you are doing dark therapy right if your eyes stay accommodated to darkness (ie, dilated pupils letting more light rays entering in) all the time during your circadian evening.
    • Pro tip2: even a short burst of artificial bright light during your circadian evening is enough to modify your circadian phase durably, so equip your environment with smart lighting such as RGB LED lamps programmable with an app (such as Yeelight), or dim portable led lamps with automatic movement detection, so that you can go to the bathroom, kitchen, toilets without getting exposed to bright lights.
    • During the night, eliminate sources of noise and sleep interruptions. Tools such as black silk eye masks, earplugs, and very-low-profile earmuffs such as the Hibermate headset, white/brown noise machines or apps such as Noice can allow to greatly reduce the impact of environmental noise on your sleep. The Hibermate combined with in-ear plugs is a highly recommended aid to reduce sleep fragmentations due to sleep disruptions such as noise and unwanted light exposure. Bright light during sleep directly damages cardiometabolic health.
    • The 3h-5h rule is not really precise, it should work for most people but the timing of the start of the circadian evening, but there is actually a wide window of variability between different people, so if this does not work, feel free to start dark therapy and melatonin earlier or later until you find the sweet spot, effect should happen the same night or the night after at worst, so feedback is near instantaneous and makes this an easy to iterate process.
    • If you cannot fall asleep:
      • If you tend to watch TV or a computer screen as half of americans do in 2023, prefer instead to use a smartphone: with its smaller screen, and settings set to minimum brightness and a reddish blue light filter app, such properly configured smartphones screens will have minimal impact on the circadian rhythm (you can check with another smartphone with a lux meter app that your eyes get 0-1 lux from the smartphone screen).
      • If it takes really too long (40min), you can wake up and do interruptible activities so that you don't lose all your time, but prioritize going back to bed at anytime at the slightest feeling of tiredness.
      • Avoid any bright light exposure whatever you do until you fall asleep. Bright light during the circadian evening or night will inhibit melatonin and phase delay your circadian phase.
    • Optional: You can take melatonin at the same time you start dark therapy, dosage 0.3mg up to 3mg (or sometimes more for some people - melatonin has been tested safe for all ages including toddlers with dosages up to 10mg for infants and 6600mg for adults), instant release and in blister packs. For some people, taking melatonin 12h before the natural wake up time is a good starting point, the effects should work the very same night, and it's possible to then modify the timing (earlier or later) each day by increments of 30min until the sweet spot of maximal effect is found. If feeling drowsy during days after melatonin intake, you can reduce melatonin dosage or stop it once entrainment to light therapy works and only if you do not consume any stimulant (eg, caffeine in coffee or tea or energy drinks, ADHD medications, etc).
      • Note: Melatonin and bright light therapy work on distinct (so-called "EM") circadian oscillators: melatonin affects directly the sleep onset time, whereas bright light affects the wake up time. To simplify, melatonin kickstarts the circadian night, whereas bright light kickstart the circadian day. Bright light also affects the sleep onset time after a few days of "catching up" with the new wake up time, whereas melatonin has almost no effect on the wake up time. Hence, melatonin is only optional for circadian entrainment, and mainly serves to accelerate phase advancing of sleep onset or amplify sleep drowsiness, whereas bright light is mandatory.
      • Melatonin and other compounds will degrade with exposure to light, humidity or hot temperature. To slow down degradation, place the melatonin contener inside a resealable plastic bags (or tie an air-tight knot with the plastic bag opening), and place the bag in an obscure place at ambient, normal temperature. Avoid liquid melatonin, as it degrades under a few days after opening, prefer solid form tablets. Prefer pure melatonin products, with no other compounds (eg, valeriane) as they will have higher quality control standards (ie, dosage will more likely be as labelled).
  • Maintenance: Once entrainment is achieved, the treatment must be continued as-is with the parameters (ie, light therapy timing and duration, melatonin timing and dosage, dark therapy setup, etc) you found effective for maintenance of benefits. Indeed, the therapy is effective only as long as it is used, otherwise effects are lost under a few weeks, but the therapy can always be restarted later. Of course some adjustments can be done on a day-to-day basis: if waking up later, you can do light therapy longer the next day ; if waking up too early, you can start light therapy later at the usual time you found effective for entrainment to avoid waking up earlier and earlier ; melatonin and dark therapy should usually be started always at the same time but can be advanced to ensure you do not miss the window, etc. Do not expect a totally immutable circadian phase, this is not a mechanical clock: even when fully entrained, sleep remains a biological process and hence naturally noisy, so it is likely perfectly normal to observe over time natural variations in the fall asleep time and wake up time under a window of one sleep cycle (ie, 1h30-2h00 for adults, 1h-1h30 for children). Note also that between seasons it is normal to sleep and wake up later or earlier depending on the varying sunrise and sunset times.
    • Previously, it was here noted that "the therapy could not be 100% effective and freeze totally in place the circadian rhythm due to uncontrollable environmental factors", but the author achieved in 2023-2024 a highly robust circadian phase and set at a time that cannot be caused by environment (eg, consistently waking up 2h earlier than sunrise during winter, the same absolute time defined in autumn and even before DST change) and only varying under one sleep cycle window, and most often under a window less than 30min. However, this requires extreme mastery of the protocol and of exposure to environmental factors such as sunlight, hence for less experienced users, expect to get misaligned from time to time: for individuals with non-24, simply discontinue therapy temporarily to freerun a few weeks until the ideal time is reached again; for DSPD, increase the exposure duration, or discontinue therapy temporarily to find where your circadian phase currently is, to re-time light therapy optimally after the minimum core body temperature, or use a core body temperature sensor to find it right away.

Most helpful tools, used on a daily basis by the document's author:

  • Sleep diary (Sleepmeter Free on Android, and its widget for an electronic diary, or the AASM template for a paper diary, 2021 updated version here, or there is a digital spreadsheet , or the plees-tracker open-source app on Android)
    • On Android 14+, SleepMeter cannot normally be installed, but it is possible to force installation (thanks to eatnerdsgetshredded for the tip!): enable USB debugging on your phone (you need to enable Developer Mode, no root needed), then connect your phone to a PC with USB debugging, and then you can use the following ADB command: `adb install --bypass-low-target-sdk-block app.apk`
  • Luminette v3 (for light therapy)
  • Hibermate (includes eyemask, to eliminate sleep disruptions)
  • Earplugs (to eliminate sleep disruptions)
  • Core body temperature or melatonin sampling (for circadian phase monitoring)
    • Some labs offer direct circadian rhythm estimation through core body temperature (usually via a rectal probe, sometimes with a 3M SpotOn or another zero-heat-flux thermometer) or via melatonin sampling. This has the great advantage of allowing to observe the circadian rhythm despite masking effects, such as social obligations (eg, having to set up an alarm clock to go to work or school, then the sleep diary won't allow to robustly estimate the circadian rhythm profile and parameters, but the core body temperature or melatonin sampling can).
    • Don't try to use skin temperature sensors to derive your circadian profile. They may be much cheaper, but skin temperature does not reflect the circadian rhythm since humans are homeothermic animals, so only core (internal) body temperature is self-regulated, whereas skin temperature is affected by ambient temperature. There is an exception for wrist skin temperature but this requires a very specific kind of setup and analysis.
  • Yeelight 1S RGB light bulb (automatic dark therapy)
  • Blue blocker / red tinted laser safety glasses (for portable dark therapy)
  • Noice white noise machine app on Android, open-source and free. Here is a preset the current document's author made for newborns but which also works for adults: InfantWombSim for Noice v1.3.3, WombSimulator for Noice v2. A non-free equivalent software for iOS is Dark Noise, but the source-code is available.
  • The book Sleep Misfits: The reality of Delayed Sleep Phase Syndrome & Non-24 by Sally Cat is highly recommended, being the only book currently written compiling the experience specific to patients living with non-24 and DSPD handicaps. Reviews note that this book can help in validating one's own experience, and help with acceptance and coping with the handicap.
  • Optional, and only when freerunning and NOT using bright light therapy: Long release caffeine tablets (Lucovitaal 200mg per tablet). Just tike one tablet (200mg) during the circadian morning, usually at natural wake-up. The long-release form ensures a constant inhibition of adhenosine and hence of sleep pressure, and the tablet form avoids the diuretic effect of hot liquid coffee. The long release tablet form makes caffeine a pharmacological compound with more stable pharmacodynamic properties, more reproducible and dosable. However, the same usual issue with caffeine are also present here: caffeine tends to delay the circadian rhythm, and for slow caffeine metabolizers (this is defined genetically), then it can stay in the bloodstream too long and carry over into the night and next day. In practice, this should only be used while freerunning (when phase delays are not an issue). When using both light therapy and caffeine, caffeine can often cause a weird insomnia the night just after intake, with a wide sleep fragmentation gap during the circadian night sleep session, that resorbs after discontinuation of either light therapy (but hence causing freerunning resuming), or long-release caffeine. Nevertheless, it can be a great tool to ensure being able to perform for a whole day, even under sleep deprivation, and reduce the likelihood of random wakefulness drowsiness bouts that is intrinsic to non-24, but it can only be used as a "wildcard" for a single day, with a necessary rest day the next day, it certainly cannot be used on a daily basis (except if freerunning). In that, it can be seen as a non-prescription alternative to modafinil, another wakefulness-promoter that was found to produce effects of similar magnitude to caffeine.

Variants of the protocol:

  • Phase-delay bright light therapy, which is to get exposed to bright light such as Luminette in the circadian evening and night (ie, start 3-5h before circadian night and up to 4h after the start of the circadian night but no later than 4h before the circadian wake up time) can be used only for individuals with non-24 (not DSPD, there is a theoretical risk to turn into non-24!) to speed up the circadian freerunning by 2x up to 3x. This can be used as a complementary therapy to VLiDACMel, when the circadian phase slipped out too late due to the residual uncorrectable freerunning, to realign one's circadian phase with the day-night cycle, and then restart the VLiDACMel therapy.
  • If you need to restrict your sleep (eg, for work or other circumstances), consider adopting a biphasic sleep pattern, which is to sleep twice under your circadian period: once during the latter half of your circadian night, and once during the circadian siesta which is about 12-15h after the start of the circadian night. For example, if your circadian night is currently at 2am-10am, then you can try to have a nap between 2pm-5pm, and then sleep the latter half of your circadian night between 6am-10am (you won't be able to sleep the first half because of a lack of sleep pressure due to the nap). You will usually sleep less during the nap than during your circadian night. This works because for most purposes (health, cognitive performance), what matters most is the total sum of sleep durations over one circadian period. This strategy is commonly used by successfully adapted shift workers. It however does not prevent freerunning, but it can be combined with VLiDACMel to slow it down.

Simplified protocol

This is a simplified version of the full protocol presented as a straigh-to-the-point set of rules, without the rationale nor the explanations, which may be easier to present the therapy to patients. See the Full Protocol and the Troubleshooting sections below for more detailed explanations and references.


  • phase shift: earlier or later shift in the timing of the circadian rhythm and hence of the natural wake up and bedtime, with phase advance being earlier and phase delay later
  • biological or circadian night/day: relative day or night in phase with the individual's circadian rhythm (respectively low period and high period - core body temperature reflects the same trends). The biological/circadian night is the ideal time for the individual to get a long and reparative sleep, and inversely it will be very difficult to sleep during the biological/circadian day.

Who can use this therapy?

  • Target populations: individuals with a circadian rhythm disorder, especially sighted non-24 for whom this protocol is optimized for, with undamaged ipRGC retinal cells as evidenced by preserved pupillary light reflex (PLR), since the ipRGC cells regulate both the PLR and circadian manipulation and the PLR was found to be a reliable discriminator to detect DSPD. Thus, it is arguably likely that this therapy should work for any individual with a preserved pupillary light reflex. Hence, this protocol should work for individuals with a sighted non-24 disorder, some blind non-24 (those sensitive to relative coordination to sunlight), and those with a delayed sleep-phase disorder (DSPD) with some slight modifications as indicated in the "Adaptations for DSPD" section. With further adaptations, as indicated in the relative sections, the protocol should also work for other circadian rhythm disorders (night shift work disorder, ASPD, etc). If you don't know what these disorders are or if you are unsure if you are affected, please read in the "Diagnosis" section (inside the Troubleshooting part) the instructions to monitor your sleep-wake patterns using a sleep diary or a core body temperature sensor at home, or via salivary melatonin sampling in a hospital.
  • Contra-indications: If you have an ocular illness, ask your doctor before if you can use light therapy, otherwise melatonin can still be used. If after starting the therapy, motor dysfunctions appear or are worsened (eg, restless legs) then stop the whole therapy (both light therapy and melatonin) right now, and talk to your doctor about getting tested for a motor disoder (PLMD, RLS) or ADHD. If on the other hand you can sustain being under the sunlight, you will probably be fine. If you don't have a contra-indication to sunlight or light therapy exposure, then apriori you can safely use certified light therapy devices such as Luminette as they are medically screened and validated against FDA or european health safety norms, and the effect of light therapy on the circadian rhythm is always reversible under a few weeks of discontinuation (there is unfortunately no circadian plasticity contrary to what was presumed in the past).

What results can be expected

  • Freerunning should stop or get slower for those with a long circadian period (ie, >26h). This means there won't be "night-walking" phases anymore, where you sleep during the day and are awake the whole night.
    • However, this therapy does not guarantee a constant sleep-wake schedule, which will likely remain highly variable from day-to-day in a 6h timeframe: one day you can wake up at 1pm, the next at 11am, the next at 2pm, the next at 9am (and feel sleepy at according times).
  • Longer sleep on average than without the therapy, and with a higher quality and less to no interruptions.
    • However, biphasic sleep (ie, "weird insomnia") and irresistible naps will still occur somewhat regularly, mostly at random.
  • Improved overall health, especially cognitive performance and mood.
    • However, mood swings and cognitive drops (ie, "zombie-like" states) will still happen somewhat regularly, mainly dependent on how long you slept earlier.


  • Start to write a sleep diary (template) with the fall asleep time and wake up time, everyday, including naps. Continue to curate this sleep diary all the time, this is the most essential tool to self-monitor the circadian rhythm and better manage the disorder. Digital sleep diary such as Sleepmeter Free on Android are recommended as they also generate sleep charts, which are easier to monitor and diagnose by doctors.
  • Before starting the therapy: Freerun (ie, sleep when naturally tired and wake up without an alarm clock) until you wake up close to your ideal wake up time. The therapy will then freeze in place the circadian rhythm and sleep-wake schedule. Nap as much as needed to reduce as much sleep deprivation as possible, this improves the therapy's efficacy. This applies only for non-24, other circadian rhythm disorders such as DSPD should not freerun.

Start the VLiDACMel therapy

  • At natural wake-up (biological morning):
    • Avoid alarm clocks, allow yourself to wake up naturally.
    • Use light therapy glasses (Luminette, Re-Timer) at wake-up every day for several hours (2-8h) with the minimal intensity setting (500lux).
      • Start with eyes closed for the first minute or so to help the pupil gently accomodate and avoid dizziness due to sudden bright light exposure, which may otherwise cause headaches and migraines due to the sudden pump in cortisol secretion due to sudden bright light exposure.
      • Light therapy is the strongest tool for circadian rhythm entrainment, and is the foundation of this protocol: it modulates both the wake up time, the minimal core body temperature (and hence circadian rhythm) and the stop of endogenous melatonin secretion (DLMOff).
      • Light therapy has two major effects: 1) it advances earlier your circadian rhythm phase (circadian shifting effect), making you wake up earlier, and 2) it improves your mood, energy levels and productivity (antidepressant effect). The antidepressant effect is as crucial as the phase advance effect, as it allows to enjoy activities even when the phase advance effect may not be sufficient for some individuals to fully stabilize their sleep schedule.
        • Note that light therapy only has an indirect effect on sleep onset time, so it won't make you fall asleep earlier nor even feel sleepy earlier, because sleep onset and wake up times are regulated by distinct circadian oscillators ("EM" oscillators). You either need to wait several days for the sleep onset to "catch up" with the new wake up time, or you can try to use melatonin as indicated below to force a phase advance in the sleep onset, since melatonin directly affects the sleep onset oscillator.
      • At first, light therapy will slow down the daily phase delay in the wake up time (wake up earlier), but not the bed time, so it's possible to experience a reduced sleep duration at first. Both times gets synchronized after several days.
      • After 10 days you should see the full effect of the light therapy, with a reduction of your daily phase delay (ie, you'll sleep less later every day, or hopefully be entrained). This delay is due to photic history.
      • If after 10 days that's not enough to stay entrained, increase the duration, not light intensity. Indeed, increasing the duration is more effective than increasing the intensity of light therapy. There is no limit to how much phase shift can be gained from light therapy since there is no PRC dead zone, which can allow to achieve 8h of phase advance in 5 days by using 5-8h/day of bright light therapy.
      • If you cannot wake up naturally without an alarm clock due to obligations, then do not use light therapy and postpone this therapy, as it's crucial to use it after the minimal core body temperature point, which happens slightly before the natural wake up time, and not before, as confirmed by the AASM CRSWD 2015 Guidelines. Once you know when your natural wake up time is, then you can use light therapy even if you need to use an alarm clock, based on your approximative prediction of when is your circadian morning and day (tools such as Circalog can help - but are still in development).
      • Do not restrict your sleep and nap as much as needed to feel rested (so don't use alarm clocks), as sleep deprivation and sleep restriction reduce the effectiveness of light therapy due to adenosine buildup.
      • About consistency and room for error: what happens if you cannot use light therapy at the same time and for the same duration every days?
        • In practice, this is a very common occurrence, nobody can comply 100% all the time with such a long and constraining protocol. What matters is that you can start light therapy at about the same time around natural wake up on most day (more or less 1h), and that you can use about the same duration (more or less 2h). With experience, you will learn what is your sweet spot in terms of duration to achieve your goal (entrainment for non24, phase advance for DSPD), memorize this duration as it is very important.
        • On other days, when you cannot use light therapy as you optimally would need to, then you can always use light therapy partially, this will maintain some if not most of light therapy effects thanks to photic history inertia (as long as the partial light therapy days are less frequent than the full light therapy days).
        • What if you wake up earlier than usual? If it's 1-2h earlier, you can start using light therapy if you want to progressively wake up earlier. On the other hand, if you are satisfied with your current circadian phase and just want to keep it, then wait later to start light therapy at around a similar time you naturally wake up usually. If you wake up more than 2h earlier, there is a risk that exposure to bright light can fall before the minimal core body temperature point and hence cause a phase delay, so in this case you should avoid all bright light exposure (not just light therapy!) until later around your usual natural wake up time, then start light therapy and you can get exposed to other bright light sources such as sunlight.
        • What if you wake up later than usual? Start light therapy at wake up, and then use light therapy longer to compensate with more duration to increase efficacy, BUT always stop before the circadian evening. Eg, if usually you do light therapy at 10am and stop at 2pm, but today you wake up at noon, then you start light therapy asap and stop at 4pm. However, if you do light therapy at 10am and usually stop at 5pm, and today you wake up at 2pm, then you should do light therapy from 2pm to 5pm or max 6pm, then stop because sun sets and your circadian evening is starting.
          • Why this works: Since there is no PRC dead zone, it's ok to start light therapy later if waking up later than usual or if unable to start light therapy at wake up, even hours after natural wake up and it will still be effective, as long as it can be finished before the biological evening and night (just like for SAD therapy). Starting later than in the circadian morning (ie, hours later than natural wake up) is less effective, but this can be compensated by increasing duration.
        • What if you have to stop light therapy in the middle of the session? No problem, you can restart later. Studies shown that intermittent light therapy (15min of light therapy per hour) is as effective as continuous light therapy to shift the circadian phase. The same principle applies if you need to take a nap in the middle of your light therapy session: you can do light therapy before and after, as long as you stop before your circadian evening. Note however that blue light therapy tends to reduce the ability to nap and drowsiness according to studies.
        • What if you stop light therapy during several days?
          • Missing one or two days of light therapy is not catastrophic thanks to the inertia induced by photic history, but it should be resumed as soon as possible.
          • If missing a longer time, do not worry: the circadian rhythm takes time to return to its original state after treatment discontinuation, about as long as it takes for the therapy to reach maximum efficacy (ie, maximum phase advance). Just try to resume therapy, to resume progress to maximum efficacy. Nobody can follow any therapy systematically all the time, this therapy was designed with practicity in mind, and is field tested daily by its author as well as hundreds others under freeliving conditions.
          • In the worst case scenario, if light therapy is discontinued for a week or two, most effects will be gone, but no worries: if you are responsive to light therapy, that's all that matters, you can achieve again the same results you got before by just restarting the protocol from 0.
        • Some people claim that light therapy only works when done with an extreme rigor, as missing one day is enough to lose all progress. This is false, just like having to skip lunch because it's past noon would be inane. Just like any biological process, there is some margin we can use.
      • Needs some trial-and-error to find the sweet spot for how long and when to use the light therapy, some people are light hypersensitive while others are hyposensitive. Timing is taken care of with this protocol, since you just need to start at natural wake up.
      • During winter or in latitudes where days are shorter and sunlight dimmer, longer light therapy sessions are needed. For the author, up to 9h/day is necessary during winter.
      • Very long bright light therapy alone should be sufficient to entrain you. After 10 days, you should start to feel the sleepiness sensation appearing every day at the same time (although it can be feeble and fleeting), hinting that you are entrained and the time you can fall asleep even if you still feel slightly energized. If this sensation does not appear, check if there is any hidden caffeine in the food or beverages you consume such as 0% coke, as caffeine's effects carry over up to 48h including phase delay. It's likely good idea to also avoid any wakefulness inducing drug such as tea and modafinil and nootropics.
      • The phase advance obtained is proportional to the duration of exposure to bright light, eg, 5-8h of daily bright light exposure can produce a phase advance of 8h over 5 days.
      • Some drugs can increase the entrainment to bright light therapy such as hyper photosensitizing drugs (antidepressants, dopaminergic stimulants such as ADHD medication, histaminics), and be decreased with others (eg, antihistaminics, alcohol, caffeine).
      • Naps are allowed. Naps are the main tool to manage sleep pressure, just like bright light therapy is the main tool to regulate the circadian rhythm. Reducing the sleep pressure via naps likely improves the efficacy of bright light therapy.
      • WARNING: do NOT use bright light therapy while driving, as you need your full vision for your safety!
      • Also, bright light therapy is unnecessary when exposed to outdoors sunlight, even if cloudy or behind a glass (eg, driving), it counts as additional bright light therapy (ie, UVs filtering does NOT matter). But as a rule of thumb, artificial bright light therapy using Luminettes is always necessary indoors (this is not 100% accurate as some indoors conditions can be sufficient, but it is highly variable with just head orientation, hence this rule of thumb - use a lux sensor app on your smartphone to see how much lux varies indoors).
      • Light therapy effect does not dissipate over time (ie, no tolerance buildup, no desensitization), its efficacy only depends on the duration and intensity and timing you use it, and a few device related factors that are taken care of by certified devices such as Luminette.
  • In the biological evening (3-5h before naturally falling asleep or 12-15h before the last wake up time):
    • Start dark therapy 2-3h before expected fall asleep time, which means avoiding bright and blue-green lights, but dimmed red light is ok.
    • Optional: Use melatonin pills in the biological evening several hours before bedtime (not just 1h before), as melatonin needs to be taken before the body start producing melatonin (DLMO point).
      • Prefer instant-release, sublingual, pure melatonin tablets as they are more effective, are generally of higher quality in over-the-counter products and degrade more slowly (especially in in blister packs). Over-the-counter melatonin (without prescription) fitting these criteria can be as good as medical-grade melatonin, but for inexperienced beginners, it's highly recommended to ask a doctor for a prescription for medical melatonin, to ensure to test with high quality melatonin. Otherwise, low quality melatonin may have no effect, or have effect at first and then quickly dissipate after just a few days due to degradation to light or humidity.
      • Dosage should be between 0.5-3mg for first timers. The optimal dosage can vary a lot between individuals and by age, so it's possible to use higher dosage, such as 10mg especially for children who naturally have higher endogenous melatonin levels. There is no risk of overdosage in practice (humans have consumed up to 6600mg/day without any serious side effect). A good starting point for adults is to try 2-3mg, and after 2 weeks if you feel drowsy during the days after melatonin intakes, try to lower the dose below 0.5mg.
      • Trial-and-error is required to find the sweet spot for optimal timing and dosage to maximize effect on the circadian rhythm while minimizing next-morning drowsiness. The effect should be felt the very same night, so if the effect is mild or negligible, you can try to change the timing of melatonin intake by increments of 30min each day under the window of 12h-15h before the natural wake up time, until you find the sweet spot of maximal effect.
      • If melatonin is used in combination with bright light therapy, then timing does not matter much and it can be taken just 1h before the expected fall asleep time, because then melatonin mostly serves to induce sleep (by stimulating melatonin type 1 receptors) and maintain the circadian rhythm in place (ie, prevents delays), whereas bright light therapy serves to advance/shorten the circadian rhythm.
      • Melatonin is not necessary for entrainment if very long bright light therapy and dark therapy are used and no stimulant (eg, caffeine) is consumed. But it is still recommended to use melatonin at first, to consolidate the circadian rhythm faster and magnify the sleepiness feeling so that you can better recognize when your body can sleep. However, it can cause drowsiness up to 48h, hence after a few weeks, either lower dosage or melatonin can be discontinued.
      • Melatonin has a direct effect on the sleep onset timing, but not on the wake up time, since both are regulated by distinct circadian oscillators ("EM" oscillators). Hence, if you only use melatonin, you will still continue to wake up later than you want. Thus, melatonin necessarily needs to be combined with another therapy that primarily work on the wake up time circadian oscillator, such as bright light. Indeed, we can view bright light as the tool to activate the circadian day/light oscillator, and melatonin the one to activate the circadian darkness/night oscillator.
    • Avoid eating and caloric drinks when melatonin is high in the blood(R1, R2) + avoid alcohol: no meals, especially carbohydrates, in the biological evening and night and also after taking melatonin pills(R) and not too early in the biological morning (ie, skip breakfast if waking with an alarm clock or if waking up before sunrise in winter), because melatonin impairs insulin and glucose processing (including in typical sleepers).
    • Prepare a good sleeping environment:
      • Sleep with a black silk eye mask or use thick curtains to reduce unwanted exposure to sunlight during your sleep (inhibits your melatonin levels and increases sleep fragmentation). Cut a straight line in the middle of a standard eye mask to make a nose hole which will greatly improve the fit and hence light obstruction.
      • Reduce environmental noise, sleep with ear plugs and a very-low-profile sleep earmuffs such as the Hibermate if necessary. Try various kinds of ear plugs, some will be more comfortable than others depending on your ears. Very-low-profile sleep earmuffs such as the Hibermate can be used alone or in combination with in-earplugs, providing excellent portable isolation to noisy environments. This combination is highly recommended.
      • If you can't sleep under 30min of going to bed, wake up and do something else, come back about 1h30-2h (one ultradian cycle) later when you feel some hints of tiredness.
      • Talk with your co-living relatives to let them know you need to sleep, potentially at odd hours, without interruptions.
      • Avoid sleeping pills (hypnotics drugs) such as benzodiazepines and non-benzodiazepines, they are inadequate to treat circadian rhythm disorders and insomnia.
      • If you snore regularly, this means your airways are obstructed and sleep quality is impaired. Consider getting a sleep study for sleep apnea, although snoring is not a reliable sign of sleep apnea. Meanwhile, you can try to sleep more on your sides by removing your pillows (as we are more likely to snore on our backs), and use nasal sprays to clean the airways before sleep.
      • If you have other health issues that disturb your sleep (such as sleep apnea, digestive issues, fungal infections, restless legs syndrome or any kind of inflammation), treat them too. Comorbid physical diseases often cause or worsen sleep issues and can hence jeopardize anything you try to improve your circadian rhythm disorder, potentially both by decreasing sleep quality (ie, being a sleep disturbance) and by directly affecting your circadian rhythm in some cases. This is especially the case for comorbid disorders that have a circadian pattern (ie, they trigger more often during the circadian night, such as RLS and PLMD and night legs cramps).
        • The VLiDACMel therapy will stop your freerunning, but your sleep quality depends on more than that. If you still feel tired under the VLiDACMel therapy, look for those other health issues that may be the cause of sleep disturbances and hence decreasing drastically your sleep quality and make you feeling tired the whole day after, without guilt or shame for taking care of this essential and universal need.
        • Sleep apnea is a relatively common cause of insomnia and circadian rhythm disorders. If you snore loudly and regularly and have impaired sleep quality, call sleep clinics until you find one that provides an at-home sleep study kit, so that you can get diagnosed of sleep apnea at home. Meanwhile, you can screen yourself by recording your snoring at night, there are free apps such as Do I Snore Or Grind app on Android, or a simple audio recorder will do, then look at the waveform to find the most loud events. However, note that snoring is not a reliable sign of sleep apnea.
        • Grinding teeth during sleep, formally called bruxism, can be a sign of another sleep disorder that requires treatment.
        • Although comorbid physical disorders need proper treatment to reduce their impact on sleep, the sleep issues always need to also be treated in their own rights with treatments targeted at sleep, even when there are co-morbid physiological diseases or psychological disorders.
        • Check StuffThatWorks and other online medical resources for potential non prescription treatments or management strategies for your other afflictions. StuffThatWorks is a database collecting feedbacks from patients themselves about their symptoms and what treatments worked best for them. For instance, FODMAP elimination diet was reported to be the most effective to manage Irritable Bowel Syndrome (IBS). For night legs cramps (NLC), supplementation in potassium and magnesium can eliminate the issue, especially if following a restrictive diet such as the ketogenic diet or FODMAP elimination diet. Anecdotally, both of these management strategies worked for the author of the present document.
      • Disregard your mental states, cognitive activity and stress, they can not affect your circadian rhythm, as by design, core body temperature cannot be altered by psychological processes since its maintenance is crucial for human's survival (homeothermic endothermic animals). When the entrainment therapy works, you should feel tired at the end of your circadian day, no matter what cognitive activity you are engaged in. Mental states may however affect your sleep quality, but not your circadian rhythm.
    • Maintenance: Once entrainment is achieved, the treatment must be continued as-is with the parameters (ie, light therapy timing and duration, melatonin timing and dosage, dark therapy setup, etc) you found effective for maintenance of benefits. Indeed, the therapy is effective only as long as it is used, otherwise effects are lost under a few weeks, but the therapy can always be restarted later. Note however that the therapy is not 100% effective, it cannot totally freeze the circadian rhythm in place (due to disturbances in daily life that prevent following consistently the therapy, and varying uncontrollable external factors such as sunlight intensity and duration exposure), hence expect to get misaligned from time to time: for individuals with non-24, simply discontinue therapy temporarily to freerun a few weeks until the ideal time is reached again; for DSPD, increase the exposure duration, or discontinue therapy temporarily to find where your circadian phase is, to re-time properly light therapy.

Other advices

  • Always put one's sleep first.
    • Disregard sleep hygiene. Your sleep is not "dirty", you have a disease, that needs special accommodations and tools to manage. Evidence shows sleep hygiene does not work. Avoid behavioral chronotherapy too.
    • Some sleep is always better than no sleep.
  • Plan how to handle sleepless nights:
    • Sleepless nights and premature wake ups will always continue to randomly happen due to non-24, as there is unfortunately an uncurable insomnia component.
    • It's important to plan what to do during these sleepless nights. Trying to sleep for hours, alone, in the dark, will only cause a loss of time, running thoughts and depressive feelings of powerlessness. Realizing that doing activities during sleepless nights is acceptable and even advisable is definitely the most important realization of people with non-24, as this reduces time spent in a depressive setting while allowing more time for activities.
    • A good strategy is to strike a deal with oneself to always put one's sleep first, but to allow to get up and do activities if unable to sleep for more than 30min. If you can't sleep and do not feel tired after 30min of trying, get up and do something. But whenever you feel tired, try to go back to sleep/nap as your top priority. If again it does not work after 30min, you can get back up and do activities. This is similar to the core tenets of sleep hygiene, do not stay in bed for too long if you cannot sleep.
    • Make sure to avoid getting exposed to bright light (ie, use dark therapy) during sleepless nights. Hence, screens are allowed, but only dimmed to the minimum and with a blue light filtering software.
  • Learn how to detect and handle sleep deprivation and circadian misalignment:
  • Are there other effective therapies? Maybe, but there are a lot that are not working or even detrimental. Check if these interventions are known to modify the core body temperature (search on google scholar or pubmed), if not they are likely ineffective to shift the circadian rhythm.
    • Some therapies may work better for some than others, but effective therapies have an objectively measurable effect on everybody. And of course there are therapies that have no effect at all for everybody.
    • If you hear someone claim they were treated with a miracle therapy, ask for how long and a proof such as a sleep diary. If they can't produce a sleep diary over at least 1 month post-treatment of a stable sleep pattern, consider the therapy ineffective unless more follow-up data is provided. Transient improvements are common due to how elastic sleep can be, but it does not last more than a few weeks if the therapy is ineffective.
    • Avoid benzodiazepines and non-benzodiazepines (Z drug) sleeping pills. They work for some weeks, then they stop working because of tolerance, and then if you stop you'll have an even worse insomnia, so that you'll be compelled to continue using them just to sleep as bad as you were before starting the sleeping pills. That's why current medical guidelines recommend the use of sleeping pills to be limited to 4 weeks maximum, to then be phased out for other alternatives such as melatonin. This applies to all sleep disorders, including insomnia. For circadian rhythm disorders, sleeping pills are never recommended and even disadvised.
    • Avoid studies using "self-reported sleep measures", as they are the worst and most inaccurate kind of measure. This usually refers to periodically asking the subject to say how much they think they sleep on average. This kind of self-reported, subjective measure is known to have very poor accuracy due to poor recall. Prefer studies using objective measures of sleep such as actigraphy and core body temperature, or at least a sleep diary.
  • As we grow older, we typically need more light therapy (due to lens darkening) and smaller dosage of melatonin (due to lower endogenous levels) to get the same effects.
  • Work on accepting the disorder. This will likely involve going through the grieving process of foregoing your previous life or comparison with the social expectations. But that doesn't mean passively suffering from the disorder, but rather to actively improve your management of it and organizing your life in a sustainable manner around it, putting your sleep needs first. For additional infos on the steps of the acceptance process, see the dedicated section below.
  • There are variant therapies such as phase-delay bright light therapy and sleep schedules or tricks such as adopting a biphasic sleep that can be used in practice to complement the VLiDACMel protocol, for example if you want a faster phase resetting, phase-delay bright light therapy can be helpful. Most of these therapies and tricks are described elsewhere in this document.

WIP: self-monitoring: core body temperature modulation is the core signalling way to propagate circadian rhythm changes throughout all body's cells. Can allow to monitor both the circadian rhythm, and optimally time melatonin and other therapies by observing their direct effect on the core body temperature.

This protocol should result after about 10 days in at least a significantly reduced daily phase delay, or even entrainment.

Following this protocol should not be exhausting, on the contrary, it requires that the participant is fully rested before starting and during the therapy, as sleep deprivation reduces the therapy's efficacy, hence alarm clocks should be avoided, as they not only reduce the therapy's efficacy but also mask the sleep-wake patterns and hence make individualized assessment and monitoring of sleep-wake patterns and therapeutic adjustments difficult.

Belief, strictness and self-discipline are not required. Only compliance to use the devices at the indicated time is necessary for the therapy to be effective. The goal is to get educated on how sleep works and what (external) factors can influence it, not wish it into working how we want. By controlling these factors, this allows to get some control over the sleep-wake patterns.

It's also crucial for the clinical practitioner to explain the complexity of this therapy and instruct the patient how to adapt it to his needs.

Full protocol

This therapy aims to allow for the entrainment of the circadian rhythm to a 24h cycle (ie, entrainment is the stabilization of the sleep schedule) for individuals with a non-24 circadian rhythm sleep-wake disorder (ie, a circadian period longer than 24h). The therapy works by first waiting for the circadian rhythm to naturally and progressively shift towards the ideal wake up time, at which point the therapy should be started to "freeze"/entrain the circadian rhythm in its current state. In practice, this works by using tools that will phase advance (ie, reduce the circadian period), their combination being additive. Since the individual's sleeping schedule does not necessarily follows the circadian rhythm, we will use the terms of "biological day" and "biological night" to refer to the day and night as defined by the circadian rhythm and hence the ideal sleeping schedule, not by the individual's current sleeping schedule.

A previous study found that a combination of melatonin and light therapy could entrain all 6 individuals with non-24, but with limited long term success. The protocol below attempts to address the long term issues by identifying the key parameters for successful entrainment and clarifying how to adjust the therapy on an individual basis to get the optimal results for long term entrainment and for the necessary day-to-day adjustments (eg, spectral composition and duration of light therapy, timing of melatonin, etc.), as well as adding new tools that were not explored before (such as food control).

The therapy was self-experimented by the author (34 years-old, formally diagnosed thrice over 10 years).

The target populations for this therapy includes individuals with a circadian rhythm disorder, especially sighted non-24 for whom this protocol is optimized for, with undamaged ipRGC retinal cells as evidenced by preserved pupillary light reflex (PLR), since the ipRGC cells regulate both the PLR and circadian manipulation and the PLR was found to be a reliable discriminator to detect DSPD. Thus, it is arguably likely that this therapy should work for any individual with a preserved pupillary light reflex. Hence, this protocol should work for individuals with a sighted non-24 disorder, some blind non-24 (those sensitive to relative coordination to sunlight), and those with a delayed sleep-phase disorder (DSPD) with some slight modifications as indicated in the "Adaptations for DSPD" section. With further adaptations, as indicated in the relative sections, the protocol should also work for other circadian rhythm disorders (night shift work disorder, ASPD, etc). If you don't know what these disorders are or if you are unsure if you are affected, please read in the "Diagnosis" section (inside the Troubleshooting part) the instructions to monitor your sleep-wake patterns using a sleep diary or a core body temperature sensor at home, or via salivary melatonin sampling in a hospital.

Disclaimer: The author thoroughly designed and self-tested this protocol after several failed variations. The author does not guarantee that this protocol will work for anyone else, or that all steps are necessary, but all steps laid down below were tested under many variations (by elimination and by changing parameters), and this is the only combination that was found to consistently work so far. Please keep in mind that if the protocol is only done partially (eg, skipping some steps), this may reduce the effectiveness (or not work at all). But even when all steps are followed, this may not work for some individuals. This protocol is shared in the hope it can be helpful for future research or to other individuals with non24.

Preparation phase

Two weeks before doing the therapy: sleep without alarms to fulfill your sleeping needs, and wait for your circadian rhythm to shift naturally until it's close to the target sleep schedule (particularly the wake up time):

  1. Sleep according to your own natural rhythm for 2 weeks. It is crucial to be well rested before starting the therapy, as this is necessary to reduce fragmentation in your sleep schedule and circadian rhythm by eliminating sleep deprivation, which was also shown to reduce light therapy effectiveness. Indeed, sleep deprivation can cause chronic insomnia as shown by Randy Gardner's experiment. If necessary, buy an eye mask and ear plugs to prevent external factors from disrupting your sleep.
  2. Write down your wake-up time and falling asleep time every day in a journal (use Sleepmeter on Android). This will serve 2 purposes: you can get a formal diagnosis from a specialized sleep doctor with 2 weeks of sleep logs showing a non24 pattern, and it also allows you to better know what affect your sleep and better know your own sleep patterns. Indeed, it's not uncommon that we overestimate the duration of our sleep, and for non24 individuals the daily phase delay (ie, it's often shorter than you think).
  3. Take this opportunity to get to better listen to your body and recognize the signs of sleepiness tiredness signalling your body is ready to sleep. It takes at least 2-3 days of good sleep (good duration AND circadian alignment) for the body to recover and feel fully working. For individuals with non-24, this can be a genuinely new experience to NOT feel sleep deprived, since they only lived under sleep deprivation before. It is extremely helpful to know what it's like to not be sleep deprived, and to learn to differenciate when you are sleep deprived and when you are not, as it will help in knowing when to adjust the treatments timing and dosage for you.
  4. After the 2 weeks, calculate the average wake-up time over the last 3 days. Subtract the sleep duration you need to feel the most refreshed after sleep (usually 7-8h for adults) + 2 hours from this average wake-up time to calculate the DLMO (dim-light melatonin onset). Example: if the average wake-up time over 3 days was 6am, and you need 7h of sleep to feel refreshed, your DLMO is at 6-7-2 = 9pm. Subtract 2-4 hours from this DLMO time to get the ideal time window to take melatonin. Using the previous example, the melatonin intake window would be between 5-7pm.
  5. Now, wait for your sleep to cycle and come close to the ideal time you would like to freeze in-place. Indeed, there is no proven way to cycle backward (ie, wake up earlier and earlier, also called phase advance), but if you phase delay enough (ie, sleep later and later, which happens naturally for people with non-24 and is called "freerunning"), you'll eventually reach the wake-up time you would like. If you are too eager and start the therapies while sleeping out of phase with your circadian rhythm, this will not work, may worsen your phase delay and increase sleep deprivation temporarily, and hence ultimately discourage you. Hence, it's crucial to be patient to wait for your biological night to be in phase with the actual night. This is usually noticeable as when the circadian rhythm is in phase with the day-night cycle, your sleep will be on average more restorative and longer. Start the next steps below when your wake-up time is around 2-4h before the ideal time you would like to wake up. Meanwhile, continue to write a sleep log.

Note: Be careful to track the biological night's sleep and using this sleep session as a reference for all the calculations in this protocol, and not the siesta (nap time). Humans circadian rhythms naturally have a biphasic sleep with 2 sleep gates : one for the biological night sleep, and one for the siesta about 12h later, but then when sleeping during the siesta only a half night (3-5h) can be slept at most. Since both sleep gates are regulated by the circadian rhythm, knowing the timing of one allows to estimate the timing of the other: for example, if the siesta happens at 6-7pm, the biological night (the other sleep gate) is at 6-7am. See the Biphasic sleep section for more info. A very good indicator to differenciate both types of sleep in practice is the sleep duration, as the siesta can only lasts for half (3-5h) of the biological night sleep (7-9h on average for adult humans). Also, humans are more prone to do a siesta if chronically sleep deprivated (but do not avoid the siesta if you are chronically sleep deprived, as this will allow to reduce the sleep pressure and increase the likelihood you sleep during your biological night on the next days). Furthermore, the biological night sleep duration is dependent on sleep pressure, so that as a rule of thumb, if an individual sleeps a siesta, this amount will be subtracted from the biological night sleep: for example, if you sleep for 4h during the siesta, you can only sleep 4h during the biological night sleep ; if you sleep 2h during the siesta, you can sleep 6h during the biological night sleep. It's the bedtime that will be delayed, not the wake up time (eg, if your biological night sleep is 6am-2pm, and you take a 4h siesta at 6pm-10pm, then you'll be able to sleep your biological night sleep at 10am-2pm, not 6am-10pm, due to reduced sleep pressure so you'll need more time to build it before being able to fall asleep).

Reminder: it is crucial to wait for your circadian rhythm to be in phase with the ideal timing you wish before starting the therapy, as otherwise the treatments will be mistimed and hence will not work or even make your sleep temporarily worse, as for example light therapy can increase sleep fragmentation if mistimed.

For researchers, technically this preparatory phase is akin to a combination of a multiple nap protocol and a constant bed rest protocol, in that sleep and naps are permitted ad libitum in order to reduce or eliminate the effect of sleep pressure and avoid masking by alarm clocks or other factors. However, some factors such as light exposure, food timing and social events are not controlled since this is done in the wild. For these factors, asking the patient to log them such as by using the Pevlog app can allow to take them into account when assessing the circadian rhythm from sleep logs or actigraphy.

Entrainment therapy

After the 2 weeks of natural sleep, use now this combination of therapies everyday, laid out here in chronological order of use during the day, and the major steps emboldened:

  1. Continue to write down a sleep diary of your sleep and wake up times, optionally along with any other information you think pertinent for your sleep. This is the swiss army knife of non-24 management: the sleep diary not only helps with diagnosis, but it's also crucial to properly time the treatments relatively to the circadian rhythm and spot early signs of transient (dis)entrainment and other changes in your circadian rhythm once you get entrained, so that you can react fast enough to adapt your therapy to stay entrained (eg, by increasing or shortening the light therapy's duration or melatonin timing or dosage). Due to the ever changing circadian rhythm in this disorder, it's necessary for individuals with the non-24 disorder to always maintain a sleep diary.
  2. Very long light therapy: use 500 lux bright light therapy at wake-up for 2-8h with an angle towards your nose to "freeze" your circadian rhythm by constant phase advance or even reduce circadian period to less than 24h. Light therapy also inhibits melatonin secretion and increases vigilance and mood. This is the strongest tool (zeitgeber) to manipulate the circadian rhythm, for both for the central clock (suprachiasmatic nucleus in the brain) but also for all peripheral clocks of all the organs throughout the body. Light therapy has two major effects: it can shift the circadian rhythm phase earlier or later (circadian shifting effect), making the individual more likely to wake up earlier or later accordingly, and it improves energy levels, mood and productivity (antidepressant effect). The antidepressant effect is as crucial as the phase advance effect, as it allows to enjoy activities even when the phase advance effect may not be sufficient for some individuals to fully stabilize their sleep schedule. Light therapy is optimally delivered via light therapy glasses such as Luminette v3 or v2 for 2-8h directly as soon as you wake up. If you are in a dimly lit environment, start with the eyes closed for a few seconds to allow for the eyes pupils to contract, before opening your eyes for the rest of the session, this will reduce minor side effects of sudden bright light exposure such as dizziness and migraines, which may otherwise be caused by the sudden pump in cortisol secretion due to sudden bright light exposure. The longer the exposure, the proportionally more phase advance you will get (see also here). It's possible to increase the duration of light exposure to more than 5h (see also here), in which case you may wake up earlier and earlier (but be careful because the effect increases over time, being maximal at 10 days due to photic history, so you may end up waking up too early!). The lowest setting, 500 lux, is sufficient with the Luminette. In case of incomplete entrainment after 10 days, increasing the duration is more effective than increasing the intensity of light therapy, as the author of the present document self-experimentally arrived at the same conclusion before finding previously published validation, which means that this effect is so robust that it is noticeable and reproducible on an individual basis. This is likely because light intensity has a low saturation point (1000lux to 2000lux), whereas duration has none (no PRC dead zone). Longer exposure to bright light also eliminates biphasic sleep. In theory, longer exposure to light may be necessary depending on age, as the eyes lens (cristallin) are obscuring and acting as a blue-light filter with age (see also here), although in practice age does not affect the response to light therapy as only melatonin inhibition is impaired by age but not the circadian phase advance which remains the same, and with some studies showing that light therapy produce the same phase shifting effects regardless of age or sex.
    • Do not restrict your sleep and nap as much as needed to feel rested, as sleep deprivation and sleep restriction reduce the effectiveness of light therapy, as adenosine buildup was shown to inhibit the effects of bright light on the circadian rhythm.
    • At first, light therapy will slow down the daily phase delay in the wake up time (wake up earlier), but not the bed time, so it's possible to experience a reduced sleep duration at first. This is because light therapy instantly synchronizes the DLMOff (stop of endogenous melatonin secretion, which coupled with the wake up time and production of cortisol) but it takes several days to entrain the DLMOn (start of melatonin secretion).
    • If you are unsure whether light therapy will work for you, the sleep diary may help: if over the course of one full freerunning revolution, a pattern of relative coordination can be observed (ie, faster freerunning when out of phase with the day-night cycle, and slower when in phase), this is due to sunlight, and hence is strongly suggestive of responsiveness to light therapy. See the extended section below about relative coordination.
    • If you want a cheaper alternative to the Luminette, any bright light should be sufficient to get some phase advance, although it will be less effective and reliable than the Luminette since it's enriched with blue light and it's very ergonomic with a precise and constant distance to the eyes. A computer screen at max brightness can be sufficient (if it emits at least 100 lux), or simply changing the orientation of your work desk to get more sunlight can make for a "free" light therapy, as long as you get at least 500 lux. This can be tested with a lux meter app on most smartphone by using the light sensor that is usually included to automatically adjust the screen brightness depending on environmental light exposure. Several users reported success with various DIY devices, such as make-up mirror lights, strong neon lights or with a cheap $30 Beurer TL30 lamp. Just ensure the light is close enough to your eyes to get enough lux. The light source also needs to be oriented in the peripheral view as to target either the parafoveal or nasal region of the retina as these regions much more effectively suppress melatonin, not the inferior nor superior nor temporal regions of the retina. There is also the Lys Circadian app on iOS which can use the phone's camera to finetune the result using color with a proprietary algorithm, or their dedicated LYS button sensor that can be worn as a necklace and detects more accurately melanopic circadian lighting.
    • When going outdoors during the day, and if you are living in a timezone with a wide range of hours of daylight (eg, NOT northern Norway, where there can be as few as 4h of indirect sunlight per 24h during winters), then you do not need to use light therapy glasses during the time you are exposed to direct outdoors sunlight, even if cloudy, since sunlight is the most intense bright light therapy that exists. Keep in mind the spectral composition of light is bluer in the mornings than in the afternoon and evening, hence if you only get exposed to outdoors sunlight late in the day, it may be worth to use light therapy glasses a hour to get the benefits of optimal spectral composition. Just count outdoors sunlight exposure as additional bright light therapy. Indoors sunlight exposure is more tricky and may be insufficient, see above for ways to measure with apps.
    • Bright light therapy is even more important if you use more than 1mg of melatonin (supraphisiological levels), because there will be residually higher levels of melatonin next morning that will cause drowsiness, and bright light therapy can forcefully inhibit that. Suppressing melatonin by light in the morning can reduce the carry-over hangover when taking a supraphysiological dose because of the photic history (see also here) and because light eliminates melatonin faster than natural elimination.
    • Light is likely the most powerful tool we have to control the circadian rhythm, as it was shown in animals that light can entrain even without the SCN pacemaker.
    • Light also increases serotonin levels and hence vigilance, particularly at wake-up when sleep inertia is at its highest, since light impacts both the circadian rhythm C and the homeostatic (sleep pressure) process S (which makes sense since cordycepin, an adenosine analog and adenosine being the biological basis of the homeostatic process S, has a huge impact on the circadian rhythm C, showing that both processes are inter-dependent). Hence, the control of light exposure using a combination of light therapy and dark therapy, through the modulation of both light intensity and color, is an optimized therapy.
    • Light therapy improves mood as much as antidepressants, and is even recommended by systematic reviews authors as a first-line treatement for seasonal and non-seasonal major depression.
    • During the rest of the day, after the wake-up light therapy, it is advisable to continue to be exposed to bright light throughout the rest of your natural day, in order to optimize photic history, as it was shown that 6.5h of bright light exposure (whether continuous or intermittent) at wake-up shifts the circadian phase way more than only 1h of light exposure, and with continuous light suppressing melatonin more than pulsed light (hence continuous light is likely more efficient to increase vigilance). Another study shown that exposure to 5-8h of bright light daily phase advance the circadian rhythm of 14 typical sleepers by 8h over 5 days of treatments only, confirming the viability of very long bright light therapy to treat severe circadian rhythm misalignments. Hence, contrary to what previous research suggested, light PRC curve has no dead zone (see also here), hence it seems there is virtually no limit to how much phase advance can be obtained with longer exposure to bright light. This also means that bright light always affect the circadian rhythm, so that a thorough control of exposure to light is necessary (ie, dark therapy). See also this reddit comment.
      • Although bright light exposure matters more in the morning for circadian rhythm entrainment, being exposed to bright light during the whole biological day allows for a more consolidated sleep, as prior light therapy during the circadian day increases endogenous melatonin levels at night. Hence, after the morning light therapy session is done, it's preferable to stay exposed to bright light of at least 500 lux for most the rest of the day. If this is not possible, either buy a bright neon light, or do a longer light therapy session in the morning to compensate for the lack of light exposure the rest of the day.
    • During the first few days of light therapy, the sleep schedule may see some chaotic variations in the timing. This is normal and shows that the light therapy works, the sleep schedule should stabilize over the next days.
    • Just like melatonin, the optimal light intensity and duration will need some trial-and-error, since there is a 50-fold difference in light sensitivity across individuals.
    • It takes about 10 days for light therapy to be fully effective, because of photic history. This means you will notice a snowball effect where light therapy may produce more phase advance over time (ie, your wake up time will stabilize more and more or even be earlier and earlier depending on the light therapy duration).
    • Why use low light intensity (500lux on Luminette and Re-Timer) and long duration instead?
    • During winter or in latitudes where days are shorter and sunlight dimmer, longer light therapy sessions are needed. For the author, up to 9h/day is necessary during winter.
    • If you plan on taking a nap, you can use light therapy after the nap, as long as you are waking up before your circadian night. If you use light therapy before, you may not be able to nap. If you are sleep deprived (sleep duration < 6h for most adults), then it's preferable to prioritize napping, as sleep deprivation reduces light therapy efficacy due to adenosine buildup.
    • Very long bright light therapy + dark therapy alone should be sufficient to entrain you. After 10 days, you should start to feel the sleepiness sensation appearing every day at the same time (although it can be feeble and fleeting), hinting that you are entrained and the time you can fall asleep even if you still feel slightly energized. If this sensation does not appear, check if there is any hidden caffeine in the food or beverages you consume such as 0% coke, as caffeine's effects carry over up to 48h including phase delay since caffeine can modify core body temperature and is hence a zeitgeber. It's likely good idea to also avoid any wakefulness inducing drug such as tea and modafinil and nootropics.
    • Most light therapy glasses including Luminette can be used with prescription glasses, however make sure they do not have a blue light filtering coating.
    • Experimental: hyper photosensitizing drugs such as aripiprazole and antidepressants may be used as a complement to bright light therapy, due to the agonism of histaminergic H1 receptors which increases photosensitivity and entrainment to bright light. This can explain why low doses of aripiprazole was found to be effective to treat DSPD (see here and here). This may be useful for treatment-resistant cases or periods of very diminished sunlight exposure such as winter in occidental countries. But due to their fast tolerance build-up and side effects such as akathisia, it's not recommended for the sole treatment of circadian rhythm disorders, although their hyper photosensitizing effect can be leveraged if they are needed to treat a co-morbid disorder such as ADHD or depression.
    • CONTRA-INDICATIONS: bright light therapy can NOT be used by individuals with epilepsy or macular degeneration or other retinal diseases or malformations (eg, aphakic people born without crystalline lens and pseudophakic who received intraocular lens implants), as these populations are at higher risk when using light therapy. Light hypersensitivity (photophobia), as is common in people with ADHD and can be caused by drugs such as methylphenidate, should be considered carefully. Here is a list of drugs potentially causing light hypersensitivity (photophobia). Ask your physician if light therapy is safe if you have light hypensensitivity, and restrict usage of Luminette to the lowest light intensity setting of 500lux, and always start by closing your eyes for 30 seconds when turning on the light therapy to allow the pupil to contract and avoid side-effects associated with sudden bright light exposure.
    • WARNING: Do NOT use light therapy glasses while driving! You need your full vision unhampered for your own safety. Also they are unnecessary under outdoors conditions as you will be exposed to plenty of direct sunlight.
    • Naps are allowed. Naps are the main tool to manage sleep pressure, just like bright light therapy is the main tool to regulate the circadian rhythm. Reducing the sleep pressure via naps likely improves the efficacy of bright light therapy.
    • Given bright light therapy provides the most phase advance when done a hour or two before the natural wake-up time, why don't we use an alarm clock to increase the therapy's efficacy? Because it's at this point, a hour or two before the natural wake-up time, that the PRC curve flips from maximally negative to maximally positive. So if one get exposed to bright light a bit too early, the risk is to be exposed in the maximally phase delaying part instead of the maximally phase advancing part, and hence causing an unwanted phase delay that can totally negate the phase advance obtained in the later part of the PRC curve or even worsen the freerunning speed. Furthermore, this flipping point is very hard to estimate and varies a lot between individuals. Hence, by recommending to start light therapy only at the natural wake up time, we indeed miss some of the maximal phase advancing part, but we avoid all risks of getting (maximally) phase delayed. In other words, we aren't too greedy, we play it safe.
    • Analogy: imagine that light therapy is like a pince that is stretching your circadian rhythm, a spring, to the left (earlier time). If you stop using light therapy, the spring naturally tends to contract more and more to the right (later time). But it doesn't happen at once. You can use light therapy again at any point in time to stretch the spring again. It may take a few days to go back to where you were depending on how long you missed light therapy (eg, if you missed one day, you can recover usually in one day, if you missed 2, you need 2 days of light therapy, etc).
  3. Optional: Timed big main meal, which is to take your main meal at the middle of your circadian rythm's day. This synchronizes your circadian rhythm thanks to your intestines regulation of the circadian clocks (it's the biggest producer of melatonin). You can eat a breakfast, but it should be relatively small, and there should be only one big meal during the day (eg, the sort of meal that you feel like you ate enough for the whole rest of the day - but be careful of not over-eating!). More than entraining your circadian rhythm, timing meals allows to avoid circadian misalignment, as eating food during your biological night or too close to it can impair several regulatory functions such as insulin and glucose. This is true not only for non24 and DSPD but also for typical sleepers as well, although the former may be even more at risk due to a mutation in melatonin type 2 receptor (MT2) which seems to be more prevalent in individuals with a circadian rhythm disorder.
    • Important: Reducing the quantity of consumed carbohydrates is highly beneficial in any case, as each 1% reduction improves the metabolism and reduces risks of obesity and metabolic disorders, including sleep, according to a meta-analysis. It's also an advised treatment to deal with postprandial sleepiness and particularly reactive hypoglycemia.
    • Timed big meals provide very little additional circadian stability apriori and it's disadvised for those who try to manage their weight, so it's not recommended to focus in this step, rather focus on light and dark therapy and melatonin, and simply avoid ingesting calories and especially carbohydrates during the circadian night.
    • If you really need to eat in the evenings, prefer to consume tropical fruits such as bananas, which were shown to cause an uptick of melatonin in the blood 2h after consumption, although note that it is likely only the receptor-independent antioxydative activity that is promoted, it is unlikely to help with sleep, but this hypothesis was not tested so we don't know. But at least, fruits are a healthy kind of meal and stack if you need to eat, especially when late in the evenings.
    • Optionally, it's possible to follow a strict ketogenic diet with timed big main meal.
      • The ketogenic diet is not necessary for entrainment, but it allows to eliminate the effect of carbs (postprandial sleepiness, sugar crash) as well as disconnect the digestive clock with the brain circadian clock, hence it can ease entrainment. The effects will start only after you reach a ketosis state as indicated by the highest 2 levels on the ketostix (measurement bands of ketosis from urine). Following a strict ketogenic diet is kind of the extreme of the carbohydrate reduction treatment for postprandial sleepiness. A strict ketogenic diet, as defined for epilepsy treatment and diabetes management, is a diet with limited carbohydrates (<=50g of wet carbs (sugar+fibers), including <= 20g of sugar carbs per day), medium proteins and lots of lipids (fat). Proteins should be kept in limited amounts, as to not compensate for the lack of carbs by eating too much proteins, as proteins will get converted to carbs, preventing reaching the highest levels of ketosis as indicated by the last 2 colors on the ketostix.
      • In practice, the author of the present document observed the following phenomena during self-experimentation, which fits with recent research findings:
        • Desynchronization of the whole body circadian clock, which has two paradoxical effects in practice: 1- a faster daily phase delay during freerunning (1h of delay per day in the author's case, instead of 30min/day usually); 2- reduced daily phase delay (ie, shorter circadian period) during the entrainment phase. This may be explained by the preliminary evidence on mice showing that the ketogenic diet can modulates the body's circadian clock, so that under ketosis, food has an increased circadian rhythm resetting effect, by increasing the intestines time clock gene expression and switching off liver's time clock genes and melatonin secretion — in other words, the peripheral (ie, body) circadian clocks will rely more on the food timing, which is a lot easier to control than other zeitgebers, and with bigger meals having an increased resetting effect. Another study on mice also observed that the ketogenic diet induced a shorter circadian period and hence a phase advance.
        • DEPRECATED: Reduction of the sleep duration (by one ultradian cycle, so about 1h30-2h shorter sleep) while improving sleep quality (so there is no loss in sleep even though the duration is smaller, which eases the maintenance of a stable sleep by compensating the too long awake period of individuals with non24 by a shorter sleep), as also observed on a study on epileptic children under the ketogenic diet.
          • UPDATE 2021: although during the first ketogenic diet run (over 3 months) seemed to reduce sleep duration with no side effect, the second ketogenic diet trial over 3 more months 1 year later did not show similar benefits. The difference is that coke beverages (containing caffeine) were excluded in the second run. It seems the caffeine's effects remains well over one day and carry over to the next day, so that this is the likely cause of reduction of sleep duration in the first run. In the second run, when sleeping in circadian alignment, the author could sleep a full 8h night and a bit more. Hence, the ketogenic diet did not show any significant effect on sleep nor on dreams during the 2nd run, which means that the ketogenic diet does not appear to improve, nor impair, sleep. It can hence be used by individuals with the non-24 disorder for other purposes in parallel to an entrainment therapy (eg, the ketogenic diet may be part of a diabetes management therapy).
        • Reduction of hunger (eases the avoidance of the detrimental melatonin/insulin/carbs interaction in the biological evening).
      • If you choose to do a ketogenic diet, plan to start it ahead, at least 2 weeks before the rest of this protocol, as to have enough time for your sleep to adapt and stabilize with the new diet. Also make sure to use vitamins and minerals supplement, and salt a bit your homemade food, to avoid the risk of electrolytes insuffisance contributing to the dreaded keto flu. If the strict ketogenic diet shows efficacy to you for entrainment, you can later transition back to a healthy diet (such as the scientifically designed DASH diet as recommended by the NIH, and combine with the openfoodfacts.org search engine filtered by Nutri-Score and NOVA to find healthier food products in practice) with carbs in reduced quantities compared to your old diet, and you should also keep the benefits in insulin resistance reduction even after stopping the ketogenic diet (as long as you don't revert back to your old diet).
      • The ketogenic diet may also improve sleep indirectly by:
        • weight loss, as weight surplus is associated with obstructive sleep apnea and snoring, which may resolve with weight loss.
        • reducing digestive issues for individuals with irritable bowel syndrome disorder as it reduces or eliminates the intake of FODMAP, since they are specific kinds of carbohydrates, which are avoided in the ketogenic diet. In other words, there are no FODMAPs in lipids nor proteins, so the ketogenic diet is a good option for those with FODMAP allergy.
      • To learn more about the ketogenic diet both in theory and in practice, read this and this excellent reddit posts.
  4. Start dark therapy, which is the avoidance of bright blue-green lights, 2-3h before natural bedtime. Dimmed red lights are OK, either by changing room lights with RGB LED such as Yeelight 1S, or by using orange or red-tinted blue blocker sunglasses (or laser safety glasses) if you can't change the environment lights. Start dark therapy simultaneously to ingesting melatonin pills (if you use melatonin). Doing dark therapy allows to both preserve the natural secretion of melatonin, and avoid unwanted circadian phase shifting and detrimental health effects of night-time bright light exposure such as on the cardiometabolic system. Indeed, light can suppress both melatonin and shift the circadian rhythm (independently of whether melatonin is suppressed, see also here and here). Both the intensity and color of light (see also here and here) matter in circadian rhythm shifting and melatonin suppression by modulating the ipRGCs receptors (see here for intensity, and here and here for color), hence you need to avoid bright lights in your biological evening, both by dimming down all lights, and by filtering blue light. Dark therapy is necessary to keep a robust gain from the other therapies, by ensuring there is no unwanted shift in your circadian rhythm by uncontrolled factors such as uncontrolled light exposure.
    • The author strongly recommends red-tinted laser safety glasses, which are the most filtering kind of glasses and will filter both blue and green parts of the spectrum as well as dim light (as they often include a dimming layer like sunglasses). For more infos to find these glasses, look in the dedicated section on Dark Therapy in Troubleshooting below. If not available, a good alternative but less filtering and with no dimming layer are the UVEX glasses with SCT-Orange coating as blue light filters, they are very inexpensive and highly effective according to several independent reviews (see the dedicated section on Dark Therapy below). Use the UVEX Skyper if you want to hang outside with it, or the UVEX S0360X Ultra Spec if you want to use prescription glasses under, as the Ultra-Spec are big enough to fit prescription glasses under, but not the Skyper. A dimming layer can be manually added to UVEX amber glasses, by using VLT shading films for cars windows.
    • If you don't have access to such glasses, a more inconvenient and less reliable but working alternative is to modify the environment: dim down / switch off all lamps (including your computer screen intensity) and install blue light filters softwares on your computer (advised: LightBulb or f.lux) and smartphone (Twilight on Android). If you have a changing color LED lamp (eg, Living Colors), use it as a bed lamp by setting it to full red color (the blue LED should be switched off if you selected an appropriately full red color).
    • Why start the dark therapy about 2-4h before target bedtime? Because melatonin takes 1-2h to produce drowsiness effects from its DLMO point, and it takes 1-2h for melatonin secretion to reach it's DLMO level from the moment it starts its production (or from when the light inhibition/exposure is stopped). Hence, the dark therapy should be started 2-4h before the natural bedtime. This is further supported by evidence from a study of home lighting, which found that increased melanopic illuminance 3h before bedtime was correlated with increased wakefulness for 90 more minutes past bedtime.
    • Dark therapy is the natural complement to light therapy: whereas light therapy phase advances your circadian rhythm (ie, you wake up earlier), dark therapy prevents unwanted phase delays due to light exposure, which concretely makes you feel more fatigued at the wanted time.
  5. Optional: Kickstart your melatonin secretion with a melatonin pill and hence sleep and help its consolidation, several hours before bedtim, by taking melatonin at the same time you start dark therapy: take melatonin in instant release form, if possible sublingually dissolving tablets. The optimal efficacy of melatonin is dictated by two factors: 1. ingestion before DLMO, 2. dosage high enough or timing close enough to DLMO for exogenous melatonin in bloodstream to overlap with DLMO. The timing is crucial and requires some trial-and-error, as melatonin must be taken relatively to one's current circadian rhythm (ie, bedtime and wake up time), NOT the target bedtime contrary to what current regulations state. Indeed, it's necessary to take melatonin before the body starts producing it (called the DLMO point), and the body starts producing melatonin a few hours before you go to bed, as melatonin is one of the things that cause sleepiness feelings and allow to sleep a full night (sleep consolidation). The dosage does not change the magnitude of circadian phase shifting effect, so it can be as low as 0.1mg or up to 3mg, but only higher doses > 1mg (supraphysiological) can produce hypothermia (as also shown here), so that "nighttime increase in sleepiness was achieved only after administration of high doses" and doses such as 3mg are "more likely to produce a substantial phase shift" although this needs confirmation. However, dosage does matter for the timing of intake, as it's necessary for melatonin from pills to overlap with the natural endogenous melatonin secretion (DLMO), as to simulate an earlier dusk and trick the body into thinking it started producing melatonin earlier. Since higher dosages remain longer in the bloodstream (see also here), they provide more leeway in timing and produce effects even if taken very early, whereas lower dosages need to be taken much closer to DLMO (but never after - hence lower dosages require more accurate calculations of DLMO), hence higher melatonin doses (1-3mg) are likely easier to time for beginners. However, both the DLMO timing (60% have a DLMO outside the 2-3h before bedtime range) and the dosage (between 10-fold variability and 35-fold variability) required are highly variable between individuals. Although melatonin can shift the circadian rhythm via the type 2 receptors, its main purpose is to stabilize the circadian rhythm and consolidate sleep, hence to maintain the benefits from more efficient tools for phase advance such as light therapy. Melatonin is also a powerful antioxydant that reduces or eliminates the detrimental health effects of sleep loss, but this (receptor-independent extracellular) effect is only obtained with very high doses (8mg/kg/day for humans).
  6. Avoid eating and caloric drinks (especially carbs) when melatonin is high in the blood, to prevent insulin inhibition and hyperglycemia before and during the circadian night and early circadian morning + avoid alcohol, as Panda et al also recommend in a review. As a practical rule, apply the rule above when starting dark therapy, consider melatonin is rising and that you should avoid eating and caloric drinks. The pancreas has both insulin and melatonin receptors so that each one inhibits the other at the protein level. When melatonin is high, insulin is inhibited and if you eat, then glucose will remain high in your blood and cause a superficial diabetes throughout the night, as insulin is necessary to process glucose. Hence, melatonin impairs insulin production and glucose processing (even in typical sleepers), and insulin impairs melatonin processing. This may have detrimental effects on health as it's hypothesized to be one of the cause of chronic diabetes type 2 and obesity, and may also disturb the ability to sleep as the high blood glucose and hence available energy will cause the individual to feel more energetic past bedtime. Researchers suggest that this may be a biological safeguard mechanism to avoid hypoglycemia during the night since we spend a long time without eating while we sleep, and hypoglycemia can be very dangerous (diabetics often have this issue at night time), but this safeguard assumes that the individual do not eat when supposed to sleep by the circadian rhythm and melatonin rhythm.
  7. Optimize sleep preparations and quality:
  • For the ear plugs for sleep, the most comfortable are outer ear plugs in silicon such as Medigrade or Mack's. But they do not work well during winter, as the cold temperature makes it hard to stick to the outer ear. During these periods, switch to Howard Leight Laser-Lite (Honeywell 3301105) earplugs, which are very soft foam inner ear plugs, they are less comfortable than outer ear plugs but they are much more comfortable than any other type in the author's experience (a lot of brands and types were tested!). Nevertheless, it will regularly happen that the ears get itchy and so you can't stand having earplugs in your ears for the night, or unconsciously rip them off during your sleep. This is to be expected from time to time, but if it happens most of the time, try other brands/material of earplugs, and make sure to clean your ears with cotton tips before sleep.

  • Very-low-profile sleep earmuffs such as the Hibermate can be used alone or in combination with in-earplugs, providing excellent portable isolation to noisy environments. Using the Hibermate, alone (for more ear comfort, less risks of ear canal itchiness) or in combination with in-earplugs (for more noise isolation) is highly recommended, this works very well in practice, including for side sleepers. The sleep earmuff will take the user's head shape after some weeks of use.
  • Using music as a non-drug stimulant during the day can be a good strategy. However, earbuds will make it more likely to experience itchiness at nighttime, and it's more important to be able to use night time earplugs for sleep quality. An alternative is to use bone conduction headsets, which do not put anything in-ear. The sound quality is more mediocre than with earbuds though, but still good enough to enjoy, and there are several other major advantages: silent to others, and the ability to hear and react to every surrounding sounds since the ears aren't filled with earbuds. They are hence perfect for use at night or in silent environments. Bone conduction headphones can be used in combination with in-ear plugs. AfterShockz is the leader in bone conduction headphones, but mimicking brands at a much lower price are available with an acceptable audio quality. They can also be comfortably worn simultaneously with Luminette light therapy glasses. Tip: after each use, cross the branches so that the headphone keeps its tight fitting form to maintain good contact with the skin, which is necessary for good sound quality.
  • Mind the ultradian cycles (20 minutes "sleep gates" every 1h30) and the dopaminergic forbidden zone of sleeping. When you feel sleepy, you can expect this feeling to last only 20 min, and then to go away. The next sleep gate, where the tiredness feeling will reappear for 20 min, will be about 1h30 after the last gate. The gates aren't all equal, there is one with a maximum sleepiness feeling, and the others will have a reduced feeling. Trying to sleep at these 20min sleep gates allow to fall asleep fast, sleeping outside may be possible but will be more difficult. See the relevant subsection below for more information on sleep gates.
  • If you can't sleep (eg, missed the ultradian cycle window), then wake up or sit and do something else than trying to sleep until the next window to sleep.
  • Identify any factor that can impair your sleep and buy the necessary workarounds. Anything that can prevent disturbances on your sleep is well worth it. If it's too warm temperature, buy a fan. If it's mosquitos, buy an anti-mosquito net for beds and/or a anti-mosquito lamp.
  • We are the product of our environment. If your environment is not adequate for good sleep, such as noisy neighbors, no tools can completely fix it. Consider moving to another place if you can.
  • If you snore regularly, this means your airways are obstructed, and that your sleep quality is impaired. Regular snoring is never normal. Consider getting a sleep study for sleep apnea. Meanwhile, you can try:
    • to sleep more on your sides by removing your pillows (as we are more likely to snore on our backs). Indeed, position-related snoring is a known phenomenon and is why military soldiers keep their backpacks while sleeping during missions, to avoid sleeping on their backs which increases the likelihood of snoring and hence of giving their position to their enemies. Furthermore, tribal populations have shown that they sleep without any pillow but on their arms, hence on their sides, and the researchers noticed they have a much lower prevalence of musculoskelettal disorders in addition to no snoring issues.
    • to use nasal sprays to clean the airways before sleep. This is an advice given by a nurse in a sleep study, this claim needs to be tested and double-checked.
  • If you have other afflictions that impair your sleep or blatantly wake you up in the middle of your sleep, then treat them. This is especially important for comorbid disorders that have a circadian pattern (ie, they trigger more often during the circadian night, such as RLS and PLMD and night legs cramps). The VLiDACMel protocol prevents entrainment, but having a restful night requires more than entrainment, it requires uninterrupted sleep.
  1. Optional but strongly advised: take multivitamins and minerals, including vitamin B12, vitamin A and magnesium supplementation every mornings. B12 vitamin is known to amplify the magnitude of the circadian rhythm shift of light therapies (see also here) and B12 supplementation entrained a few individuals with non24 (see also here and here). Vitamin A is necessary to synthesize all opsins in the eyes, including the melanopsin pigment necessary for ipRGC cells and entrainment to bright light to work, hence it is necessary to ensure adequate levels of vitamin A, via supplementation if needed. Magnesium also affects the circadian rhythm (studies here and here). Vitamin D deficiencies can affect the circadian rhythm and it interacts with at least 2 clock genes, and vitamin D appears to inhibit melatonin, as the body does not expect to get exposed to Vitamin D unless there is skin exposure to sunlight with UVs, so that Vitamin D supplements should preferably be taken in the circadian morning rather than the evening to avoid fragmenting sleep. Vitamin B6 helps with serotonin and melatonin secretion. Supplements are not going to fix your circadian rhythm, but deficiencies can have a detrimental effect on it, although it's not always a fix as shown by the ineffectiveness of B12 in a placebo controlled trial on DSPD. These vitamin deficiencies may be caused by gut microbiota dysbiosis, such as bacterial overgrowth (ie, candida albicans). Furthermore, deficiencies in other vitamins and minerals may impact mood (eg, magnesium), neurology (eg, vitamin B6, B12) and the circadian rhythm (magnesium and B12), so by taking a multivitamins and minerals supplementation you eliminate these potential factors on your sleep easily. Plus, if you do a strict ketogenic diet, this supplementation will help avoid electrolytes imbalance (but you may also need to supplement in salt). For B12 supplementation, use cyanocobalamin form, as it can be converted by the body into both forms of B12 (methylcobalamin or adenosylcobalamin). Some Discord users with diagnosed chronic B12 deficiencies influencing their circadian rhythm reported the B12 shots are more effective than the pills. Vitamins B3 and B5 are necessary for the production of cortisol, the hormone that prepare the body to fight stress and which interacts with the circadian rhythm, and which release can be boosted with bright blue light therapy. Over supplementation in vitamin D may inhibit melatonin which is hypothesized to result from a cross side effect of vitamin D production, which is triggered by skin exposure to UV, so the eyes are often also concurrently exposed to bright light, so a inhibiting pathway between vitamin D and the circadian rhythm may have hence developed as a byproduct of light exposure, although other individuals with non-24 and DSPD reported that treating their vitamin D deficiency significantly improved their sleep and circadian rhythm stability, so it seems there needs to be not too little but not too much vitamin D to avoid impairing sleep.
    • Although optional for entrainment, vitamins and minerals supplementation can be necessary for some individuals in order to sleep, as in the author's case. Indeed, without supplementation over 40 days, the author experienced limbs swelling, hands cramps, muscular weakness and joints and chest and limbs pain, to the point where these symptoms prevented sleeping more than 1h30 in one go, which was of course unsustainable. These symptoms were signs of a peripheral neuropathy, due to vitamins or minerals deficiency. Although the exact deficiency could not be determined yet, it was likely a combination of genetic predisposition in Vitamin B12 deficiency (the author possesses the AG variant in the FUT2 rs602662 location), which is known to be capable of causing peripheral neuropathy (although other vitamins deficiencies can also be responsible — see also here), and a too restrictive diet (due to this experiment, a very precise diet was devised and used everyday to reduce the effect of food composition on the circadian rhythm). Vitamin-induced peripheral neuropathy is a serious disease that can cause permanent nerves damages. There are anecdotal reports from discord members with the non24 disorder that intravenous administration of vitamin B12 was much more effective than oral supplementation, similarly to how intravenous iron supplementation seem to be more effective at treating RLS than oral iron supplementation.
    • Leverage the increased availability of rare and specific products in online stores such as Amazon. Although these stores certainly have a detrimental impact on local commercial shops, there is certainly an advantage in allowing rare products to be available worldwide and able to reach the target audience, whereas before such specific products were impossible to obtain even in big cities.
    • The author took multivitamins everyday in the morning (at wake up or later if forgot) for the whole duration of the experiment.
    • If you don't know what to choose as a multivitamins supplement, try to get a vitamins+minerals supplement with as many different vitamins/minerals as possible, and with each vitamin/mineral fulfilling only a fraction of the daily needs, eg, at least 15% and not more than 50-60%. This way, you are more than likely within safe bounds even if you include vitamins and minerals intake from food. This works because to avoid vitamins/minerals deficiencies, you don't need 100%, you just need more than 0-10% of daily needs, enough for the body's essential processes to work. Generally, you want metals to remain low, because they have a higher risk of overdosing with deleterious side effects, especially since some is ingested from food. Prefer pills or tablets, but not chewable gummies, because the latter have poorer quality control, and dosage can vary wildly from what is written on the package.
  2. Plan out how to handle the sleepless nights and premature wake ups. Sleepless nights and premature wake ups will always continue to randomly happen due to non-24, as there is unfortunately an uncurable insomnia component, even when under an effective entrainment therapy. In fact, these sleepless nights and premature wake ups become even more apparent during entrainment, as it becomes clear it's not due to the circadian rhythm. Most individuals with non-24 lose invaluable time trying to desperately sleep for hours, without succeeding. Alone in the dark for hours, with nothing to do but think, this creates the perfect opportunity for the brain to generate running thoughts, as nobody is able to suppress all thoughts for hours. This can ultimately cause a depressive feeling of powerlessness. That's why the core of sleep hygiene is to avoid staying in bed if you can't sleep. Hence, it's important to plan what to do during these sleepless nights.
      • A good strategy is to strike a deal with oneself to always put one's sleep first, but to allow to get up and do activities if unable to sleep for more than 30min. If you can't sleep and do not feel tired after 30min of trying, get up and do something. But whenever you feel tired, try to go back to sleep/nap as your top priority. If again it does not work after 30min, you can get back up and do activities. This is similar to the core tenets of sleep hygiene, do not stay in bed for too long if you cannot sleep.
      • Make sure to avoid getting exposed to bright light (ie, use dark therapy) during sleepless nights. Hence, screens are allowed, but only dimmed to the minimum and with a blue light filtering software.
      • Although not a therapy per se, planning out how to handle sleepless nights is definitely the most liberating realization for individuals with non-24. Being unable to sleep is already a huge handicap, but losing this time altogether by not doing any activity is even worse. Being sleepless does not mean you are not allowed to enjoy yourself and the activities you like.

Continue this combination of therapy strictly (respect the hours and use melatonin and light therapy everyday!) for at least 10 days. Indeed, because of carry-over effects such as photic history and gut microbiota adaptation, it takes several days to a few weeks for the body to adapt to both light and dietary (including melatonin) changes. This means that when starting a circadian rhythm therapy, it will take about 10 days for the full effects to be seen, and it will take as much time when stopping the therapy for the effects to wear off. But you should already see some effects a few days in, such as mood and vigilance boost from the first use of light therapy, and some circadian rhythm phase advance after 2 days of light therapy.

In practice, the first week you should see a reduction of your phase delay, and the next week your circadian rhythm (in particular your wake-up time) should be somewhat stable, and it will get more stable along time as you continue with the therapy. The time windows need to be respected, but a slight change of +-30min from day to day is OK in my experience (eg, taking melatonin 30min later or earlier, and there is more room for food timing as long as you do not eat past the melatonin intake time).

In case there is some unexpected event and you miss the therapy one day or use an alarm clock to wake up to get to an appointment, keep in mind that long napping is allowed and advised, as it reduces most of the health issues that sleep deprivation causes.

It should be emphasized that it is crucial that all the non-optional steps should be followed for the therapy to be effective, at least at first. Indeed, this therapy combines multiple approaches to increase the likelihood and robustness of entrainment. Once entrainment is achieved, the patient can try to eliminate some steps as they see fit if they can stay entrained. Indeed, some patients with a less treatment-resistant form of non-24 can be entrained with solely using melatonin pills, others with the ketogenic diet alone, and others with light therapy glasses alone as evidenced by several anecdotal patients accounts.

Maintenance: Once entrainment is achieved, the treatment must be continued as-is with the parameters (ie, light therapy timing and duration, melatonin timing and dosage, dark therapy setup, etc) you found effective for maintenance of benefits. Indeed, the therapy is effective only as long as it is used, otherwise effects are lost under a few weeks, but the therapy can always be restarted later. Note however that the therapy is not 100% effective, it cannot totally freeze the circadian rhythm in place (due to disturbances in daily life that prevent following consistently the therapy, and varying uncontrollable external factors such as sunlight intensity and duration exposure), hence expect to get misaligned from time to time: for individuals with non-24, simply discontinue therapy temporarily to freerun a few weeks until the ideal time is reached again; for DSPD, increase the exposure duration, or discontinue therapy temporarily to find where your circadian phase is, to re-time properly light therapy.


  • To optimize dark therapy, you can use a free "lux meter" app on your smartphone, with the screen directed at the light source to check the light intensity (lux). Lux varies with placement, orientation and distance, so it is important to orient the light sensor on the smartphone screen (usually at the top) directed at the light source, at eye level and at the distance you will usually be from the lamp. What lux intensity is low enough for dark therapy? The lower the better, but below 40lux should be fine, below 20 lux is great. If a light source (eg, lamp) is too intense, try playing with distance by placing the light source further from where you will be in your room when you'll use the lamp. If you have a Luminette, you can calibrate your lux meter app by measuring the Luminette 3 settings, the readings should be 500 lux, 1000 lux and 1500 lux. Remember that light intensity is only one factor, the other being the light color, which should be as red as possible (to reduce/eliminate blue and green colored light). Spectral sensors exist but not in smartphones unfortunately so just use your eyes: if a light source is red, it's fine; if it's yellow, it's good enough but not ideal.
  • body temperature monitoring as a proxy for the circadian rhythm even when not sleeping or sleeping in circadian misalignment (eg, such as when using alarm clocks due to appointments/work), in which cases the sleep diary is unreliable but temperature monitoring is reliable to reflect the circadian rhythm. TODO: expand this section when milestone 2 is completed.

Safety-Risk analysis


Although this therapy can allow for a robust entrainment, entrainment can still be lost under some circumstances, which reminds us that this is not a cure:

  • During winter, the shortening and intensity reduction in sunlight can cause a desynchronization. Increasing the duration of artificial light therapy may compensate but may not be sufficient.
  • Any illness lasting for more than a week is likely to cause a desynchronization. Some acute severe diseases can as well. Anesthesia also impairs the circadian rhythm. Restless Legs Syndrome (PLMD), PLMD and night legs cramps can also significantly impair sleep and indirectly cause a loss of entrainment, especially since their acute (painful) symptoms show a circadian pattern, which means they are more likely to appear during the circadian night, which naturally push the individual to sleep outside of their circadian night.
  • The effect of artificial bright light therapy on the circadian rhythm is variable on a day-to-day basis due to various factors (eg, sunlight exposure in addition to artificial light, and artificial light exposure in the evening, other environmental factors). Hence, light therapy may start producing less phase advance than expected and required at some point, even if the user did not change their usage. This would cause a progressive desynchronization. Likewise, light therapy may start producing more phase advance than expected, and this would cause a desynchronization as well. If noticed early enough, this can be adjust by varying the duration of exposure to light therapy, but in practice it's difficult to assess what direction the desynchronization is happening, as the primary sign is a reduction of sleep duration and efficiency (ie, more fragmentation, lower restorative quality), which provides no information about whether it's because the circadian rhythm shifted later or too much earlier. The introduction of wearable monitoring devices could tremendously improve, or solve, this issue.
  • For some individuals, the therapy can be too effective and cause a too short sleep, by phase advancing the wake up time too much compared to the fall asleep time. Here are some tips to reduce the therapy's effectiveness.
  • Why is it so hard to treat non-24, and why does it seem like non-24 require much longer or intense light therapy to be temporarily entrained, whereas DSPD seem to require much less? There are logical reasons to assume this holds true, because of the differences in the therapeutic goals. DSPD need a phase advance, which can always be achieved with light therapy, the intensity and duration only modulating how much phase advance is obtained. Non24 on the other hand aims for entrainment, which also involves phase advance but what is required is a stable phase advance, and this changes everything. If stable phase advancing cannot be achieved, it doesn't matter how much phase advance you get, you won't be entrained. https://www.reddit.com/r/DSPD/comments/pvsfjy/comment/hec7o5h/?utm_source=share&utm_medium=web2x&context=3

This is one of the first protocols I tried, and failed, and why I devised the VLiDACMel protocol, which is the only protocol that recommends to use light therapy at the natural wake up time, instead of a set time with an alarm clock. And the results have so far been much better. Not only because it is more effective (if you use light therapy too early, you can phase DELAY and hence worsen your DSPD, instead of phase advance), but also much easier because you suffer from less sleep deprivation, so there is more compliance.

Of course, a combination of multiple factors (eg, getting sick during winter) increases drastically further the likelihood of losing entrainment compared to any single disturbance.

Useful equipment

Some suggestions of useful equipments to monitor or manage circadian rhythm sleep-wake disorders.

Equipment for circadian rhythm entrainment

  • Light therapy tools: Luminette 3 (229€). Will be the primary treatment AND a calibration tool to evaluate other light emitting devices (to avoid them during dark therapy). It has a 30-days money back warranty (+ of course a 2 years warranty for defects in European Union), so you can test it for a month to see if it affects your circadian rhythm (it should work under 2 weeks of daily use), and if not you can send it back for free.
  • Dark therapy tools:
    • If the expected use is only to filter evening/night time artificial light: Blue blocker glasses such as UVEX with the SCT Orange coating glasses (there are multiple models: Skyper, Astro OTG, Protégé and Ultra-spec 2000, the latter being the best model to wear with other glasses below) ;
    • If the expected use is to filter daytime sunlight, whether indoors or outdoors: wrap-around blue blocker sunglasses such as hair removal laser safety amber/red tinted glasses filtering wavelengths in the range 400-550nm (example), as these laser safety glasses are made to ensure protection against the much more dangerous lasers and hence also include a VLT (light dimming) filter in addition to a color wavelength filter.
      • Complement: use blue light filtering softwares such as f.lux or LightBulb on computers and Twilight on smartphones, in addition to screen dimmers such as Nelson Pires Dimmer v2 on Windows or Twilight on Android smartphones.
      • Complement: buy RGB smart LED bulbs that can be controlled by wifi or a remote. These can usually be programmed to automatically switch to a dimmed red light at a specific time every day, hence automating dark therapy at home. One inexpensive example is Yeelight 1S, which costs about 15 euros to 20 euros apiece.
      • Alternative: Add clip-on or VLT shading films to dim down light sources, these can be added on any normal glasses, but usually they do not filter much and do not adapt well.
      • Optional: SwitchBot automatic curtains opener. SwitchBot is a brand that specializes in domotic automatization of non connected furnitures. The automatic curtains opener is programmable with a smartphone app and has several variants depending on the type of fixture: U-rail, I-rail or rod, and it has an optional solar panel to avoid the need to recharge. It is relatively affordable, at about 80 euros one device, plus 20 euros for one solar panel. This can be a great alternative to sunrise lamps, or be useful to automatically take care of pets.
  • Melatonin instant-release <= 3mg. The author of this document strongly recommends the sublingual Valdispert Melatonin 1.9mg Instant Release (mirror) (it's the one with pure melatonin only, not the one with "4 actions" because of including other compounds). This will help with stabilizing the circadian rhythm at the time you wish and feel sleepiness. Always prefer sublingual (orodispersible in french) tablets with no other compound than melatonin (besides of course a few conservative or flavor additives that are always present), as sublingual pure melatonin tablets are of higher quality in general, particularly for over-the-counter melatonin.
    • Another person with non-24 recommended "Vitality NUTRITIONALS" which are sublingual instant release melatonin like Valdispert's, distributed by VitaminExpress www.vitaminexpress.org Made in the Netherlands, dosed at 1.5mg. However this is a bottle, not packaged in individually sealed blister pack, hence this may degrade after a week of opening the bottle. Another untested product is Chronobiane 1mg.
    • In UK, Pharma Nord Melatonine 3mg (not Melatonin Complex) was licensed in the UK for the treatment of jet lag, and hence should be appropriate for circadian rhythm disorders too.
    • In the USA, there are only a few recommendable pure sublingual melatonin tablets in blister packs. One is Major Melatonin Tablets, 3 mg, 100 Count as sold by Walmart, another is webber naturals Melatonin 3 mg - 15 Tablet Blister Pack sometimes sold in 2 packs (30 days = 1 month). Alternatively, search for "melatonin blister pack sublingual tablet" or if no blister pack is available, at least search for "melatonin usp sublingual" (the USP label being a self-validation process). Do not worry about instant release or prolonged release, both should work anyway and if you take a sublingual tablet, it can only be an instant release since it's the coating that makes a prolonged release, hence prolonged release melatonin is always presented as an ingestible pill that will dissolves slowly in the guts. The author did not try these products. Another product is Herbatonin 0.3mg, also in blister packs.
  • Optional: DNA testing using Nebula Genomics, if MT2 receptor mutation, then also need to control food/glucose and melatonin mixup?
  • Optional: smart alarm / chronobiological alarm clock, such as Sleeptracker Pro watches (discontinued) or FitBit, or smartphone apps such as Sleep As Android, which can vibrate when it detects that the user is in a light sleep stage via actigraphy, it's very efficient to forcefully wake up despite sleep deprivation. Indeed, humans are highly sensitive and alert to touch and vibration, much more than sound. In addition, waking up during a light sleep stage is highly effective as to the user it feels like they are already awake when the alarm triggers, so that they are much less likely to fall back asleep or snooze. The window of detection of the light sleep stage is configurable, usually the default is 30min, which means that at the earliest, the smart alarm triggers 30min before the programmed alarm time if a light sleep stage is detected, and at worst at the programmed alarm time if no light sleep stage is detected. The combination of both features (smart alarm + vibration) is hence highly effective to wake up, and has the distinct advantage over sound that it doesn't bother partners living close by or in the same bed (which would induce sleep deprivation for them, a common but avoidable side effect that partners of individuals with circadian rhythm disorders often experience). However, they do not fix sleep deprivation so the tiredness and cognitive impairments will still appear during the day. Alternatives include Axbo and Sleep As Android app on Android smartphones (but apps are less accurate than wearables). Avoid faradic stimulation (electrically induced pain) devices such as Pavlok which are not supported modern science and will only increase sleep deprivation and pain. Combine with napping whenever possible to reduce sleep deprivation.

Tools for circadian rhythm disorder management

  • Sleepmeter Free on Android and its widget, to log a sleep diary and generate sleep charts. Just tap the Sleepmeter Widget before sleep and tap again when you wake up, it will record your sleep timing and duration, and optionally you can add tags and comments after if you want to add more infos for yourself. In early 2021, Sleepmeter mysteriously disappeared from the Play Store and the developer is unresponsive to sollicitations, but the app can still be downloaded on APK Pure, its widget also.
    • Sleepmeter Free can also be used on computers (Windows, MacOS and Linux) via BlueStacks 4, an Android emulator. Simply install BlueStacks, then download Sleepmeter Free APK (APK = installation file for Android app), and simply double click on the downloaded APK. BlueStacks should automatically install the app and it should show up in "My Games" tab inside BlueStacks.
    • Note: Sleepmeter Widget does not work correctly on Android 10+: if it doesn't switch from sleep to wake or inversely when tapping on the widget, then it's necessary to open the app, then minimize it and then try to tap again, then switching states should work. This appears to be because newer Android versions do not allow widgets to update data in sqlite databases. It appears the app will stop functioning sooner or later. If you know how to program in javascrit/typescrit/react-native, please help us make an open-source digital sleep diary app to replace Sleepmeter, see the circalog project for more infos, a sketchboard and a relational database graph are available.
    • On Android 14+, SleepMeter cannot normally be installed, but it is possible to force installation (thanks to eatnerdsgetshredded for the tip!): enable USB debugging on your phone (you need to enable Developer Mode, no root needed), then connect your phone to a PC with USB debugging, and then you can use the following ADB command: `adb install --bypass-low-target-sdk-block app.apk`
    • Paper sleep diary alternative: the AASM sleep diary / sleep graph template is recommended (mirror here, 2021 updated version here).
      • Here is an unofficial digital spreadsheet version of the AASM sleep diary template, which presents two major advantages: 1) can store unlimited data and hence eases assessment of chronicity of sleep patterns, 2) easier to carry everywhere in a smartphone or computer and hence input data at any time and anywhere and hence reduces misrecalls and data loss.
    • Alternative opensource free electronic diary with a similar tapping system: https://andrew-sayers.github.io/sleep-diary/
    • Another alternative opensource electronic diary for Android is Plees-Tracker: https://github.com/vmiklos/plees-tracker
    • Another alternative for Windows PC computers is SleepChart, by the developer of SuperMemo, who has non-24. The main advantage of this app is the ease to input data from a paper sleep diary for example, simply click on the chart to draw the sleep graph.
    • Alternative: For sleep tracker wearables users such as Fitbit wristbands, the data from these sensors can be converted to a sleep graph using Kizari's tool: https://sleepcharter.z13.web.core.windows.net/
    • Alternative: For individuals with sleep apnea, the CPAP machine may be able to record usage data, which can then be converted to a sleep diary using the opensource tool OSCAR, as was done by DSPD reddit member EarendilStar.
    • Alternative: Sleep Diary Dashboard by Andrew Sayers, another wonderful opensource tool that can convert various sleep diary formats including Sleepmeter, Plees-tracker and custom excel sheets into a generic sleep diary format and then generate a standard medical sleep report to present to doctors.
    • Alternative: for owners of FitBit devices, sleep graphs can be generated very easily using this open-source software: https://fitbit-sleep-vis.netlify.app/ (sourcecode is here: https://github.com/carrotflakes/fitbit-sleep-vis )
    • Alternative: not free, but this is a baby tracker which can generate a nice sleep graph but also tracks other things such as meal times, etc: Huckleberry.
    • Alternative: Track & Graph, an open-source Android app to track various factors that are completely customizable by the user, with customizable graphs and data import/export as csv files (thanks to Yetscrape for the tip!): https://github.com/SamAmco/track-and-graph
  • Lux meter apps on smartphones. Any free lux meter app will do, what matters is the light sensor included in the smartphone, but nowadays most light sensors mimic pretty well the eyes responsivity to bright light, so the measurement is quite accurate between 5 lux to 30k lux usually.
  • Online Actogram by Barrett Davis, an opensource preliminary python tool to potentially massively screen for circadian rhythm disorders using browser's history (examples here).
  • Noice, an opensource multisounds whitenoise generator for Android. I recommend enabling a mix of pink noise, brown noise and a natural noise (such as gentle raindrops) to efficiently mask out external noises. Here is a preset the current document's author made for newborns but which also works for adults: InfantWombSim for Noice v1.3.3, WombSimulator fo Noice v2.
    • Other opensource white noise generators on Android include Chroma Doze and White Noise Plus.
    • An equivalent non-free app for iOS/iPhone is Dark Noise by Charlie Chapman, but the source-code is available so maybe it can be installed for free from the app files?
  • HabitLab to ease sleep hygiene (reduce disruption from social apps).
  • LightBulb, an opensource blue light filter and brightness dimmer for Windows
    • An alternative on Linux is GammaStep, which automatically change the gamma (brightness and color) of the screen depending on your surroundings (acquired from the webcam). An awesome idea that partially automates dark therapy.
  • Dark modes for various apps are highly recommended, they can greatly reduce eye strain and the potential impact of screens on the circadian rhythm while improving readability.
    • A dark mode is when the background is made dark or black, and the text or interesting features in light color or white. Since the background represents most of the displayed space, this greatly reduces the total emitted lux, without losing any content visibility. A basic dark mode can often be implemented by simply inverting colors, but this does not always work (eg, pictures should not get color inverted but icons should), hence good dark modes are tailored for each app/websites.
    • Set the OS into a dark mode, not only the windows bars will be darker, but also apps that support native dark mode will also switch automatically.
    • Most web browsers now offer a dark mode, either as an app setting or depending on whether the OS is set to a dark mode, such as Chrome and Firefox on desktop, or Firefox and Opera Touch on mobile.
    • Adobe Reader offers a native dark mode to read PDFs on desktop, Xodo PDF offers the same on mobiles (Android and iOS).
    • DarkReader web plugin allows to open online PDFs in Chrome with a dark background.
    • A lot of text editors offer a dark mode: Notepad++, Zim Desktop Wiki, Zettlr, etc.
    • Some apps provide more dynamic features for context-specific dark modes, such as dimming more the unnecessary background on websites such as YouTube or even unfocused apps, such as the opensource Turn Off The Lights browser extension and app.
  • The book Sleep Misfits: The reality of Delayed Sleep Phase Syndrome & Non-24 by Sally Cat is highly recommended, being the only book currently written compiling the experience specific to patients living with non-24 and DSPD handicaps. Reviews note that this book can help in validating one's own experience, and help with acceptance and coping with the handicap.
  • Rotime is a web app available for desktop (Windows, Linux, MacOSX) and mobile (Android, iOS) specifically tailored for people with non-24 and other circadian rhythm disorders. The main demographic is workers with circadian rhythm disorders or shift work, but it can be used by anyone who want to schedule their days on a dynamic non-24 timeframe. You can enter your tasks, their durations, and then the app allows to easily rotate the time you start these tasks. It's a great app for designing a work schedule in general, but not for specific tasks. There is a free version for one day, or an older free version all the time in WebArchive, or a paid version with more features and to support further development.

Wearable circadian rhythm monitor

TODO: This section is a work-in-progress, come back later for updates.
Although there is currently a "wearables revolution", it is still hard to find devices that can continuously (24/7) record vital signs with a sufficient quality (sampling rate, low noise) to be considered adequate for research or medical purposes. However, there are a few, which we could use and determine as adequate for the purpose of ambulatory circadian rhythm monitoring, potentially by the patients themselves.

The two major sensors that are the most informative to monitor the circadian rhythm are the temperature sensors and the ECG (with an accelerometer). The total for one iButton and a Polar H10 is less than 200 euros, and these devices will last for several years.

The following is a practical, hands-on summary for the more complete setup instructions found in the Wearadian project: https://circadiaware.github.io/wearadian/docs/SleepNon24BiologicalMeasures.html

Usage advices: A critically important technique to properly wear these devices is to move them regularly to let the skin breathe, so as to avoid rashes (caused by sweat and warmness but not allergies since they are made of cotton and silicon), it's necessary to move the sensors (and belt) up and down to slightly different body sites to let the skin breathe. Hence, the sensors should be moved at least twice a day (once at wake up, once before sleep), and they should also be moved as soon as there is a feeling of itchiness. For example, the chest belt can be placed above the solar plexus during the day, and below (overlapping with the belly) before sleep and for the duration of the night. Cleaning the sensors and belt with a tissues imbibed with alcohol everytime after shower and every half week is also a good practice.
Also, it's important to avoid any wearable that requires the use of medical tape or sticky gel patches/electrodes, as they may feel comfortable at first but will invariable produce a skin reaction after some time (usually a few days). For continuous wear, it's necessary to use wearables that can be in contact with the skin without any adhesive, such as by strapping a belt.

  • Wrist skin temperature sensor for circadian rhythm phase assessment: Maxim Thermocron iButton DS1925EVKIT (Starter kit including one DS1925L iButton and the DS9490R and DS1402D-DR8+ connectors to retrieve the iButton's data on computers via USB as a CSV file). Cost: about ~$100. If DS1925L is unavailable, can also use DS1922L but the internal memory and battery are much shorter (4 years for DS1925L with 5min sampling rate (setup 300s in the config), 6 months for DS1922L for 2min sampling rate). The iButton does not need to be recharged, but unfortunately once it runs out of battery, it cannot be replaced (although there is one academic paper which shows how to replace an iButton's battery, but this is not an official instruction, do it at your own risk, and of course the device will be much less airtight after).
    • Advantages: Wrist skin temperature has no delay, it shows the current state of the circadian phase because it directly captures changes in body heat flux, whereas core body temperature lags behind by a hour or two due to thermoregulation lag.
    • Disadvantages: rarely painful on the wrist especially when using a brand new cotton sport wristband until it loosen with use, clunky software suite (no smartphone app, transfert is wired via USB, need to export to CSV and then plot yourself the data or use Circalizer), prone to bias (the cotton wristband insulates the iButton from environment but still skin temperature can be biased by a lot of environmental factors, and it's just more noisy by nature compared to core body temperature).
    • Interpretation tips: opposite of the core body temperature: a steep increase of wrist skin temperature signals the start of the circadian night, while a slow decrease signals its end and the start of the circadian morning and day. There is no time lag. The data needs to be smoothed because it is very noisy.
    • Tips for usage:
      • Buy a cotton sports wrist band such as is used for tennis ("sweat bands"). The Under Armour wristbands are recommended, they exist in various lengths, even tiny ones which are great during summer.
      • Buy also velcro stripes (hooks type, not loop) with adhesive, to glue on the iButton and then attach it on the inside of the cotton sports wrist band (the velcro hooks will hook well on the cotton as it naturally forms loops).
      • How to wear: Wear the cotton wristband + iButton on the non-dominant arm, and place the iButton on contact with the skin, positioned at about the middle of the width of the arm to be on the radial artery. Technically, the radiar artery runs from the wrist to the elbow's interior, so you can place the iButton anywhere on the length of the forearm. In fact, you should regularly move the wristband up and down your forearm, to avoid the sweat and warmth accumulation from itching and damaging the skin (move twice a day at least, and whenever it's itching). If necessary, the wristband can be placed on the dominant arm for some time if you need the non-dominant one to rest.
      • This setup provides true 24/7 skin temperature monitoring setup, as the iButton DS1925L can last 4 years with its integrated battery (then need to buy another one or can try to manually replace the battery as some researchers have done).
      • Data need to be transferred to a computer every 6 months (for the DS1925L, the interval is much smaller with DS1922L, about 10 days), and the device memory (mission) needs to be reset, otherwise it will stop recording new records.

  • ECG (heart rate and heart rhythm) + 3-axis accelerometer (chest actigraphy): Polar H10. Costs about 80€. Comes with a chest strap. Battery: 16.5 days with one button (CR2320) battery.
    • Advantages: ECG is useful to assess sleep quality and discriminate out of phase sleep (ie, naps) vs in phase sleep sessions (ie, biological night sleep sessions), by observing the heart rate. ECG is also useful to evaluate some health parameters especially cardiac, and can allow to pre-screen for further assessments by a cardiologist using ECG devices with more channels. The accelerometer can be used as an actigraphic diagnostic tool, although being on the chest means it is less accurate than on the wrist (as laying down can be sufficient to appear as being asleep). The accelerometer can foremost be used to regress motion artefacts.
    • Disadvantages: Wearing a chest belt can be uncomfortable until you get accustomed to it ; requires a phone that is always connected to the ECG (ie, you will likely need to buy a dedicated phone and wear it at all times) ; storage consumption (ECG generates a LOT of data).
    • Interpretation tips: Heart rate is generally higher during high wakefulness phases of the circadian rhythm, and lower during the circadian night. Posture also plays a role, with laying down decreasing the heart rate (just like core body temperature), but not as much as the circadian night. Heart rate variability may also be interesting to observe but this needs to be calculated manually.
    • Tips for usage:
      • The Polar H10 chest strap sensor was selected because it's the only chest strap ECG available with a long battery (2 weeks!), and all other consumer devices can only capture heart rate. Furthermore, chest strap ECG is more reliable for long-term ECG acquisition than wet electrodes or other systems, because there is no wires and hence chest strap ECG is the only ECG technology reliable enough to capture ECG during motion (ie, cheststrap ECG is robust to motion artifacts), as motion is unavoidable in continuous 24/7 use (and especially during the biological night for sleep acquisition!).
      • The Polar H10 sensor needs to be paired via Bluetooth to a smartphone, and an app needs to be used at all times to record the ECG (because only heart rate can be stored on the internal memory). No cloud service registration required, all data is stored locally.
      • Use the Polar Sensor Logger app on Android by Jukka Happonen to log both the ECG and accelerometer data with the sampling rate of your choice (up to 200Hz/8G for the accelerometer and 130Hz for the ECG). It also saves the Heart Rate in a separate CSV file, and the extra columns represent the RR-interval in milliseconds. The timestamp format is in nanoseconds and the epoch is 1.1.2000. Note that the app requires both bluetooth and location (GPS), hence to save battery, the phone can be set to Plane mode and wi-fi can be disabled, everything can be disabled except bluetooth and location, and the screen can be turned off during data collection. Data is stored in realtime in csv files in the sensorDataLogs folder at the device's root, so that even if the logging is interrupted due to a bug or the device being out of battery, the last logging session won't be lost.
        • Note that although the app can work with only bluetooth, it won't be able to seek and automatically reconnect to the Polar H10 sensor in case of disconnection without location (GPS) enabled.
        • Also to ensure automatic reconnection, it's necessary to enable the dual Bluetooth stream/pairing on the Polar H10 after each change of battery (the memory is flushed then) using the official Polar Beats app. Note that this app requires enabling wi-fi temporarily (in addition to Bluetooth and GPS location) to pair with the Polar H10. This can be a good opportunity to also disable GymLink and ANT+ to extend the H10's battery life.
        • It might be a good idea to buy a dedicated Android phone with a long battery, which can allow to continuously record up to 10 days with a single charge (the generated data with accelerometer set to 100Hz and 2G is 400KB/min total for accelerometer+ECG+Heart Rate, so this makes for 6GB for 10 days, or 17GB/month, or 200GB/year of data, so it all fits in any modern smartphone's internal memory).
          • Using as a bluetooth receiver the Realme 6i and its 5000mAh battery (cost about 170 euros), the battery consumption rate is 10%/24h, hence up to 9-10 days can be acquired with one full charge.
          • To achieve this and avoid background app kill, the Realme 6i with Android 10 needs to be setup as follows: set Background Processes Limit to 4 instead of standard limit in Developers Options ; disable Do Not Disturb mode ; in battery optimizations options (specific to Realme UI), disable all optimizations except for screen optimizations and standby optimizations ; finally, launch the Polar Sensor Logger app and Lock it (show the list of apps and then click on the 3 dots in the corner to see the Lock option), then launch the acquisition, setup 100Hz/4G for the accelerometer, then click on the Graph tab and click on the Pause button (after checking that the graphs were alright). Now switch back to the Main tab and you can turn off the screen and let the acquisition run. The data will be continuously saved in CSV files in the sensorDataLogs folder, even if the app or phone crashes at some point.
        • Alternative to get an even longer battery bluetooth receptor: make an Arduino-based bluetooth low energy (BLE = BT 4.0) logger to microsd card. Some developers already made heart rate loggers for Arduino and Polar H7 chest bands (see also here and here), but not the ECG, although the SDK is open so that should also be possible to do.
      • Using the Polar Beat app, the H10 sensor can be configured to have a dual Bluetooth stream, so that it can send data to two different devices/apps simultaneously. This can be used advantageously to concurrently continuously record the ECG data on one device, and use another device (the day-to-day smartphone) for when you want to visualize your current heart rhythm in real-time. To do this, install the Polar Beat app, pair the sensor, then go to the settings, click on the sensor and the sensor's options will show up, and then you can enable the "2 BLE receptors" option.
      • Combined with the EliteHRV Android and iOS app, the Polar H10 can be used for breathing relaxation exercises (fundamental resonance breathing etc), and also be used as a biofeedback tool.
      • Big advantage of this setup compared to others: it really allows for continuous ECG, since there is no need to transfer data to restart a new session, as the phone's memory is used and it's vast. So only the smartphone's battery is the limitation, but it can be recharged while the acquisition continues, and even the data can be transferred concurrently using FTP or similar apps. This is a true 24/7 continuous ECG monitoring setup.
      • Main limitation: a receiver bluetooth smartphone needs to ALWAYS be in range to capture the data. Since the bitrate necessary to transfer ECG is quite high, and the signal is greatly attenuated by going through objects, it's easy for the ECG signal to be lost. Fortunately, the Polar Sensor Logger app by Jukka Happonen was kindly updated following the author's feedbacks to automatically reconnect on signal loss, as long as GPS is enabled (due to a limitation of how Bluetooth is managed by Android OS).

Innovations of this protocol

  • Does not require prior sleep deprivation nor behavioral constraints (ie, a "strict sleep schedule"), which was shown to reduce the effectiveness of light therapy (due to adenosine buildup) and has highly deleterious consequences.
    • Why don't we use a gradual wake up time forced by an alarm clock, eg, asking the patient to forcefully wake up 15min earlier each day to start light therapy? Firstly, because this does not work for individuals with non-24, as the goal here is to shorten the circadian period, and not phase advance, which is way too difficult to achieve anyway with currently available technologies (we simply don't get enough phase shifting to allow for a reliable consisteent phase advance with non-24). Secondly, and this is more applicable to DSPD, as those with DSPD can indeed get a phase advance, but not if they are exposed too early: indeed, if they get exposed before the core body temperature minimum, which can very well happen late in the objective morning due to their delayed phase, then light therapy will actually DELAY their phase further and hence worsen their DSPD symptoms, instead of phase advancing as wished. Although advancing by 15min each day should not apriori cause this issue, it will after long enough, because advancing by 15min/day is MORE advance than the circadian phase advance that can be obtained by circadian shifting therapies, so after 2 weeks or so, the individual will forcefully wake up ~3.5h before their natural wake up time, and it may very well be before their minimum core body temperature point. In fact, most clinicians (incorrectly) recommend their DSPD patients to start light therapy before their CURRENT wake up time, which is ver likely a restricted wake up and hence happening much earlier than their natural wake up time, ond so this further reduces the margin with the core body temperature minimum, and hence starting light therapy just 1h before the restricted wake up time can very well already fall on the phase delay part of the bright light PRC curve. Thirdly, non-24 and DSPD patients who seek therapies are most likely already chronically sleep deprived, hence asking them to further restrict their sleep by subtracting an additional 15min/day of their already short sleep runs the high risk of uncompliance and increases dropout rates, hence it's not surprising that studies using such a protocol always display high dropout rates. Fourthly, the only viable reason to suggest this scheme is because with the effect of light therapy, we can assume that the patient's phase will progressively advance, and hence to optimize and get the most phase advance we have to adapt light therapy's administration timing to be earlier, moving alongside the patient's circadian phase. However, this assumption is flawed in practice, because: 1) 15/day is way too much, bright light therapy does not move the circadian phase this fast, 2) there is a delay (called photic history) of several days up to a week for bright light therapy to affect the circadian rhythm, 3) it is unnecessary, because if light therapy is effective, the patient will naturally wake up earlier and earlier, and so they can simply be instructed to start light therapy as soon as they naturally wake up, which is not only easier and increases compliance, but also allows the therapy to be more individualized as then we are more guaranteed that the patient is not at risk of starting the therapy too early, they will start earlier and earlier but at the pace of their circadian rhythm phase advances, 4) there is still a risk of mistiming and getting exposed too early, because there is a sudden reversal at the core body temperature minimum point, so it's much safer to ensure we get exposed AFTER (to get a phase advance for sure), even if the phase advance magnitude is a bit reduced, we can just increase light therapy intensity and/or duration to compensate; hence in practice even this viable reason is not worth it. Also, don't be mistaken, clinicians don't prescribe this 15min/day scheme to optimize administration timing relative to the PRC curve, tmost have no idea and don't even consider the PRC curve at all, their reasoning is much more simplistic, as they simply assume that we wake up when we get exposed to bright sunlight, so you simply need to get exposed to bright light earlier, and you will magically wake up earlier! But that's not how the circadian rhythm works, it moves with specific and strange rules depending on where you get exposed, it does NOT just synchronize to the time you get exposed to bright light. In summary, there are only drawbacks, and no positive reason to require the patient to follow a scheme of forcefully waking up 15min earlier each day to start bright light therapy.
  • Allows not only for entrainment but for sleep schedule correction by waking up earlier and earlier by using very long light therapy with the duration as a variable of adjustment. This allows to adjust the wake up time after entrainment, which no other therapy on non24 could achieve a constantly earlier wake up, the subjects having to freerun until they get in phase again with their ideal sleep schedule, which is highly impractical.
    • A previous study by Czeisler's team conducted a study in 2012 on 14 healthy men with a very long bright light therapy regimen of 5-8h of bright light exposure everyday for 5 days, which allowed them to achieve 8h of phase advance on average. This landmark and unfortunately poorly known study shows the viability of very long bright light therapy to produce significant phase advances in a short time span on the human circadian rhythm, in line with a subsequent study by the same lab and the current document's author's experiments results, which were found independently before finding these sources. However, one difference is that Czeisler's study required a concomittant sleep restriction scheme with a behaviorally progressively advanced wake up time (ie, using an alarm clock), whereas the present protocol does not. Also, the present protocol is the first to use very long bright light therapy as a treatment for circadian rhythm disorders. Another difference is the use of Luminette, a portable light therapy device, instead of constraining the patient to a light-filled room. A final difference is that the experiment spanned only one week, whereas for circadian rhythm disorders it's crucial to ensure stability of the new sleep-wake schedule over the long term.
  • A step-by-step comprehensive multi-system approach to entrain not only the central clock but also key peripheral clocks, and with multiple treatments with complementary effects to increase the likelihood and robustness of successful entrainment. The goal is to gain control of as many important zeitgebers as possible, while staying implementable in an at-home setting by non medically trained patients.
    • Another multi cases study also provided a combined therapy with melatonin and bright light therapy timed relatively to the circadian rhythm phase of non24 patients. However, as in nearly all studies, this was combined with sleep restriction (ie, forced progressively earlier wake up time by an alarm clock) which reduces effectiveness of light therapy, and hence is likely the reason of the high relapse rate. However, the study does not describe meals timing.
  • A focus on exogenous factor that can shift the circadian rhythm while accounting for endogenous specificities (eg, photosensitivity, timing of light therapy and melatonin relatively to current circadian rhythm phase, etc). Mental states and behaviors are disregarded as the author found them irrelevant.
  • Designed for at-home use in a realistic setting, not in a controlled lab environment.
  • Conception of an at-home circadian monitoring protocol, similarly to diabetes insulin and glucose monitoring devices, for the patient to make informed decisions and adequately time the therapies.
  • A complete cohesive therapy that can be directly applied in the clinical setting or at home under medical supervision. All the necessary tools and the margin of adjustments (eg, light therapy duration) are described along with the scientific justifications. All other currently available therapies only use one or 2 tools at most and with very precise values for the parameters as the purpose was to study their effects, there is no currently available protocol to use in the clinical practice.
  • Easier to implement and follow but also more flexible for the patient in practice than other combination therapies (see also here).
  • Low burden diagnostic and monitoring solution through temperature for the patient, more applicable in practice.
  • Designed and assessed for long-term use, whereas most circadian shifting interventions are only monitored for one week up to one month rarely.

Associated dataset

A continuously updated dataset covering experiments prior and during this protocol is available including a continuously maintained and annotated electronic sleep diary continuously and a record of a set of vital parameters including core body temperature (via dual-heat-flux method), skin temperature (via Thermocron iButtons), 6-axis actigraphy (using Axivity AX6), light intensity and spectral composition (using in-house recorder, open hardware details to be published) and ECG. This public dataset is available at https://github.com/lrq3000/non24article/tree/master/analysis . It will continue to be expanded as the experiment progresses over time, in order to provide for an as exhaustive as possible view of an individual's circadian rhythm. MRI (3T structural, functional and diffusion) and 30x whole-genome sequence are available upon request by academics.

Going further

  • Join an online community to share coping tips and tricks or just your complaints. Medical doctors recommendations do not cover coping tips, that's why patients communities can be very helpful. The r/N24 subreddit is a good place to start. There is also a chatroom on Discord.

Protocol variants

This section contains variants of the VLiDACMel therapy repurposing the same tools and principles but for other aims.

Backward cycling therapy

WIP section: this is a work-in-progress, the content may change at anytime. Please consider this section to be experimental and requires further testing and validation.

The VLiDACMel therapy can be slightly modified to cycle the circadian rhythm backward, in other words to produce so much phase advance that the non-24 individual will wake up earlier and earlier (instead of later and later naturally). In fact, a previous study by Czeisler et al in 2012 did the same with a 5-8h/day regimen of bright light therapy, which achieved 8h of phase advance under 5 days. However, this was never tested before on individuals with non-24, no therapy ever demonstrated such a significant phase advance in their core body temperature. But in the current document's author's experience, this is possible.

To do so, use the VLiDACMel therapy as indicated above for entrainment, and modify the following points:

  • Use a very long duration of exposure to blue light therapy glasses, such as 5h or more during summer and 8h or more during winter solstice. This is the key component to cycle backward, increase the duration as much as needed, with longer duration allowing for a nearly proportionally increased phase advance and hence faster backward cycling.
  • Expect to sleep less than the full night, because the fall asleep time (melatonin onset) shifts with a delay whereas the wake up time (melatonin offset) instantly reflects the new circadian rhythm phase shifted by light therapy. But it can still be expected to sleep more than when completely out of phase (ie, for adults who on average need 7-8h of sleep, the user of this therapy can expect to still be able to sleep 6-7h/day if they find they can monitor when their circadian rhythm night is and follow their sleep schedule along).
    • To reduce the delay between melatonin onset and melatonin offset, one can use melatonin pills 1-2h before the estimated start of the circadian night. Taking exogenous melatonin this late will not result in a circadian phase advance, but this is already taken care of by very long light therapy. Instead, exogenous melatonin is here used very close to the expected fall asleep time to induce sleep a bit earlier and consolidate sleep.
  • Avoid eating meals several hours before the biological night. Since it's difficult to estimate especially during backward cycling since the circadian night will be always moving, ideally the user should rather eat a breakfast and lunch (can be eaten later, in the middle of the day, instead of just a few hours after breakfast) and completely skip dinner. This will help avoid digestive issues and the melatonin-insulin-carbohydrates interaction that can slow down the backward cycling and fragment sleep.
  • Always prioritize reducing sleep deprivation, as it significantly reduces light therapy and melatonin efficacy: if the individual slept less than 1 ultradian cycle away from what they ideally need should be considered sleep deprivation (eg, if ideal sleep duration is 7-8h, then any sleep session less than 6h is sleep deprivation as it is 1 ultradian cycle = 1h30 to 2h less than ideal sleep duration). If sleep deprived, always take a nap whenever possible to reduce sleep deprivation. The individual can start light therapy after, and for as long as they stop light therapy 3-4h before their (estimated) circadian night. In the author's experience, having trying both avoiding naps and doing naps whenever possible, the latter always improved the backward cycling therapy and made it much faster. Use a sleep eye mask and ear plugs to isolate from environmental sleep disturbances such as sound noises.
  • If wearing a body temperature monitoring wearable, avoid bright light and eating if wake up earlier than the end of the circadian night. Wait until the circadian night ends (core body temperature raises above the lower phase, limb temperature: lowers below higher phase).

From preliminary results, the author observed a possibility to backward cycle 1 to 2h/day by using 9h during winter solstice and 5h/day in February. At the time of this writing, the author tried this strategy 5 times and it worked 3 times. However, for the 2 failed attempts, it still allowed to entrain the circadian phase to a stable schedule.

Effect of very long bright light therapy (6-8h/daily) using Luminette v3 on the sleep-wake pattern. On the right, we can see the backward cycling effect thanks to the great phase advance produced by bright light therapy.

A reddit member of the N24 subreddit also reported similar results with 6-8h of artificial bright light therapy daily using Luminette, see here for a chart.

Daylight simulation, an extreme but simpler bright light therapy protocol

This variant protocol is an extreme form of bright light therapy, where we don't just do artificial light therapy to complement sunlight, but to replace it completely. In other words, using this variant, we are not reliant on sunlight anymore for entrainment. This may be a potential strategy to overcome the loss of entrainment during winter and the reduced sunlight exposure, as happens commonly to individuals with non-24 and DSPD. Timing light therapy administration with this protocol is also easier.


  • Simply do at least 5h of light therapy, but closer to 10h is better, during the 14h of wakefulness after wake up, as these 14h are your circadian day. Light therapy can be started and ended at any time during these 14 hours. The hours after 14h of wakefulness are to be assumed to be the circadian evening and night, when dark therapy needs to be used instead (ie, staying in the dark, dimming all light sources and filtering blue and green colors to keep red or orange lights).
  • If we don't care about the exact timing of the circadian night and wake up time but we just want a stable, consistent sleep schedule, this variant can be started right away, at any point in the circadian phase, no need to wait to be in phase.

This is what the author of the present document is using, and has used several times in the past. This allows to "freeze" the circadian rhythm in place at any timing, it can hence allow non-24 individuals to mimic any chronotype, such as ASPD, morning lark, evening owl, or even DSPD. There are also side benefits such as mood and energy level increases thanks to the anti-depressant effects of bright light exposure, which increase productivity compared to freerunning, even when the circadian rhythm is frozen in an extreme DSPD-like chronotype (eg, sleeping at 8am and waking up at 4pm). This does not however fix all issues and energy levels dysregulations and irrepressible naps/siesta, nor the weird insomnia phenomenon, nor the reliability of the therapy and variability of wake up time is still an issue (ie, the wake up time will still vary in a 1-3h window between different days, but will not delay further, it will remain in this window).

A recent study published in 2022 on patients having developed a non-24 like disorder following severe brain injury found that the use of very long bright light therapy to simulate a whole artificial day allowed to reduce the freerunning period by 3h, which is a staggering amount! Although not directly targeted at true non-24 disorder patients, this paper is the first to demonstrate in practice the clinical usefulness of daylight simulation, and hence is a first step towards a potential validation.

Phase-delay bright light therapy (true chronotherapy)

WARNING: Avoid this protocol if you have DSPD! Indeed, there may be a possibility for some individuals that freerunning can't be stopped once it is started, since there are some case reports of individuals with DSPD turning into Non24 after doing (behavioral) chronotherapy! Phase-delay bright light therapy works differently but still has the same effect of causing a freerunning, albeit more controlled, so that the same risks likely apply!

In the case the entrainment fails at some point and freerunning restarts, it is possible to use bright light therapy in the circadian evening and night, instead of the circadian morning and day, to accelerate the daily phase delay and hence the freerunning period. This can be advantageously used to reduce the periods in inverse phase with the day-night cycle (ie, nightwalking) and restart the VLiDACMel entrainment therapy earlier. In the author's experience, this usually allows for a 2x up to 3x freerunning speed increase (and hence it shortens the time to complete a circadian phase reversal, ie, a 12h phase shift, by the same amount).

This is in effect what behavioral chronotherapy was designed to do, but unsuccessfully in practice, as sleep deprivation does not affect the circadian rhythm but only the sleep homeostat, so that the freerunning observed with chronotherapy can only be caused by the uncontrolled and inoptimal exposure to sunlight. Indeed, sunlight rise time and intensity cannot be controlled. Whereas here with bright light therapy in the evening and night, the circadian rhythm is directly manipulated at the optimal timing to cause a (near) maximal phase delay. There is another major difference: whereas chronotherapy relies on willful sleep deprivation by staying later and later everyday by sheer will, this tiresome procedure is unnecessary with phase-delay bright light therapy, as the circadian rhythm will shift thanks to the exposure to bright light, the individual can simply sleep whenever they feel tired. They should feel tired later and later everyday, with no effort required. In addition, they can use this additional time when they still feel energized to do activities and hence productivity loss is reduced contrary to chronotherapy.

To summarize the steps of phase-delay bright light therapy:

  • Get exposed to bright light during the circadian evening and the first part of the circadian night. Do not continue in the second part as there are risks of getting exposed after the minimum core body temperature point, which would phase advance (instead of phase delay, because of exposure before the minimum core body temperature point, as is the objective here).
  • Use dark therapy in the circadian morning, which means that at wake up, you can use red tinted "blue blocking" glasses and/or blackout curtains to avoid exposure to bright light (both artificial and sunlight).
  • Avoid pulling all-nighters (complete sleep deprivation), instead, try to nap during the circadian siesta and sleep during the second part of the circadian night (ie, partial sleep deprivation, since exposure to bright light during the circadian evening and first part of the circadian night necessarily reduces the sleep window opportunity, as only the second part of the circadian night can be slept, and in addition melatonin is inhibited which delays sleep onset and impairs sleep quality). Keep in mind that total sleep deprivation is not necessary to shift the circadian rhythm, napping during the circadian siesta and sleeping during the remainder of the circadian night are allowed, this won't slow down the freerunning since sleeping (or not) has no effect on the circadian rhythm. Keep in mind that when naps are done, the sleep homeostat gets partially reset, so that it can be expected that the sleep session during the next circadian night will be shorter.
  • (Optional, do this for faster freerunning but at the expense of impaired mood and decreased daytime energy): avoid bright light, including sunlight, in the circadian morning and day, ie, do dark therapy during the circadian day. Circadian rhythm shifting is kind of a zero-sum game: the phase delay obtained by being exposed to bright light during the circadian evening and night will be reduced by the phase advance obtained during the circadian morning and day, hence a greater phase delay can be obtained by reducing phase advances.
  • Stop when your wake up time is a few hours before your target ideal wake up time. Eg, after 10 days of phase-delay bright light therapy, I will be waking up at 4am, whereas I would prefer 7-9am. But I stop before to have some days for the photic history of evening bright light therapy to wear off, otherwise I may overshoot the time I target.

This procedure was used by the current document's author more than 4 times and systematically allowed for a faster cycling back into phase with the objective day-night cycle compared to waiting for the natural phase-delay freerunning (no therapy) to achieve the same.
Given circadian plasticity is disproven by empirical results of the VLiDACMel protocol, in that phase advancing/period shortening using bright light therapy in the advance phase of the light PRC curve does not produce long lasting changes of the individual's circadian rhythm after therapy's discontinuation, it is highly unlikely that phase-delay bright light therapy can neither affect the circadian rhythm with long lasting changes. Rather, it is much more likely that any effect of phase delay bright light therapy also disappear following therapy's discontinuation (after a few days of photic history washout period), which is the current document's author's experience.
Furthermore, the author of this document could successfully switch to the VLiDACMel entrainment therapy right after 2 weeks of phase-delay bright light therapy, with the entrainment building up over about 10 days as usual, hence this suggests that phase-advance bright light therapy (such as VLiDACMel) can be started right away after discontinuing phase-delay bright light therapy.

Note that this variant protocol of using bright light therapy in the phase delaying part of the PRC curve is the standardly recommended treatment for Advanced Sleep-Phase Disorder (ASPD) by both the AASM and the french sleep health organization, since it was discovered in a case study by Czeisler et al. Indeed, the treatment for ASPD is very well defined, it's simply the opposite of the treatment for DSPD, but it is usually much more effective because it's easier to phase delay than to phase advance (because our circadian rhythm reacts in an asymmetrical way - more scientifically, we say that the PRC curve amplitude of bright light is asymmetrical).
In practice, to treat ASPD, just try to get exposed to bright light in your circadian evening, ie, 2-3h before the time you fall asleep usually, and then stop 2-3h before the time you want to fall asleep. You can use bright room light, a computer screen at max intensity, or if you need a stronger effect you can buy a Luminette. Some sleep researchers hypothesized that melatonin may also be administered inversely to DSPD, during the circadian morning instead of evening, to get a phase advance, but this was not confirmed in practice, and the sleep drowsiness inducing effect of melatonin (type 1 receptors) are also not conducive to being used during daytime. Lastly, even though bright light therapy is a well defined effective treatment for ASPD, in practice it still forces the individual to stretch their circadian day and hence cause circadian misalignment side effects common to other circadian rhythm disorders similarly to jetlag, such as headache, brainfog, fatigue, cognitive issue, cardiometabolic dysregulations in the evening, etc... as well as specific issues such as melatonin inhibition due to bright light therapy exposure in the circadian evening and first part of the circadian night. This may be circumvented by using intermittent bright light therapy instead of continuous bright light therapy, which produces as much circadian shifting but only a fraction of melatonin suppression.

Mood, energy and motivation regulation

If what matters to you is not the time at which you are entrained but your productivity, whatever time you sleep or are awake, then light therapy can always be used, even through the periods when there is some freerunning (eg, winter). Indeed, several studies and systematic reviews demonstrated that bright light therapy is as effective as antidepressants to regulate mood and motivation. Furthermore, several studies demonstrated that sleep deprivation and circadian misalignment independently cause depressive-like symptoms in healthy individuals. Blue light therapy also reduces the circadian siesta dip performance decrease and triggers cortisol production, one of the major hormones of wakefulness.

Hence, even when blue light therapy cannot achieve complete entrainment, it can still allow to be productive thanks to its mood, energy and motivation regulating effects.

In the present document's author's experience, the two most important factors for motivation and mood regulations are:

  1. long bright light exposure
  2. sleeping sufficiently long every day (and in circadian alignment)

For example, if sleeping long enough but without exposure to bright light (eg, freerunning but staying mostly indoors), then the individual will stay in a motivation-less zombie-like state most of the time and is more likely to need to sleep during the siesta (ie, biphasic sleep). If exposed to long bright light but not sleeping sufficiently long or in circadian misalignment, the individual will retain some if not most motivation although it can be variable and with variable mood, napping can then be necessary to recover sufficient energy levels to work. Only when both conditions are satisfied can motivation be fully restored.

Intermittent bright light therapy

WIP: this is an experimental protocol. It needs more validation before being recommendable.

Intermittent bright light therapy (IBL) consists in getting exposed to bright light therapy intermittently instead of continuously (Continuous bright light therapy - CBL). For example, instead of being exposed to bright light for 4h, one can get exposed to bright light for 15min every hour, and repeat 4 times over the 4h, which in total would equal to just a hour of bright light exposure over 4h. Yet, despite the total exposure duration being shorter than with continuous exposure, intermittent bright light exposure was demonstrated by a study by circadian rhythm science pioneers Czeisler et al to be nearly as effective as continuous bright light exposure to shift the circadian phase, with a similar dose-dependent response. In other words, whether you get exposed to 4h of bright light exposure or 15min every hour 4x will produce nearly the same phase shift, and you can get more phase shift by repeating intermittent bright light therapy more (eg, more than 4x), just like extending continuous bright light. The main difference of effect between IBL and CBL is in the suppression of melatonin: whereas CBL almost completely suppresses melatonin, IBL suppress only a fraction, about 20-30%, of melatonin.

Given the above, IBL may potentially be useful in some cases:

  • since it can phase shift without suppressing melatonin, it is less effective than CBL to suppress sleep inertia and brain fog, but on the contrary it can be helpful when used as a phase delaying bright light therapy for individuals with ASPD, since they can then get exposed to IBL during their circadian evening without fully inhibiting their endogenously secreted melatonin.
  • when the user requires a strong phase shift, and hence a very long duration of bright light, but more than the battery of their device can provide. For example, Luminette can provide 11h of continuous bright light therapy at the lowest intensity setting of 500 lux, but some individuals may need a stronger phase shift and hence a stronger intensity. When using Luminette on the highest intensity setting of 1500 lux, the battery lasts only 3h. Some users reported they then had to resort to using a light therapy lamp to complement their bright light therapy session. Using IBL could allow to obtain as much shift while saving on battery, by getting exposed intermittently, such as 20min as the automatic switch off duration setting on the highest intensity of Luminette, and then keep the device switched off for the rest of the hour, then restart next hour, etc. This would eliminate the need to use a light therapy lamp, while still theoretically getting as much phase shift, but less melatonin inhibition, although the latter should not be a problem since we can assume that the individual is unlikely to secrete melatonin during their circadian day, which is when individuals with non-24 and DSPD likely would like to get exposed to bright light therapy (and individuals with ASPD need much less light therapy since the human circadian rhythm is much more exquisitively sensitive to phase delays compared to phase advances, the PRC curve being asymmetrical).
  • for comfort for those who cannot use bright light therapy for so long as they would need. For example, those who experience dizziness and migraines (then combining with a blue-only light therapy glasses such as Ayo could further reduce side effects caused by the sudden exposure to bright white light), or simply those who are at work or in situations where wearing a bright light therapy device such as Luminette can appear as socially awkward.

The VLiDACMel protocol can be straightforwardly converted to use intermittent bright light exposure instead of continuous bright light exposure. This may greatly reduce the dropout rate and increase compliance, but potentially at the expense of losing some of the benefits such as less energizing/wakefulness promotion and less mood improvements with IBL compared to CBL (because of a reduction in melatonin suppression).

Note that the current document's author did not yet try the IBL protocol, so I have no personally acquired empirical evidence of whether this is really as effective or not as the study above claims.

Weaker forms of bright light therapy in case of hyperphotosensitivity

Some people are hyperphotosensitive, which means that they are more sensitive to bright light than others. In most cases, this is not pathological, as they can still get exposed to sunlight without much side effects, but they feel uncomfortable side effects such as migraines to artificial bright light therapy. There are however more extreme forms of hyperphotosensitivity, such as sunlight photophobia, where exposure to sunlight is also painful.

In case of hyperphotosensitivity, there are alternative forms of bright light therapy that can produce weaker but still effective circadian manipulation:

  • Reduce the duration and intensity of bright light therapy. Hyperphotosensitivity can indicate a higher sensitivity to the circadian rhythm modulating effects of bright light too, so that it can be unnecessary to use very long bright light therapy, a short light therapy of less than 60min/day can be amply sufficient.
  • A blue-only light therapy glasses, such as Ayo, because blue only light may cause less side effects than blue-enriched white light (such as Luminette) while providing the same circadian manipulation effects. A member of r/DSPD or r/N24 who use this model recently told me it seems what I describe above hold true in practice, although they could not directly compare to a Luminette which they don't own.
  • A green light therapy glasses, such as ReTimer, as green light not only cause less side effects than blue and white light, but it is even used to reduce pain. The drawback is that it is also less effective at circadian phase shifting than blue light, and it does not cause cortisol secretion, so green light does not clear brain fog / sleep inertia unfortunately, and you may need to use green light longer than blue light to get a similar amount of phase shifting. There is some feedback from reddit that this indeed reduces side effects while still being effective.
  • If you already possess a Luminette, it emits white light, which includes all other colors, so if you want to try blue-only or green light therapy, you can tape on the Luminette's LEDs a colored gel filter such as those sold for VJing, they are usually inexpensive and can be found anywhere including on Amazon. Note that the wavelength will not be as optimized as you would get with a green or blue-only light therapy glasses, but it should still have an effect similar to these glasses. Doing the opposite (ie, trying to emulate a Luminette white light enriched with blue light out of a blue-only or green-only light therapy glasses) is not possible.
  • A light therapy lamp, so you can position your head or orient it further away to reduce the lux your eyes receive.
  • Use light therapy glasses with an Intermittent Bright Light (IBL) pattern instead of Continuous Bright Light. IBL involves using the light therapy device only a fraction of the time, eg, the first 20min of every hours, instead of the full hour. So for example, if to get the phase advance you wish you needed 3h of continuous bright light, you can instead get exposed to 20min each hour and you repeat x3. Studies have shown that IBL produces nearly as much phase shifts as continuous bright light, but it suppresses melatonin less, so you can expect less energizing/wakefulness-promotion effect, but the circadian rhythm shifting effect should be equivalent. For more infos on IBL, see the dedicated subsection above.
  • Check whether some of your medications may cause or increase your photosensitivity. In particular, ADHD drugs often increase photosensitivity. If this is the case, you may want to discuss with your doctor to try other replacement drugs with similar effects but no hyperphotosensitivity.
  • Avoid light therapy altogether and only use dark therapy. Circadian entrainmen works when our eyes detect a contrast between light and dark phases. By increasing the contrast during the dark phases, we also increase the efficacy of entrainment to the light phases even without using light therapy. Then, sunlight or simple room lights can be used.

Before using any of the possibilities listed above, please first talk with a physician if this is safe for you, especially if you have a more extreme, pathological form of hyperphotosensitivity, such as sunlight photophobia.


Introduction - A workbook of how sleep works, and how it can be manipulated to manage circadian sleep-wake disorders

Sleep is a very intuitive, natural process for most living beings, and is essential for survival. Yet, it is a widespread assumption that sleep can be controlled by will. In reality, science has now well demonstrated that sleep is an unconscious and mostly incontrollable process: our bodies are genetically programmed to sleep during some periods, and be awake at others, with most of this sleep-wake programming being regulated by what is called the circadian rhythm. Every living organisms need to sleep, and, interestingly, every living organisms possess their very own circadian rhythms: some particularities are shared across the specie (e.g., nocturnal rodents tend to be awake at night and sleep during the day), while other sleep parameters vary from individual to individual in a random, bell-shaped manner and which can be shared across species but not by all individuals (e.g., some individuals will sleep and wake up later than others, sometimes much later, usually called the night owl phenotype, and it exists in all species).

Anybody can conduct their own experiment to check the validity of this statement, from the safety and coziness of their very own bed: simply try to sleep all the time you can during 24h, and write down the periods you were asleep, and those you were awake. For nearly all adults, this should invariably result in either 1 or 2 periods of sleep per 24h, since human sleep is naturally biphasic or monophasic depending on the duration of bright light exposure. These two sleep periods can vary in terms of duration and of timing, but they tend to happen during two precise periods defined by the circadian rhythm: the circadian night, which is when the body expects to sleep the longest and do most of its restorative antioxydative magic, and the circadian siesta, a shorter sleep window opportunity for those who could not sleep to their fullest during their circadian night.

A sleep period is defined by the sleep onset (when we fall asleep) and the sleep offset (when we wake up, also called the "wake up time"). Both parameters are very much controlled by the circadian rhythm: assuming no sleep pressure (more on that later), it is nearly impossible to fall asleep before one of the two sleep windows, and nearly impossible to stay asleep past the wake up time of the sleep windows. The at-home experiment outlined previously is a clear demonstration of this hard fact.

The rest of this document is essentially a workbook that describes what we know about these circadian sleep-wake parameters, what we may know, what we don't know, how to manipulate them especially in the context of circadian sleep-wake disorders management, and some personal suggestions on the matter.

A few notes on the design choices before you read on

The rest of this document is designed in a way as to both provide technical details with scientific references for any non-trivial statement, while also trying to answer several common and less common but crucial questions about circadian rhythm phenomena, disorders and potential treatments or strategies to manage.

There are two kinds of solutions usually: either change your environment, or wear gadgets to isolate from the environment. This guide focuses on wearables, because although the results may be similar, wearables are much more comfortable and controllable, and hence more reliable than modifying the environment. Indeed, it's much easier to just put on your light therapy glasses and do your things such as preparing yourself for work, than standing in front of a light therapy lamp for 1-3h without doing anything else. You can even bring your light therapy glasses with you to work and use it while commuting if you don't have enough time beforehand.

Also, wearables are a lot less expensive than older solutions. A proper light therapy setup used to cost thousands of dollars to get enough lux (most cheap lamps don't provide enough lux unless you are literally on the nose with the lamp). Nowadays, light therapy glasses cost only $100-200. For other things such as dark therapy, blue blocker glasses cost only $10. That's why for example we prefer an eye mask and ear plugs instead of using cardboard on the window and soundproofing the walls. We also prefer using blue blocker sunglasses and light therapy glasses such as Luminette instead of advising to buy bright light neon fixtures that you'll need to setup up all around your house at the correct orientation for you or to go outside for a walk early in the morning: it's far easier to just put some glasses on your nose when your alarm rings.

The content in this section initially aimed to be a shorter version of an older 200+ page document, but has grown into its own, much longer thing (500+ pages if we count the references!), with a lot more information and less approximations than the original document (which was written when I had much less knowledge and experience on the topic).

If you have a circadian rhythm disorder (non24 or DSPD or other), you can continue reading with the next section. Otherwise, you can jump directly to the "Introduction to zeitgebers" section to learn more about the foundations of circadian sleep-wake rhythm science. Then, depending on your interests, you can read the "Light and dark therapy", "Melatonin" and "Food timing, diet composition and meal size" sections for more information about specific zeitgebers.

General informations about the non24 disorder

What is the non24 sleep-wake circadian rhythm disorder?

The non24 sleep-wake circadian rhythm disorder, also called freerunning sleep-wake pattern or hypernycthemeral syndrome, is a severe and rare intrinsic circadian rhythm sleep-wake disorder (CRSWD) with no cure currently known. A hallmark of circadian rhythm disorders is experiencing difficulties or inability to follow socially acceptable sleep schedules in the long run. Non24 can appear since birth or later in life, as the circadian rhythm changes with age. Although very common in blind individuals (two thirds are affected), it also affects more rarely some sighted individuals. It is a severely disabling, debilitating disease characterized by an inability to sleep and wake up on a 24-hour schedule, and which impacts not only sleep but also wakefulness, hence why this disorder belongs to the family of circadian rhythm sleep-wake disorders. Indeed, if untreated, this disorder produces constant sleep deprivation which compounds with circadian misalignment, which in turn causes excessive sleepiness during wakeful periods, accompanied by near constant brain fog, reduced cognitive abilities, slower reaction time and health issues such as cardiovascular diseases and metabolic disorders such as diabetes and obesity. This is in addition to the social exclusion directly caused by this irregular schedule. This worsen comorbid organic and mental disorders such as autism, adhd and depression. Unfortunately, no cure is known, and management therapies rarely work, with some commonly prescribed treatments such as benzodiazepines (sleeping pills) and modafinil worsening the condition and its associated chronic sleep deprivation, which in turns can cause chronic insomnia. Although insomnia is the most common complaint accompanying the non24 disorder, hypersomnia complaints are also possible.

Although all humans naturally have a non24 circadian rhythm when in isolation from external timecues (~24.2h - bigger estimates were false), the non24 disorder presents a necessary and unpreventable freerunning (ie, their circadian night delays later and later, which in practice means they wake up later and later each next day) despite exposure to external timecues (ref) (ie, zeitgebers, such as sunlight). Indeed, humans circadian clock, which defines different periods of activities such as the circadian day for wakefulness and the circadian night for sleep, is usually synchronized with the objective day-night cycle, mostly via sunlight, but in individuals with non-24, the circadian clock cannot align and hence the circadian night and day are ever shifting and misaligned with the objective day-night cycle. In practice, this means that individuals with non-24 cannot control not only their ideal sleep time, but (more problematically) neither their body's wake up time, even when they try to control their bedtime. If they do sleep earlier, they will simply take a nap that will be shorter and less restorative than a circadian night sleep (eg, often lasting only 2h — which is one ultradian cycle — even if they sleep during the objective night). Likewise, if they try to sleep later, they will wake up at their natural wake up time, no matter how short their sleep is (eg, if their current circadian night is from 8pm to 4pm, sleeping at midnight will see them incontrollably wake up at 4pm anyway, for a total sleep duration of 4h, which can appear to the untrained eye to be a form of insomnia, when it simply is the consequence of sleeping in circadian misalignment). These principles are governed by the generic sleep processes all animals share, but they are more apparent with circadian rhythm disorders such as non-24 due to the circadian misalignment with the day-night cycle.

The clinical signs characterizing the non-24 disorder is, when the individual is left free to choose their own schedule, to experience days longer than 24h (with some having an extreme form with days longer than 32h) with longer wakefulness periods than typical sleepers experience (eg, 8h of ideal sleep duration and 18h of wakefulness period instead of 16h). In practice, an individual with non-24 will feel more refreshed under a 24+h sleep-wake schedule, whereas a typical sleeper would feel a gradually more unbearable pain and decrease in sleep quality. The circadian night duration can be of similar length to typical sleepers of the same age group or there can be hypersomnia (including daytime drowsiness or long naps sessions), although individuals with non-24 often sleep less than they need to due to sleep restriction because of circadian misalignment or social/work obligations. Although the non-24 disorder is often just described as "having a day longer than 24h", this is a layman description of a lengthened circadian period, the latter being the scientifically accurate description of non-24, as it is the lengthened circadian period that in turns increases the length of the behaioral sleep-wake period. In practice, the sleeping pattern can be highly variable and unpredictable from one day to the next, even in the absence of external disturbances, due to naturally reoccurring endogenous transient changes in the circadian rhythm, scientifically termed "relative coordination and transient (dis-)entrainment", as sleep bouts can happen at any random unexpected times, as well as experiencing premature wake-ups. A common example experienced by individuals with non-24 is to see their circadian rhythm delay faster when they are awake at night than when they are awake during the day (ie, see the "relative coordination" phenomenon). This shows that the circadian rhythm is always changing, and hence, a "steady freerunning sleep pattern" should not be expected but rather an average freerunning pattern with chaotic noise and disturbances. Non-24 is sometimes incorrectly labelled as a chronotype, when more accurately, non-24 is precisely the lack of any chronotype, as the timing of the circadian night progressively changes all the time and will revolve around the clock, covering all possible timings after a while. Since non-24 is the lack of a preferential chronotype, there cannot be a concurrent diagnosis of another chronotype (such as DSPD) as this would be antinomic to the very definition of non-24, although the individual may be temporarily/transiently entrained to a schedule during specific and limited periods of time due to relative coordination to sunlight or to a medical therapy, or appear as a delayed or an irregular sleep-wake pattern when restricted by duties and alarm clocks.

Although there exists a few therapeutic options for management, there is no permanent cure, and a sizeable part of this population appears to be treatment-resistant, especially those with some comorbidities that interact with the circadian rhythm and contraindicate melatoninergic therapies, such as restless legs syndrome (RLS) and periodic limbs movement disorder (PLMD).

The non-24 circadian sleep disorder was first clinically documented in 1971 in a sighted individual, and only later in 1977 in a blind individual (see also here), hence predating the advent of ubiquitous exposure to screens and bright artificial lighting. Although it was initially suspected to be associated with mental disorders, studies have since then failed to demonstrate specific associations (eg, bipolar disorder), although there is a documented higher prevalence of circadian rhythm disorders in individuals with neurodigergence such as autism and adhd, or mood disorders such as major depression.

Since their circadian rhythm, and hence ideal sleep period as dictated by their biology, is often in mismatch with societal needs and the day-night cycle, individuals with non-24 are often chronically sleep deprived or at best living in circadian misalignment. At first, disregarding their circadian rhythm will cause the same transient symptoms as for jet lag: foggy thoughts, headaches, digestive issues, daytime tiredness, chronic fatigue, insomnia (inability to sleep when allowed to). If this circadian misalignment becomes chronic over years, more serious health issues will appear, such as cardiovascular diseases, metabolic disorders like diabetes type 2 and obesity, cancer as well as severe depression among other diseases that can be caused or worsened by severe chronic sleep deprivation and circadian misalignment. These health issues are not specific to non-24, but are the consequences of of chronic circadian misalignment and/or chronic sleep deprivation, and hence are observed in all circadian rhythm disorders, including exogenous circadian rhythm disorders (ie, disorders that are caused by external constraints such as work obligations, as opposed to endogenous circadian rhythm disorders which are caused by internal, presumably biological causes) such as night shift work disorder (ie, the circadian misalignment caused by night shift work).

Maintaining social obligations can worsen the symptoms of individuals with non-24, as this can not only lead to further sleep deprivation worsening all cognitive and mood capacities, but also additional disruption of their circadian rhythm from external cues (eg, unwanted light exposure mistimed with their circadian rhythm) depending on the time of the activity. Having non-24 is not inherently unhealthy, but trying to restrict sleep to fit into social expectations is, due to the chronic circadian misalignment and sleep deprivation. Furthermore, research has demonstrated that it's crucial to sleep in phase with one's own circadian rhythm, especially during childhood, to prevent the development of other diseases, such as metabolic disorders.

Unfortunately, even without social obligations, individuals with non-24 have no means of monitoring reliably their circadian rhythm, and hence often sleep in circadian misalignment and hence sleep too little. This makes them live in a nearly always exhausted state, only waiting for the next opportunity to sleep (since they cannot sleep just whenever they wish to due to the homeostatic sleep pressure and circadian process regulating the sleep-wake schedule), and when they finally fall asleep at a random unexpected time, they often get a sleep too short to be reparative, waking up prematurely because of sleeping in circadian misalignment, so that they continue to be exhausted and the cycle repeats. Hence, individuals with non-24 are often prone to undersleeping due to the lack of circadian rhythm monitoring tools, and sometimes oversleeping in proportion with the time they last spent awake or when sleeping in partial alignment with the circadian rhythm. On top of these endogenous issues, their sleep can often be impaired by external disturbances such as noise, sunlight, warm temperatures. Although there are unavoidable social constraints on sleep when living in society, it is worth noting that forcing someone else to wake up repeatedly despite knowing they need to sleep is physical and mental abuse, and is as such an established and practiced torture method.

Non24 and other circadian rhythm disorders are invisible diseases, with sleep-shaming being a common occurrence. Sleep shaming is due to the general public's misconceptions about how sleep works, which is not specific to sleep disorders but also affects typical sleepers doing night shifts. This also affects typical sleepers working on usual 9-5 office hours, with an endemic chronic sleep loss due to voluntary bedtime restriction to fit in the 24h society, which was termed "social jet lag". More generally, the general ableism culture does not help with the recognition of chronic diseases. This even leads some scientists, who clearly lack an expertise in circadian rhythm science, to suggest to avoid prolonging the work career of evening chronotypes, despite the latter being much more manageable than non-24. Michael Reed wrote for Metro.co.uk an excellent first-hand account of what it's like to live with the non-24 circadian rhythm disorder. See also this Youtube video by Leslie Exp: Non-24 Hour Sleep-Wake Disorder: My Experience.

Although non24 can be easily diagnosed with clear guidelines, medical and in particular psychiatric misdiagnosis is unfortunately a common iatrogenic occurrence for individuals with a circadian rhythm disorder, including for children, which can be very distressing and cause further harm. Indeed, although being so common that the non-24 disorder is the norm for blind individuals, the awareness about the existence of this disorder is still very low among the public, even more so for sighted non-24. That's why November 24th was chosen as the International Non-24 Disorder Awareness Day, with the "Think Zebras" theme of the 2015 edition as a reference to the common but error-prone medical saying to "diagnose common diseases first", as this has the unfortunate side consequence of increasing the rate of misdiagnosis of rare diseases such as non-24.

Often, non-24 is a multifactorial and complex disorder, which means that it is suspected to be in a similar class of disorders as autism, where multiple causes can lead to developing a non-24 disorder. This is also hinted at by the fact that some individuals are born with the disorder inherited from parents, such as is the case for the author of this document, while others seem to develop it later in life (although this may be due to misdiagnosis in childhood).

An excellent description of what non-24 is and what it entails is presented by Dr. Helene Emsellem for The Balacing Act TV show: https://www.youtube.com/watch?v=wOqwRik-WpU

Are circadian rhythm disorders real diseases and disabilities?

Are non-24 and other circadian rhythm disorders considered to be disabilities?

Technically, non-24, among with other circadian rhythm disorders, are "lifelong untreatable pathology of the circadian time structure" which are functionally chronically affecting the individual in their everyday life and tasks to an extent that is in the accepted definition of what is a disability. Some authors argue for another definition of disability, in that since these disorders are currently not curable (only merely manageable for some individuals), these treatment-resistant individuals with a circadian rhythm disorder should be recognized as disabilities. And even for those who are responsive, having effective management therapies does not change the fact that circadian rhythm disorders are lifelong disabilities with no cure that require constant management and merit accommodations.

Is non-24 and other circadian rhythm disorders diseases?

Although there is no generally accepted definition on what constitutes a disease, one definition consists in conditions that can be improved with treatments, which is the case for circadian rhythm disorders. Another consensual approach to defining what constitutes a disease is whether the condition is included in a well established medical corpus of diseases, such as in the World Health Organization's International Classification of Diseases, which is the case for both non-24 and DSPD as well as other circadian rhythm disorders. Yet another definition is whether the condition reduces life expectancy or increases the risk of fatal outcomes, such as cardiovascular diseases or car accidents or cancer, which is again the case for circadian rhythm disorders (see more details below in the relevant section on "Health issues of a circadian rhythm disorder"). Another common definition is whether it significantly impairs day to day functions and the possibilities to get employed, which is evident given the testimonials from individuals with non-24 and DSPD (including for business owners, not just employees). Finally, another definition can be whether the condition can be artificially mimicked by the patient or not, demonstrating whether the patient lacks control over the condition, in which case thi could be deemed a disease. In this case, it was demonstrated in numerous studies on highly trained crews such as the NASA Mars crew and submarines military crews that forcing a non-24 sleep-wake schedule onto individuals without the disorder fails very fast, with the personnel systematically deeming such a schedule inhuman after a few weeks of attempting it under natural living conditions (see also the "Malingering the non24 disorder subsection" below). Anecdotally, most individuals with non-24 live and sleep in a shared environment with relatives, who usually do not display the non-24 sleep-wake schedule, again demonstrating on a case-by-case basis that non-24 is an endogenous uncontrollable condition and hence a disease.
Hence, whatever the definition chosen, the non-24 circadian sleep-wake disorder fits the criteria of a disease.

Non-24 is a well established disease, this is not a "fashion illness", as it is recognized internationally as a disability by the World Health Organization's International Classification of Diseases (WHO ICD) since ICD-9 (1975 see also here) and up to the latest ICD-11 as of this writing. The WHO ICD is the international standard for the classification and billing of all diseases and disorders. Essentially, if it's in the WHO ICD, it's a disease. You don't need to know what the WHO ICD is or how it works, but your doctor should (and if they don't, run away!).

The WHO ICD codes of non-24 for each version are as follow:

  • ICD-9-CM: 327.34—"Circadian rhythm sleep disorder, free-running type"
  • ICD-10-CM: G47.24—"Circadian rhythm sleep disorder, free running type"
  • ICD-11: 7A63—"Non-24 hour sleep-wake rhythm disorder", "Circadian rhythm sleep-wake disorder, non-entrained disorder type", "Circadian rhythm sleep-wake disorder, non-24 hour type"

There are similar codes and recognition for DSPD (ICD-10 code: G47.21). See for example this french redditor who got their DSPD officially recognized by their country's social security system or this other one.

Organic vs non-organic in DSM, recognized and billable in ICD-10. TODO: update the above using: https://www.reddit.com/r/N24/comments/h8tnco/does_it_make_sense_to_try_to_get_a_diagnosis/

Sighted non-24 is considered an orphan disease (a rare and commercially unattractive disease). Non-24 is also included in Orphanet and NORD classifications of orphan and rare diseases respectively. It is a billable disease in all countries where ICD-10 or DSM is used for billing medical disorders, and hence open to disabilities accomodation, especially in USA under the Disabilities Act.

Disabilities recognition and accommodations should be available in most countries in the world, as 164 countries ratified the United Nations' Convention on the Rights of Persons with Disabilities (CRPD), although these disabilities rights are often poorly communicated about or are slow to be implemented by governments despite the convention existing since 2006 (see also here). Reading the convention is highly recommended to disabled individuals to understand their rights, and easy read versions are available here and here. The list of countries that ratified the convention can be found here. However, since this is only a convention, not a law, and hence not legally binding, it amounts to a commitment that states who ratified it make towards their citizens. The convention can however be part of a legal argument and may be considered by judges, but it cannot constitute the sole argument and it may be ignored. The convention can also potentially be a legally binding argument in constitutional courts. Note also that several countries made laws to implement the convention when they ratified it, such as Belgium, so it is worth looking at national laws to see if there are some that are in link with the CRPD.

Given that the AASM, the leading american and worldwide scientific organization on sleep science, has published a position statement in 2021 stating that "sleep is essential to health", with an importance on par with healthy nutrition or physical exercise, that was endorsed by more than 25 medical, scientific, patients and safety organizations, there is a case to be made that sleep disorders can qualify as disabilities, as without accommodations this would amount to deny the individual from his right to live healthily.
(NB: It could maybe even be argued that discrimination based on sleep patterns can be similar to preventing access to facilities by not providing adapted access to people with mobility issues, with both being inherent and hardly changeable with current medical technology.)

At the individual level, non-24 brings many burdens that undoubtedly qualify it as a disability. On a personal level, living with a chronic disease such as non-24 is extremely straining. Being unable to do what others can do not only easily but unconsciously, such as sleeping, is hard to accept and live with, which requires a long grief process, as the individual must grieve the loss of their past self and future plans.

On a professional level, employment is certainly more difficult to access for those with a non morning chronotype, such as DSPD and non-24, which could be framed as a chronotype discrimination. This discrimination has very real and far reaching consequences at a societal level, impacting all citizens beyond those with a different chronotype, and also those who have a typical chronotype but must do a night shift work. There is no better example than healthcare, where the morning chronotype mindset ("the early bird catch the worm") reigns supreme, which is barring entry to medical candidates who get rejected because of their chronotype or circadian rhythm disorder. On top of that, night staff is almost always shunned and put aside, considered as a lesser group than the daytime staff, and is often forgotten from invitation to staff meetings. This is unfortunate, as healthcare is always necessary, day and night. Currently, clinical workers with non-evening chronotypes are required to work during their biological night as part of the night staff, as a way to "iron them out" (a nonsensical notion), which is undoubtedly the reason why iatrogenic events (medical errors) and accidents occur more often during night shifts compared to daytime healthcare (see also here, here, here and here), especially when there is increased sleep deprivation (see also here) although circadian misalignment also plays a key role (see also here). Integrating workers with an evening or night (DSPD) chronotype would allow to reduce these errors as these workers would be at their peak efficacy during night shifts, just like morning chronotypes have their peak during daytime.
This example shows that with increased awareness and integration of different chronotypes into the workforce, costs and accidents can be reduced and productivity increased, at little to no cost for society or the company, as this simply requires accounting for the staff chronotypes and offering alternative organizations (eg, remote or recorded meeting sessions, asynchronous communication between teams by e-mail - which is already the case between dayshift and nightshift staff). Due to the detrimental health effect of shift work on misaligned circadian rhythms and the decreased performance and increased risk of work accidents, some scientists call to match employees chronotypes to shift work positions (see also here). Indeed, a study demonstrated that aligning work schedules with chronotypes allowed for clinically significantly improved workers sleep and mood, including 0.5h more sleep on work days and 1h less social jet lag, and that evening chronotypes better tolerated frequent night shifts. In 2021, a large-scale study demonstrated that mismatching the work schedule with the individual's genetical chronotype led to decreased well-being and increased anxiety and depression, in line with a previous study showing that mismatching chronotype and work schedule leads to a much more variable sleep schedule and increased circadian misalignment. Unfortunately, night shift schedules are still poorly regarded, despite their necessity in our 24/7 society and whether they are the result of occupational requirements or the endogenous rhythm of the individual. Furthermore, employers often apply a chronotype discrimination for their hiring process, by looking for morning owl chronotype individuals even when the job schedule is at night. This ideological prejudice of the immorality of night schedules can be traced back centuries ago up to modern day, despite being disproven by several studies, with immorality increasing when the subject needs to perform a task when in circadian misalignment, regardless of the genetic chronotype (source studies here).

Smart business owners with wide office hours (ie, night shift) or where teleworking is possible could flexibly organize employees schedules based on their circadian alignment to optimize production and reduce work accidents, with "sleepiness surpassing alcohol and drugs as the greatest identifiable and preventable cause of accidents in all modes of transport", as indeed driving accidents are much more likely for night shift workers with a misaligned circadian rhythm. There is also ample evidence that shift work increases the risks of developing cardiovascular and metabolic diseases likely due to circadian misalignment. Preliminary evidence indeed suggests that aligning the work schedule of shift workers with their circadian rhythm can reduce health issues and increase productivity. Indeed, morning larks perform badly and lack attention in the evening or worse at night (despite subjectively thinking they have the same performance), whereas night owls perform better in the evening and DSPDs during the night. Furthermore, non-evening chronotypes working on nightshift often suffer from depression as a result of the mismatch between their work schedule and their circadian rhythm and also the lack of bright light exposure as accounts from nightshift workers show, whereas individuals with DSPDs instead are more than happy to get such jobs. In addition, individuals with DSPD would arguably have reduced risks of health complications as they would not suffer from shift work disorder, which theoretically can result in a much lower economical burden of illness vacancies of shift workers, which would here be replaced by permanent night workers. Hence, with some societal recognition and work culture evolutions, the variety of chronotypes could be leveraged to ensure optimal work conditions and productivity with minimal risks to health in our already 24/7 society, at no cost for neither companies nor the wider society as it would only necessitate a rescheduling of employees work hours depending on their respective chronotypes. Given the notable advantages with no downside, it rather strikes as peculiar that in our 24/7 society, where everything is expected to be available at all time, society as a whole reject the very people who can make this omnidisponibility possible.

Here is a saddening compilation of personal stories of adults with DSPD who had to drop out of school or their work career due to missing accommodations and recognition of their DSPD disorder. All fields of work, and all education degrees, including healthcare, are affected. The r/shiftwork reddit is also full of sleep shaming stories recounting how their work and out of office time is systematically disregarded by higher ups, who often are not shift working themselves and hence lack the understanding of what night shift working entails (ie, that everybody need to sleep sometime, and work done at night is still work done, even if the higher ups were sleeping at the time). Unfortunately, sleep shaming and sleep deprivation appear to only be worsening societal issues between 2010 and 2018 in the USA.

The challenge to employment and schooling is far greater for non-24, which can be considered as a non-chronotype, with no preferential and stable sleep-wake schedule, it changes from one day to the next. Since there are hardly any job, even with accomodations, that can allow for unplanned flexible schedules, which would require minimal to no social interactions (ie, clients business relationships, work meetings, etc.), it's highly likely that most individuals with non-24 remain unemployed for most of their lives. Furthermore, although societal awareness of different chronotypes could certainly reduce or eliminate most issues for DSPD and similar delayed disorders, it would not help non-24 employment, as the issue with non-24 is the lack of any regular schedule and hence of any possibility to predict, in addition to the consequent constant sleep deprivation due to unpreventable sleep interruptions by external factors making energy levels and cognitive performance (and risk of accidents) highly variable from one day to the next. Hence, although employment data are lacking, it is safe to assume given the volume of testimonies that most individuals with non-24 remain unemployed. Indeed, there are only a handful of jobs where a constantly shifting schedule would be an advantage, such as NASA's Mars monitoring missions which require ideally a martian schedule of 24.6h, and maybe healthcare with an adapted rotating schedule with smaller increments. On the off chance that someone with non-24 lands a job with a typical 9-5 daytime work schedule, they will end up missing more and more appointments as time goes by and their circadian rhythm continues to shift and hence are more and more unable to sleep when required, then doing overwork to try to compensate, to finally end up either burnout by the overwork or by the sleep deprivation (or a combination of both). Making one's own company is not any better, as although the office hours are certainly more flexible, the necessary customer relationship will still dictate a mostly diurnal working schedule. Working with remote companies will also enforce a regular although delayed working schedule, which again cannot fit with the non-24 circadian rhythm disorder.

In addition to these employment issues, individuals with non-24 can be qualified as unlucky. The most obvious reason is the acquisition of, or being born with, an crippling inheritable chronic disorder that is non-24. But beyond that, individuals with non-24 get much less opportunities than those with a 24h circadian rhythm: they are (almost) never there at the right time. Opportunities are mostly a product of interpersonal connections, which means that the more interpersonal interactions one can get, the more likely they will get opportunities. Hence, these opportunities happen mostly when most of the rest of the world is awake. Mechanically, the always changing schedule of non-24 bars the individual from a lot of these opportunities to only the short period of time (days/weeks) where the individual's circadian rhythm is in phases with the day-night cycle of their timezone (or timezone of interaction if working remotely). This lower probability of experiencing opportunities due to the always changing mismatched circadian rhythm is what makes individuals with non24 objectively unlucky.

It's crucial to understand that constraining someone with non-24 to fit within a fixed schedule does not just imply they will sleep less than optimally, as for typical sleepers, but that they will not sleep or so little this will be unsustainable healthwise. Sleep is an essential need for all living animals to survive, just like food and water. Hence, accommodations are not a convenience to increase the quality of life, they are a necessity for individuals with non-24 to live and preserve their dignity as human beings. Unfortunately, it is unclear what accommodations are required, since flexible schedules still need to be planned in advance and hence cannot accommodate the chaotic schedules of non-24, and the same goes for appointments and meetings. Asynchronous work and schooling, whenever needed depending on the current circadian phase of the individual, may be a potential, but partial, accommodation.

Even at home, circadian rhythm disorders are very debilitating. Due to the mismatch with social expectations, the individuals are drastically limited as to which activities they can carry out at night without bothering neighbors or violating laws about night noise, or simply by the opening hours of commodities and services. Some patients describe this situation as being "encaged" and "walking permenanently on eggshells", with computers with internet access being their only daily window to a lively world.

For a more in-depth discussion about non-24 and disabilities, watch this excellent video by Leslie Exp (textual script here) and this critique of the 24/7 society by Johnathan Crary (summary here).

Finally, seeking the help of disabilities associations can be very fruitful, these associations can help with the formalities to get the disability recognized and they likely won't judge the patients.

TODO: add info about remote work from: https://www.reddit.com/r/N24/comments/jewt6z/what_accommodations_have_you_successfully_got/

Diagnosis and sleep diary

Why seek a diagnosis for sighted non24 (or DSPD), when it's a rare and hence costly disorder to diagnose, and with no known cure? Because non-24 is a severe handicap, with undiagnosed non-24 typically causing an involuntary and uncontrollable absenteeism that, without adequate diagnosis and institutional accommodations and support, cause professional or scholastic failure for adults and children respectively, with on top an unwarranted blaming and shaming for being unable to control the consequences of a severe handicap they have no knowledge of. The failure of these individuals is a failure of medical support and institutional handicap integration laws, not the individual's.

Furthermore, even beside institutional recognition and accommodations of the handicap, knowing the accurate diagnosis allows the patient to better understand their constraints and adapt their lifestyle around it to improve by themselves their quality of life and alleviate unwarranted guilt. This also opens the access of the patient to more therapies and to accommodations, which are known to be crucial steps for handicaps caused by any chronic disorder to reduce the impact of the pathology on their quality of life.

DSPD is less disabling than sighted non-24, but it is still a disorder that is poorly acknowledged, accommodated and underdiagnosed, despite having a significantly detrimental impact on daily life, wellbeing and relationships, especially when unmanaged.

Hence, the next subsections will describe how the diagnosis for sighted non-24 is done in practice, what are the steps, and a later section describe how to get accommodations once a medical diagnosis has been obtained.

How can I get diagnosed of non-24 or DSPD?

Two things are needed: a sleep diary over 2+ weeks of unrestricted sleep (no alarm clock), and to know that non-24 and DSPD are recognized as diseases in the World Health's International Classification of Diseases manual (WHO ICD) as it means that both sleep disorders should be recognized by insurances and workplaces as diseases that open rights to disabilities accommodations. According to current medical guidelines as of 2022, for non-24, the sleep diary should show at least 2 weeks of freerunning sleep (staircase pattern), whereas for DSPD, one week of delayed sleep is sufficient for diagnosis. However, in practice, at least one month of a sleep diary is required for doctors to ensure it is not a temporary sleep pattern.

Curating a sleep diary (also called a sleep log) is the basic and most essential tool for the diagnosis and management of any circadian rhythm disorder, especially for individuals with a non-24 disorder as their sleep schedule constantly changes. The curation of a sleep diary (also called a sleep log) is hence not only strongly recommended for diagnosis, but should also be continually done even long after as a self-management tool. Writing a sleep diary consists of writing when we fall asleep and when we wake up, including naps, for at least 2 weeks for diagnosis, and preferably to continue after for self-management. More exhaustive sleep diaries also include the bedtime (so that the sleep latency, aka the time taken to fall asleep, can be estimated) and the standing up time (ie, at what time the individual gets out of bed), as well as the timing of various compounds such as melatonin, caffeine, alcohol, etc. This sleep diary will not only be helpful to you to better understand your sleep patterns (ie, determine the circadian misalignment), but also can be used for diagnosis with a sleep specialist according to the official USA (executive summary here) and UK guidelines and also is necessary to correctly time the only few treatment options (see also here and here and here) that exist currently, as sleep diaries are reliable estimators of the circadian rhythm. Indeed, due to the unstable nature of the sleep schedule of individuals with non-24, it may be necessary to adjust the timing of the therapies from day-to-day, or sometimes reduce/increase the dosage (eg, of melatonin) or duration (of light therapy). Curating a sleep diary does not only allow to keep track of bedtime and wake up times, but also of sleep duration, which is a strong predictor of cognitive performance and mood during the day, as well as sleep pressure the next day/night, as too little sleep strongly indicates sleep deprivation, whereas a too long sleep indicates the body attempted to correct for previous sleep deprivation. Interestingly, a sleep diary over at least 2 weeks but preferably longer as a management tool is also the gold standard assessment of insomnia, hence sleep diaries should be systematically be requested in any sleep study updated to the latest medical guidelines.

It is crucial to try to write the sleep diary, at least for some weeks, with an unrestricted sleep schedule (no alarm clocks nor appointments requiring to forcefully wake up at a specific time). Indeed, restricted sleep will not only hide the freerunning pattern characteristic of non-24, but can also cause sleep deprivation which may produce chaoticity in the sleep patterns. It is also crucial to log all sleep sessions, including naps, however short they are.

The author strongly recommends the app Sleepmeter Free on Android (mirror) and its widget to write a digital sleep log which will produce nice sleep graphs that are easier for humans to read and hence for doctors to diagnose. It can also be installed on a computer using the Bluestacks emulator. A paper sleep diary is also fine, and there are plenty of templates available online, but the AASM sleep diary / sleep graph template is recommended (mirror here, 2021 updated version here , or the unofficial digital spreadsheet version). A sleep graph such as with this template or software is much preferable over simply writing the fall asleep and wake up times, as a graph is much more legible for observers including sleep doctors, this will drastically reduce the rate of misdiagnosis. Write down your last sleep session as soon as you wake up, to avoid forgetting the accurate timing after you go on with your day. Other standard sleep diary templates (but not sleep graphs) include the Consensus Sleep Diary and its 3 variants.

Once you have a sleep diary over at least 2 weeks, or preferably 1 month or more to get a clearer pattern, look for a sleep specialist experienced with circadian rhythm disorders or a chronobiology clinic (not a sleep clinic) to diagnose your circadian rhythm disorder, preferably a chronobiologist with a background in neurology. Alternatively, psychiatrists with a well established research experience in circadian rhythm science, and hence who also are chronobiologists, can also diagnose non24. Sleep clinics often only test for sleep apnea and narcolepsy, not circadian rhythm disorders, although they should according to guidelines. Sleep specialists cover a wide range of background, but pneumologists, psychiatrists, psychologists and psychotherapists should generally be avoided unless they have a recognized experience in circadian rhythm disorders as they are highly prone to misdiagnosis and mistreatment due to systematic issues in the practice of psy* clinicians, such as the unfounded "secondary" classification of sleep disorders and circadian rhythm disorders¹. Indeed, sleep disorders, including insomnia and circadian rhythm disorders, should always be treated as they rarely resolve on their own and always with specific treatments for the sleep disorder, irrespective of any co-morbid psychological condition, which is why the DSM-5 dropped the terms "secondary" and "primary" insomnia to only keep "insomnia disorder", as the assumption that sleep disorders stem from psychological disorders (ie, is secondary to psychological disorders) is not supported by empirical evidence for the reasons reviewed here. Pneumologists focus on sleep apnea, and while it's good to be tested for this too, these clinicians usually disregard circadian rhythm disorders. Indeed, most sleep clinics will only test for sleep apnea and narcolepsy, ignoring any circadian rhythm disorder as a side effect (see also here), despite there being no evidence supporting this view, as indeed the comorbid circadian rhythm disorders usually do not resolve with sleep apnea treatments, both disorders appear to require independent therapies.

To find a chronobiologist doctor, who will be properly trained or experienced with circadian rhythm disorders, the Circadian Sleep Disorders Network patients association curates a list of chronobiology doctors from recommendations by previously diagnosed DSPD and non-24 patients:


If you find a competent doctor who could diagnose you with a circadian rhythm disorder and isn't on this list please send the Circadian Sleep Disorders Network association an email to add your doctor in the list, this will help your future peers.

If you are still having difficulties in getting diagnosed, you may try to find a local/national association partnering with the International Rare Diseases Research Consortium (IRDiRC), such as EspeRare, as the IRDiRC aims to allow all patients with a rare disease to get diagnosed under one year of coming to medical attention.

If in this list there is no doctor in your area, either travel to one if possible or if really too far, try to look by yourself for a specialist in circadian rhythm disorders. A good method is to look for scientific publications using scholar.google.com and then contact the authors that are in your region (eg, local university or hospital).

An especially excellent chronobiology center of worldwide reputation for non-24 diagnosis is the Centre for Chronobiology in Basel, Switzerland, they should be recommended especially for children diagnosis.

If you find a properly trained doctor who successfully diagnose you, make sure to ask them to write down a description of your diagnosis and an accommodation letter describing how it impairs your daily functioning, this will help later on to continue to get your treatment (eg, melatonin) if your doctor goes out of business and you need to find someone else, and to get disability recognition and work/school accommodations. Indeed, given that these disorders are uncurable, accommodations will become a necessity at some point, and asking for it as soon as you get your diagnosis will save you a lot of trouble later on. Example letters of accommodations for DSPD are available in the members section of the Circadian Sleep Disorders Network website (for those in hardship, membership only costs $5).

In some countries, you may have an institution that oversees sleep medicine facilities and provide a standard path of care. For example in France, In France, there are two partnering medical associations that are relevant for sleep disorders medical care : SFRMS and Réseau Morphée. SFRMS is a medical facility certification body that also produces diagnostic and treatment guidelines for circadian rhythm disorders such as recommending the diagnosis of non-24 with the sampling of melatonin at two timepoints separated by 2-4 weeks, and they provide a national map of all sleep medicine centers that are certified for the diagnosis of all sleep disorders including circadian rhythm disorders. Réseau Morphée is a network of sleep research professionals (instead of institutions), and it provides additional resources that complement SFRMS resources. They designed a standard path of care for people who suspect they have a sleep disorder: First complete the online questionnaire on sleep disorders by the Réseau Morphée, you will get as a result a report PDF and an ID you can communicate to any SFRMS sleep doctor for them to access your results directly online. Secondly, find a SFRMS certified medical sleep center close to you. Thirdly, call them to confirm whether they can diagnose the non24 disorder by sampling urinary or blood melatonin twice at 2-4 weeks interval as is the standard procedure defined by the SFRMS guidelines, if unsure that the center you found can perform this test, then call another SFRMS certified center. Fourthly, after clinical assessment of your sleep which needs to include melatonin sampling and may include a sleep chart and a polysomnography, if a non24 disorder is indeed diagnosed, ensure or ask the doctors to write a report confirming you have the non24 disorder, as a written trace of your disorders is crucial for you and future medical professionals you will see to manage your healthcare and also eventually for public social support if necessary such as handicap recognition or indemnity.

Whichever doctor you meet, specialized or not, they should never shrug off your sleep issues as a side issue. It is a primary disorder that always requires independent treatment (it's NOT secondary to another psychological issue). Patient generated health data should always be considered by clinicians, including your sleep diary. As the non-24 disorder, especially among sighted individuals, is poorly known, it is necessary for patients to go online and collect information by themselves to come armed with knowledge to share with their physicians. But even then, there is no guarantee physicians will consider the patient's complaint seriously, altthough they should according to medical guidelines.

If the clinician is not considering your complaint seriously, you can mention that non-24 is recognized by the WHO ICD. This stands for the World Health Organization's International Classification of Disease. The WHO ICD is the international standard for the classification and billing of all diseases and disorders. Basically, if it's in the WHO ICD, it's a disease. You don't need to understand what the WHO ICD is or how it works, but your doctor should (and if they don't, run away!).

The WHO ICD codes of non-24 for each version are as follow:

  • ICD-9-CM: 327.34—"Circadian rhythm sleep disorder, free-running type"
  • ICD-10-CM: G47.24—"Circadian rhythm sleep disorder, free running type"
  • ICD-11: 7A63—"Non-24 hour sleep-wake rhythm disorder", "Circadian rhythm sleep-wake disorder, non-entrained disorder type", "Circadian rhythm sleep-wake disorder, non-24 hour type"

The non-24 disorder is not a newly recognized disorder, it has been recognized since 1979 as the Non-24-Hour Sleep–Wake Syndrome code: C.2.d in the DCSAD, and as the Non-24-Hour Sleep–Wake Rhythm Disorder (no code) in the ICSD-3 (International Classification Of Sleep Disorders) released in 2014. While the American Psychiatric Association recognizes the DSM-5 since 2013 the disorder as "Circadian rhythm sleep–wake disorders, Non-24-hour sleep–wake type", it recommends to use the ICD-9-CM code 307.45, or ICD-10-CM code G47.24 when it goes into effect (see p390 of DSM-5).

You can also mention that the non-24 is not rare at all in blind people, as it's estimated that 2/3rd of blind people suffer from non-24. It's rarer in sighted individuals, but this is the same disorder. So if your doctor ever saw a blind individual, chances are they had non-24 (although they were likely undiagnosed if your doctor doesn't know about non-24...).

Unfortunately, with sighted non-24 being a rare orphan disorder, the standard care pathway is often made more difficult by untrained clinicians than it should be. This is unfortunately a common issue with chronic illnesses, even those that are not rare (see for example r/ChronicIllness), but the rarity causes additional struggles.

¹ Indeed, both sleep disorders such as insomnia and circadian rhythm disorders are often ignored and left untreated as these fields assume that sleep issues are secondary to other psychiatric disorders, which means that the psy practitioners will try to diagnose and treat any other disorder except the sleep issues. This distinction was criticized as being unfounded and detrimental to the patients' proper treatment since at least 2001 for insomnia and more recently in 2020 for circadian rhythm disorders, but the unfounded primary/secondary insomnia distinction still perseveres in the clinical practice, so it's unlikely that there will be any change soon for circadian rhythm disorders either. See the subsection about misdiagnosis below for more information.

Diagnosis methods for circadian rhythm disorders

This section describes more technically the diagnostic methods and tools for non-24, which are also applicable with little adaptation to other circadian rhythm disorders such as DSPD.

Circadian rhythm disorders are common in the clinical practice, despite being underdiagnosed. Nevertheless, diagnosis is theoretically easy and inexpensive. According to the latest medical guidelines, sleep diaries over at least 2 weeks are the main diagnostic tool for circadian rhythm disorders (see also here) and insomnia (see also here) as explained in the previous section. However, due to potential masking biases, it is recommended to curate a longer sleep diary over at least 1 month or even more, until a clear pattern emerges.

Specifically, non-24 is characterized by staircase-like freerunning circadian phase and sleep-wake pattern typical of non-24, whereas DSPD is characterized by a delayed but relatively stable circadian phase and sleep-wake pattern especially during week-ends for workers (social jet lag) or every days if sleep is not restricted. In practice, it's necessary for the patient to sleep unrestricted (no alarm clock, going to sleep when feeling tired and waking up naturally) over at least 2 weeks, and preferably longer as relative coordination to sunlight can mask the freerunning pattern by creating an illusory and temporary entrainment and to continue monitoring and manage the sleep disorder whenever there is a relapse, as is recommended for insomnia.

Although current medical guidelines only state freerunning over 2 weeks as the sole and sufficient criteria to diagnose non-24, the current document's author recommends to use a stricter criterion:

We propose the following updated non24 diagnosis criteria: Given either a sleep diary or circadian phase proxy measures (melatonin sampling, core body temperature) over at least 2 weeks, if a freerunning pattern is observed despite periodic zeitgebers exposure and unrestricted sleep opportunities, then this should be sufficient to diagnose non24.

Indeed, all humans naturally freerun when left in a completely dark environment void of zeitgebers, especially light. But if the individual is exposed to zeitgebers on a daily basis, especially sunlight, and still display a freerunning pattern (eg, with alarm clocks), then this demonstrate a robust freerunning drive resistant to zeitgebers exposure and hence this condition would clearly demonstrate an endogenous non-24 disorder. The criterion of being sufficiently exposed to zeitgebers was already proposed by a 2015 review, however the proposition of allowing the individual to sleep unrestricted by alarm clocks nor obligations is a new criterion.

The AASM states in its latest meta-analysis of behavioral therapies for insomnia some of the reasons why sleep diaries have become the standard assessment tool for sleep disorders, preferred over behavioral questionnaires, as sleep diaries allow for a more accurate tracking of the sleep patterns and also allow to measure a wide array of sleep metrics and their daily variability:

> In the study of insomnia treatments, nighttime sleep and insomnia symptoms are most commonly measured with daily sleep diaries,29 which capture information about the timing of sleep (bedtime, rise time) in addition to individual sleep parameters, such as sleep latency (time to fall asleep initially), wake after sleep onset (WASO; duration of nighttime wakefulness), and early morning awakenings (waking in advance of the desired rise time) that are commonly the primary symptoms targeted in insomnia treatments. Additional summary metrics commonly derived from daily sleep diaries include total sleep time and sleep efficiency (total sleep time/time in bed*100%). Daytime napping/sleeping behaviors are also commonly tracked in daily diaries when delivering treatment. The primary advantage of sleep diaries is that they allow for the daily collection of information on nighttime symptoms, making them less subject to recall bias than questionnaires. Treatment effects are most commonly assessed with aggregated mean-level changes in individual sleep diary parameters across time, generally every 1 or 2 weeks, but increasingly, the variability of these parameters across days is also being viewed as clinically important.

In other words, humans are very bad in estimating their own sleep patterns without an adequate measurement instrument. We are prone to overestimating the amount of time we spend asleep and underestimate the time spent in bed awake trying to sleep.

As written earlier, the clinical signs characterizing the non-24 disorder is to experience days longer than 24h, with longer wakefulness periods than typical sleepers experience (eg, 8h of ideal sleep duration and 18h of wakefulness period). Hence, patients complaining of a "too long day" and of "sleeping later and later" should tip the clinician on to proceed to instruct the patient to curate a sleep diary in order to assess the presence of a circadian rhythm disorder. It is important to do a differential diagnosing by recognizing and excluding other circadian rhythm disorders, such as delayed sleep phase disorder (DSPD) with a delayed sleep schedule but not abnormally long wakefulness period nor sleep period, hypersomnia with a longer sleep period but standard wakefulness period duration, and advanced sleep phase disorder (ASPD) with an earlier sleep schedule (much rarer and usually only observed in elders). Other sleep disorders such as sleep apnea should also be investigated, as treating them can improve or more rarely resolve the circadian rhythm disorder, although a diagnosis for a sleep disorder does not preclude the diagnosis of a circadian rhythm disorder, they are not mutually exclusive.

TODO: add figure showing prototypical sleep graphs for each circadian rhythm disorder.

A longer sleep diary with no constraint on sleep is preferred, as the non-24 disorder can be missed or misdiagnosed with DSPD due to sleep restriction and relative coordination (transient entrainment) to sunlight or other zeitgebers. However, for the trained eye, it can be possible to suspect non-24 with a restricted sleep schedule, see for example this figure kindly provided by Kieran Wood and annotated by the current document's author (note that age in the following figures is defined at the end point of the sleep diary):

This is an actigraphic sleep graph of a sighted non24 man of ~25 years old over 4 months, acquired using a Samsung Galaxy Watch wearable sports band. The individual's freerunning period is ~27min, which means that a full circadian revolution is completed under ~2 months. We can see the staircase-like pattern typical of freerunning during the period of unrestricted sleep. On both sides, we can see restricted sleep patterns. On the left, there is a period of restricted sleep, starting in phase with the day-night cycle for about 1 month, and progressively becoming chaotic as the individual's circadian rhythm continued to freerun and become out of phase (up to being in total opposition) with the day-night cycle during the 2nd month. However, due to the sleep restriction (work commitments, which required using alarm clocks), the freerunning pattern of the circadian rhythm was masked and hence is not apparent in the sleep pattern, but it was still happening and was expressed as chaotic sleep patterns during the out of phase period, with alternating patterns of short sleep (duration < 5h), hypersomnia (>9h), drastically varying fall asleep and wake up times by several hours, and missed sleep (all-nighters). The alternance between "stable" sleep for one period and chaotic sleep for the other period is a sign of (restricted) non24 disorder. The period of chaotic sleep is usually accompanied by other health symptoms such as more frequent illnesses. Although this graph was generated out of actigraphic data, the same patterns can be observed on manually curated sleep diaries.

Such a restricted sleep-wake schedule may appear as a very slow freerunning phase on the surface (ie, 1h of phase delay per month), but there are gaps, nights without any sleep, that must not be ignored. Very very slow freerunning phase delay is unheard of, this is most likely an estimation error, as in this case as demonstrated by the much faster freerunning phase delay when unrestricted (~25h) but without sleep gaps. More likely, the masking due to the restricted wake up time makes it look like the delay is very slow, but in fact the circadian phase is running around the clock. There are a few potential reasons:

  • When the fall asleep time seems to "reset" backward suddenly, it's because of the sleep pressure buildup due to accumulated sleep deprivation.
  • Another thing that is happening is that the siesta, which start is 12h apart from the circadian night start, also delays progressively forward, until it matches with the current sleep schedule. Assuming a 45min of daily phase delay, this would mean that a full freerunning cycle is completed under 32 days, and half a cycle, a 12 hour shift, is completed under 16 days. This means that every 16 days, the individual can sleep at, let's say, 3 am, at first because of alignment with the circadian night, then 16 days later at the same time because of alignment with the siesta (but then the duration is limited to about 5h), then 16 days later it's again in alignment with the circadian night, etc. In-between, the subject cannot sleep at 3am, but will either sleep later or not sleep at all if too much in circadian misalignment with either the circadian night and the siesta (ie, trying to sleep in the middle between both, during the wakefulness period of the circadian phase).
  • Finally, there is the effect of relative coordination which can increase or slow down the freerunning phase delay.

Here is another example of a restricted non-24 sleep-wake schedule:

Sleep diary over 1.5 years of a 31 years-old man (2 years post female-to-male hormonal replacement therapy) with sighted non-24. Yellow blocks represent the wake up times, red blocks the sleep times. This sleep diary was recorded before the individual knew about the existence of the non-24 disorder or that he was affected, and hence the sleep diary contains gaps of a few days, and then a 6 months hiatus (right-click to open the image in full resolution to see the dates in more details). The middle section shows a restricted non-24 sleep pattern, when the individual had to restrict their sleep due to their social duties, trying to target a 8-9 am wake up time. We can observe in the middle section that the individual appears at first to succeed at the expense of reduced sleep duration (chronic sleep deprivation), but ends up failing to maintain such a schedule even at the expense of reduced sleep duration towards the end, with the innate freerunning sleep-wake pattern reappearing progressively. We also observe high variability in the sleep and wake up times, which is not due to uncompliance and lack of rigor, but is a hallmark of a restricted non-24 sleep-wake schedule, caused by the misalignment between the always shifting endogenous circadian phase and the day-night cycle. Sections before and after show a clear typical non-24 "staircase" sleep-wake pattern when the individual could sleep freely at his own natural schedule. The wake times, which is known to be a much more reliable proxy measure of the circadian phase and is more difficult to influence, reveals the staircase sleep pattern typical of non-24 much more clearly than the sleep times. Original data can be found here.

Five sleep diary excerpts over 35 days each at different points in time over 2 years, of a sighted 27 years-old man (under continuous female-to-male hormonal replacement therapy started years before, with male hormonal levels in the range of male born individuals during the covered period). Magenta blocks represent sleep periods, gray blocks represents periods of missing data or days when the individual did not sleep at all for at least 24h (between 12am and 12am). The top sleep diary excerpt shows the individual's sleep-wake pattern when fully unrestricted, when they were completely free of defining their own schedule during the COVID-19 lockdown of 2020, and displaying a staircase-like freerunning sleep-wake pattern, very typical of non-24. The three sleep diary excerpts in the middle show their sleep-wake patterns at different points over 2 years when their sleep is semi-restricted, which is when their sleep is regularly being disrupted by various obligations such as work schedules, doctors appointments, errands, etc. The last sleep diary excerpt at the bottom shows their sleep-wake pattern when their sleep-wake pattern is fully restricted by an obligation to constantly wake up at the same time for work. We can observe that during unrestricted sleep, although there is a constant daily phase delay due to endogenous circadian freerunning, sleep duration and sleep timing is relatively consistent and predictable, the daily offset being almost constant. However, during semi-restricted periods, a pattern emerges: sleep duration shortens, likely as the individual tries to maintain a constant wake up time despite their endogenous clock freerunning which makes their sleep onset happen later and later, until sleep duration becomes so short that they either do not sleep (all-nighter) or experience a sleep so short that next days their sleep-wake pattern becomes very chaotic, with both abnormally long and mistimed sleep periods. Finally, the fully restricted period shows similar phenomena than semi-restricted periods, but happening more frequently, with in addition the individual developing workaround strategies such as late afternoon or even evening naps to cope with the chronic sleep deprivation, and their sleep is also much more fragmented, even when they manage to fall asleep relatively early, they unwillingly wake up in the middle of the night due to the misalignment of their circadian clock (their circadian clock likely experiencing a siesta during the night, and hence a low drive to maintain sleep, and their real circadian night likely happening later during the day, when the individual is at work). Given the variability of their wake up time (despite trying to forcefully maintain a constant wake up time), they were likely unwillingly frequently late or absent, impacting their moral and mood on top of the effect chronic sleep deprivation already has on mood. This example clearly shows how sleep-wake pattern regularity and predictability is directly in inverse relationship with restriction.

Note that in all of the above examples, none of the displayed periods involved any chronobiological/circadian therapy. Restricted and semi-restricted sleep-wake patterns involve the use of alarm clocks and other behavioral interventions with the goal of trying to forcefully maintain a constant sleep-wake pattern. Circadian waveform manipulation via therapies such as zeitgebers-based are not here considered restrictive, as they aim to manipulate the endogenous circadian rhythm, without directly restricting the sleep-wake pattern itself.

The above examples demonstrate that while the staircase pattern is typical of freerunning, it is not necessarily observable as it can be masked by sleep restriction, despite the presence of the non-24 disorder. The staircase pattern is also insufficient to diagnose non24. Indeed, any human can freerun when isolated from zeitgebers influence. Hence, the proper diagnosis of non24 must also take into account whether the individual is sufficiently exposed to zeitgebers, and still freeruns, and also if the individual sleeps better while freerunning than when not. A reliable measure is the sleep duration. Individuals who freerun but do not sleep well while doing so are likely not non24, and may rather be experiencing a temporary freerunning period consequently to a loss of entrainment, as it can regularly happen to DSPD individuals, especially during seasons changes (ie, winter, DST time change, etc).

TODO: a new study (see also here) released in 2020 explored the criteria to diagnose "latent circadian rhythm sleep-wake disorders" or LCRSWD, which are an alternative name for what we above name "restricted sleep" or "covert sleep".

It's worth noting that there are various forms of non-24. The example graphs above cover the arguably more common cases of non-24, with a circadian period slightly above 24h but less than 27h. However, there are more extreme forms of non-24, with a 30h+ circadian period. These extreme forms usually involve hypersomnia, with a much longer sleep period than typical (eg, 10-15h/circadian period), while the wakefulness period remains in a typical range (16-18h) for adults. These cases are more likely to be misdiagnosed as irregular sleep pattern when they are restricted, as these individuals often need to fragment their ever-moving extended sleep periods.
TODO: add an example graph of restricted vs unrestricted non-24 + hypersomnia.

This review outlines a standardized approach to diagnose circadian rhythm disorders solely from sleep diary and patient history.

Alternatively to a sleep diary, medical-grade actigraphy can be used for diagnosis (see also here), although this does not replace a polysomnography. Actigraphy is essentially a way to automatically generate a sleep diary. Consumer-grade actigraphy (eg, fitbit) cannot be used for diagnosis, but clinicians should still take into account patient-generated health data to investigate further. Actigraphs are generally wrist-worn on the non-dominant arm, but for children and toddlers it can be waist-worn on cloths, although a slight overestimation of total sleep time and sleep efficiency is to be expected.

In the clinical setting, dim-light melatonin onset (DLMO) salivary sampling is the gold standard, preferably over a period of time longer than 24h, such as by sampling at one appointment and then sampling melatonin again 2-4 weeks later to observe if there is a shift between the two melatonin profiles as recommended by the SFRMS (french sleep medicine association), and diagnosis is done just like for sleep diaries by looking for a specific pattern (freerunning, delay, advance, etc), but this test is unfortunately seldom used due to constraints and cost (see also here), most clinics not being equipped to do that and this procedure not being reimbursed by health insurances in most European countries, and hence can be a high financial burden for the patient, with an estimated cost of up to $US10 per sample to assay in 2003. It is also highly cumbersome for the patient, as it requires the patient to be maintained in a dim lit environment to avoid melatonin suppression by light and with samples being taken every 30 min to 1h during at least 6h at night but preferably >= 24h especially for circadian rhythm disorders since the rhythm can be variable between days, causing further sleep disruptions. Hence, individuals' DLMO remain largely undetermined in the clinical setting. However, DLMO can be reliably estimated from sleep diaries, especially when using the sleep midpoint or wake up time. An alternative is to measure melatonin metabolites (6-sulfatoxymelatonin) from urine (see also here). Most currently available objective diagnostic methods are of a high burden to the patient.

Sometimes, salivary sampling over 24h is proposed at home with a home kit (see also here for Europe, recommended in this clinical review on DSPD in children, and here for USA). This setting is a very great proposition, but the instructions sometimes fail to account for circadian rhythm disorders. To properly do a home test of salivary sampling, you need to test every x hours as instructed (if you have 12 sampling units, you do one sample every 2h) over 24h, and you need to stay in a black room all day long. Hence, you need to prepare up beforehand, try to do a test day & night without using the sampling kit yet but measure the lux: cover light sources including sunlight as much as possible, check with an lux meter app on Android or iPhone to check that your room is illuminated with less than 10lux during daytime - and of course it's forbidden to light up any artificial light source at any time during 24h! Indeed, to be representative of your circadian rhythm and not have any masking artifact, it's necessary to stay in a dark room during the whole sampling period (usually 24h) as any light source, even low light such as a computer screen, can inhibit melatonin, and here you want to sample your natural melatonin rhythm free of any confounding factor that could influence or inhibit it, especially light.

Clinicians should be aware of the limitations of DLMO sampling, especially that DLMO will vary for a few weeks after melatonin discontinuation. Hence, if the individual is already using melatonin, DLMO sampling should be scheduled no earlier than 4-6 weeks after the patient stopped melatonin intake.

For example, the excellent Centre for Chronobiology in Basel offer at-home melatonin sampling kits, with a protocol involving 8 samples throughout the day and night while staying in a darkened environment, over 2 days that are one week apart (which makes for 16 samples in total), for a cost of about 230 euros in 2021. This melatonin sampling protocol allows to objectively assess a phase delay between the timing of the circadian night sampled on the first day versus the second day a week later, and hence objectively confirm a freerunning circadian rhythm (not just the sleep-wake pattern) and hence a diagnosis of non-24. Hopefully, this testing protocol for non-24 can get generalized in the future, the design is very elegant and efficient.

Novel very promising diagnostic methods that could be faster or used at home include non-invasive core body temperature monitoring which should be the most accurate measure of the circadian rhythm given that body temperature modulation is how cells clocks are synchronized to the circadian rhythm throughout the body, wrist skin temperature monitoring. New non-invasive devices based on heat-flux (zero-heat-flux and dual-heat-flux) technology allow to non-invasively monitor the circadian rhythm continuously, which would allow for a cheaper objective assessment of circadian rhythm disorders such as non-24, as the device can then be re used, and could easily be sent at home for a week for the patient to collect the data themselves. Heat flux devices include the 3M Spot-On (zero-heat-flux) and experimental dual-heat-flux as well as other brands. The difference between zero heat flux and dual heat flux is that dual heat flux uses two heat flux sensors and consumes much less energy, making it perfect for wearables, whereas zero heat flux needs to be plugged to an electrical outlet due to the higher energy consumption. Core body temperature can be used for diagnosis similarly to sleep diaries, by looking at the patterns of the low phases (freerunning, delayed phase, advanced phase, etc), with the advantage of being less biased by the sleep homeostat, behavior and other factors compared to sleep diaries.

Another novel and very promising diagnostic method is testing the pupil's contraction reflex speed in response to bright white light, which was found to be a reliable discrimination method for DSPD, by assessing the response of both the ipRGC cells but also the cones and rods to bright light. There is however evidence that the pupillary light response (PLR) to bright white light is not necessarily associated with objective sleepiness, the latter being closely linked to circadian dysregulations. An alternative is to test the PLR to only blue light, often called the circadian light, exposure, which is the cause of the maximum post-illumination pupil response (PIPR) test, which can be done either after blue light exposure with varying light intensities or via a chemically induced photosensitivity test. Pupillary diameter and reaction time to bright light exposure can also reflect ultradian cycles. Photic history does not appear to impact PIPR and hence pupillary light response, but supine position (laid down) does increase PIPR, hence being laid down may increase photosensitivity. A 2021 study found that individuals with DSPD have a reduced PIPR, in other words a reduced pupillary diameter in response to blue light exposure, compared to controls, and individuals with sighted non24 had an extremely reduced PIPR and pupillary diameter response (0.88 ± 0.58 mm for sighted non-24 vs 1.82 ± 1.44 mm for DSPD, vs 2.05 ± 1.04 mm for controls). However, these methods are not yet officially accepted for medical diagnosis, and their novelty makes them hard to find at a local clinician in practice. Two known places where they are conducted are Northwestern University and Monash University according to Dr Jackie Lane, both being research facilities, not clinical labs. She also mentioned the Reflex app, a PLR testing app (but not PIPR).

In the future, a blood test may also allow to diagnose circadian rhythm disorders as accurately as melatonin sampling, but since melatonin levels are only an imperfect proxy to measure the circadian rhythm (see also here), the blood test, just like melatonin sampling, can get a negative result for some individuals who do have a circadian rhythm disorder, but when the test is positive, it can be expected to be accurate, and hence provide a less expensive alternative to melatonin sampling for medical practitioners inexperienced with circadian rhythm disorders.

Sleep clinics offer to do a sleep study, which consists of a set of tests usually including polysomnography, either at home with a home kit or at the clinic (the latter meaning it's necessary to sleep at the clinic). A sleep study allows to mostly assess if there is a sleep disorder and especially sleep apnea and narcolepsy, but they rarely investigate circadian rhythm disorders since they are done only for one night, and circadian rhythm disorders are only revealed in multi-days patterns of sleep. According to a sleep lab technician (see also here), circadian rhythm disorders are not usually assessed during sleep studies as they are considered a diagnosis of exclusion from sleep studies, which is unfortunate since circadian rhythm disorders are a separate clinical entity that is not mutually exclusive with other sleep disorders and can be as disruptive. In fact, most sleep studies often require the subjects to phase advance their circadian phase to ensure the subject will sleep enough during the study, but hence biasing totally all potential results about the circadian rhythm. It is not uncommon for individuals to have both sleep apnea and a circadian rhythm disorder such as DSPD or non-24, and the treatment of sleep apnea usually does not improve the circadian rhythm disorder.
In addition, due to the "first night effect" (ie difficulty in sleeping in an unfamiliar environment), activity and sleep based measures won't be reliable since they only reflect the participant's sleep and hence will be majorly biased by the first night effect, they can only be used if the participant sleeps at home or multiple nights at the clinic and the first night's measures are discarded. Furthermore, sleep clinics often have a defined schedule, so the patient has to fit in and come to sleep only under specific hours, which may not align with the patient's circadian rhythm's current phase, prevent the patient from sleeping when allowed to by the staff and appointment time, although sometimes some sleep clinics can agree to accommodate different schedules so it's worth asking.
Hence, at-home sleep studies are more indicated to diagnose circadian rhythm disorders, and they can also diagnose sleep apnea if present, and this eliminates the risk of not sleeping during the sleep study (the "first night effect"). The only advantage of at-clinic sleep study is to allow to differenciate between the different kinds of sleep apnea (obstructive sleep apnea - where the respiratory tract is mechanically obstructed - versus central sleep apnea - where the cause for sleep apnea is neurological). The best course of action in case of suspected circadian rhythm disorder is hence to first make the patient write a sleep diary, then if a sleep study is required to eliminate other causes of sleep disorders such as sleep apnea, an at-home sleep study should be done first and then only if sleep apnea is detected, an at-clinic sleep study can be done to discriminate the type of sleep apnea.
Doing an at-clinic sleep study as a first indication is a nonsence for circadian rhythm disorders which can only logically result in a lot of misdiagnoses or null results. There is one exception, being at-clinic sleep studies including melatonin sampling and body temperature monitoring under a constantly dim-lit environment, as they can be reliable measures of the circadian rhythm in a one night clinical setting, whereas activity and sleep quality based measures such as EEG, polysomnography or actigraphy cannot (at least in one night). In addition, melatonin and body temperature reflect the circadian rhythm even when not sleeping, so the first night effect has negligible impact on these, but these measures are reliable only when in a constantly dim lit environment, as light can suppress the circadian rhythmicity. However, even with melatonin sampling or body temperature monitoring, a one-night sleep study can only diagnose a delay in circadian phase, hence diagnose DSPD, but not the non-24 disorder since by definition the non-24 disorder needs to display a freerunning pattern over several days. Hence, if a sleep study is required, prefer to conduct it over several days and at-home. Also make sure to ask for an at-home clinic that can be activated by the patient before sleep (and not with a preset time window where the patient needs to sleep - which is unfit to diagnose circadian rhythm disorders in particular non-24).
Note that sleep clinics are fundamentally different from chronobiology clinics, the latter being specialized in treating circadian rhythm disorders, and are hence a good choice for individuals with non-24. But they are rare.

To interpret the results of a sleep study with polysomnography, please refer to this excellent tutorial aimed to primary care physicians but written clearly enough to be interpretable for the general public.

It's worth noting that most studies on animals actually use proxy measures of wake schedules, and infer indirectly the sleep schedule. This is crucial to keep in mind when interpreting animals studies, most are actually not directly studying sleep but wake patterns. Likewise, a lot of studies on human sleep use questionnaires, which are correlated with sleep measures but can be hugely biased since humans are particularly bad at estimating their own sleep-wake patterns.

Multiple Sleep Latency Test (MSLT) is the oldest vigilance test. It is often conducted during sleep studies. This test is mostly used to diagnose narcolepsy and sometimes insomnia, but it has no diagnostic value for circadian rhythm disorders, especially since it does not account for the circadian rhythm: indeed, the test consists in monitoring how long it takes for the subject to fall asleep in "conducive conditions" during the period of observation which usually lasts 7h. Ideally, this period should happen during the individual's circadian night, but there is no indication in the MSLT standards to do that. For example, if the MSLT test was to be conducted during the day, all typical sleepers would fail the test and be diagnosed with insomnia since they would take more than 15 min.

The morningness-eveningness questionnaire should not be used as a circadian disorder screening tool as it was never designed nor validated for this purpose.

At first, you may have to be screened for sleep disorders of respiratory cause such as sleep apnea. Priori to that, you can yourself do a self-screening using a snoring detection app. The author strongly suggest to use Do I Snore Or Grind app on Android (it also detects sleep stages using sound and/or actigraphy on bed - although the accuracy is debatable). If you cannot find such an app for your device, a simple audio recorder will do, then look at the waveform to find the most loud events recorded during your sleep. Indeed, snoring is always a sign of a respiratory disorder, so if you score high on snoring, this may indicate an issue such as sleep apnea, but it is not necessarily the case, so snoring just indicates that further tests at a medical facility are necessary. However, if you score low or no snoring on several days (as it's normal to snore a bit from time to time), then it's unlikely you have a respiratory sleep disorder. Once you got screened for a respiratory sleep disorder and got a negative result, you need to ask your GP to be referred to a sleep specialist to be tested for "non-respiratory sleep disorder", or better a circadian rhythm disorder, although specialists of circadian rhythm disorders are much rarer than more general sleep specialists. It may be more difficult to get to a sleep specialist depending on the country you live in and whether you need to be referred or whether you can go directly. The UK falls in the first category, you can follow these instructions. For other countries such as France, you may be able to search a sleep specialist by yourself and go directly.

Proxy measures of sleep for self-screening

While the previous section describes the currently accepted or future methods of assessing accurately the human circadian rhythm of individuals, there are proxy methods that can offer instantaneous, low-cost and at-home results, which patients may want to use or may be instructed to do by their sleep clinicians to screen them for possible clues of circadian rhythm disturbances first before orienting them towards a more costly sleep assessment in lab or at-home with adequate, but more expensive, tools.

The first is to manually curate a sleep diary, either electronic or paper based. This is a special case, as it can not only be used for screening but also doubles as a diagnostic tool for circadian rhythm disorders as well as a couple other sleep disorders per current clinical guidelines worldwide. But although current guidelines recommend sleep diaries as the primary and standalone diagnostic method for circadian rhythm disorders, it only assesses sleep-wake patterns directly, and hence remains a proxy of the circadian rhythm. See the previous section for more infos.

A second method is to use computer usage, smartphone usage, and/or browser history, as a proxy of wakeful periods and hence indirect measure of sleep periods. This is a very imperfect proxy, the least reliable, as it is a proxy of wakefulness, not sleep, and themselves being proxies of the circadian rhythm. But it can allow to access weeks if not months of backlogged data instantaneously. A tool called online_actogram to plot computer internet browser usage is already available. Computer usage and smartphone usage (across apps, not just internet browser) can be recorded with the ActivityWatch open-source app, but we don't yet have a tool to plot a sleep-wake diary out of it (help is welcome if you are a developer!).

A third method is to use a proxy method of sleep periods, such as the data that can be recorded from sleep apnea CPAP devices via the open-source OSCAR software. Although this is again an imperfect, proxy measure of sleep periods and hence of the circadian rhythm, the usage of CPAP machines is theoretically more directly associated with sleep periods, and can assumedly produce proxy sleep graphs of similar accuracy to manually curated sleep diaries. In practice, CPAP data through OSCAR can indeed reveal non-24 sleep-wake pattern pretty well.

Experimental simpler self-screening procedure

This produce of diagnosis was devised by this document's author, it was not yet tested nor peer-reviewed.

If you don't have a sleep diary nor the possibility to do a sleep study in a sleep clinic, here is a self-screening procedure:

  • Just try going to sleep when you are tired and avoid alarm clocks for one or two weeks if possible. If not possible, try to focus on weekends sleep, when you can sleep in.
  • Your natural wake up time is the best indicator of where is your circadian night.
  • After a few days without an alarm clock it should either:
    • stabilize to a late, afternoon time if you may have DSPD.
    • keep on shifting later and later if have non24. This is an average over a week, the change can be more chaotic from one day to the next.
  • How to ensure that you slept in circadian alignment with the circadian night and hence that the estimation is accurate:
    • Pay attention to the duration of your sleep sessions, if they last less than 5h30 (assuming your optimal sleep duration is 7-8h, otherwise calculate the minimal duration of a circadian night sleep = your optimal sleep duration minus one ultradian cycle which last about 2h ; eg, on average for adults, 8h of optimal sleep needed - 2h = 6h minimum duration for a sleep session to be considered in circadian alignment with the circadian night) and are not fragmented nor interrupted and there is no 2-4h nap during the rest of the day/night, then this is strongly indicative of a sleep in circadian misalignment with the circadian night, and can suggest a circadian rhythm disorder.
    • Falling asleep faster is a good sign you are sleeping more in circadian alignment within your circadian night.
  • Naps are allowed, but this will reduce the duration of your main circadian night sleep, and can delay the fall asleep time, but the natural wake up time will remain unchanged and hence a good estimator. The rule of how it works is that we generally cannot sleep more than the optimal duration we need under 24h. So if you need 8h of sleep daily optimally, then you can either sleep 8h at once during the circadian night, or 8h minus the duration of naps you did the rest of the day for a combined total of 8h of sleep over 24h. And if you sleep only outside of the circadian night (ie, circadian misalignment), the maximum duration will be 8h minus one ultradian cycle of 2h = 6h over 24h.

If the result of this procedure is that you may have non24 or DSPD, consider trying to get a formal diagnosis by professionals (see the sections above).

Additional signs of a potential circadian rhythm disorder:

  • irrepressible daytime sleepiness/chronic fatigue, this is a strong sign. This can manifest as staying in bed most of the day whenever allowed to.
  • taking a long time to fall asleep, more than 45min, regularly. When sleeping in circadian phase, falling asleep should take less than 30min, and usually it takes less than 10-15min.
  • frequent inability to wake-up with alarm clocks, deep slumber robust to noise. Chronic sleep deprivation induces deeper sleep, whereas chronic good sleep duration and quality can make the individual transition into being a lighter sleeper.
  • more frequent than average susceptibility to catching illnesses such as influenza (common flu) or rhinopharyngitis, which is a sign of an immunodepression potentially caused by chronic sleep deprivation and/or circadian misalignment. This is especially applicable to children.
  • being often (or almost always) late.

It's worth noting that all of the additional signs above are drastically reduced or eliminated when the circadian rhythm disorder is properly treated or accommodated when there is no effective treatment available, which tends to suggest that these are causal to the circadian rhythm disorder.

Early detection of non-24 in toddlers and infants

As of this writing, there is no documented cases of non-24 in toddlers and infants in the scientific and medical literatures. This does not mean that non-24 cannot affect young children, it just means there is no known information on this question. Hence, there is currently no clinicial who would be willing to diagnose non-24 in a toddler or infant, given there is no medical guideline or even just documented case on how to handle this rare scenario. Nevertheless, given that non-24 can have a genetic inheritance such as in the author's case, it is arguable that non-24 can appear very early. But is it detectable?

A well designed single case study of a newborn monitored from their 2nd week of age to 6 months determined that the circadian rhythm appears very early in life in some infants, with temperature circadian rhythm appearing as soon as birth but with a statistically significant signal at 1 week, and the sleep circadian rhythm at day 56. The study also suggested that newborns are already responsive to sunlight exposure during the day and dark therapy at night. This strongly suggests that circadian rhythm disorders may be detectable very early in life.

A few parents who were suspecting non-24 kindly provided some very valuable data on their toddler and infant's sleep patterns. The author is very grateful for their kind data sharing, with the hopes this will allow researchers and clinicians provide better medical support for infants with non24. The data was anonymized per the common standards in clinical research. Please note the data displayed below is exclusive, this is the first ever documented cases of potential non-24 in toddlers and infants. Feel free to reuse the data, following the requirements of the open-source license that cover this entire documentation.

Top image: Six months sleep diary of a 1 year old girl toddler with a clear non24 sleep-wake pattern. The sleep graph was generated with the smartphone app Huckleberry and manually stitched together in The Gimp, with some missing data gaps. The parents and child travelled between July 17 midnight until July 22 noon but stayed in the same timezone. The source is from private communications, the parents wished to remain anonymous. Bottom image: Sleep graph from a sleep diary of a typically sleeping baby from 3 months old to 17 months, collected by u/jitney86. For comparison purposes, only the right side of the right sleep graph will be here considered (ie, at around 1 year of age, when the sleep stabilizes in a triphasic sleep pattern). To view in high resolution, right-click and select "Open image in new tab". For fun, see here the initial image with just 1 month of data, try to see if you could have diagnosed the non24 pattern with less data.

In both cases, we can observe how both toddlers experience a daily occurring major block of long sleep, which is likely aligned with the circadian night, and several shorter bouts of sleeps, which are naps periods. Interestingly, in both cases, there seem to be on average 2 naps periods in addition to the major long sleep period, hence a triphasic sleep pattern. We can observe that not only does the long sleep period (the circadian night) of the non-24 toddler gets inexorably delayed every days, revealing a characteristic staircase pattern typical of the non-24 disorder, but the nap periods also appear to be delayed as well. This data is very precious, and demonstrates that the non-24 sleep-wake patterns can be observed very early in life, as early as 1 year old. This strongly support the hypothesis of an endogenous pathophysiology (ie, that some individuals get born with the non24 disorder, regardless of environmental and psychological factors).

Six months double-plot sleep diary of a 4 year old girl infant (turned 4 year old about in the middle of the graph), logged in a spreadsheet. The x axis (hour) is duplicated to allow to better observe the sleep pattern, as is commonly done in studies of non24. Right-click on the image and choose "Open image in a new tab" to see in full resolution. The blue colored sections represent the sleep pattern under a prescribed therapeutic protocol by sleep doctors, which involved sunlight therapy, melatonin and sleep restriction. During this period, the girl infant cognitively regressed, losing all the developmental progress obtained so far by the parents since the diagnosis of non24 and allowing their children to sleep in freerunning, and the infant suffered from severe narcolepsy-like daytime sleepiness, falling asleep whenever the infant wasn't stimulated (eg, just going to the toilets and coming back, the infant was asleep in plain day). This daytime sleepiness was a clear sign of severe sleep deprivation. The parents decided to stop the protocol and allowed again their infant to sleep as they need, with a freerunning pattern. The developmental progress was then restored and resumed. According to the parents, the daily freerunning delay is on average 45 min, except when the circadian night overlaps with the objective day period, then the freerunning accelerates due to relative coordination with sunlight. The M label in some cells represent the time of exogenous melatonin intake. The source is from private communications, the parents wished to remain anonymous.

Just like the previous one, this sleep graph reveal a clear staircase-like sleep pattern, very typical of the non-24 disorder and its freerunning circadian rhythm phase. But here the child is older, hence with a more consolidated sleep, with much rarer naps at ~4 years old than the child above at ~1 year old. This graph also allow us to observe the sleep pattern over a much longer period of 6 months, which demonstrate how the freerunning sleep pattern is quite stable over time, repeating indefinitely at approximatively equal periods. The sleep disruptions due to environmental disturbances or social (school) requirements are also apparent, especially during the phases when the circadian night is opposite to the day-night cycle (ie, the child sleeping during the day).

The child was also diagnosed with autism, and her cognitive development tremendously progressed when her freerunning sleep was left unrestricted (ie, sleeping whenever she needed to, including naps), which brought praises from the medical staff. The naps also progressively disappeared (this can be already observed towards the end of the above sleep graph, and the trend continued beyond), as the circadian rhythm and sleep processes matured, in line with what can be observed in typically sleeping children. The impressive cognitive development and the natural reduction in naps at the expected age suggest that, at least in this case, letting the child sleep according to their circadian rhythm (including naps) contributed to their natural cognitive and sleep development, contrary to what could have been assumed.
Nevertheless, this is in line with previous research. Indeed, it is now widely recognized that "poor sleep exacerbates problematic daytime behavior", especially for children and adolescents with severe symptoms associated with ASD, as sleep patterns predict with a 81% accuracy worsened behavior in individuals with low-functioning autism. Sleep deficits also lead to difficulties in communication, as well as increased restrictive and repetitive behaviors. The American Academy of Neurology published guidelines in 2020 to recommend to systematically screen autistic individuals for sleep issues, and for sleep to be a primary target of treatment as a major way of improving the quality of life and the symptoms of autism. A 2018 review even suggested that autistic children should be profiled based to design better targeted interventions. Sleep issues are indeed highly prevalent with individuals with ASD: 44% to 83% of children and adolescents with ASD have sleep issues.

These two sleep graphs provide the first recorded evidence that the non-24 circadian rhythm sleep disorder is potentially detectable very early in life, potentially even towards the end of the 1st year of life in toddlers.

Unfortunately, some clinicians confuse non-24 in toddlers and infants with an irregular sleep-wake pattern, which is common for very young toddlers in the first 3 months of life, when the circadian rhythm has not yet matured. But even then, the major, long sleep period in phase with the immature circadian night can be clearly separated from the daytime fragmented sleep-wake periods (ie, lots of daytime naps):

A sleep graph for an even younger infant from 3 days old to 3 months old, showing a irregular sleep pattern due to an immature circadian rhythm system. By u/AtmosChemist.

Although data is lacking for children this young, given the evidence collected above about the non-24 pattern clearly appearing as a staircase-like pattern of the long sleep period, it can be argued that the same staircase-like pattern may appear in sleep diaries or actigraphy logs of even younger children, regardless of the daytime sleep-wake fragmentation.

Although all sleep graphs above were generated manually by the parents curating a sleep diary for their children, it's alternatively possible to use actigraphy to record children's sleep-wake patterns, by attaching the actigraph on their chest using a chest strap, as it is not possible to attach it on their arms since they are so small. This harmless procedure is common in medical studies. However, only clinical-grade actigraphs should be used, since commercially available actigraphs, and even some clinical-grade actigraphs, are unable to reliably record daytime naps, which can explain why most studies on children sleep do not account for naps, and hence they are also unreliable to detect the circadian night of children with non-24 when their phase is opposite to the objective day-night cycle.

Some practitioners, when treating a toddler or infant with non24, prescribe sleep or nap restriction, ie, avoiding naps or even restricting sleep. This is a very unfortunate and uninformed decision that impairs the child's cognitive and neurological development. Indeed, it was demonstrated that napping toddlers retain learnt spatial information, whereas toddlers who remain awake forget. Memory consolidation is crucial in the child's development, as it precedes lexical development, and is mostly done during sleep. But sleep also affects semantic development, since infants who napped, but not those who remained awake, could remember 1.5h after the learning event what was the precise word meaning and moreover how to classify new category exemplars they did not see before, demonstrating a capacity for generalization that infants who avoided naps could not. Another study demonstrated that naps promoted abstraction in language learning of infants, another high level cognitive capacity. In fact, a study shown that 3-years-old infants could only remember a visual stimuli, a cartoon face, 1.5h-2h after presentation only if there was a period of sleep/nap in-between, even if short, hence the authors concluding that even short naps are beneficial for infants memory development (and likely other cognitive functions). Chronic sleep loss impairs neurodevelopment and incurs neuronal loss, especially if from a young age. In summary, sleep including naps is necessary for children's neurocognitive development. Sleep and nap restriction should hence be avoided. It's worth noting that most of the studies promoting sleep restriction on children were using imprecise actigraphs or behavioral questionnaires, which were so imprecise they couldn't record daytime naps.

Why detect a circadian rhythm disorder so early in life? Early detection of disease is well established to be the main method to obtain more favorable outcomes. Despite widespread assumption that children may outgrow their sleep issues, there is no evidence of that for either non-24 or DSPD, as of course the presence of these disorders in adults demonstrate they do not necessarily disappear with age. An unaccommodated and untreated circadian rhythm disorder cause chronic sleep deprivation and chronic circadian misalignment, both having serious detrimental effects on the health of adults and even more severe effects on the development of children. Chronic sleep loss impairs neurodevelopment and incurs neuronal loss, especially if from a young age. Chronic sleep deprivation increases the risk of cardiometabolic diseases, even in children. Chronic sleep deprivation greatly impairs academic performance of children and teenagers. Growth hormones are mainly released during sleep, so that it can be expected that chronic sleep deprivation may stunt height growth. Innovative thinking and flexible decision making to adapt to new situations and find new solutions, crucial skills for academic success, are drastically impaired by sleep deprivation. Indeed, sleeping allows to find innovative mathematical solutions and patterns compared to individuals who do not sleep during the time gap between problem presentation and restitution (see here for a layman presentation). Even if the patients have comorbid diseases, clinicians should be cognizant about sleep disruption complaints, especially with children and teenagers, as sleep disruption worsen all risks of comorbidities. It is hence no surprise the AASM released a recent (as of 2021) scientific statement emphasizing sleep as essential to health, especially for children. Indeed, sleep medicine researchers previously called for the recommendation of systematically assessing pediatric sleep disturbances using standardized scales.

Sleep data can be non invasively monitored even in newborns without any loss of comfort, either by manually curating a sleep diary of the infant's sleep by the parents, or by an automatically generated sleep graph from an actigraphic device attached via velcro to the cloths of the infant on their waist level or their wrist when they are older (so that they are unlikely to try ingesting the device) for more reliable data.

Quantifying parameters of a non24 case

(TODO: work-in-progress)
The major characteristic to quantify a non-24 pattern is to calculate the circadian period/length (tau), which is informally the length of the internal day and night for an individual with non-24.

Formula to calculate the circadian period: tau = average of daywise differences of midpoint of sleep or wake up times + 24h.

Step-by-step calculation of the circadian period:

  1. From a sleep diary, write down the midpoint of sleep for each day. The midpoint of sleep is calculated as latest wake-up time - earliest fall asleep time.
  2. Start from the latest date, and calculate midpoint_n - midpoint_n-1 (ie, subtract the midpoint time of the day before the last day from the midpoint time of the last day). Then continue with the other days similarly, ie: midpoint_n-1 - midpoint_n-2, etc. You will end up with a serie of n-1 values, which represent the daily freerunning delay, which is the amount of phase shift observed between each day.
  3. Calculate the median of this serie. This gives the median daily freerunning delay, aka median daily phase shift. An average works too but is more sensitive to noise.
  4. Finally, add 24h to this average. This should end up with a value greater than 24h if there is a non-24 pattern.

The above is the ideal, most accurate way to calculate the circadian period. It requires data over at least 2 weeks with unrestricted sleep (ie, no alarm clock).

There are other simpler methods to calculate the circadian period:

  • By doing the same calculation as detailed above but using the wake up times of the longest sleep session each 24h instead of the midpoint of sleep, as the wake up times are easier to collect.
  • By counting the duration of a full freerunning cycle: allow the individual with non24 to make a complete around-the-clock freerunning course and record a sleep diary during this whole period. This means that the individual must wait until they record a sleep session for which the wake up time is close to the wake up time that happened at the start of the freerunning course. In other words, count the number of days it takes for the individual to do a full freerunning cycle, the sleep diary is there to know more precisely when the freerunning course is completed. Then, the circadian period is simply 24h + 24h/(the number of days that separate the two sleep sessions). For example: if it takes 12 days to do a full freerunning course, the individual's circadian period is: 24 + 24/12 = 26h circadian period length. The disadvantage with this method is that if the individual has a short circadian period (ie, 24.3h to 25h), and hence a long freerunning cycle, they will have to wait a long time before being able to calculate their circadian period.
  • By calculating the difference between 2 wake up times at least 2 weeks apart (or longer for more accuracy). This method is much less accurate than the others above as it is more prone to noise since there is no averaging, so the estimated period is very imprecise and can change a lot when using different time points (ie, days). The wake up times need to be less than 24h apart, ie, less than a full freerunning cycle between these two timepoints. To calculate: circadian-period = 24h + (last-wake-up-time - earliest-wake-up-time) / number-of-days-between-the-two-timepoints. For example, let's say the circadian phase shifted from 8am to 2pm over the course of 12 days. The circadian period can be calculated as follows (note: 2pm represented in 24h format as 14h): 24h + (14h - 8h)/12 days = 24.5h. Tip: for a much increased accuracy, select only the sleep sessions that are long enough, ie, with a duration close to the ideal sleep duration needed by the individual (look at the excerpt below for reference of average sleep durations by age). This is because a long sleep session is likely an indication of a sleep in phase with the circadian night, so that there is more confidence that a long sleep session does represent the circadian phase of the circadian night at the time, and not a circadian misaligned sleep session that happened only thanks to the sleep homeostat.
  • By calculating the difference between the number of internal days versus the number of objective days. This method was devised by reddit member u/non-24 and explained here (and here).

(TODO: average sleep durations per age ref: https://pubmed.ncbi.nlm.nih.gov/29073412/
> Results: The panel agreed that, for healthy individuals with normal sleep, the appropriate sleep duration for newborns is between 14 and 17 hours, infants between 12 and 15 hours, toddlers between 11 and 14 hours, preschoolers between 10 and 13 hours, and school-aged children between 9 and 11 hours. For teenagers, 8 to 10 hours was considered appropriate, 7 to 9 hours for young adults and adults, and 7 to 8 hours of sleep for older adults.
> Conclusions: Sufficient sleep duration requirements vary across the lifespan and from person to person. The recommendations reported here represent guidelines for healthy individuals and those not suffering from a sleep disorder. Sleep durations outside the recommended range may be appropriate, but deviating far from the normal range is rare. Individuals who habitually sleep outside the normal range may be exhibiting signs or symptoms of serious health problems or, if done volitionally, may be compromising their health and well-being.)

Hypersomnia and non24, which we could classify as a subcategory of non24, is when the non24 disorder is not caused by a too long period of wakefulness, but when the sleep period is too long for a 24h day.
To know if hypersomnia, (TODO: check criteria, is it sleeping more than 12h?)

Severity can be considered to be proportionate to the length of the circadian period, as indeed stronger phase advance therapies are required to offset more the longer the period. In practice, it can be assumed (and from anecdotal feedback) that periods up to 26h are likely responsive at least partially (although this does not mean that full entrainment can be reached with current therapies). Periods of more than 28h are likely too wide to be responsive enough to current treatments (this does not mean that they are not responsive, but that the phase advanced benefit from currently available therapies are likely not enough to reach any satisfactory reduction of the circadian period, which anecdotally match with the feedback received in private communications). Extreme periods of 30+h are usually associated with intensive past use of benzodiazepines and other strong psychotropic medications, and/or alcohol, and/or RLS/PLMD (which symptoms can be triggered/worsened by melatonin and hence indirectly by bright light through photic history's increase of melatonin). There appears to be a sweet spot for periods of about 25h-26h, as this represents an average daily freerunning delay of 1h to 2h, which means that the individual goes through a complete phase reversal (ie, a 12h shift, which means going from wakefulness during the day to during the night and vice versa) every 1 to 2 weeks, which according to private communications feedbacks and public posts on reddit seem to allow for a better quality of life as they can expect to be able to resume typical daytime activities every 1 to 2 weeks, alternating with 1 to 2 weeks of nocturnal activities. This rapid-but-not-too-rapid cycling allows them to find consistency in the alternance of this schedule. Indeed, slower circadian periods such as 24.5h cycle phase reverse about every 1 month, which means they cannot do typical daytime activities for a full month, and is especially problematic with work (severe chronic sleep deprivation may be powered through for 1 to 2 weeks, but not a full month). Faster circadian periods more than 28h cycle so fast that they complete a phase reversal under less than half a week.

Medical misdiagnoses

How to detect and avoid a misdiagnosis?
The greatest early sign of misdiagnosis is the dismissal of sleep diaries by a doctor. If the doctors you met shrugged off the sleep diary, or the sleep clinic where you had your sleep study did not include a 2-weeks sleep diary, then that's a clear sign they are not properly trained to diagnose circadian rhythm disorders, as sleep diaries over at least 2 weeks are the standard method to diagnose insomnia since 2008 and circadian rhythm disorders according to american and british guidelines. Furthermore, the american guidelines on patient-generated health data (PGHD) using consumer-grade sleep technology such as fitbit or sleep diaries state that this data should be used to (at least) open dialogue with the patient, that the clinician should understand the data and that "clinicians should recognize the patient's use of consumer sleep technology as a commitment to focus on sleep wellness". In other words, handing over your sleep diary of at least 2 weeks should be sufficient for any properly trained sleep specialist to diagnose you if you have a circadian rhythm disorder, should be considered an indication of your motivation to get better, and should certainly never be shrugged off (see for example these unacceptable patient experiences, with general practitioners denying specialized testing despite adequate data). If this happens to you, seek counseling from another medical professional.

Although there is an official diagnosis criterion according to the AASM (simply to have a sleep diary over at least 2 weeks showing a freerunning pattern), the author is convinced this criterion is both too vague and too restrictive. Indeed, it is too restrictive as it doesn't account for people who constraint their sleep schedule and hence can't freerun, and too vague because all humans can freerun given an environment devoid of timecues, the specificity of non-24 is that freerunning (and the cyclical inability to sleep and wake up) happens continuously despite environmental timecues (ie, zeitgebers).

Causes of misdiagnoses: psychology misdiagnoses
Circadian rhythm disorders are often misdiagnosed (see also here), which can cascade and leads to unnecessary distress despite being easily diagnosable and may lead to inappropriate prescriptions of psychoactive drugs. Most often, the misdiagnosis is confusing non-24 or other circadian rhythm disorders for DSPD, since this is the most commonly known circadian rhythm disorder in non specialists fields of medicine, but misdiagnoses of inexistent psychiatric disorders is also common. Misdiagnosis and medication errors are frequent and the most common types of medical errors. A psychological misdiagnosis (such as the ill-defined and evidence-lacking psychosomatic disorder, medically unexplained symptoms, or others as seen below) worsen these issues, as this can have dramatically detrimental consequences for the patient with a rare disease such as non-24, as they already wait an average of 4.8 years to be diagnosed, and a psychological misdiagnosis delays 2.5 to 14 times longer the proper diagnosis of their chronic rare disease, according to a survey of 12,000 European patients, with this delay being harmful for a majority of patients. Psychological misdiagnosis does not affect only new and rare diseases but also well-documented physical diseases such as epilepsy. This was sadly illustrated in a horrible case of iatrogenic (medical) mistake from both psychiatry and psychology practitioners on a 14-year-old boy as reported in this study:

> A 14-year-old male was referred for sleep disorder assessment with the complaint of daytime sleepiness and lack of motivation. [...] During the 4 years before referral, the patient suffered from major functioning difficulties including conflicts with teachers, parents, and peers. He was described by a licensed child psychologist as being extremely introverted with severe narcissistic traits, poverty of thought, and disturbed thinking, including thoughts with persecutory content and self-destruction that led to a paralyzing anxiety, anhedonia, social isolation, and withdrawal. [...] Two years before referral, the patient dropped out of school and was sent to an inpatient child psychiatry center. Three months of psychiatric evaluation yielded diagnoses of atypical depressive disorder with possible schizotypal personality disorder. He was described as sleepy and passive, especially in the mornings. The patients psychiatrist suggested further assessment, including assessment of sleep disorders. [...] Failure to make a correct diagnosis led to psychological distress and personal turmoil for a boy whose sleep disorder was easily diagnosable and treatable with melatonin. [...] Greater awareness of sleep disorders may prevent psychiatric misdiagnosis of treatable sleep-wake schedule disorders.

It's worth noting that the misdiagnosis of sleep disorders is much more frequent in children, as historically, sleep disturbances in children have largely been ignored by the psychomedical field.

As demonstrated by this case, misdiagnosis of sleep disorders (here non-24) as a psychological disorder is common, especially of schizotypical, schizoid or schizophrenic disorders. Indeed, two major items of the schizo* spectrum are dissociative symptoms such as depersonalization/derealization (see also here and here), and social isolation, both being also caused by severe chronic sleep deprivation due to sleep disorders. Add on top the specific difficulties of non-24, such as the nightwalking phases during which the individual will be exclusively living at night and sleep during the day for months, which necessarily leads to social isolation due to the mismatch of the individual's sleep-wake schedule with the rest of the world and cause feelings of being "disconnected from reality" which are perfectly normal as they were also experienced by typical sleeper archeologists such as Siffre during their "expériences hors du temps" in caves disconnected from external interactions and zeitgebers for months. Furthermore, episodes of depersonalization and derealization are extremely common in the general population, as 26% to 74% experience them at some points in their lifetime according to a systematic review (see also here). For healthy, typical sleeper participants, 52% experience dissociative symptoms including depersonalization and derealization after 24h to 48h of acute sleep deprivation according to a systematic review. Despite the normalcy of these feelings, and the challenged unproven assumptions that dissociative disorders cause sleep disorders in response to trauma, whereas empirical evidence demonstrate the opposite to be true as shown by the excellent works of Dr. Dalena van der Kloet (see also here), the mere evocation of these feelings by the patient is a recipe for a misdiagnosis of a schizotypical disorder by psy* clinicians, regardless of the chronicity and context of their occurrences.

Unfortunately, although these effects of sleep deprivation are well documented, most psychiatrists and psychologists are unaware of this knowledge about sleep, even when they practice in a sleep clinic. Even in the rare instances they are, they tend to focus on treating the psychological symptoms (assumption of an intrapsychic cause), assuming this is the cause of the sleep disorder. However, the results of a rsystematic review state that sleep disorders often precede psychological disorders symptoms onset, they persist even when psychological disorders are well controlled and hence that "sleep problems require independent attention irrespective of co-morbid conditions". Unfortunately, psy* clinicians are unlikely to consider sleep disorders as anything other than secondary to psychological disorders contrary to the evidence, as otherwise they would be unable to provide any service to their insomniac patients. This kind of misdiagnosis also happens at sleep clinics, since they often have psychiatrists and psychologists in their staff.

These misdiagnoses are unfortunate, as an accurate diagnosis of their medical condition allows circadian rhythm disorders sufferers from being relieved from the "humiliation" and social guilt of their self-perceived "bad behavior", which can dramatically improve their and their family's wellbeing.

These misdiagnoses, especially psychological ones, are often due to a failure in adequately testing the potential hypotheses. For example, studies on "paradoxical insomnia" always fail to test the circadian rhythm, and a reddit member even reported that the sleep clinicians, after misdiagnosing non24 as paradoxical insomnia, argued that testing for a circadian rhythm disorder was unnecessary as it was useless, given there is "no cure anyway" according to them (which fails to consider the possibility for handicap recognition and accommodations). It's surprising some clinicians consider that getting an appropriate diagnosis for a condition that is partially treatable, versus another condition that is not, is useless. A simple sleep diary, or more stringent objective tests such as an actigraph or melatonin sampling, would have elucidated the issue at little to no cost.

The crux of this issue lies in the fact that psychiatrical clinical guidelines (but not other fields of medicine obviously) still consider circadian dysregulation as secondary to a primary psychiatric disorder, as explained by this 2019 systematic review:

> Historically sleep problems have been neglected in groups with neuropsychiatric disorders due to diagnostic overshadowing, and assumptions that sleep problems are purely secondary to psychiatric symptoms. Unfortunately sleep problems often persist even if affective or psychotic symptoms are well-controlled. There is increasing recognition that sleep problems require independent attention irrespective of co-morbid conditions. In accordance with this the ‘primary’/‘secondary’ insomnia distinction was removed from DSM-5 and ICSD-3. Circadian dysregulation disorder definitions have not been similarly modified; the ICSD-3 stipulates for diagnosis of CRSD the sleep disturbance must not be “better explained” by another medical, neurologic or mental disorder. Further, it contains no category for CRSD secondary to another disorder [27]. Studies which examine circadian dysregulation in samples with neuropsychiatric disorders find high prevalence of patterns similar to ASPD, DSPD, ISWD and non-24hr, but usually CRSD terminology is not applied.

This is unfortunately a common pattern, with newly discovered disorders with unknown causes being misdiagnosed as idiopathic (ie, self-caused) instead of cryptogenic (ie, of unknown causes, as defined by Walter Dandy in 1932) until more evidence arise that they are in fact not caused by mental issues, as happened for epilepsy:
> A number of general thoughts arise from this historical survey. First is the importance of societal and nonscientific influences on theories of epilepsy etiology. Examples are numerous. Concerns about degeneration at the end of the nineteenth century for instance were widely discussed in politics, the arts, sociology, and criminality. Eugenic research in epilepsy was primarily driven by economic, political, and social forces. Psychoanalytic thought was found in almost all social discourse, and the similar tendencies are arising now in relation to molecular genetics. It is a delusion of neuroscience that its progress is linear or that contemporary position inevitably is the most scientifically advanced. The awkward reality is that the march of neuroscience has had an erratic course sometimes in a backward direction and veering up many cul-de-sacs. It is partly subjective largely and markedly influenced by fashion and social forces, socioeconomic factors, dominant personalities, and the full gamut of human failings. Science is never neutral or objective, and thus has a social responsibility, a fact often forgotten in the laboratory sometimes with disastrous results as was the case in the 1930s. Second, it should be realized that clinical neurology, being an essentially applied science, is heavily methodology- driven, and methodology in large part sets the agenda. We know only the etiologies we can measure, and what we cannot measure we cannot know. The introduction of clinical chemistry, EEG, neuroimaging, and neurogenetics has each changed our fundamental perception of etiology, and over the last 150 years, the focus has moved from one category to another, often overstating the importance of that in fashion (the switching interest between inherited and symptomatic causes for instance).

Some argue that the first case of diagnosed hysteria, an old form of the somatoform disorder diagnosis, was in fact just a case of misdiagnosed epilepsy. But just like epilepsy now has a well documented wide set of causes, all being of biological or physiological origins (see also here and here), circadian rhythm disorders are also progressing towards a path of being recognized as biophysiological disorders.

In practice, avoid psychiatrists, psychologists and psychotherapists when looking for a clinician to diagnose a sleep disorder, as they will rather favor intrapsychic explanations and hence diagnose and treat psychological disorder (even if there is none) rather than the sleep disorder. For example, epilepsy is still being heavily underdiagnosed (32-38%) in individuals with intellectual disabilities because of "the misinterpretation of behavioural, physiological, syndrome related, medication related or psychological events by parents, paid carers and health professionals". They are in any case not the field of preference to treat these disorders, just like psychiatrists have no pertinent training to treat lung damages, they should not be considered competent to treat sleep disorders, both being biophysiological diseases. Furthermore, avoid any clinician recommending sleep deprivation, chronotherapy or any form of sleep deprivation such as avoiding naps, as sleep restriction is never a treatment for sleep deprivation, just like dietary restriction is never a treatment for malnutrition. Timing therapies to an absolute/fixed target bedtime or wake up time instead of relative to the current circadian phase (eg, natural bedtime and wake up time) is a red flag too, as it is a fundamental error no sleep chronobiology expert would do, it's literally nonsensical given how zeitgebers work (ie, PRC curve).

Causes of misdiagnoses: medical procedure and cognitive errors
All fields of medicine are plagued by systematic procedure and cognitive errors that can lead to misdiagnoses. Although studies on this topic are sparse, especially for mistreatments and prognosis, several authors could identify the most common errors that account for misdiagnoses.

Among systemic errors, the lack of education on the latest findings in sleep medicine is certainly a major factor:

  • An important factor to consider is that the clinical practice (medicine) lags on average 17 years behind translational research. Note this is an average! The paper shows the intervals for various domains, and in some cases the clinical practice can be "221 years" behind the current scientific knowledge! This is why the consensus found in scientific papers can seem very remote, even opposite at times, to the clinical practice (eg, insomnia being wrongly assumed to be secondary to psychological disorders).
  • In the case of sleep medicine, this lag is verified. Historically, sleep disturbances have been largely ignored by the psychomedical field, missing unique opportunities for improved health outcomes. Even nowadays (as of 2021), "education about sleep and sleep disorders is lacking in medical school curricula, graduate medical education, and education programs for other health professionals" according to the AASM (see also here), which the AASM recommends to change by teaching sleep health as a prominent element since a young age at school and up to medical school curricula. As the authors write: "A multi-nation survey of medical schools found that the average amount of time spent on sleep education is just under 2.5 hours, with 27% responding that their medical school provides no sleep education."
  • More generally, there seems to be a lack of adequate training in the medical cursus for the handling of chronic illnesses, and the public is now discovering this at large now that they experience the widespread long covid chronic illness.
  • Gender also plays a role, since women are much more likely to be discharged without a physiological illness diagnosis but instead with a "junkbin diagnosis" such as anxiety or stress (TODO: add refs). For example, sleep apnea has historically been underdiagnosed in women.
  • "Iatrogenesis is the fifth leading cause of death in the world. There are about 5%–8% of deaths due to adverse drug reactions worldwide. [...] Among the European Union Member states, WHO concluded that the healthcare-related errors occur in 8% to 12% of hospitalizations." https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC6060929/
  • The medical work culture is not tolerant of chronic illnesses in their workforce, which removes profiles who could provide a interesting transversal contribution to the field. See for example the reddit r/DisabledMedStudents. More specifically, there are lots of complaints from medical students with DSPD, despite DSPD med students being ideal to work night shifts, but the prevalent dogma is that med students should work the day, and those who work the night are expected to be available day and night (see r/NightShift).

Another major factor is burnout (at least) partially caused by chronic sleep deprivation and the "no sleep culture as a badge of honor" in the clinical workplace:

Given the above, it is understandable that actors of the medical field, which is one of the profession with the most endemic and dire chronic sleep deprivation out of all professions, are reluctant or even feel unempathetic or hateful when patients with disordered sleep come to share their sleep complaints, when they themselves are desperately lacking sleep. Yet, this is obviously inadequate and unacceptable, just like it would be unacceptable to for clinical professionals to be spiteful of diabetics having difficulties with their diet because clinical staff rarely have the time to eat at all during their shifts.

Cause of misdiagnoses: Rare illnesses are poorly treated by modern medicine
Modern medicine is optimized in an utilitarian way due to economical constraints, by aiming to treat the greatest number of cases, hence the most common diseases, but with fewer or no resources allocated to rare illnesses care.

However, rare diseases are not that rare:
>Although every single rare disease affects only an extremely limited number of patients (defined as incidence <1/2000 in Europe and <1/1250 in the United States), approximately 6000–8000 disorders are classified as rare diseases along with 250–280 new additional ones annually, which accounts for 6%–10% of the global population being affected. Among the numerous and varied problems experienced by rare disease patients and their families, the first and perhaps most significant problem that prevents them from achieving a better quality of life is the difficulty in accessing a definitive diagnosis. A definitive diagnosis does not only mean a possible treatment and relief from pain, but also means release from pressure of not knowing, access to ancillary social welfare or subsidies for special needs, connection with rare disease support groups, and obtaining information for life planning and reproductive decision-making.

An online 2018 survey of people with a circadian rhythm disorder by the Circadian Rhythm Sleep Disorders Network found that "of those formally diagnosed, 22% took 10 years or more to receive an accurate diagnosis, from when they first sought help for their circadian rhythm disorders", and "about half were wrongly diagnosed initially, many with multiple incorrect diagnoses over the years" with the main incorect diagnoses being the usual suspects: depression, insomnia, and no diagnosis ("nothing is wrong").

This is unfortunately unsurprising, and not even specific to circadian rhythm disorders. Indeed, misdiagnosis, diagnosis delay, and a lengthy journey to diagnosis are a common experience for people with a rare disease:
> A 2006 study of eight rare illnesses in 17 European nations revealed that up to 25% of patients had spent 5–30 years to access the correct diagnosis, and 40% of the patients experienced an erroneous diagnosis. [...]
> [...] The impact of the geographic distribution of healthcare and patient mobility should also be taken into consideration. Due to the uneven distribution of healthcare, many patients have to travel across regions to obtain a definitive diagnosis. Eurordis’ survey revealed that 25% of rare disease patients in Europe had to travel to a different region to receive the definitive diagnosis, and 2% even had to travel to a different country. The variance of accessibility to healthcare can also be caused by differences in patient mobility, such as affordability, physical disability, and education level.
> The first national survey on rare diseases in 2016, covering 1771 patients across the country, reported that the various social and economic difficulties faced by these people are “beyond imagination”.

In countries with a less developed healthcare system such as China, the situation seems even more dire:
> (1) Accessibility: 72.97% of patients were misdiagnosed; they waited an average of 4.30 years and visited 2.97 hospitals before the definitive diagnosis; 67.13% were diagnosed outside the home city and traveled an average of 562 km. (2) Interrelationships among accessibility indicators: the experience of misdiagnosis significantly increased diagnosis delay and the number of hospitals visited, but had no significant effect on healthcare utilization across cities. (3) Impact factors: the rarity of disease only increased the number of hospitals visited and residence–hospital distance; high-quality healthcare distribution was key in determining accessibility; the older, disabled, poor, and less-educated individuals, and those in Central/West China were disadvantaged.

Some factors appear to indirectly affect the misdiagnosis rate. A 2020 study of individuals with rare illnesses in China found that misdiagnosis was more likely for those with less accessibility to information on rare diseases (ie, less health literacy), and those with disease multimorbidity, which when the individual reports multiple ailments. These findings were true for both adults and children.
Misdiagnosis of physical illnesses is much more frequent when the patient has a psychological illness, even if properly treated and controlled.

Modern medicine often disregard patient's feedbacks and personal knowledge on their own diseases, which some argue is a loss of opportunity for furthering medical knowledge.

It's worth noting that the International Rare Diseases Research Consortium aims in its 2017-2027 agenda to enable all people living with a rare disease to receive a definitive diagnosis within one year of coming to medical attention (see original publication here), but this vision currently falls short of what the current clinical practice can achieve.

Developing health literacy to avoid misdiagnoses and improve health outcomes
Given the findings in the previous subsections, it appears necessary for people with a circadian rhythm disorder to be resilient and develop their health literacy as recommended by medical organizations in order to navigate the information and circumvent the potential misdiagnoses they may encounter during their journey to get medical help for the diagnosis and management of their condition. Indeed, it was demonstrated by several studies across various subpopulations that people that have more understanding of their health and medicine have better health outcomes (see also here). Online forums have plenty of anecdotes of life-saving self-diagnoses. Hence, monitoring of one's own symptoms and vital signs, as well as reading about one's own (suspected) ailment ought to be recommended to the patients, and these patient-generated data should be taken into account by the medical practitioners.

Indeed, excluding patients' personal knowledge from medicine is not scientific but scientism which impairs the medical practice and ethics:
> Medical scientism is the imperative to define and achieve all medical goals through science. This imperative manifests in numerous ways and is particularly evident in the objective−subjective dichotomy, whereby objective knowledge is viewed as superior and subjective knowledge is regarded as inherently suspect. In this paper, we argue that medical scientism is flawed because it only recognizes what we call general and explicit knowledge and excludes what we call tacit and particular knowledge. This exclusion is epistemic, in that tacit and particular knowledge may be implicitly recognized by scientism, though not as genuine knowledge but as some modulating factor in the application of scientific knowledge (from a Kuhnian perspective [Kuhn 1996]; this is because recognizing tacit and particular knowledge as valid knowledge would undermine the foundational assumption of the scientistic paradigm that the quality of knowledge is related to the extent and rigour of its justification). Such factors, which are invoked through terms like clinical expertise or patient preferences, we suggest are more accurately described as valid and necessary forms of medical knowledge, with features that distinguish it from the knowledge science delivers. We argue that the exclusion of tacit and particular knowledge impairs our ability to achieve medicine’s goals, primarily because these knowledge forms are essential to doing medicine and secondarily because the overemphasis of general-explicit knowledge distorts our perceptions of what legitimate medicine should be. These impairments relate to a range of domains of medical practice, from the reasons supporting one treatment over another through to health policy and even to the legitimacy of different kinds of ethical arguments. [...] Scientism, we argue, excludes tacit and particular knowledge and thereby distorts "clinical reality" and impairs medical practice and medical ethics.

Paradoxically, the clinician's personal knowledge is often used to guide diagnostic and theurapeutic courses, regardless of their (lack of) evidence base, which is usually termed "clinical lores".

TODO: also read Michel Foucalt on history of medicine and how it was used to control populations as part of "biopolitics", term that he coined.

Malingering the non24 disorder

WORK-IN-PROGRESS SECTION: need to add links to references (they are already present elsewhere in this doc).
Can the non24 disorder be faked? This is the issue this subsection will explore.

Some clinicians may doubt of the existence of the sighted non24 disorder as a real illness. While it is true that the human circadian rhythm is naturally slightly greater than 24h as was demonstrated by experiments under constant conditions such as the cave experiments "ee dehors du temps", there is no evidence it can be greater than non24 when the individual is exposed daily to indoor or outdoor sunlight (under the same timezone). Indeed, the human circadian rhythm is normally supremely responsive to bright light, hence there is no way for an individual to freerun under normal urban conditions.

Some will argue that the modern urban lifestyle, with most work positions in closed offices, reduce our exposure to natural sunlight and weaken our circadian pacemaker. While this is certainly true, this does not explain why the vast majority of humans are still untrained to a 24h sleep-wake schedule. Furthermore, studies have now demonstrated that the circadian pacemaker uses several tricks to be more robust, such as using color, not just light intensity, hence it is well know that it is extremely difficult for scientists to isolate subjects from natural zeitgebers under lab experiments, and impossible in freeliving conditions. The latter is strongly supported by the experiment on the NASA Mars monitoring crew, who, despite being highly trained and (financially and scientifically) motivated, revolted after just one month of trying to forcefully follow a non24 sleep-wake pattern (see also here). Similarly, numerous studies have observed severe cognitive, physical and mood impairments in highly trained submarine military crews subjected to non-24 sleep-wake cycles. Furthermore, the much more common occurrence of night shift wake disorder, which is essentially when typical sleepers try to forcefully shift their circadian rhythm but fail to do so, show that just phase shifting, not even constant freerunning, is extremely hard to achieve under freeliving conditions.

Anecdotally, the first clinically documented case of sighted non-24 was reported in 1971 along with a "trick" experiment performed on the participant: "He was then confined in an isolation unit, without a timepiece, and his habits were recorded by a remote signalling device; he there followed an activity cycle of 26hr. After 5 days a clock, which he knew could be adjusted to gain or lose several hours a day, was started, and he was asked to try to conform his habits to the time recorded on the clock; unknown to the subject, this clock was running at a normal rate, though its absolute time was in error since it was started at the time which he believed it to be. He was still unable to conform his habits to a 24hr cycle, just as when living in nychthemeral surroundings (Fig.1). Measurements of his plasma 11-hydroxycorticosteroids, body temperature and excretion of sodium, chloride, potassium and steroid indicated that these followed a rhythm in accordance with his activity cycle."

Hence, sighted non24 can NOT be faked, nor simulated, nor forcefully induced, except by complete isolation from zeitgebers especially sunlight. Hence, if a clinician doubts whether a patient really has sighted non24, they only need 2 items: a sleep diary or an actigraph over weebs showing a non24 sleep-wake pattern, and they can ask the patient whethes they are living in a cave or are systematically isolated from sunlight and other bright light sources. If the patient is not, there is no logical reason nor evidence based motivation to deny a non24 diagnosis. The author of the present document challenges any critic of the above statement to demonstrate empirically by forcefully inducing a non24 sleep-wake schedule in a sighted individual or animal under freeliving conditions exposed to daily sunlight at least in indoors. Until such a demonstration can be produced, the possibility of malingering a signted non24 disorder should ve dismissed as nothing more than prejudice based on ignorance of the empirical circadian rhythm science. In summary, sighted non24 is a disorder that cannot be simulated nor faked, except by isolating completely the subject from any zeitgeber.

While an assessed non24 sleep-wake pattern cannot be faked, the assessment can be manipulated depending on the acquisition modality : if a sleep diary is used, it can of course be faked by the patient since this a patient reported metric. The simplest and cost effective solution is to make the patient wear an actigraph on their wrist (adults and older kids) or ankle (for infants), as this will allow an objective monitoring of the sleep-wake pattern, and is very hard or impossible to fake, as it is obviously insufficient to detach the sensor to fake sleeping, since humans do move during their sleep, but with very specific patterns that are different for each sleep stages and along the night. If there still remains some doubts, even more objective metrics such as melatonin sampling in saliva or urine, or the non invasive core body temperature monitoring with zero or dual heat flux sensors can be used to produce internal vitals monitoring that cannot be faked nor manipulated by the patient.

Lastly, it is worth questioning the potential motivation for malingering. Indeed, it is hardly understandable why anyone would fake an obscure disorder that, due to being poorly recognized, only rarely opens any recognition or rights, when easier and more known disorder and diseases can be faked more easily and for more profits.

Why can't people with non-24 simply sleep when needed? Why trying to do so causes a chaotic sleep?

Sleep is not a matter of personal preferences. Humans cannot control the circadian rhythm by will, that is a common misconception and the root cause of ineffective treatments. Otherwise, if sleep control by will was possible, sleep disorders such as insomnia and non24 would not exist. Night shift would not lead to chronic insomnia and major health issues such as cancer. Humans cannot control their circadian rhythm by will, just like they cannot control their insulin levels by will, as they both are biological processes.

However, we can manipulate our insulin levels to some extent by controlling our carbs intake, just like we can manipulate our circadian rhythm to some extent with external tools such as zeitgebers (eg, bright light and melatonin). But not by will. That is a common misconception about sleep and the major cause of improper management and lacking development of proper tools to manage sleep disorders. This major realization underlies the VLiDACMel protocol, after countless of failed attempts with various will-based schemes (eg, chronotherapy), only the use of external tools allowed some degree of manipulation of the circadian rhythm.

The intuition that sleep is controllable is only natural, as the circadian rhythm is deeply hidden and often imperceptible. When everything works, it's only natural to think it's easy. But there are a few cases where anyone can experience circadian disruptions and hence the existence of their own circadian rhythm: jet lag and night shift work. Indeed, anyone travelling between timezones will feel restless for days/weeks, having difficulties falling asleep at the local night time, until magically after a few days/weeks we become accustomed. That's because of the circadian rhythm progressively readjusting, which takes some time. If we could sleep whenever we wanted/needed, jet lag and night shift work disorder wouldn't exist. Now imagine being constantly jet lagged, as if your body never recovers from jet lag after a travel, and you can get an idea of what non-24 and other circadian rhythm disorders (eg, DSPD, night shift work) are like.

Another way to experience the hidden sleep processes such as the circadian rhythm and sleep homeostat is to try to do the opposite: to avoid sleeping altogether for 48h, in an environment with no artificial light. Kleitman, the father of sleep research, describe extensively the difficulties in preventing participants from sleeping, even when they are just allowed to sit for a few minutes every few hours, they still fall asleep, and in the end failed to fully prevent them from sleeping. Nowadays, artificial bright light from screens or home fixtures can alleviate sleep by directly modifying the circadian rhythm, but without, the individual will necessarily fall asleep uncontrollably upon the pressure of their endogenous sleep processes, whether they wish it or not.

The previous two simple experiments that can be done by anyone demonstrate two things: 1) it is almost impossible to stay awake when the biological processes underlying sleep signal that the body should sleep, and 2) it is almost impossible to fall asleep when these biological processes are not signalling it is time to sleep. Hence, sleeping is not a matter of when someone wants to, but when someone can, as regulated by their biology.

When an individual tries to sleep outside of their circadian rhythm to meet social obligations, this means that they then have to rely only on the second sleep process, the sleep pressure (aka sleep homeostat or process S of Borbély's model), to be able to initiate sleep while fighting the natural sleep propensity induced by the circadian rhythm (process C). Since the circadian rhythm continues to periodically cycle in the background, it will periodically enhance the ability to sleep (too early or too late compared to the individual's social constraints), which will compound with the sleep pressure and produce alternating periods of hyposomnia (sleep deprivation because of social constraints preventing sleep initiation when the circadian rhythm allows it) and then hypersomnia (because of the accumulated sleep debt that will magnify the circadian rhythm). Adding in the ultradian gates to sleep, this all combines into producing a chaotic sleep pattern, where the individual with a circadian rhythm disorder or doing night shifts will alternate between sleeping little to none one day, and then crash into bed for a very early and long night of sleep the next day, or even unexpectedly fall asleep suddenly even in an unfit situation such as while driving, because of the huge sleep debt, and this alternating cycle will repeat until the body can't take it anymore.

Case study: the MyNon24Sleep dataset contains several examples of sleeping solely using the sleep homeostat but not the circadian rhythm, for example day 2021-12-19. Indeed, it is possible to build up enough sleep homeostat pressure to sleep even outside of the circadian night, either earlier or later, but at the cost of a shorter sleep duration and less reparative sleep, which happened in this example from 1.35am to 7.33am. In this case, the individual still felt an energy crash during the circadian night as evidenced by the core body temperature minimum for this 24h period, which in this case happened suddenly later that day, starting from 2.00pm and lasting up to 4.30pm, despite the use of bright light therapy and having slept almost 6h, which is sufficient to not feel daytime sleepiness unless if caused by the circadian night. The same scenario got repeated the day after, only for a nap to be done between 1.00pm to 4.30pm. During both days, the individual (the current document's author) felt a confusing mixed signal where both a lack of sleepiness, but some form of sleepiness/brain fog were concomittantly present throughout the days, which only disappeared after sleeping/napping during the circadian night. In other words, even a long sleep session is not fully restorative when it is happening outside of the circadian night, and the body will still be exhausted during the lowest period of the circadian night. The energy loss, extreme coldness (due to very low core body temperature, causing shivering and inability to stay in room in ambient temperature), headaches, mind confusion and motor incoordination during the circadian night are so sudden and extreme that even if the individual can stay awake as in this example, activities such as work and driving are obviously too dangerous to perform in this state. Given the worsening between day 1 and day 2 with this schedule under circadian misalignment, the individual felt that if this schedule was maintained for just a few more days, it would cause major dysfunctions on par with sleep deprivation, which is in line with the results from previous studies.

Hence, an individual with non-24 who tries to maintain a socially acceptable schedule will necessarily restrict their sleep in some way (either a shorter sleep duration, or an unrestorative sleep in circadian misalignment, or both) which will only cause more sleep deprivation and chaoticity in their sleep patterns, which then reduces their productivity and their ability to plan appointments, which makes this whole approach highly counter-productive. As this study explains:

> The pattern of sleep disruption experienced by patients with the disorder does not always present as a shift in sleep timing each day. A majority of individuals will attempt to maintain sleep at a socially normal time. As a result, some individuals will produce a sleep pattern with the nocturnal sleep episode expanding and contracting as they move in and out of phase and with the build up and pay-back of homeostatic sleep pressure. Due to the pleomorphic variation in patient's sleep timing, a review of sleep history may not reveal a clear cyclic pattern to indicate the presence of N24HSWD. These more subtle cyclic changes are termed “relative coordination” and often require an expert to review.

People with no circadian disturbances often advise to "just try to sleep at the time you need". More formally, this is a form of sleep hygiene, the oldest supposed treatment for insomnia. However, AASM guidelines since 2008 and in a 2021 systematic review state that sleep hygiene is not supported as a single therapy, it is not sufficient to improve sleep disturbances, which should not come as a surprise given the above insights on how the circadian rhythm orchestrates sleep.

The use of sleeping pills is also inappropriate for non-24: "The circadian basis of N24HSWD distinguishes it from other sleep-wake disorders, and therefore use of hypnotics and stimulants to address the sleep and sleepiness symptoms, respectively, is not appropriate."

When you sleep outside your circadian phase, it's the sleep pressure that you will then use to sleep. The first day you can't sleep so you'll sleep late, but since your sleep is restricted you'll wake up with some residual sleep pressure, so the next day you'll sleep early because you'll have today's sleep pressure, plus yesterday's residual. This day you'll sleep a long night, maybe even too early and too long. Bu the next day the vicious loop starts again: can't sleep until late because your biological night is delayed compared to the objective night, so you'll keep some residual sleep pressure at wakeup, etc...

If your biological night is just a bit delayed, let's say a few hours at most, you can sustain like that for a long time although it's unhealthy and straining. But if your biological night is a lot later, let's say into the day, then you'll accumuate too much sleep pressure debt to repay in one night, and so you'll keep residual sleep pressure and eventually just collapse with a behavioral sign thad resembles hypersomnia or narcolepsy.

Hence, a pattern of chaotic sleep is likely a sign of oscillation of sleep pressure. This suggests that chaotic sleep can simply be caused by sleeping outside of one's own biological night as defined by the circadian rhythm. This is not specific to individuals with circadian rhythm disorders, but it more often happen to them due to their circadian rhythm being out of phase with social obligations.

TODO: add graphic and sourcecode of model reproducing a chaotic sleep pattern from simply: process C, process S, ultradian cycle, exogenous sleep onset constraint: only outside of process C (can define anytime to see what happens when can sleep in the process C), endogenous sleep onset constraint: addition of all processes must reach a certain threshold for sleep to occur (hyposomnia, can't sleep) + high threshold when sleep onset is irresistible (hypersomnia). Sleep onset is not deterministic but is probabilistic. Generate graphs with various values for these parameters, should reproduce non24 pattern with chaoticity. Can extend the usefulness of the model by learning with viterbi the hidden parameters from real sleep logs to make a predictive model and estimate the parameters on an individual bases (may help in differenciating different subkinds of non24 and adapt therapies accordingly, ie some may have a stronger process S than others compared to process C). ADDENDUM: meanwhile, there was a post on reddit ELI5 that more or less describe the same idea in more layman terms.

Health issues of a circadian rhythm disorder

Keep in mind that ignorance doesn't shield from detrimental health effects. But knowledge may allow to overcome.

Why do we need to sleep?

It's common to hear among insomniacs claims that one sustained a month without sleeping at all, while another didn't sleep in years. This is false. Dangerously false.

The almost mythologic search for a way tfor humans to live without sleeping to free up more time to achieve goals is not new. In fact, a lot of funding has been devoted to this goal by the military, with no significant result.

The world record for the longest sleep deprivation is held by Randy Gardner, who could stay awake for a little more than 11 days straight with the help of friends and families keeping him awake, until he had to stop for health reasons. Indeed, he was on the verge of dying, plainly. After achieving his world record, this "good sleeper" according to his own words became a very severe insomniac ("unbearable insomnia"), being unable to sleep more than a few hours in a single session for decades. His extremely prolonged sleep deprivation streak left his sleep process dysregulated for decades, making him publicly state that he regreted his world record. He is not the only one, before him, Peter Tripp did a similar experiment, which shown that sleep deprivation detrimental effects on health and cognition appear much earlier, as soon as the next day without sleep. Indeed, it's now well established by systematic reviews that sleep deprivation causes hallucinations, depersonalization, derealization and delusions.

Contrary to what was previously assumed by scientists, sleep deprivation kills not because of impairment in the cleanup of brain's generated junk, but instead of the guts' junk: indeed, sleep primary function is to clean up and relieve the oxydative stress from the guts that is produced by ingested food, the greatest source of reactive oxydative species (ROS). These ROS elements accumulate in the guts, and sleep cleans them up. In the absence of sleep (or melatonin), ROS continues to accumulate unchecked and leads up to a swift death. The brain has nothing to do with sleep deprivation induced death, it's irrelevant whether the brain sleeps (or secrete melatonin) or not, what matters is only whether the guts are cleaned up. Interestingly, the effect of antioxydants on the reduction of ROS is in parts because antioxydants hyperactivate the HPA axis.

The AASM (finally) published a position statement in 2021 affirming sleep as an essential need, just like food and water, for all humans and especially children (see also here for a vulgarized article):

> Healthy sleep is as important as proper nutrition and regular exercise for our health and well-being, and sleep is critical for performance and safety. It is the position of the AASM that sleep is essential to health, and we are urging educators, health care professionals, government agencies, and employers to prioritize the promotion of healthy sleep.

They further state four points to implement:

> * Sleep education should have a prominent place in K-12 and college health education, medical school and graduate medical education, and educational programs for other health professionals.
> * During patient visits, clinicians should ask about sleep patterns and symptoms of sleep and circadian rhythm sleep-wake disorders, and hospitals and long-term care institutions should improve sleep environments.
> * To enhance health-related outcomes, public health and workplace interventions should focus on good sleep, and habits that assist people in achieving healthy sleep should be actively supported.
> * To better understand the relevance of sleep for public health and the implications of insufficient sleep to health inequalities, more sleep and circadian research is needed.

Overview of health risks of circadian disruption and sleep deprivation

Why modify your circadian rhythm? What are the health costs of free-running, circadian disruption/misalignment or chronic sleep deprivation?

Sleep is a highly conserved functionality throughout the animal kingdom, despite the dangerosity for animals to sleep and be defenseless against predators. All species also have a "profound drive to maintain a regular sleep-wake cycle" (ie, circadian alignment), with disruptions having wide reaching detrimental effects in performance, safety and health. On a scale of urgency of importance for survival, sleep deprivation kills in a few days, whereas food in a few weeks. Hence, both sleep and circadian alignment must serve at least one or several vital purposes.

Everybody has a set period to sleep, even typical sleepers: those who have a night shift job but can't sleep a full night during the day have shift work disorder. The difference with (endogenous) circadian rhythm disorders as that the individual's circadian rhythm is different from the socially acceptable norm. Those who can't sleep as early as socially acceptable have Delayed Sleep Phase Disorder (DSPD), and those who have a sleep period that changes everyday have non-24. In all of these cases, including shift work disorder, sleeping outside of the biological night leads to detrimental health issues. Indeed, everybody can wake up at any time for some time at the expense of sleep deprivation, but doing so for too long or too regularly will invariably lead to death.

Initially, increases in health risks due to circadian misalignment and/or sleep deprivation were widely observed and studied in shift workers, and when it was observed these could not be explained by differences in socioeconomics and life style factors, further studies tried to find other factors, with circadian misalignment emerging as a major factor of health risks.

The primary issue with having a circadian rhythm disorder is obviously the huge chronic sleep deprivation that is constantly induced by the social jetlag (ie, the attempts to constraints to social expectations/requirements for work, family, hobbies, etc). Chronic sleep deprivation is a major health issue, not only for circadian rhythm disorders, as most people in modern society are sleep deprived (social jetlag), although usually not to the extent and frequency that individuals with a circadian rhythm disorder or shift workers experience. There are plenty of resources showing how harmful and dangerous sleep deprivation is, and is one of the rare disorders that can directly and swiftly cause death if too prolonged or too chronic. Circadian misalignment, also called chronodisruption, was also shown to lead to a higher mortality in general.

According to the AASM and CDC:
> Chronic inadequate sleep and untreated sleep problems, according to the study’s authors, are associated with an increased risk of cardiovascular disease, diabetes, obesity, occupational accidents, and motor vehicle collisions.
> According to the CDC and the Maternal and Child Health Bureau, 34.1 percent of children, 74.6 percent of high school students, and 32.5 percent of adults in the United States do not get enough sleep on a regular basis. As a result, one of the aims of Healthy Individuals 2030, which sets 10-year, quantifiable public health goals for the United States, is to help people get adequate sleep.

A large-scale epidemiological cohort study on the UK BIOBANK found the following factors that increase the risk of heart failure (summary here):

  • 34% higher in those reporting daytime sleepiness — in other words chronic sleep deprivation.
  • 17% higher in those with frequent insomnia,
  • 12% higher in those who had a short sleep (slept less than 7 hours daily),
  • 8% higher in later risers — note however that the authors did not control for the individuals' circadian misalignment with their job's hours, which is likely the main factor for health and not the chronotype per se. This result was barely significant when controlling for other factors.

What is impressive about this cohort observational study is that the first 3 effects were highly significant independently of other factors across 3 different models: age, gender, alcohol intake, medication, diabetes, hypertension, even the first 10 genetic principal components, etc. (see Table 1 legend). This shows these effects are very strong, the only exception being the morning lark chronotype with a very weak p-value across models and getting weaker with better controlled models, barely reaching significance on the most controlled Model 3 (p-value = 0.04, whereas for the most lenient Model 1 p-value = 0.002). Another similar study found that "poor sleep efficiency and long wake after sleep onset" increase the risk of cardiovascular diseases. Given that daytime sleepiness and brain fog are very common for people with circadian rhythm disorders, this is a serious risk to consider for this population. Another study on the same dataset but investing healthspan reduction from a variety of mortality causes that are related to sleep found similar results.

This increase in the risk of heart failure, as well as the variety of other diseases caused by sleep deprivation, is likely primarily caused by the increase in oxydative stress, in other words cellular damage, which is the primary purpose of sleep as evidenced by a landmark 2020 study. Indeed, the authors found that prolonged sleep deprivation causes death by the accumulation of reactive oxydative species, in other words a buildup of cellular damage. During sleep, there is a widespread release of strong antioxydative agents such as melatonin which cleans up and keep under control the oxydative damage and inflammation, especially in the digestive system (the primary source of oxydative damage due to food ingestion). Indeed, it is now strongly suspected the core pathway of sleep-deprivation-induced damages is via increased oxidative stress and inflammation. For instance, a study on mice found that continually phase advancing (chronic jet lag) mice by 6h/daily led to a 4.2x increased death rate (89% versus 21% in unshifted mices), which is in practice what individuals with non-24 experience when they restrict their sleep to fit into a typical schedule without entrainment therapies.

Sleep disruption was found to affect cognition and mood in the short-term in otherwise healthy adults, and on the long-term increase the risks of virtually all physiological illnesses including metabolic disorders, cardiovascular diseases, diabetes and colorectal cancer:

> In otherwise healthy adults, short-term consequences of sleep disruption include increased stress responsivity, somatic pain, reduced quality of life, emotional distress and mood disorders, and cognitive, memory, and performance deficits. For adolescents, psychosocial health, school performance, and risk-taking behaviors are impacted by sleep disruption. Behavioral problems and cognitive functioning are associated with sleep disruption in children. Long-term consequences of sleep disruption in otherwise healthy individuals include hypertension, dyslipidemia, cardiovascular disease, weight-related issues, metabolic syndrome, type 2 diabetes mellitus, and colorectal cancer. All-cause mortality is also increased in men with sleep disturbances. For those with underlying medical conditions, sleep disruption may diminish the health-related quality of life of children and adolescents and may worsen the severity of common gastrointestinal disorders. As a result of the potential consequences of sleep disruption, health care professionals should be cognizant of how managing underlying medical conditions may help to optimize sleep continuity and consider prescribing interventions that minimize sleep disruption.

A non-managed circadian rhythm disorder such as non-24 results in all 4 of the issues above, suggesting that unmanaged circadian rhythm disorders such as non-24 likely significantly increases the risk of cardiovascular complications. Indeed, the cardiometabolic system shows a clear circadian component, and the suprachiasmatic nucleus (SCN) "innervates the heart and other organs involved in hemodynamic control, such as kidney, vasculature and adrenal, via a multisynaptic pathway, probably including direct projections form the SCN to the paraventricular nucleus of the hypothalamus (PVN)" (see also here for an updated review).

Although we do not have data for non-24 specifically, there is some data about evening chronotypes, which we can infer to share similar albeit lesser chronic sleep deprivation. Evening chronotypes are 5 times more likely than morning larks and intermediate chronotypes to retire early on a disability pension. It's likely much worse for non-24.

Sleep deprivation, which is likely the root cause of most of the issues above, can either be resolved by free-running or by being entrained, the latter being very difficult if not impossible to reach for most non24 at this stage of scientific knowledge. So is free-running enough to live heathily? Unfortunately, that's unlikely.

Indeed, free-running means that there is an almost constant environmental-circadian misalignment (ie, misalignment between the individual's circadian rhythm and the day/night cycle). But the production of some hormones, such as melatonin, is dependent on the external day/night cycle. Melatonin is produced most at night, as it is inhibited by bright light. Hence, a free-running individual is likely to have reduced levels of melatonin due to unwanted inhibition by light exposure.

What are the consequences of melatonin reduction? Well, melatonin is a strong (maybe the strongest) naturally secreted anti-oxydant in the body. It is also immunomodulatory. Hence, a lack of melatonin is linked in animal models with various diseases and immunodepression.

Furthermore, mistimed eating when melatonin is at high levels in the body has been linked with metabolic dysregulations, and even directly caused diabetes in an animal model, without any other change of any other factor (TODO: add links to refs). Hence, both the lack of melatonin and the mistiming of melatonin with other factors such as food can produce detrimental effects on health, whether or not the individual is sleeping enough by free-running. (But of course these risks are far lower than what chronic sleep deprivation causes, so health-wise it's preferable to freerun rather than suffer from sleep deprivation, but it's also preferable to be entrained than to freerun, if of course an efficient treatment is possible for the individual).

Hence, supplementation of melatonin serves two purposes: to both supplement to overcome the lack of melatonin, and help with entrainment which directly reduces unwanted inhibition of melatonin by light. Would an oral supplementation of melatonin be enough to reduce the rate of diseases due to circadian misalignment and/or sleep deprivation? Likely yes, but it depends on the dosage: a study on animals shown that totally sleep-deprived animals could survive if supplemented orally (or intraveinously) with melatonin, and it's known that blind individuals have a much lower rate of cancers which is hypothesized to be because of higher melatonin levels since their melatonin is never inhibited by light, and since then melatonin was shown to indeed reduce cancer progression. Future trials are needed to know the proper dosage and how much benefits can be expected in humans, see the section on Melatonin below for more infos about the few already conducted trials (such as on sepsis and cancer).

Beyond sleep deprivation and melatonin reduction, circadian misalignment reduces our immunological response. Indeed, the circadian rhythm modulates the immunological response, especially the macrophages, as a 2021 study found. This means that our immunological system works better during our biological day, but worse at night so we are more likely to get ill or more severe diseases at night. For example, an individual with a circadian night happening in the day, as is always the case for DSPD and cyclically for non-24, means that if these individuals try to force themselves to stay awake during the objective day, they will be more prone to getting infections, contrary to typical sleepers who would be more vulnerable during the objective night since their circadian night happens during the objective night. This also means that even without sleep deprivation, sleeping in circadian misalignment increases the risks and severity of illnesses. This finding shows that individuals with circadian rhythm disorders are more prone to infections when they try to follow a typical sleep-wake schedule. The authors also found that the circadian rhythm mechanisms in the cells are much more complex than previously thought, with their study showing one of these new mechanisms, and suggesting that there is likely much more to discover on the ways the circadian rhythm controls the immunological system. Hence, it is crucial to sleep in phase with the circadian rhythm, as "the latest research has demonstrated that life habits coherent with the internal clocks should be adopted, especially during childhood, to prevent metabolic diseases." For instance, it was found that shift workers were 2 to 3 times more likely to get infected by COVID-19, with the highest odd being for those who performed irregular/rotating night shift work.

> Most immunological functions, from leukocyte numbers, activity and cytokine secretion undergo circadian variations, which might affect susceptibility to infections. The intensity of symptoms and disease severity show a 24 h pattern in many immunological and allergic diseases, including rheumatoid arthritis, bronchial asthma, atopic eczema and chronic urticaria. This is accompanied by altered sleep duration and quality, a major determinant of quality of life. Shift work and travel through time zones as well as artificial light pose new health threats by disrupting the circadian rhythms. Finally, the field of chronopharmacology uses these concepts for delivering drugs in synchrony with biological rhythms. https://doi.org/10.1186/s12948-018-0080-0

NB: chronopharmacology dates back to at least 1973 or 1971.

Furthermore, beyond general health damages, chronic sleep deprivation and circadian misalignment drastically increase the risk of transportation and work accidents, with sleepiness being the major cause of preventable accidents in all modes of transport, surpassing alcohol and drugs. Indeed, drowsy driving due to even slight small sleep deprivation, such as staying awake for 1-3h later than usual, is more dangerous than driving drunk.

The potential therapeutic benefits of circadian-based medical interventions, or at least medical interventions integrating the circadian rhythm in their protocol, are such, not only for circadian rhythm disorders but for all pathologies beyond sleep, that well established researchers are confident of the advent of "circadian medicine" as a crucial step forward in future medicine.

Historically, the "father of sleep research" Nathaniel Kleitman published his first research work on the effects of prolonged sleep deprivation in humans, in the 1920s (original paper here). This paper is worth a read, although knowledge has much progressed since then, a lot of what is known nowadays can already be glimpsed at in it, with additional historical context such as the prevalence of psychologists in sleep research being due to the lack of technological tools at the time to study sleep biologically, and also the lack of a robust definition of sleep at the time which brought some authors to even argue that plants could be sleeping.

An excellent military medical review investigated the severe health effects of subjecting military and commercial personnel to non-24 sleep-wake schedules. The same effects are likely to be expected for individuals with the non-24 disorder when subjected to a forced typical sleep-wake schedule.

While the independent but additive effects of sleep deprivation and circadian misalignment adverse effects on health, and the great health improvements that can be obtained by restoring these issues, is well documented in the scientific and medical literature, most people with circadian rhythm disorders still report feeling tired despite sleeping in alignment with their circadian phase. Beyond the possibility of bias, such as misidentifying one's circadian phase due to the lack of wide availability of unattended circadian rhythm monitoring tools such as actigraphy with circadian rhythm detection algorithms or non-invasive core body temperature monitoring, this is actually very likely caused by the almost unavoidable effect of sunlight exposure. Indeed, even though the individual with a circadian rhythm disorder has a shifted circadian night, sunlight will still affect the individual by shifting the circadian phase chaotically around due to uncontrolled exposure, melatonin inhibition, cortisol secretion and a whole lot of other bio-hormonal changes throughout the body due to sunlight exposure. Hence, there are likely only two solutions to ensure a completely healthy lifestyle for people with a circadian rhythm disorder: 1) find a therapy that allows to entrain to a typical schedule, in phase with the day-night cycle and hence aligning sunlight exposure with their circadian day, this is the approach taken by the present document; 2) live in an environment completely isolated from sunlight, but still connected to an electrical network to allow for a dynamically timed artificial light system to reproduce a day-night cycle but aligned with the individual's circadian phase, which is more easily achievable for DSPD since the timing does not change much from day to day, but would be more challenging for non-24. In both cases, the solution is to either change one's phase to align with the environment's zeitgebers, or to exchange the environment's zeitgebers for an artificial replacement that can be aligned with one's circadian phase. Hence, it appears there is no perfectly healthy solution that does not involve alignment between one's circadian phase and environmental zeitgebers, especially sunlight.
That said, the survey reported that some tiredness is still felt even after sleeping in circadian alignment without control of environmental zeitgebers, but it is highly likely this is always a significant improvement in health outcomes over sleeping in circadian misalignment.

Due to the paucity of research, and because sleep and the circadian rhythm are highly conserved vital biological processes throughout evolution and species indicating that the same results should apply to all organisms, other health issues involving circadian misalignment and sleep deprivation were included below, similarly to what was done by other studies. For example, a very close model of non-24 (endogenous disorder) is chronic jet lag disorder (exogenous disorder) as experienced by flight staff, and a similarly analogous model for DSPD (endogenous) would be night shift work disorder (exogenous), we can assume similar health issues although the cause differ for these pairs of circadian rhythm disorders.

A classification of the health risks of circadian rhythm disorders

Unfortunately, the potential health issues of free-running non-24 or DSPD sleeping according to their natural schedule remain unexplored in the medical scientific literature. But we do have indirect evidence from extrinsic circadian rhythm disorders, such as night shift disorder or jet lag disorder, which are much more common. We can define 4 different broad classes of health risks related to circadian rhythm disorders:

Sleep deprivation, usually chronic (ie, regularly experienced)
Sleep deprivation happens when not sleeping enough, and it becomes "chronic" when it happens regularly. Sleep deprivation not only has major impacts on health that majorly increases all-cause mortality, including by cardiovascular diseases and cancer (see also here), and can even lead to sudden death by cardiac arrhythmic arrest through oxidants accumulation in the body, particularly, but not only (see also here and here), for those with obstructive sleep apnea (see also here), and sleep deprivation is now a primary target of treatment for the modern comprehensive approach for cardiac diseases prevention. The influence of subqualitative sleep on cardiovascular risks is so important that the American Heart Association acknowledged the issue since its 2016 guidelines and aims to run public health campaigns on the importance of sleep for cardiac health. The increase in cardiovascular risks also affects children, and it may be dependent on predisposition to metabolic syndromes. It can also curb the benefits of diet or lifestyle changes and it impairs the evaluation of risks by causing an overly optimistic bias. Sleep loss majorly impairs the immune system. Sleep and the immune system are interacting bidirectionally: severe infections can cause sleep deprivation, and a shorter sleep impairs the immune response to infections and inflammations so that the risk of infections is increased and vaccines efficacy is decreased by directly decreasing the number of antibodies produces, since sleep promotes their production. During the COVID-19 pandemic, short sleep was assessed as a risk factor for more severe symptoms, and scientists suggested that requiring longer sleep prior and after vaccination may be an effective and inexpensive way to increase a COVID-19 vaccine's efficacy. Furthermore, again with COVID-19, each 1-hour decrease in sleep was associated with 12% higher odds of infection (see also here). Indeed, sleep deprivation can alter the DNA, RNA and proteins. An informal survey reported that half of COVID-19 long-haulers complained about new sleep disturbances. All these risks also affects children and teenagers ("general pediatric population") and lead to poor academic performance. Since sleep deprivation reduces light therapy effectiveness, a vicious cycle can appear where chronic sleep deprivation impairs the very therapies that could reduce sleep deprivation. Chronic sleep deprivation has a dose-dependent cumulative effect on cognitive impairment: sleeping 4h per night is worse than 6h per night, and the impairment will only increase day by day, even though subjectively the individual doesn't feel more sleepy than on the first day sleep deprivation started. Compared to partial sleep deprivation (eg, 4h), total sleep deprivation (0h for 3 days) results in a "disproportionately large" neurobehavioral impairment. Hence, fixing sleep deprivation by allowing the individual to sleep according to their natural sleep schedule or by napping (or to another schedule with entrainment) should be a primary target for general health improvement. Ironically, chronic sleep deprivation can cause treatment-resistance chronic insomnia as suggested by the Randy Gardner case, or even lifelong psychoses and personality changes even after recovery sleep as shown by the Peter Tripp's case (although he lost his job due to the payola scandal and not due to the lasting effects of sleep deprivation), which shows that all-nighters can only worsen the condition. Personality makes little difference, but if anything and if you believe in the psychological concept of personality, extroverts performed worse after sleep deprivation than introverts. Interestingly, it seems that partial chronic sleep deprivation requires more time for cognitive recovery than total sleep deprivation. A neuroimaging fMRI study found that sleep deprivation affects differentially various brain regions, with decreased activation in the posterior cerebellum, right fusiform gyrus and precuneus, and left lingual and inferior temporal gyri, and increased activation in the bilateral insula, claustrum and right putamen. A neuroimaging review details that the DMN in particular demonstrates significant alterations under sleep deprivation, including decreased connectivity between the anterior and posterior cingulate gyrii of the DMN and a degraded connectivity segregation with the external awareness network, which is the type and areas of connectivity that is impaired in disorders of consciousness. Chronic sleep loss impairs neurodevelopment and incurs neuronal loss, especially if from a young age, hence the necessity for accomodations of children with sleep disorders as chronic sleep deprivation can not only stunts cognitive performance, but pave the way for the development of neurological disorders. Sleep deprivation impairs auditory attention cognitive performance (see also here and here). Sleep deprivation causes more impairments and damages than just the loss of the benefits of sleeping. Three nights of consecutive, chronic sleep loss of just a few hours per day was sufficient to significantly impair mood and cognitive functions. Multitasking is impaired by sleep deprivation, as well as innovative thinking and adaptation to new situations (flexible decision making). Medical students' judgment and reaction time are also impaired by sleep deprivation. A lot of evidence is emerging that sleep deprivation, whether acute or chronic, drastically increases the risk of cardiac events, including arrythmias, atrial fibrillations and bradyarrhythmia and regardless of other traditional factors (see also here for an overview). Sleep disturbances have also been shown to increase the rate of cardiac arrests and ventricular ectopy.

Unfortunately, chronic sleep deprivation has been much less studied than acute sleep deprivation, and it remains mostly unknown the full extent of sleep-deprivation-induced damages, especially neuronal, and the potential for recovery, if any. The authors also note:

> The basic scientific findings regarding sleep loss have not yet been routinely applied in the clinic. [...] Sleep abnormalities are robustly observed in every major disorder of the brain, both neurological and psychiatric. Sleep disruption merits recognition as a key relevant factor in these disorders at all levels, from diagnosis and underlying aetiology, to therapy and prevention. More collaborative work between basic and clinical scientists in the field will be necessary to accomplish this goal. Notably, the answers to all these questions have perhaps never been more pressing considering the professional, societal and clinical implications that continue to scale in lockstep with the precipitous decline in sleep duration throughout industrialized nations.

Circadian misalignment
This is when you sleep the duration you need, but outside of your biological night. The detrimental health effects is well known and experimented worldwide every year because of daylight saving timezone (DST) changes, causing an increase of 8% in strokes, an increase of depression disorders and of car accidents due to decreased vigilance, and 25% increased rate of cardiac arrests, all due to one single hour of sleep lost after the timezone change. The most common type of circadian misalignment, social jet lag, which happens weekly in the transition between weekends to weekdays, is likely the reason why the vast majority of cardiac arrests happen on Mondays (or in other words, due to the sudden circadian misalignment and slight sleep deprivation after the week-end). Furthermore, it was observed that most adverse cardiovascular events happen between 6AM and noon, although the data is more reliable at 6AM than noon due to a possible under-reporting at night. Sleep-wake cycle is the most robust output rhythm of the circadian system, is significantly affected by neurodegenerative disorders, and may precede them by decades, and hence emerging evidence suggests that circadian disruption (ie, non24, shift work) may be a risk factor for these neurologic disorders. Circadian misalignment alone can lead to life-threatening cardiac arrhythmias (without sleep deprivation) and increases general cardiovascular risks (see also here). Circadian misalignment is associated with increased risk of metabolic syndromes such as diabetes and obesity as shown by epidemiological studies, prompting the renaming of metabolic syndromes as Circadian Syndromes, as circadian misalignment can actually directly cause diabetes in mice by causing a loss of pancreatic beta cells and by impairing the insulin-regulated glucose metabolism in hepatocytes (liver cells) (see the section about Food and metabolic syndromes for more information). Several studies have demonstrated a clear circadian regulation of the cardiometabolic system, with strong evidence suggesting circadian disruptions "may impact cardiometabolic and overall health", with for example a study finding "a 4% increased risk of ischemic stroke for each 5 years of shift work" (see also here and here). There is now a general consensus in the scientific medical community that circadian misalignment is a major risk factor for metabolic disorders, independently from sleep deprivation (see here, here, here). Furthermore, circadian misalignment is the major cause of accidents by far, as "sleepiness surpasses alcohol and drugs as the greatest identifiable and preventable cause of accidents in all modes of transport [...] industrial accidents associated with night work are common, perhaps the most famous being Chernobyl, Three Mile Island, and Bhopal." The IARC, the highest authority on defining probable causes of cancer, recognizes that "circadian disorganization" in night shift work is a "probable carcinogen in humans" (group 2A) (see also here). Circadian misalignment, in particular with aberrant light exposure, can also cause major cognitive, learning and mood impairment. Circadian misalignment affects wounds healing, with wounds happening during the biological night healing more slowly than those during the day. Circadian misalignment in women is associated with disturbances in menstrual function, particularly menstrual irregularity and longer menstrual cycles and may increase the risk of breast cancer. Circadian misalignment is not only observed in non-24 and DSPD but also night shift work disorder and social jet lag. The reduction of light exposure can worsen mood since bright light exposure has antidepressant effects. Sleep apnea is known to be a major cause of cardiovascular death, but it interestingly shows a marked circadian rhythm, with more deaths by sleep apnea during the biological night, whereas for other cardiovascular deaths it's rather during the day. Circadian misalignment also reduces the immunologic system and hence may increase the risk of infections such as COVID-19 and its severity. It was further found that shift workers were 2 to 3 times more likely to get infected by COVID-19, with the highest odd being for those who performed irregular/rotating night shift work. Circadian misalignment due to aberrant light exposure or melatonin inhibition is associated with increased breast cancer rates, and inversely timezones where melatonin is less inhibited by light such as the Arctic zones have lower rates of breast cancers. Circadian misalignment (chronodisruption) caused by chronic melatonin inhibition/deficiency due to urban artificial lighting increases the risk of cancers. Breast cancer survivors have a shorter disease free interval in metastatic breast cancer if bedtimes are misaligned with their circadian rhythm according to a meta-analysis. The disruption of cellular-level functional clocks has been evidenced by biologist as a pathway that can cause cancers, and in practice a 2020 systematic review found moderate grade evidence that shift work and long work hours increase the risk of (breast) cancer and strokes. Circadian dysregulation can cause metabolic disorders including non-alcoholic fatty liver disease (NAFLD - the most common liver disease worldwide) (see also here), and circadian realignment may improve NAFLD. Circadian misalignment is associated with digestive pathologies such as constipation and irritable bowel syndrome. The cognitive impairment induced by circadian misalignment can be objectively observed neurologically with a reduced default mode network's functional connectivity in night owls. Circadian misalignment can also affect proper administration of medication (chronopharmacology), since depending on the time of administration, a drug can have more potent and beneficial effect, whereas at the wrong time (usually during the circadian night), a drug may have more adverse effects (see also this talk). Neurologically, chronic circadian disruption impairs temporal lobe's and especially hippocampal neurogenesis (see also here), which explains the wide range of cognitive funcitons impairements observed in chronic jet lag and circadian rhythm disorders, such as decreased performance, memory, reaction time and depressive symptoms, with an estimated 6.5 years of cognitive decline in long-time shift workers compared to age-related controls, which persists for 5 years after conclusion of shift work. Ample evidence from animal studies strongly suggest that circadian rhythm disorder underlies several psychological disorders, such as major depression, anxiety and schizophrenia. Circadian disruption is common (20%) among survivors of traumatic brain injuries such as car accidents, and is a primary target of treatment as it can "precede, exacerbate or perpetuate many of the other sequelae". A study on mice demonstrated premature aging and prediabetic profiles in circadian misaligned mices (see also here). The circadian rhythm and sleep regulate the blood brain barrier notably by increasing endocytosis and re-equilibrium of metabolites, which may be relevant for brain cleanup and sleep inertia. Bright light exposure during the circadian night can also cause decreased insulin secretion and overall failure of pancreatic islet cells as shown in a rats study, which suggests that bright light exposure in circadian misalignment may increase the risk of metabolic disorders such as diabetes. A rigorous forced desynchrony protocol demonstrated in humans that acute circadian misalignment (here a 12h phase reversal) per se increases postprandial glucose and insulin responses, suggesting increased insulinoresistance, as well as increased blood pressure and decreased sleep efficiency and leptin levels (hunger). In old mice, chronic jet lag drastically increased mortality, especially for mice who were phase advanced by 6h, with a 53% mortality rate, whereas 32% for a 6h phase delay and 17% for unshifted mice, and interestingly it was not caused by chronic stress since daily fecal corticosterone levels were unchanged. Circadian alignment of drug therapies, ie pharmaceutical chronotherapy, is also a "plausible strategy" to optimize the therapeutic effects while reducing adverse effects of medication for gut infections. Circadian misalignment has been demonstrated to hamper development in plants and longevity in insects, especially when the environmental cycle is shorter or longer than the range the individual can sustain (ie, non-24 cycles forced onto typical sleepers). Forcing individuals, even when highly trained such as military personnel of NASA and submarines, to follow a non-24 sleep-wake cycle, cause a wide array of cognitive, physical and mood impairments. A 2019 study found thatsleep deprivation or a non-24-h working schedule independently lead to extensive alterations in physiology and behavior, including changes in insulin levels, significantly delayed reaction time and microbiota bacteria composition and concentration. Evidence is emerging in the 2020s that circadian and sleep disturbances are harbingers of neurodegenerative diseases, with sleep disruptions predicting beta amyloid accumulation and hence Alzheimer disease.

Hormonal suppression (especially melatonin) by unwanted/uncontrolled light exposure
Given the wide range of protective actions of melatonin on all cells in the body, unwanted inhibition of endogenous melatonin by bright light exposure during the biological evening and night is a serious health issue. This can happen without circadian misalignment because of artificial lighting, as it often happens for night shift work. There is some evidence that the lack of light exposure and reduced melatonin secretion may be the cause of the increase in breast cancer due to circadian misalignment. It's difficult to discriminate what is due to melatonin inhibition or what is due to circadian misalignment as this field of medical research is still in its infancy, so apriori the health risks associated with circadian misalignment should be considered to overlap those of hormonal, especially melatonin, suppression.

Cognitive impairments, social isolation and accidents
Sleep deprivation impairs the ability to suppress unwanted thoughts especially when presented with reminders and hence to multitask. Sleep deprivation largely impairs attention, but not reasoning abilities. Drowsy driving is responsible for a million crashes and 500 000 injuries each year in the USA, with "sleepiness surpassing alcohol and drugs as the greatest identifiable and preventable cause of accidents in all modes of transport". Indeed, driving with even the slightest sleep deprivation is akin to driving drunk with alcohol: even slight small sleep deprivation, such as staying awake for 1-3h later than usual, leads to more cognitive disruptions than 0.05% of blood-alcohol level, which is considered a "drunk state" in most European countries (see also here), hence "a drowsy driver may be as dangerous as a drunk driver". A review found an almost linear increase in accident risk in shift workers beyond 8h of work. There is a 15x increase in driving accident risk for truckers after more than 13h awake compared to the first hour. Cognitive performance and memory, including short-term and long-term memory formation and recall, are greatly diminished when occurring out of phase with the natural circadian rhythm, and can even manifest as other cognitive deficits. Catastrophic industrial accidents associated with night work are common, including Chernobyl and the space shuttle Challenger catastrophic accidents were mostly attributed to poor judgment consecutive of chronic sleep deprivation induced by extended night shiftwork (see also this video). Crew accidents due to sleep deprivation is also common in aviation and military and responsible for hundreds of millions of material loss (see also here, here). The Navy started in 2021 to acknowledge sleep deprivation as a major issue and pledged to try to find new solutions to better manage it. Sleeping allows to find innovative mathematical solutions and patterns compared to individuals who do not sleep during the time gap between problem presentation and restitution (see here for a layman presentation). The excellent 1998 review "Black times: temporal determinants of transport safety" by Folkard "confirmed the presence of a clear circadian (ca 24 hour) rhythm in road accident risk with a major peak at ca 03:00" not due to drivers falling asleep at the wheel, but rather because of lowered performance capabilities due to the circadian misalignment.

Sleep fragmentation
Sleep fragmentation, which can be caused by melatonin deficiency or sleep disturbances such as noise and unwanted exposure to bright light, can cause various impairments. Sleep fragmentation impairs motor skills learning. Sleep fragmentation is associated with more periods of unconscious wakefulness, also called cortical arousal, which may increase the risk of premature death and cardiometabolic diseases. Sleep fragmentation is one of the primary factors increasing the likelihood of delirium in hospitals' intensive care units' (ICU) patients, along with aberrant bright light exposure (see also here and here), with some scientists even suggesting that the expression of delirium is very similar to sleep deprivation. Sleep disturbances can have a very strong detrimental effect on sleep efficiency, sleep quality and the circadian rhythm especially when there is unwanted exposure to bright light, that can carry over several days after the disturbances happened.

Social inadaptation
Non-24 inherently disrupts the social network around the individual, which has a direct consequence on both socioprofessional and health. Non-24 was found to be a worsening comorbid condition for blind people compared with a control group of blind people without non-24. For individuals with autism, the often comorbid sleep disorder further impairs the employability. An informal survey of individuals with non-24 suggest a very high rate of unemployment, with a vast majority of respondents feeling that non-24 is fully or partly to blame. A lifetime longitudinal study using biomarkers found that social isolation, which is worsened by sleep deprivation and non-24 (circadian freerunning) independently, was associated with vastly elevated risks of health conditions such as inflammation at all stages of life, and even exceed the clinical risk factors of old age. This association between social isolation and survival is well established in both humans and other social animals, as highlighted by a 2020 Science review.

Note that non24 likely has worse health prospects than DSPD, due to the increased frequency and magnitude of circadian misalignment and potential of chronic sleep deprivation.

TODO: add content from https://www.reddit.com/r/DSPD/comments/h8och2/i_sleep_between_9am_and_16pm_every_day_i_this/fuw6h3k and https://www.reddit.com/r/N24/comments/hqz5ix/does_n24_have_long_term_effects_on_health/fy25ppz

For more detailed information on the detrimental health effects of sleep deprivation and circadian misalignment, these two great reviews are recommended:
> Foster RG. Sleep, circadian rhythms and health. Interface Focus. 2020 Jun 6;10(3):20190098. doi: 10.1098/rsfs.2019.0098. Epub 2020 Apr 17. PMID: 32382406; PMCID: PMC7202392. https://doi.org/10.1098/rsfs.2019.0098
> Baron KG, Reid KJ. Circadian misalignment and health. Int Rev Psychiatry. 2014;26(2):139-154. doi:10.3109/09540261.2014.911149 . URL: https://pubmed.ncbi.nlm.nih.gov/24892891/

Depression, anhedonia, running thoughts and social isolation

Although a lesser known fact, depression, anhedonia (lack of pleasure and will, feelings of being empty) and social isolation are normal part of circadian rhythm disorders, and especially in non24 where they appear cyclically depending on the current phase (nightwalking) and season (winter is worse).

> In anhedonia, both wanting and liking are muted.
Source of the quote.

Although prevalence data is sparse for sighted non-24, depression appears to be a common comorbidity similarly to other sleep disorders, as this 2005 study of 57 sighted non-24 participants cohort found that 34% of them also suffered from depression after the onset of non-24. For DSPD, there is ample evidence that depression is the most common comorbid disorder.

Both a single night of sleep deprivation and lack of bright light exposure or aberrant exposure in the biological night (see also here) independently cause depressive symptoms such as anxiety and moodiness in non depressive, healthy individuals, with the combination likely causing even greater distress. There is a two-fold risk of developing depression when chronically sleep deprived. Severely sleep deprived individuals "manifest an anxious, depressed, negative cognitive-affective set". Plenty of evidence from animal studies strongly suggest that chronic circadian disruption likely cause depressive symptoms such as anhedonia and memory impairements as well as anxiety and psychological disorders such as major depression, regardless of sleep deprivation. A large-scale study using the UK BioBank dataset found a causal link between the genetical chronotype and circadian misalignment on depressive and generalized anxiety disorder symptoms, explaining why morning owls on a day job have higher well-being, whereas intermediate chronotypes and night owls who constantly defy their circadian rhythm (body) clock suffer from lower well-being and increased anxiety and depression, in line with previous studies (see here and here). Sleep disorders during childhood are robustly associated with a modest increase in the risk of early onset of major mental mood and psychotic disorders in teenagers and young adults. Sleep deprivation has been linked to an increased risk of suicide in a systematic review. Although some psychologists claim (REM) sleep deprivation may treat depression, most studies were not properly controlled, and a 2021 systematic review only found 9 controlled studies to review, from which it appears that sleep deprivation only has a temporary and often non-significant effect on depression, but it can increase by 4-fold the risk of transition to mania. Since sleep deprivation and circadian misalignment independently cause depressive symptoms, it has been established that on the first day of the work week, the day with the most social jet lag due to the transition from weekend to work days, is the most likely time for suicidal posts on Reddit, which interestingly enough mirrors the increase of cardiac arrest, both pointing to circadian misalignment as the likely main cause.

In fact, there is a study by Soomi Lee et al that precisely modeled with mathematical equations how mood and cognitive impairments are related to chronic sleep deprivation:

> Daily negative affect increased and positive affect decreased in curvilinear fashion as the number of consecutive sleep loss increased. For example, daily negative affect increased (linear), but the rate of increase decelerated as the number of consecutive sleep loss increased (quadratic). Results were consistent for the number and severity of physical symptoms. For negative affect and the severity of physical symptoms, cubic effect was also significant such that the rate of increase accelerated again in the days most distal to baseline (no sleep loss).

Circadian misalignment also appears to cause depressive-like behaviors, but not in all individuals. In male mice, chronic circadian phase advance induced depressive-like responses, but not anhedonia, and suppressed neuroimmune activation. Interestingly, the finding that circadian misalignment appeared to not cause anhedonia would suggest that anhedonia is rather a consequence of sleep deprivation than circadian misalignment, although more studies are required. Another study on a small number of human participants found that the effect of a circadian misalignment on mood was relatively benign, with most of the mood changes being contributed to by sleep loss. However, given the cyclical nature of depression and disturbed sleep-wake patterns and physiological rhythms, there are strong suspicions that dysfunctions in the circadian rhythm may underlie depression (see also here), and indeed a recent systematic review supports this. This strongly suggests that targeting circadian rhythm may improve depressive symptoms, such as with agomelatine (a melatonin agonist) or bright light therapy (see also here), with light therapy being effective much faster than antidepressant drugs and much fewer side effects especially of suicide.

Fatigue is also a hallmark of circadian rhythm disorders such as DSPD, but not excessive daytime sleepiness. Fatigue is defined as "tiredness and lack of energy without increased sleep propensity", and although it is a common complaint, it is underestimated both in research and clinical work. Sleepiness is defined as "a subjective difficulty in maintaining wakefulness and an increased ease of falling asleep". About 10% of the general population is affected by moderate or severe excessive daytime sleepiness, and is associated with socioeconomics (work, lifestyle, etc.), climate conditions (high temperatures) and is a cardinal symptom of sleep disorders, but not of circadian rhythm disorders, which are rather affected by insomnia and fatigue, and with DSPD individuals for example spending less time in bed, a likely consequence of insomnia and fatigue.

In addition, sleep deprivation impairs the ability to suppress unwanted thoughts (ie, increases racing thoughts, also called cognitive hyperactivity) especially when presented with reminders (see also here and here), which can partially explain the higher propensity of sleep deprived individuals to anxiety. Indeed, neurologically, sleep deprivation impairs sensory gating and reduces P50 suppression, in other words sleep deprivation reduces inhibition of irrelevant information, which leads to racing thoughts and human errors and accidents. Furthermore, a CBT-i study by Harvey et al shown that instructing the insomniac patients to suppress their thoughts before sleep (more technically called "suppression of presleep cognitive activity") led to a worsening of the sleep issues, with an increased sleep latency and reduced sleep duration. Hence, having racing thoughts before sleep is in fact a consequence of sleep deprivation, rather than the cause, and treating by suppression the running thoughts does not help and even worsen the insomnia. Actually, scientists even think sleep deprivation may be the root cause explaining the dissociative symptoms as observed in schizophrenia and schizotypical disorders as well as PTSD, although there is no link with non-24 for the moment, it just further supports that running thoughts are a common symptoms of all diseases causing chronic sleep deprivation. Another study found both running thoughts and dissociative symptoms increased after sleep deprivation. A 2021 systematic review further found that although CBT-I does improve insomnia complaints and sleep metrics, and that it also reduces the occurrences of worries, one type of repetitive negative thoughts (RNTs), this reduction in RNTs was not correlated with reductions in depression or anxiety, so that CBT-I dowas not found to be an effective mean to reduce RNTs, but is more indicated for insomnia. This hence shed some doubts about whether RNTs reare of any importance to treat sleep disorders, since CBT-I is effective without a significant effect on RNTs.

Furthermore, a study demonstrated that sleep deprivation and sleep disorders impair interoception, which is the ability to feel one's own internal body signals including the ability to feel sleep pressure, with impaired introception being associated with major depression according to a 2019 systematic review.

Practical tip: signs of anhedonia include lack of appetite, lack of motivation and lack of pleasure. If this is caused by sleep deprivation or circadian disruption, anhedonia should resorb in the following days. Otherwise, if this persists, this may be a sign of major depression and should be investigated with a clinician.

Not only does sleep deprivation cause depressive symptoms, sleep deprivation is also literally and objectively painful, with modest changes in sleep quality tremendously increasing pain experience. Indeed, this study, focusing on the neurological basis of sleep deprivation magnified pain, found that even small sleep disruptions can cause major increases in pain the subsequent day while also decreasing reactivity and quality of decision-making:

> Sleep loss increases the experience of pain. [...] Here, we demonstrate that acute sleep deprivation amplifies pain reactivity within human (male and female) primary somatosensory cortex yet blunts pain reactivity in higher-order valuation and decision-making regions of the striatum and insula cortex. Consistent with this altered neural signature, we further show that sleep deprivation expands the temperature range for classifying a stimulus as painful, specifically through a lowering of pain thresholds. Moreover, the degree of amplified reactivity within somatosensory cortex following sleep deprivation significantly predicts this expansion of experienced pain across individuals. Finally, outside of the laboratory setting, we similarly show that even modest nightly changes in sleep quality (increases and decreases) within an individual determine consequential day-to-day changes in experienced pain (decreases and increases, respectively). Together, these data provide a novel framework underlying the impact of sleep loss on pain and, furthermore, establish that the association between sleep and pain is expressed in a night-to-day, bidirectional relationship within a sample of the general population. More broadly, our findings highlight sleep as a novel therapeutic target for pain management within and outside the clinic, including circumstances where sleep is frequently short yet pain is abundant (e.g., the hospital setting).

Furthermore, another study demonstrated that pain sensitivity is mostly (~80%) modulated by the circadian rhythm, with only a minor (~20%) contribution of sleep pressure.

This is on top of the objective worsening of comorbid conditions and of general health by sleep deprivation, so that sleep deprivation increases pain both objectively and subjectively. And indeed there is an interaction, as a review found that not only sleep deprivation does increase pain perception (hyperalgesia), it also decreases the effect of pain medication such as opioid and serotoninergic analgesics:

> Chronically painful conditions are frequently associated with sleep disturbances, i.e. changes in sleep continuity and sleep architecture as well as increased sleepiness during daytime. A new hypothesis, which has attracted more and more attention, is that disturbances of sleep cause or modulate acute and chronic pain. Since it is well-known that pain disturbs sleep the relationship between the two has since recently been seen as reciprocal. To fathom the causal direction from sleep to pain we have reviewed experimental human and animal studies on the effects of sleep deprivation on pain processing. According to the majority of the studies, sleep deprivation produces hyperalgesic changes. Furthermore, sleep deprivation can interfere with analgesic treatments involving opioidergic and serotoninergic mechanisms of action. The still existing inconsistency of the human data and the exclusive focus on REM sleep deprivation in animals so far do not allow us to draw firm conclusions as to whether the hyperalgesic effects are due to the deprivation of specific sleep stages or whether they result from a generalized disruption of sleep continuity.

Sleep deprivation also causes social isolation, as individuals who are sleep deprived feel much less comfortable with other people being physically close to them. Chronic insomnia also decreases the ability to feel empathic with others emotions such as sadness and fear and also happiness. Combined with the sleep deprivation induced anhedonia, this results in a decreased engagement and enjoyability of interpersonal relationships, as was already well established for insomniac patients. To its extreme, sleep deprivation also causes paranoia, which drastically impairs communication. Paranoia being likely experienced at least a few times during the lifespan of any individual with untreated non-24. These neurocognitivo-social isolating processes compound with the mistimed wakefulness schedules of non24 individuals which further worsen the issue by making it very difficult to plan and attend to social appointments and events. This effect of sleep deprivation on social isolation seems unidirectional, as social loneliness does not impair sleep, hence treating the social isolation is unlikely to improve sleep.

Sleep deprivation is an underappreciated strong factor of interpersonal conflicts: frequency of interpersonal conflicts in romantic relationships increases with sleep deprivation, and are more often resolved when both partners are well rested, and these effects are not explained by stress, anxiety, depression, lack of relationship satisfaction, or by partners being the cause of poor sleep. According to David Randall's book Dreamland about the "no sleep" culture in military and military studies done on sleep deprivation, which may be inaccurate but there is no other sources to check given the type of sources used, air force pilots had a different vocal pattern when sleep deprived, being often unable to speak loudly to be understood and with a monotone speech that lacked emphasis on key words. Another military study was conducted on the cooperation of military duo's ability to planify and communicate together after sleep deprivation, which shown they most often were unable to succeed, whereas their sleeping counterparts could, which shows that sleep deprivation also affects professional interpersonal communications and collaboration even under highly trained and rigorous environments.

Furthermore, sleep deprivation largely impairs attention, but not reasoning abilities. Sleep deprivation also makes the patient "forget their life" as it impairs autobiographical memories.

Especially during the nightwalking phase, when completely out of phase with the day-night cycle, and the winter season, with longer nights and shorter days, the combination of sleep deprivation and lack of exposure to bright light is a perfect recipe for anhedonia and social isolation. Combined with the necessity to live on eggshells, the individual can justifiably feel like they are encaged.

The author also noticed that these cognitive and mood disruptions can go both ways in practice: often the effect of sleep deprivation is mood depressive, but sometimes there are maniac-like phases, hence chronic sleep deprivation can cause bipolar-like episodes, which may explain why it was hypothesized, but since then refuted, that non-24 was associated with the bipolar disorder.

These effects of sleep deprivation on cognition are in many respects similar to the cognitively disruptive effects of alcohol, with one sleepless night being analogous to 0.10% of blood-alcohol level, much beyond the drunk driving threshold in most European countries, with similar impairments in judgment and other cognitive functions:

> Staying awake for just 17 to 19 hours straight impacts performance more than a blood-alcohol level of .05 percent (the level considered legally drunk in most western European countries). This level of impairment slows an individual's reaction time by about 50 percent compared to someone who is well rested. Twenty-four hours of continuous wakefulness induces impairments in performance equivalent to those induced by a blood-alcohol level of 0.10 percent, beyond the legal limit for alcohol intoxication in the United States. Source (see also here for a similar statement from the Belgian police)

It is hence not surprising that sleepiness is the major cause of preventable accidents by far in all modes of transport, surpassing alcohol and drugs, being responsible for 10-20% of city car accidents and 20-30% of morotway car accidents according to Belgian police, being the first cause of motorway car accidents in several european countries since years including France (see also here and here). A driver who slept 5h on several consecutive nights is 3 to 6 times more likely to be involved in a car accidents compared to a driver who slept 8h. Hence, "a drowsy driver may be as dangerous as a drunk driver". A review found an almost linear increase in accident risk in shift workers beyond 8h of work.
Hence, a circadian rhythm disorder also limits the transportation possibilities, which further increases isolation and impairs the possibilities of getting hired, as most work positions require independent car transportation.

There is strong evidence sleep issues cause anxiety, and modest evidence circadian rhythm disturbances can cause anxiety.

Mood and cognitive dysregulations are not just limited to practical abilities, as one night of sleep deprivation drastically impairs innovative thinking and flexible decision making, in other words, sleep deprivation impairs the ability to "think outside the box" to find new solutions and adapt to new situations (see here for a layman presentation). Likewise, sleep deprivation impairs multitastking ability, in other words, when sleep deprived, there is a tendency to hyperfocalize on one task.

Often, this set of cognitive and mood disturbances are expressed by the patients as "feeling like a zombie". It's crucial not only for the clinical practitioners to recognize these signs associated or caused by sleep deprivation, but also to teach the patient how to recognize them too, in order for them to avoid risky situations (such as driving while sleep deprived, or taking important decisions - delaying to a later time after recovering some sleep is a sound strategy).

More precisely, this systematic review provides prevalence figures of the cognitive impairements due to sleep deprivation:

  • Hallucinations (visual, auditory and somatosensory) for nearly all participants in all studies, appearing after 24h to 48h of sleep deprivation.
  • Mood changes (including anxiety and irritability) for 76% of the participants in 16 studies, usually appearing under 24h (very fast!). These are followed by "depression, apathy alternating with euphoria, anger, and hostility within 45 h without sleep".
  • Disordered (running) thoughts, confusion, and bizarre behavior (14 studies, 66%), usually appearing on the 2nd day of sleep deprivation, and get to their worst from the 5th day on.
  • Dissociation including derealization and depersonalization (11 studies, 52%), usually appearing after 24-48h.
  • Delusions (9 studies, 42%), usually appearing on the 3rd day of sleep deprivation, and get to their worst from the 5th day on.
  • Distortions in the sense of time (4 studies, 20%).

These impairments are gradual, so that paying attention to these symptoms allows to know when it's crucial to get some sleep asap: "Initially, participants tend to question the veracity of the deceptive perceptual phenomena. With the passing of time and persistence of symptoms, there is a gradual acceptance that these events might be real, which precedes the appearance of full-blown delusional explanations."
Furthermore, for some participants, it took days up to weeks for the cognitive impairments to fully resolve, although usually sleeping at least 50% of the total time spent awake was sufficient.

Indeed, recognizing and remedying to sleep deprivations may allow to better manage, or even prevent, co-morbid psychiatric disorders: "given that ‘depression is announced by sleep disturbances’ (van Moffaert, 1994, p. 9), future research should explore whether an early intervention targeting sleep disturbance may prevent the development of depression (Ford & Kamerow, 1989). [...] In addition, future research should explore the utility of advising patients who have had a previous depressive episode to review relapse prevention strategies or to make an appointment with their clinician whenever they experience an ongoing sleep disturbance. In other words, relapse rates may be reduced if patients are taught to view insomnia as a signal to initiate preventative action."

Although the above review on sleep deprivation signs was done on acute, continuous sleep deprivation, the same is likely applicable to chronic sleep deprivation, but it depends on the amount of daily sleep deprivation. Indeed, a study comparing 0h, 4h, 6h and 8h of sleep "doses" demonstrated that the "neurobiological impairment" is proportional to the amount of daily sleep deprivation, so that the shorter the nights, the more frequent the impairments.

Despite a previously long held belief, morning larks do not display higher morality standards than later chronotypes such as night owls. Rather, studies have shown (see a summary here) that individuals are more susceptible to cheating when performing their tasks during their circadian night, in other words when they are in circadian misalignment. Indeed, morning larks were more susceptible to cheat during the objective night, whereas night owls were more susceptible to cheat in the early morning.

All these cognitive impairments are supported by neuroimaging studies, which found impairments in the DMN connectivity both within and in its segregation with the external awareness network, as well as impairments in the functional connectivity of the amygdata (emotions), the thalamus (memories), the dorsolateral prefrontal cortex and anterior cingulate cortex (consciousness and incentives processing), with conversely an increase of connectivity between the amygdala with the posterior cingulate cortex and the precuneus, denoting an increase in emotionally-directed behaviors. The authors also note that not all brain functions changes are maladaptive, some preserve task performance and are hence clearly compensatory and adaptive, but the extent and limitations of these adaptive strategies remain poorly characterized (ie, they are likely often overestimated by those experiencing or professing chronic sleep deprivation).

There is fortunately no quick and easy solution, as nothing can replace sleep, but some strategies may specifically help improve cognitive and mood disturbance in complement to sleep recovery:

How to reduce the health issues of sleep deprivation and circadian misalignment

WIP: TODO: add references

Obviously, an ideal scenario to reduce the health issues due to sleep deprivation and circadian misalignment would be to eliminate them in the first place through robust entrainment. Indeed, some authors suggest it is sensible to treat the circadian misalignment and chronic sleep deprivation potentially underlying some cardiometabolic diseases using zeitgebers therapies such as light therapy and melatonin.

Unfortunately, that is not always possible, as the therapies do not work for everyone or they are under conditions that prevent them from optimally using therapies (eg, they must use an alarm clock to get to work). What can be done then? Here are a few practical tips:

  • As advised for night shift work disorder, who experience similar issues and risk factors, the most adequate strategy to reduce the risks involves avoiding multifactorial causes of sleep disruptions including the "suppression of melatonin secretion by ALAN [bright light in the biological evening], sleep deprivation, and circadian disruption".
  • Always respect your circadian rhythm as much as possible. This means to strive to sleep during your circadian night, and put aside other matters. This in effect put your sleep first, as anyone should do.
  • Avoid at all cost activities, especially those requiring a high focus and are prone to accidents (eg, car driving), during your circadian night. If you really need to move during your biological night, prefer to ask someone else to drive or take public transportation.
  • Take medication during your biological day, avoid during biological night as they will be less effective and have more side effects (see chronopharmocology). Similarly, injuries and wounds heal better during the biological day than during the biological night.
  • Avoid eating during your circadian night, as melatonin will inhibit insulin which itself will inhibit your body's capacity to process carbohydrates and so you will be in hyperglycemia all night, which is highly suspected to cause metabolic disorders such as diabetes and obesity and fatty liver disease.
  • If at wake up you feel your heart pounding in your chest or head, this is tachycardia. If it happens when you get out of bed, this may be postural orthostatic tachycardia. In any case, this is a sign you are at increased risk of cardiovascular issues, so try to sleep more or take a nap as soon as you can. If not possible, avoid activities or situations that can further cause cardiovascular issues, such as exercise or fast movements (and some temperature settings?).
  • Supplement in vitamins to reduce deficiencies due to lack of exposure to sunlight and potential deficiencies due to chronic sleep deprivation such as vitamin D and vitamin B12. In the future, high doses of melatonin may be an avenue to drastically reduce the detrimental health issues of sleep deprivation due to its strong antioxydative properties, but it remains unclear what dose in humans would allow to reach the required extracellular concentration of melatonin to benefit from these antioxydative properties.

There are also a few very promising therapeutic avenues that are still experimental and thus not yet available for patients, as we do not even know the adequate dosage to achieve these effects on humans, but still the research is very promising:

Should all individuals with non-24 get entrained to be more healthy, or is freerunning acceptable? Well, freerunning for sure is much better than restricted sleep, as at least the sleep deprivation - the most acute health impairment - is reduced. However, even under freerunning, there will always be some degree of sleep deprivation and circadian misalignment, as it is impossible to completely control all environment factors such as unwanted sunlight exposure during the biological evening when nightwalking, or ambient temperature and ambient noise, all of which contribute to impair sleep. Hence, entrained non-24 likely is a more healthy state than freerunning non-24.

Interestingly, the periodicity of freerunning and restricted non-24 is also reflected in the periodicity of immunodepression, with individuals with non24 falling more often ill during their nightwalking phase than when they are in phase with the day-night cycle. Hence, being often but periodically ill, or regularly feeling daytime drowsiness, may be strong signs of chronic sleep deprivation.

How to monitor my entrainment progress?

One of the most difficult things for someone with a non-24 circadian rhythm disorder is to find when their biological night is, as it changes all the time and with high variability and sometimes chaotically.

To see if your circadian rhythm is stabilizing to a constant time, or just to find where your biological night is when freerunning, it is possible to use your sleep diary. But do not monitor your bedtime nor your falling asleep time (sleep onset), as they are both unreliable markers of the circadian rhythm and the DLMO. In other words, you can sleep more or less late with more or less variation while your circadian rhythm stays stabilized - the opposite is true, your bedtime can be regular but your circadian rhythm can still freeruns.

A much better measure is your wake up time (sleep offset), which is correlated with the DLMOff and is hence a much better marker of the circadian rhythm. This was demonstrated on both typical sleepers and DSPD. In fact, the wake up time is tightly coupled with the core body temperature, which is the core signalling pathway of circadian rhythm synchronizations throughout the body (see the Zeitgebers section for more infos). In other words, if your wake up time stays constant, this is a strong indication that you are entrained.

But the wake up time can sometimes be variable due to the random occurrence of "weird insomnia" (likely biphasic sleep) or external disturbances. An even better circadian rhythm marker is the midpoint of the sleep period(s) (see also here and here). This was also demonstrated in both typical sleepers and DSPD.
Let's say you usually sleep at 1.30am and wake up at 9.30am. The midpoint is the sleep onset time + average of (sleep onset/falling asleep - sleep offset/wake up) divided by 2 = 1.5+((9.5-1.5)/2) = 5.5 = 5.30am .
Let's now say that the next night, you experience a biphasic sleep, so you sleep earlier at midnight but wake up at 5am and then sleep again between 9am and 11am. If we look only at the wake up time, it looks like you woke up 1h30 later than usual, but if we calculate the midpoint, we get: 0 + (11-0)/2 = 5.30 = 5.30am . This is exactly the same midpoint time as usual, so in fact even if the sleep was biphasic, the circadian rhythm did not change, and you will likely be able to sleep at the same time as usual on the next night.

There are also a few other signs you may indicate that you are sleeping under your biological night:

  • if your sleep onset latency is reduced, ie, when you get to bed, you fall asleep faster than usual. In my case, I used to never take less than 30 min to fall asleep, usually it took 1 or more hours, but after entrainment it consistently took me less than 15 min, and usually under 5-10 min, to fall asleep from getting to sleep.
    • Tip: If it takes longer to fall asleep, either you are not sleeping in your biological night, or you missed the ultradian cycle window and need to wait for the next one (see below the ultradian cycle section). Accumulated sleep deprivation (eg, pulling an all-nighter) can also make it more difficult to sleep because of dopamine build-up.
  • if you wake up on your own without an alarm or disturbance but didn't sleep long, then it's likely you are not sleeping in your biological night, but are rather doing a nap. Duration, along with the wake up time, is a very good indicator of sleeping inside one's own biological night.
> Results: The panel agreed that, for healthy individuals with normal sleep, the appropriate sleep duration for newborns is between 14 and 17 hours, infants between 12 and 15 hours, toddlers between 11 and 14 hours, preschoolers between 10 and 13 hours, and school-aged children between 9 and 11 hours. For teenagers, 8 to 10 hours was considered appropriate, 7 to 9 hours for young adults and adults, and 7 to 8 hours of sleep for older adults.
> Conclusions: Sufficient sleep duration requirements vary across the lifespan and from person to person. The recommendations reported here represent guidelines for healthy individuals and those not suffering from a sleep disorder. Sleep durations outside the recommended range may be appropriate, but deviating far from the normal range is rare. Individuals who habitually sleep outside the normal range may be exhibiting signs or symptoms of serious health problems or, if done volitionally, may be compromising their health and well-being.)
Source: https://pubmed.ncbi.nlm.nih.gov/29073412/
  • However, note that sleep needs for newborns, infants and children are systematically over-estimated, and that most studies used only parental self reported measures (see here and here).
  • if your hunger and stools are more or less at the same time every day, that's a good sign your digestive system adapted to the entrainment, since these metabolic cues are linked to the circadian rhythm and directly to the suprachiasmatic nucleus. Since the digestive system is responsible for most melatonin secretion, this is certainly an important factor.
    • Furthermore, if you are entrained, you should not feel hungry late into the night. If you feel hungry so late, it's a sign your digestive system at least is not entrained, since the digestive system also follows a circadian rhythm (but its own) which should "sleep" too at night.
  • if you experience brain fog (aka performance reduction or sleep inertia), try to use light therapy, particularly blue light which is more effective at reducing brain fog and increasing vigilance. Bright light in the morning is well known to not only inhibits melatonin but also have antidepressant properties. In practice, this should clear up the brain fog under 30min to 1h of blue light therapy, as brain fog is likely due to melatonin residues in the blood stream, which can be inhibited most effectively by blue light. If the brain fog sustains all day long, then it may be a sign of circadian misalignment (ie, sleeping all your needed hours but outside of your biological circadian night). Note also that even under entrainment, it may take a few weeks before the all day brain fog disappears, the time for the digestive system to adapt (since it is the major producer of melatonin).
  • Weight loss without changing your diet or exercise can be an indication you are sleeping in phase (circadian alignment), and on the opposite weight gain a sign of circadian misalignment, since circadian misalignment is strongly associated with metabolic syndromes (see "circadian syndrome").

In the future, it may become possible to more precisely monitor our circadian rhythm with the help of wearable core body temperature sensors (see the section on Core Body Temperature and also the Wearadian project on GitHub).

Circadian rhythm disorders: body, brain or mental disorders?

Although there is a common misconception that circadian rhythm disorders are either neurological or psychological (as reflected in the DSM and ICD-10 classifications TODO: update with precise classif G vs F), hence stemming from dysregulations in the brain or thoughts, this can only be qualified as incorrect.

Summary: There is now considerable evidence that circadian rhythm disorders are associated and worsened by a delayed peripheral circadian clock (ie, the digestive system 's clock including the liver and intestines), so it's much more likely a whole body disorder. It's even now considered to be associated with metabolic syndromes such as diabetes, so much so that some researchers call for a name change to "circadian syndrome". Another evidence is that sleep is more a product of the body than of the brain, as it mainly serves to clean up the oxydants in the intestines. Another hint that circadian rhythm disorders are not psychiatrical nor neurological conditions but rather whole body conditions is the fact that usually very effective psychiatric interventions such as cognitive behavioral therapy (CBT) are ineffective for DSPD and other circadian rhythm disorders.

For a more argumented study of this question, let's tackle it step-by-step.

Can circadian rhythm disorders be psychologically caused or manipulated?

Summary: no, sleep disorders, including circadian rhythm disorders and insomnia, cannot be caused by a psychological disorder. This is an archaic belief that is not supported by evidence nor the current medical guidelines. Sleep disorders require their own treatment, independently from possibly co-occurring psychological disorders. Circadian rhythm disorders can be indirectly manipulated behaviorally if the behavior changes the exposure to bright light and other zeitgebers, but there is no evidence that behavior per se can manipulate the circadian rhythm when zeitgebers are not involved.

For a long time, sleep disorders were considered secondary disorders, which means that they were considered a consequence of another disorder or disease, physiological or psychological, that would be the root cause, the primary cause. This view was shattered when evidence accumulated to demonstrate that sleep disorders are almost certainly generally primary. Indeed, although sleep disorders are often associated with other diseases or disorders and especially a lot of psychological disorders such as depression, increased suicide rates, emotional dysregulations, decision making impairment and ADHD-like symptoms, or even hallucinations and dissociations under extremely prolonged sleep deprivation up to death at the very worse after about a week of complete sleep deprivation, empirical evidence demonstrated that the sleep disorder almost always appeared before these psychological disorders and symptoms. Thus, since the sleep disorder predates psychological disorders and symptoms, it cannot be caused by the psychological disorders. This is why the current, modern view in sleep medicine and psychology is that psychological disorders are often comorbid to sleep disorders without being the cause, with potentially some contribution of the sleep disorder to the onset or worsening of the psychological disorder, and so both require simultaneous and dedicated treatments: one tailored for the psychological disorder, one for the sleep disorder. This was demonstrated for insomnia in a 2001 review by Harvey, and later for circadian rhythm disorders in a systematic review, concluding that "circadian rhythm disorders [...] require independent attention irrespective of co-morbid conditions".

Although almost all humans have a naturally non-24 circadian clock (~24.2h according to the NIH, bigger estimates were found by older improperly designed studies), and hence can freerun in the absence of external time cues, as shown by the "expériences hors du temps" done by several speleologists or its ancestor experiment by Kleitman in the Mammoth Cave or the modern variants of forced desynchrony protocol or nap paradigms, not everyone can follow a non-24h schedule, with morning larks having the most difficulties to adapt to other schedules (see also here and here). And even when individuals can follow a non-24h schedule (aka freerunning), it is a painful experience (see also here) and there is no evidence this can be sustained for a long time, contrary to people with intrinsic non-24 who function best when freerunning.

Work schedule experiments on the NASA crews monitoring Mars mission, where the well qualified and compensated crew of engineers and scientists was tasked with adopting a non-24h martian sleep-wake schedule to better monitor the robotic missions, ended up with the crew rebelling and dropping the schedule as they felt it was unbearable ("broken"), after ... a single month!
As the authors noted:

> The authors attributed this result to the high motivation of the crew, although motivation has limited ability to override circadian and homeostatic regulation of alertness and performance and is, in fact, subject to these influences itself. (...) Based on NASA surveys of 24 Mars Pathfinder veterans, those supporting the Sojourner Rover indicated that fatigue significantly affected their performance at work to the extent that they discontinued work on the Mars day schedule after only one month and described the schedule as “broken.” JPL managers described the scientists' and engineers' discontinuation of the Mars day schedule as a “rebellion.”

Hence, the non24 circadian rhythm sleep wake disorder is characterized not only by a freerunning sleeping pattern, but by the fact that it is unpreventable and incontrollable (ie, no obvious and easy to fix cause). This case shows that high motivation, well compensation and qualifications are not sufficient to modify the circadian rhythm period. For any humans and likely for any animals as well, the circadian rhythm cannot be overriden simply by motivation.

Besides this observational case study, there are more direct, lab controlled studies that objectively measured the circadian rhythm using physiological variables (eg, core body temperature, melatonin levels), and whether various factors can affect it.

One crucial investigated factor was whether the sleep pattern can affect the circadian rhythm, as indeed all psychological therapies rely primarily on modifying the sleep pattern through a behavioral intervention. Past studies found an effect, but recent well designed and controlled studies (see here and here) found that behavioral interventions on the sleep pattern only modify sleep pressure but not the circadian rhythm, proving that past studies were ill-designed for what they were supposed to study (this is the conclusion of the authors).

Additional evidence come from community-wide interventions in delaying college start time to adapt to teenagers. Indeed, during adolescence, the circadian rhythm experiences a transient phase delay that will gradually reduces with age, with a kind of U shape, with childhood and old age being characterized with the greatest phase advance (although it is worse noting that this does not erase interindividual differences: everyone will sleep later during their adolescence compared to their childhood and old age, but at the same age, a morning lark will always sleep earlier than an evening owl, including during adolescence). Studies have since long found that teenagers are experiencing alarming rates of sleep deprivation, sleeping several hours less than they require, because of the biologically induced phase delay. Community studies have been devised to test whether later school start time would allow them to sleep longer, or whether they would just sleep later and thus end up sleeping the same duration as before, but just later. In other words, is this a "lazy" kind of behavior, or is the sleep duration really constrained by the school start time. These community studies found that invariably nearly all teenagers ended up sleeping longer, as they kept sleeping at about the same time as before, but woke up later thanks to the later start time. This later school start time was reproduced all around the world with the same results (TODO: add ref), providing very strong evidence that this is a universal result and not culturally based, which is in line with what was expected if as hypothesized the circadian rhythm was the cause of the teenagers' increased sleep deprivation, and this hence disproves the hypothesis that this was behaviorally caused. In other words, not only is it observed in adults that behavior can not modify the circadian rhythm, but the same is observed in adolescents, which strongly suggests that this holds true for any age.

Psychologically changing one's circadian rhythm is different from forcing oneself to sleep out of phase (ie, restricting the sleep-wake schedule, in other words circadian misalignment). All individuals with non24 do restrict their sleep schedule sometimes or most of the time depending on one's responsibilities, and they hence sleep under a circadian misaligned time. But, without changing the circadian rhythm, this only leads to sleeping outside of one's biological night, which causes a short and subquality sleep accumulating sleep deprivation if reproduced repeatedly, as is shown by the fact that depression was more prevalent with the circadian DSPDs, and other health issues as described in another section above.

If we reduce the assumption of a psychological cause, but simply that psychological therapies may change the circadian rhythm, we end up with the theory of circadian plasticity and chronotherapy, which is defined as the assumption that the circadian rhythm is not only flexible but that this flexibility can be memorized, in other words, that therapies can affect the circadian rhythm beyond therapeutic discontinuation. Unfortunately, there is absolutely no empirical evidence supporting this assumption, and to the contrary, empirical evidence from this document's author and others strongly support the opposite, that the circadian rhythm is not plastic, and any effect obtained by therapies is lost upon discontinuation. This explains why behavioral chronotherapy as well as sleep hygiene have both been empirically proven to be ineffective despite decades of experiments (see the dedicated Chronotherapy section). Furthermore, usually effective therapies for psychiatric conditions, such as the cognitive behavioral therapy (CBT), have shown no efficacy for circadian rhythm disorders (when they are not confounded with zeitgebers exposure change).

To summarize the previous paragraphs:

  • There is currently no empirical evidence that an entrained person, without a non-24 circadian rhythm disorder, can become freerunning by psychological intervention only without modifying the exposure to zeitgebers. The NASA Mars crew example is a pertinent demonstration.
  • And inversely, no empirical evidence that an individual with non-24 or another circadian rhythm disorder can become entrained or sustain stable phase advances with a psychological intervention only, which is why chronotherapies nor sleep hygiene are not recommended as monotherapies anymore by the AASM guidelines.

Despite what some may claim, especially the proponents of "holistic medicine" pseudosciences, it remains highly controversial whether the mind can modify the biology. An often cited example is the placebo effect, but according to a Cochrane systematic review, placebo only affects subjective feelings, without modifying any objective measure. In other words, placebos (and nocebos) can help see things differently (eg, subjectively feel less pain), but not modify how the body works nor cure a disease (nor cause a disease). The placebo effect being the most studied and best proved psychologically induced effect, it's doubtful whether the circadian rhythm can be influenced by psychological factors at all. Firstly because the core circadian rhythm signalling pathway is body temperature modulation, hence, for psychological factors to modify the circadian rhythm, they would have to modify body temperature, which was never evidenced experimentally so far (whether by motivation, psychological stress or placebo effect). Furthermore, the chronic sleep deprivation induced by circadian rhythm disorders is not a subjective feeling: it is a real and highly dangerous health issue that can be objectively measured and which requires adequate treatments. The concept of psychological stress being a possible cause for most disorders stems from the psychoanalytical field, rooted in hysteria, renamed to conversion syndrome and later to psychosomatic syndrome. The problem with the theory of psychological stress causing other disorders is that this is mostly based on measures of cortisol, which is the hormone of wakefulness and is also and foremost regulated by the circadian rhythm and can also be modified (much more strongly) by sleep deprivation, and hence those studies are often confounded by the fact they often do not account for sleep duration, as sleep disorders and circadian dysregulations have been historically widely ignored by psychological studies. It is worth mentioning that the psychosomatic school of thoughts originates from the concept of Voodoo Death, which purports that humans can die from the sadness of being rejected by their community, which has later been debunked as death by dehydration, and has never been reproduced since then (absence of proof can be evidence of absence after so long without any empirical evidence reproduction).

The circadian rhythm plays an essential biological role: the survival chances of all living creatures are depedent on their synchronization to the external day-night cycle, whether it is to get food and regulate temperature or to flee from predators. The circadian rhythm modulates not only the core body temperature as a way to synchronize clocks throughout all cells of the body, but also regulates most body organs functions and even RNA transcriptions. The circadian rhythm is hence a biological vital function, just like blood glucose levels or insulin. Psychological factors hence likely have as much influence on the circadian rhythm as they have on diabetes, which is little to none. An analogy would be to ask whether a diabetic individual could control their glucose and insulin blood levels simply by motivation and will (or any kind of psychological therapy). The answer would obviously be no. The analogy with diabetes is not fortuitous, there are strong ties that are found between metabolic syndrome disorders such as diabetes and circadian rhythm disorders (see "circadian syndrome" or the food zeitgeber section below).

A variant of the psychological argument for circadian rhythm disorders is to cite the increase in blue light exposure in the evening due to computer and smartphone screens use. While it is true that blue light from screens can cause unwanted circadian delays and should be managed as part of an appropriate dark therapy, this cannot be used as evidence that circadian disorders are *only* due to screens misuse. One simple counter-argument is that if this argument was true, all computer scientists would have a DSPD or non-24 disorder, which is clearly not the case. Furthermore, the non-24 disorder was medically recognized in 1977 and sighted non-24 first clinically documented in 1971, before the advent of ubiquitous screens exposure. There is obviously an intrinsic component, as per the currently accepted medical definition, that makes the circadian rhythm of some people less robust to entrainment than others (or more prone to unwanted circadian shifts by uncontrolled factors), and hence being intrinsic is a hallmark of circadian rhythm disorders. Unwanted circadian shifts are merely a side consequence of the disorder.

Circadian rhythm disorders are sometimes qualified as being "idiopathic" (ie, of spontaneous and unknown cause) is only a temporary placeholder label, as the number of idiopathic diagnoses decreases over time as technology and knowledge progress, and as such some authors recommend to more properly prefer the term of "cryptogenic disorder" (disorder of yet unknown cause) instead of "idiopathic disorder" (spontaneous appearance - which can be misleading as it can suggest that disorders and diseases can have no physiological cause). As this other review for a dermatological condition states: "The more competent we are in etiological identification, the less idiopathic cases are found", which goes on to show this is a generic process happening in all medical domains.

Hence, there is currently no proof that circadian rhythm disorders can be caused or manipulated through psychological factors, and actually there is evidence of the opposite, which is that sleep disorders and circadian dysregulations actually often precede the appearance of other physiological or psychological symptoms, and the complete management of psychological disorders do not improve the sleep disorders, prompting scientists to recommend to always investigate and treat sleep and circadian rhythm disorders independently of any psychological condition. The same statement was also pronounced two decades prior for insomnia (see also here).

Can circadian rhythm disorders be neurological disorders, or a body disorder?

Since circadian rhythm disorders aren't psychologically caused, it must be a neurological disorder, right? Not necessarily, and there is some strong evidence that it's not.

Here are four arguments that contradicts the hypothesis of a brain disorder, and rather suggest that circadian rhythm disorders are body disorders:

  1. Firstly, the circadian rhythm is not solely defined by the suprachiasmatic nucleus (SCN) neurons in the hypothalamus, since there are actually molecular clocks in every organs and cells, and furthermore astrocytes arguably play an important role (see also here).
  2. Secondly, the vast majority of melatonin is produced outside the brain. Even if the pineal gland is cyclically secreting melatonin following the SCN inputs and is hence usually qualified as the "master clock", this is a highly arguable statement since the gastrointestinal tract secretes 2 orders of magnitude (at least 400x!) more melatonin in response to food than the SCN. Furthermore, even after pinealectomy, melatonin levels still increase in a dose-dependent manner (ie, proportionally) to oral intakes of melatonin in animals, just like for animals with their pineal gland, and it even restores an entrained circadian rhythm, showing that extrapineal producers of melatonin, likely the digestive tract, are producing and managing most of the circulating melatonin.
  3. Thirdly, the SCN is unnecessary for circadian shifting. Indeed, the effect of light, the strongest zeitgeber, on shifting the circadian rhythm is not impacted by the destruction of the SCN. Furthermore, a subsequent study shown that the ipRGC cells are sufficient to cause circadian rhythm and body temperature shifts without the need for the SCN, which shows that the non-visual effect of light on the circadian rhythm is independent from the SCN. Hence both the pineal gland and the SCN, the two major brain structures related to circadian rhythm modulation, are not required for circadian rhythm modulation and entrainment.
  4. Fourthly, chronic sleep deprivation (often caused by circadian rhythm disorders) causes death not through the brain but through the whole body via the accumulation of ROS in the guts (see the great abstract video or also the Inverse vulgarization article). This can be rescued (avoided) using anti-oxydants targeting the guts (through food or gene overexpression), but not when targeting neurons in the brain. It lends further credence to the consideration that the guts is a "2nd brain".
  5. Fifthly, the circadian clock and the cell cycle are coupled, which means that the circadian clock is a core regulator of all cells cycles throughout the body. By accounting for the other discoveries, this means that body temperature controls the cells cycles through the circadian clock modulation. This is another strong supporting evidence for the hypothesis that circadian rhythm disorders are bodily disorders, not just brain disorders.
  6. Sixthly, core body temperature modulation is the primary way that circadian rhythm changes are signalled across all cellular clocks throughout the body, with temperature being modulated by bright exposure through the SCN, although another study shown that the SCN is in fact unnecessary as the ipRGC cells are sufficient to control the body temperature changes. Likewise, melatonin causes a reduction in core body temperature reduction proportionally to the dose, and endogenous melatonin levels are inversely coupled with peripheral (limbs) temperature (heat transfer to limbs is a way to reduce core body temperature, so increasing limbs temperature actually decreases core body temperature). Temperature being the primary signalling pathway of circadian clock changes and synchronization especially via melatonin was already suspected since at least 2007 since supraphysiological melatonin doses were known to cause hypothermia, and it was even earlier hypothesized in 2000 that temperature may be a 3rd signalling pathway and potential treatment approach after light and melatonin. Given that humans, like most mammals, are homeothermic, which means that it's crucial for their survival that their core body temperature is always maintained inside a very specific range, and hence that body temperature control is automatic and unconscious (ie, an individual cannot manipulate their temperature by will) and is very robust to ambient temperature changes, this shows that the circadian rhythm is a very deeply ingrained and automatic biological process that is both uncontrollable without external means, and affecting the whole body.

Hence, circadian rhythm disorders should more properly be qualified as whole-body disorders, instead of neurological or psychological, as both of the latter conveys a large understatement and misunderstanding of the whole-system interactions underlying circadian rhythm disorders, and focusing on brain structures such as the SCN that are in fact unnecessary for circadian rhythm modulation.

Accepting circadian rhythm disorders are whole-body disorders does not mean that there is not a neurologic component, since of course there is given that light exposure is the strongest zeitgeber and is mediated from the eyes' ipRGC cells through the brain to then the rest of the body via core body temperature modulation and melatonin levels inhibition. However, this strongly indicate that a neurocentric approach is insufficient to fully understand and treat these disorders. In practice, this means that treating the brain (master clock) without the body (peripheral clock in the digestive system) will be at least suboptimal or even ineffective.

Circadian rhythm disorders bear strong similarities, or even links according to recent findings, with metabolic syndrome disorders such as diabetes. Hence, it is likely safe to think of circadian rhythm disorders in similar terms as diabetes: a body disorder with some neurological component, which is both varying with endogenous but majorly with exogenous (external, environmental) factors.

What causes circadian rhythm disorders such as non-24?

This section explores the potential biological or medical causes of non-24 and other circadian rhythm disorders.

Although the cause of sighted circadian rhythm disorders such as non-24 certainly is not psychological but physiological (either neurological or bodily) as explained above, the causes are currently poorly understood.

For blind individuals, the loss of pathways to conduct the signal from the eyes' ipRGC cells (the ones that are intrinsically photoreceptive and responsible for the shift in our circadian rhythm and the inhibition of melatonin) is the reason most of them suffer from the non24 circadian rhythm disorder. But for sighted individuals (whether DSPD or non-24), it's unlikely these pathways are lost as most studies found these pathways to be intact in sighted individuals.

Some scientists suggest it can be a genetic mutation in clock genes, as indeed the circadian rhythm is mostly inherited through genes. If this is correct, then circadian rhythms should be inherited among siblings and descendents, and hence diagnosis of one member should prompt the testing of close family relatives. This is the case of the author of the present document, as there is a clear lineage at least 2 direct ancestors above (paternal grand-mother -> father -> son), and anecdotal reports from other individuals with non-24 suggest this is not an isolated case (see here , or also here for a mother->daughter transmission, or here for several testimonials). Since it seems to be inheritable regardless of the parents and children sex, it does not appear to be a mutation in X nor Y chromosomes.

There is also an age effect, as some of these disorders can appear later in life, especially DSPD, with a delayed circadian rhythm phase being common at adolescence compared to childhood. However, this does not always resolve as shown by various testimonials from individuals with DSPD. Furthermore, there is no evidence that freerunning, the characteristical circadian pattern of non-24, can appear later in life and resolve on its own with age, contrary to the delayed phase. Indeed, a delayed phase is fundamentally different from an ever shifting phase.

Other scientists suggest there may be a functional or anatomical dysregulation in the brain, particularly the suprachiasmatic nucleus, which neurons orchestrate peripheral clocks throughout the body, or the pineal gland, which secretes melatonin. There is also some anecdotal evidence (see also here) that damages to the pituitary gland may cause a non-24 circadian rhythm pattern rarely. However, it appears clear that the circadian rhythm is regulated not by a single locus but by a network of brain structures, or even body organs, each with their own clocks interacting and contributing to the overall circadian clock. Furthermore, experimental evidence shows that SCN neurons of animals entrained to a non-24 schedule (ie, T-cycles) implanted in other animals will not cause them to display a non-24 sleep-wake schedule, which strongly suggests that there are other structures, either inside the brain or outside, that are critical to allow entrainment to non-24 schedules. There is some evidence from animal studies that disruptions in the BMAL1 gene of astrocytes regulating SCN neurons actually make the animals freerun in a non-24h sleep-wake pattern, and interestingly there is some evidence that astrocytes are disrupted in individuals with autism, a disorder that often has comorbid circadian rhythm disorders. Hence, it seems unlikely these disorders can be caused by one single point of failure, it's more likely they are the result of a complex set of dysregulations, as happens for other complex disorders such as autism and schizophrenia.

Can these disorders be anthropogenic? The major difference nowadays (since the industrial revolution, see also here) is NOT where we sleep, but where we spend our awake time: whereas in 1800s almost everyone (90% of americans) worked out in fields, nowadays they work in offices, with as much as 87% of americans spending their wake time indoors, in places which sometimes do not even have windows and with reduced light exposure both in light intensity, spectral composition and duration (see also here). Hence their circadian rhythm is only entrained by artificial lights. The exact same thing they use in the evening at home, which delays their circadian rhythm.

Hyposensitivity to zeitgebers such as light may be a factor, as indeed the sensitivity to zeitgebers is highly variable for everyone, with a 50-fold variability among typical sleepers. The opposite, hypersensitivity to zeitgebers, may also cause circadian rhythm disorders. However, it remains unclear whether hyposensitivity and hypersensitivity are causes or just consequences of circadian rhythm disorders, since it was demonstrated that non-24h light-dark schedules (T-cycles) cause SCN desynchrony, similarly to long days, and hence reduced responsiveness to phase shifts and that weak entrainment to a zeitgeber, such as by being entrained to a short day of bright light, causes a higher synchrony of SCN neurons and phase shifts of a wider magnitude (see also here and here). Potentially, hypo and hypersensitivity may be reinforcing feedback loops, that once set in motion worsen the symptoms. However, although there certainly are negative feedback loops, it is in the author's experience that the circadian rhythm always reverts back to its original state after just a few weeks of discontinuing any therapy and resuming exposure to environmental light, whatever environment (ie, living in more brightly lit indoor housing and going outdoors more often did not have any long lasting effect). A 2021 study that assessed alterations in ipRGC cells response to bright light using post-illumination pupil response (PIPR) found that individuals with DSPD and sighted non24 both impaire phototransduction, in other words they have reduced response and pupillary diameters compared to controls, with a much more extreme reduction for sighted non24, which strongly supports the hypothesis that hypophotosensitivity is likely a possible etiology for at least some individuals with DSPD and sighted non-24.

A similar hypothesis is that geography may play a role, with some individuals requiring more sunlight exposure than others for their circadian clock to be entrained. Although this hypothesis may have some merit, non-24 and DSPD disorders have been reported all around the world, in both low exposure and high exposure regions (eg, people with sighted non-24 were reported living since a long time in South Africa, Irak, Vietnam, Southern California, New Zealand, Australia, etc - source: private communications - and there is this study showing DSPD is present in Cyprus), which strongly suggests that although geography may be a factor (formal demographic studies are unfortunately lacking at the moment to confirm or infirm this point), it is unlikely to fully explain the existence of these disorders. However, geography does indeed affect the sunlight exposure pattern regardless, and it indeed has an effect on the circadian rhythm, as it was demonstrated that southern countries such as Spain, Cyprus and Portugal, which are exposed to longer durations of sunlight compared to northern countries, have populations that report later bedtimes. Hence, the duration of sunlight exposure, and hence geography, certainly can play a role in worsening a circadian rhythm disorder condition especially in extremums such as too short or too long exposures, and hence some world regions may have a higher prevalence of these disorders, but geography is unlikely to be the sole explanation for the existence of these disorders, given their ubiquitous distribution around the world.

Another possibility that was observed in studies is that exposure to an aberrant pattern of light exposure diminishes its effect on the circadian rhythm. A simple example to illustrate: if a human is placed in a room exposed 24/7 to bright light, with no variation whatsoever in the light intensity or color, light exposure will have less and less effect on their sleep over time (except on melatonin which will still be inhibited - melatonin inhibition is decoupled from circadian rhythm shifting). Hence that's why for light therapy to be effective, it needs to be combined with dark therapy, ie, the avoidance of bright light (especially blue and green) in the biological evening. While this hypothesis may apply to some individuals, it certainly is not a satisfactory explanation for individuals who have rigorously followed therapy or even changed their environment to maximize timely exposure to zeitgebers and who still observe their circadian rhythm reverting to the original state after artificial light therapy discontinuation, such as the author of this document.

Finally, sleep deprivation is known to reduce the effect of zeitgebers such as light on our circadian rhythm, so if an individual is chronically sleep deprivated, zeitgebers (and light therapy) won't work, hence why it's important to feel rested before starting to use them and to continue from benefitting from their use. A related hypothesis is that non-24 may be caused in parts by an abnormal buildup rate of adenosine (sleep pressure), which was shown to modulate/inhibit the response to bright light, and hence may indirectly contribute to the shifted circadian rhythm phase. However, even slight adenosine imbalances are now suspected to be a key factor of severe neurodegenerative diseases such as schizophrenia and Parkinson, so it is arguable whether non-24 could be caused by an adenosine imbalance without any other sign of a neurodegenerative disease..

Behavioral causes, although historically strongly favored by psychological theories, have never been supported empirically, with empirical observations often showing the contrary, such as a lack of effect of sleep hygiene as a standalone therapy, or the finding that individuals with DSPD actually spend less time in bed than typical sleepers. In addition, they do not require more extra sleep hours during the weekend than weekdays compared to the general population, meaning that they suffer as much social jet lag as anyone else, but not more, which means that their insomnia difficulties during the workweek are not caused by a hypothetically too different sleep pattern during the weekends. Sleep patterns have no effect whatsoever on the circadian rhythm (see also here). Sleep nor sleep pressure have no effect on the core body temperature and hence the circadian rhythm. Likewise, sleep deprivation has no incidence on the core body temperature.

Hence, there are both intrinsic (genetical hyper/hyposensitivity) and extrinsic (environmental) factors that can be at play in causing circadian rhythm disorders, and furthermore these factors are not exclusive, so that it's likely that multiple factors are at play (complex disorder) and with different causes producing the same phenotype (polygenic disease).

However, it appears that there is no single nor set of hypotheses that can satisfactorily explain how circadian rhythm are caused. It is the author's conviction that, at the most fundamental level, circadian rhythm disorders are in fact disorders of body temperature homeostatic regulation, and that future studies should explore this lead as a potentially very promising etiological explanation for these disorders, that may open new therapeutic avenues.

Why do circadian rhythm disorders exist? Do they serve a purpose?

This section is different from the last one: whereas the previous one tackles potential biological/medical explanation, here we explore the potential evolutionary reasons for a population to display a percentage of individuals with circadian rhythm disorders, ie, their potential utility for the specie.

Anthropology of sleep dates circadian rhythm diversity back to the hunter-gatherers tribes, where it is hypothesized that the various chronotypes allowed to always have someone on guard at any time. This "sentinel hypothesis" seems verified with another study on modern tribes, showing that even nowadays their members have a wide variety of chronotypes, so that the tribe has someone awake at nearly all times to stand guard (only 18 min was left unguarded over 24h). Although this study did not observe the circadian rhythm at the individual level, one interpretation is that humans have a natural genetic variability in circadian rhythm phase distributions to increase the odds of always having someone in the community awake to defend against predators and enemies at any time of day and night.

Chronotype repartition among the general population is indeed known to follow a bell shaped curve, in other words a gaussian distribution, which strongly suggests a random and natural variability. In other words, the repartition is normal (in the mathematical sense), no two individuals have the exact same chronotype/circadian rhythm, and it's ingrained in our biological, genetic code. Indeed, it is estimated that ~40% of sleep disorders are inherited, and 46% to 70% of the circadian rhythm is genetically inherited, with minor influence from environmental factors, with similar heritability for the propensity to regularly do a siesta. In fact, heritability of the circadian rhythm is so strong that it was shown that rats kept in the dark for generations maintained the same circadian rhythm, which strongly suggests that behavioral exposure to light patterns cannot affect the circadian rhythm between generations (neither negatively - by bad habits - nor positively - by following an entrainment therapy, children likely won't benefit from genetic improvements). The repartition of chronotypes in the general population is about 30% of morning larks, 40% of night owls and the rest in-between (see also this informal review). Circadian rhythm disorders such as DSPD or non-24 are not accounted in these statistics, and are likely on the tails of the bell-shaped curve ("extreme" chronotypes). This biological diversity is further supported by some evidence that prehistoric mammals were likely all nocturnal to avoid the oversized reptilian predators that were the dinosaurs, and only later some mammals, including humans, switched into bright light vision (see also here for a layman summary). Furthermore, DNA microarrays demonstrated that the central clock's circadian rhythm itself controls an estimated 8-10% of all transcriptomes in any tissue.

Although very few studies investigated this factor, the few that did observed unexpected ethnic differences in the circadian period, with european-american having longer circadian periods than african-american, which may suggest an evolutionary genetical adaptation to geographical location, with shorter intrinsic periods genetically encoded in populations living in places with longer days.

Occupation does not seem to play a role, since there are several counter-examples: 1) most computer scientists, nor professional gamers and computer graphists, do not have the non-24 disorder despite extensive or even excessive use of screens, 2) according to a November 2023 survey of the AASM on ~2000 americans, 45% use their smartphone and 50% their TV when having troubles sleeping, yet 45-50% of the population does not have circadian rhythm disorders, even if the prevalence is underestimated, this is certainly way above the pathological prevalence, and 3) 75% of the total workforce is estimated to have been involved in shift work and night work in industrialized countries. Furthermore, the first clinical documentation of a sighted non-24 disorder case was published in 1971, predating the advent of ubiquitous screen use and LEDs, with the most common type of at-home lighting at the time, incandescent bulbs, having negligible effects on the circadian rhythm. However, there is one study on animals which suggest that exposure to even very dim light during the circadian night can significantly lengthen the circadian period to an extreme non-24 pattern, although this would need to be reproduced to be confirmed.

Preliminary evidence from migrating birds suggests that the lessening of the robustness of circadian rhythm entrainment may be a natural way to allow some individuals to be more sensitive to external zeitgebers and hence more easily adapt to new environments. If this hypothesis is correct, this would mean that individuals with a circadian rhythm disorder may in fact more easily adapt to different timezones and length of day/night when the zeitgebers (particularly artificial light and food) are controlled, and play a crucial role in the survival of the species. This hypothesis is further strenghtened by findings from the "expériences hors du temps" during which humans live in an environment completely isolated from environmental timecues such as in a cave. During one of these experiments involving two individuals for about one month, one could readily adapt to a 28h/day sleep-wake pattern and core body temperature profile, demonstrating that their circadian rhythm also adapted, whereas the other one could not and stayed entrained to a 24h/day schedule as demonstrated by the core body temperature profile. Of note, after the end of the experiment, the individual who entrained to a 28h/day schedule had additional difficulties to re-entrain to a 24h/day schedule, which extent is left unreported unfortunately.

> The ease with which some people can adjust their habits to an alteration of phase or cycle length is thus no evidence against an endogenous rhythm, and the difficulty experienced by others is in favor. Perhaps the most striking of such evidence is that obtained by Kleitman (131) in the Mammoth Cave of Kentucky with 2 subjects living there on (‘days” of 28 hr. The temperature and wakefulness rhythms of one adapted readily but those of the other did not, so that at the midpoint of every week they were exactly out of phase; the poor adaptor was not constrained into feeling sleepy even by the presence of a soundly sleeping companion, nor into wakefulness by a wakeful companion. All influences, social and environmental, were working one way, but he maintained his 24-hr rhythmicity for the whole 32 days. Perhaps even more striking, the other subject, who adapted well, showed some persistence of a 28-hr sleep-wakefulness rhythm after emerging. A similar persistence of a 24-hr sleepiness rhythm is recorded in some, but not all, subjects living on a 220hr day (26, I 50). A phase shift, a common experience for travelers, is more easily accomplished: Sharp (226), studying a community of six men who altered their phase by I2 hr under almost ideal conditions, records a minimum of 2 and a maximum of 9 days before they were sleeping satisfactorily again. The regularity of sleep in Arctic communities was much the same during the continuous darkness of winter, the alternation of light and darkness around the equinoxes, and the continuous daylight of summer (220), both in the working population and in convalescent patients in a hospital.

A related hypothesis is related to the new finding that the Earth's rotation, and hence day-night cycle, has not always been of 24 hours (see also here and here and here), as they rather were 23.5h and progressively increased to 24h by 2.3ms each century. With cataclysmic environmental changes, it may also happen that the rotation duration may lengthen further in the future too. Hence, having in the genetic pool a diversity of circadian rhythm lengths different to 24h (ie, non-24) can increase the survivability of a specie in case of such a catastrophic cataclysmic event.

Hence, it's becoming increasingly apparent that endogenous circadian rhythm disorders are due to natural diversity with the purpose of increasing the survival chances of a community. Unfortunately, with the modern society expectations rooted in agriculture, chronotypes other than morning larks are at a disadvantage and suffer from social jet lag, despite the majority having an intermediate or night owl chronotype (see also here).

See also: Anthropology of sleep: Worthman, C. M. (2008). After dark: the evolutionary ecology of human sleep. In Evolutionary medicine and health (pp. 291-313). Oxford University Press.

Prevalence and demographics of sighted non-24

Let's first study the prevalence of circadian rhythm disorders in general:

The most common circadian rhythm misalignment is an exogenous one: social jet lag, which is affecting two thirds of the population worldwide, with only one third of the global population of adults achieving the recommended 7-8h of sleep. This is however not commonly considered a circadian rhythm disorder, although it could be argued that social jet lag is a lessened version of shift work disorder.

Let's first examine the prevalence of circadian rhythm disorders in the population, regardless of insomnia. Few studies have investigated the prevalence of circadian rhythm disorders in the general population, some of them estimating the prevalence between 0.13% and 0.17% in the general population. However, almost all these old studies were methodologically flawed, such as a study in an extreme north region with very short days lasting only a few hours during winter, or others using the morningness-eveningness questionnaire as a circadian disorder screening tool when it is stated it should not be used this way. A more recent 2021 study found a prevalence of 12.8% had a circadian rhythm sleep-wake disorder among a representative sample of the general population of Cyprus. The most prevalent circadian rhythm disorders were shift work disorder (6.7%) and DSPD (5.1%). The sample consisted of 195 enrolled participants out of a survey of 4118 of adults in Cyprus, a south-eastern europe region, which is exposed to plenty of sunlight. Although non-24 was included in the criteria, the diagnostic tools used (questionnaires) included no criteria that could be used to diagnose non-24, hence none were detected in the sample, and likely some were misdetected as DSPD or typical sleepers depending on their current circadian phases. The authors defined DSPD as individuals falling asleep between midnight and 3am, which is reasonable given the social expectations in the region. The key characteristic for many patients was chronically inadequate sleep, and the most common complaints were insomnia and fatigue and sometimes hypersomnia for intrinsic circadian rhythm disorders but not excessive daytime sleepiness, contrary to other sleep disorders where excessive daytime sleepiness is a key symptom. Although it was published in 2021, the study was conducted before the COVID-19 pandemic. Depression is the most common comorbid disorder with DSPD.

Let's now examine the prevalence of circadian rhythm disorders by considering them a subtype of insomnia. Sleep disorders are highly prevalent, as it is estimated that the "worldwide prevalence of sleep disorders is about 50% with even higher occurrence in psychiatric population", and is increasing over time. Other studies find a prevalence of insomnia in about one third of the general population. The most common type of intrinsic circadian rhythm disorder, Delayed Sleep Phase Disorder (DSPD), is much more prevalent than previously thought, accounting for 10% of all sleep disorders and is often misdiagnosed as sleep-onset insomnia, hence about 5% of the worldwide population by combining with the previous figure, which is exactly what the 2021 Cyprus study found. Relatively to the global population, a genetics study by Dr. Alina Patke estimated that potentially 0.6% of the population is carrying a gene mutation CRY1 that may cause Famillial DSPD (ie, inheritable DSPD). However, sighted non-24 is undoubtedly much rarer than DSPD, although it is not uncommon for non-24 to be misdiagnosed with its better known cousin disorder DSPD.

Hence, whether we examine the prevalence of circadian rhythm disorders as a subtype of insomnia, or as a standalone class of disorders, we end up with similar prevalence figures, which strengthen the case that circadian rhythm disorders are highly prevalent in the modern society.

Now, onto the prevalence of the non-24 disorder:

Non24 is very common in blind individuals, with an estimated 2/3rd of blind people having the non24 disorder. Other estimates such as in the visually impaired Japanese population found that 33% had a circadian rhythm disorder, with the most common being the non-24 disorder affecting 26.8%, followed by ASPD (3.8%) and DSPD (2.5%).
Given the rarity - or wide misdiagnosis rate - of non24 in sighted individuals (ie, sighted non-24), there is as of 2021 currently no reliable estimate of its prevalence. This may partially be caused by the fact that the same billing and diagnostic codes are assigned to both blind and sighted non-24, despite having different etiologies, which prevents researchers from querying their databases to isolate sighted non-24 from blind non-24. However, there is evidence according to the french sleep medicine institution SFRMS that circadian rhythm disorders are underdiagnosed, and some indirect evidence can allow to produce a vague estimation.

The most direct evidence, but non-statistical (because the sample was not random), of the prevalence of sighted non-24 comes from a survey done by the Circadian Rhythm Disorders Network association (mirror, and more results here). They found that out of all the respondents who declared to have a circadian rhythm disorder, between 29% to 33% declared to have sighted non-24, and at least 19% had a medical diagnosis of sighted non24, which is much higher than any previous estimate. However there are some limitations. To quote them:

> With careful questioning we could also get a rough estimate of Non-24 prevalence in sighted people, which we suspect (from our survey—see next paragraph) is considerably higher than generally believed. Currently there is almost no evidence of the prevalence of sighted Non-24 and limited evidence for the prevalence of ISWD, mostly based on its occurrence in the context of other conditions such as head injury. (We do have good estimates of the number of Non-24 cases in the totally blind population.)
> In our survey, 29% of respondents with CRDs believe they have Non-24. Some may have misunderstood the definition of Non-24. But of the people diagnosed with a CRD by a medical professional, 19% were diagnosed with Non-24. Our sample is biased by self-selection—people with Non-24 are more likely to have major problems with their lives and be more likely to participate in our survey. Still, the results suggest that the prevalence of Non-24 is much higher than is generally recognized.

Hence, if the results of this survey are valid, which needs to be verified by future controlled studies, sighted non-24 may account for at least 1/4th of all the circadian rhythm disorders (accounting only the medical diagnoses) and up to 1/3rd of all circadian rhythm disorders if we account for the self-diagnoses. But it is worth noting that, similarly to what was observed in the above mentioned survey, online communities of non-24 are overwhelmingly mostly filled with individuals with sighted non-24, not blind non-24, which suggests, but does not prove, that sighted non-24 may be much more prevalent than blind non-24 in absolute terms. Furthermore, even though sighted non-24 may be much rarer in the sighted population than blind non-24 in the blind population, given the sighted population is much bigger, it's possible sighted non-24 still represents a sizable population in absolute numbers (ie, base rate fallacy), according to James Fadden.

Sighted non-24 seem to often first appear, or at least gets noticed, at teenage: "The onset of non-24-hour sleep-wake syndrome had occurred during the teenage years in 63% of the cohort, and the mean ( +/-SD) period of the sleep-wake cycle was 24.9 +/- 0.4 hours (range 24.4-26.5 hours). The mean sleep length of the patients was 9.3 +/- 1.3 hours, and 44% of them had a sleep length of between 9 and 10 hours. Psychiatric disorders had preceded the onset of non-24-hour sleep-wake syndrome in 16 patients (28%); of the remaining 41 patients, 14 (34%) developed major depression after the onset of non-24-hour sleep-wake syndrome." From this 2005 study of 57 participants cohort. There is indeed evidence for neuroendocrine changes during adolescence that can affect the circadian rhythm.

There is a misquoted figure of a 0.03% prevalence of sighted non-24 in the general population, originating in the Sleep Misfits book, which finds its root in an estimation by the Circadian Sleep Disorders Network of 0.03% prevalence of all forms of non-24, including both blind and sighted, as per a clarification statement by the Network. However, even this figure of 0.03% prevalence among the general population is not plausible: according to the International Agency for the Prevention of Blindness’s Vision Atlas 2021 report, there is an estimated 43 millions people worldwide living with blindness, out of a global population of about 8 billions people. Given a presumed prevalence of 0.03%, this would make for an absolute prevalence of 8 billions * 0.0003 = 2.4 millions blind people with non-24 with this estimation method. However, if we estimate given the prevalence of 55-70% prevalence among blind individuals, we would get between 24 and 30 millions blind people with non-24, hence a 10x bigger order of magnitude. Likewise, using the results of the visually impaired Japanese population study, 26.8% of prevalence of non-24 among the 295 millions of people living with a moderate-to-severe visual handicap according to the IAPBVA 2021 report, we get an absolute prevalence of 79 millions blind people with non-24 globally. Hence, the 0.03% prevalence figure has currently no evidence based foundation (could not find any empirical study that produced this estimate), and it is anyway underestimate the known prevalence of non-24 in blind people, hence it also likely underestimates the prevalence in sighted individuals.

Does non24 disappear with age?

This is a common misconception that is prevalent in medicine, that cryptogenic diseases magically fade away with age (eg, adhd, autism, epilepsy, etc all are ailments that were supposed to disappear during adulthood) . While it's true that a sizeable proportion of adolescents experience a temporary phase delay in their sleep-wake patterns, this phase delay is much smaller in magnitude than the phase shifts observed in pathological circadian rhythm disorders such as DSPD or ASPD, and there is absolutely no evidence that continuous daily phase shifts as observed in non24 are common nor temporary with age. Hence, while a teenager wakinp up around noon may expect to wake up naturally around 10am or forcefully around 8am after reaching adulthood, children and adolescents with DSPD waking up past noon and those with non24 who wake up at later hours every days have no reason to expect an improvement with age without any therapeutic intervention.

How to explain non-24 to others?

Explaining what is non-24 to other people who don't have it, whether they are relatives or acquaintances, can be quite difficult as circadian rhythm disturbances are usually not comprehended by typical sleepers.

The best way to explain is your way to explain, and it's your choice whether you want to explain or not.

However, keep in mind that most people won't be able to understand, as sleep is such a covert process that most do not realize how much sleep and the circadian rhythm regulate their daily life, and thus, sleep disorders are beyond their comprehension. This is well evidenced by the experience of night shift workers, who, despite being typical sleepers required to modify their sleep-wake schedule to accomodate their work needs, experience the same difficulties in explaining their situation and their issues being recognized by their day-time colleagues and hierarchy. This is not helped, and even partially caused, by the prevalent no-sleep culture, a modern view with sleep being disregarded as a convenience, when it is an essential need.

Nevertheless, here is a list of suggestions to build your own explanation if you want to:

  • Having non-24 is like having to wake up 1h earlier everyday for the rest of your life, just to get to work on time and do your groceries, otherwise the world leaves you behind. This means that regularly you'll wake up and go through your day without any sunlight at all, for weeks at a time, until eventually you see sunlight again. You have to plan all your activities with relative time. Also regularly you'll wake up 3h earlier, sometimes 1h later, there's a lot of randomness between days.
    • To drive the point home for the recalcitrants, and if you're brave, you can call your boss/colleagues/relatives at the same shifted time relative to your biological night. For example if they can't stop calling you when you just went to sleep 2h earlier, you can call them at 2am and go over the points they wished to discuss. This method is plebiscited by r/nightshift workers on reddit.
    • Here is a variation of this approach including a figure, courtesy of u/sprawn :
> It is very difficult to describe N24 to people. Most people tend to think they themselves "don't get very much sleep." And when you describe N24, they think that you "never sleep." Or they might think you "sleep all the time." You describe it, and then they might say, "Oh yeah, I like to sleep in, too!" They just don't get it. One trick I attempt is to show them a graphic like the one below.
> Imagine this is your work schedule. At first they are excited. Oh Great! Noon to 8pm! That's easy. Even the first week seems do-able to them. After the first weekend, they begin to understand. Wait! I can't get to work at 5AM! And then 4AM the next day. No one could do that! And that's when I say, "This is what a 'normal' work or school schedule is for me." What I want to say is, "Oh, it's okay. Take some melatonin, and you'll be fine…" By week three, hopefully they can imagine how impossible it would be to live like this. Forcing yourself to sleep earlier and earlier.
> If they are imaginative, they can come to an understanding of just how difficult that life would be. They think, "Maybe I could handle the first three weeks. Maybe I could use coffee and naps to make this work for a little while." But they will eventually see that sustaining an insane schedule like this (for years) is impossible.
  • Non-24 is like being permanently jet-lagged. My internal timezone changes everyday to an unknown timezone. The change is not constant but chaotic, so it is impossible to accurately predict when to sleep. It affects all aspects of general health and can cause cardiovascular diseases and diabetes, especially when chronically sleep deprived since this disease prevents from sleeping. For some it causes throwing up, dizziness, random fainting, car accidents, sudden cardiac arrest and strokes, and a lot of other very not fun ailments. Just like jetlag, but all the time, everyday of your life.
  • Non-24 is like diabetes before the discovery of insulin: there is no monitoring tool for the circadian rhythm, and we are not sure what causes these disorders nor how to improve them. Using light therapy and melatonin is like taking insulin regulating drugs for diabetics, but here it's regulating the circadian rhythm since our body can't do it properly. Health consequences of unmanaged non-24 are similar to diabetes, leading to cardiovascular diseases such as arrhythmias and even to diabetes and obesity.
  • Even with a working treatment, social and unexpected events makes it difficult to follow the therapy. Just like for diabetics, it's hard to go out while not being able to eat or drink anything because it can kill you with a stroke. Similarly, even when entrained with a working therapy, we would likely have to forego evening and night social events. That's unfortunately the price we have to pay for a stably managed sleep.
  • Non-24 causes chaotic wake up and drowsiness, I cannot plan when I will be awake or asleep.
  • I have a chronic illness that affects my ability to sleep, and for which no cure is known yet.
  • Everybody has a set period to sleep, even typical sleepers: those who can't sleep during the day have shift work disorder, those who can't sleep as early as socially acceptable have DSPD, and those who have a defined sleep period that changes everyday have non-24.
  • For work: I cannot know beforehand when I will sleep and wake up. On top of that, I don't know when I will be productive, as every other day the illness causes a zombie-like state between wakefulness and sleep.
  • If an alarm clock could cure an illness, it wouldn't be an illness.
  • Living with non-24 is living a life in alternance: one month you are good, one month you hibernate and get ill and are fatigued and late and depressed all the time.
  • Living with non-24 is like having a rotating day and night shift work but with no off days whatsoever, including on week-ends.
  • Living with non-24 is a very solitary life, it's like COVID-19 quarantines but for the whole life instead of just a few months. Everything, every errands, every appointments need to be carefully planned and weighted given the health risk.
  • Non-24 is like working a rotating night-and-day schedule that changes all the time. No week-end, no vacations, it's all the time. (And I'm not even paid for that.)
  • An excellent accurate depiction of DSPD was written in this couple's story in the Modern Love column of the New York Times, which was later accurately adapted in the TV series Modern Love S2.2 on Amazon Prime. The story mentions the fairy tale called The Day Boy and the Night Girl, which can also be seen as a depiction of DSPD. This isn't a depiction of non24, but it is very rare to find accurate depictions of circadian rhythm disorders in video media, this can provide a valuable and easy to share and watch medium to family and friends for them to understand what a circadian rhythm disorder is.
  • Here are more suggestions (mirror).

What are effective treatments for circadian rhythm disorders?

Circadian rhythm science is still in its infancy, and hence there are a lot of unknowns and gaps in the scientific knowledge. Therefore, patients are often left to their own device, and not understanding exactly how their disorder works, they try various treatments and approaches that can illusorily appear effective in the short-term but in fact lose any positive effect pretty fast, and can even cause more harm in the mid to long term. Clinicians also often verse into the same pitfalls, with the hope of helping their patients, but given the lack of practical guidelines, they are also left just like their patients to process by trial-and-error.

There is theoretically a simple way to determine if a therapy is effective to manage circadian rhythm disorders: if a treatment can directly shift the circadian rhythm phase, it's effective. Since the circadian rhythm cannot be measured, core body temperature profile over 24h can be used as a proxy since it is strongly coupled with the circadian rhythm. If a treatment cannot shift the circadian rhythm phase nor modify the core body temperature profile, it's ineffective and useless for circadian rhythm disorders (although these treatments can still be helpful for other comorbid issues or disorders).

Hence, if you would like to try other therapies not described in the present document, you can first check the academic literature to know if these interventions change the core body temperature. If they do, it's likely the intervention can shift the circadian rhythm, but if it can't change the core body temperature, it's almost certain it can't shift the circadian rhythm either.

For example:

  • Light therapy, melatonin, and any zeitgeber, can demonstrably and objectively shift the circadian rhythm phase and change the core body temperature profile, hence they can be used as effective management therapies for circadian rhythm disorders, including non-24. See the next section for more infos on zeitgebers.
  • Sleep hygiene, chronotherapy and CBT-i have never been demonstrated to shift the circadian rhythm phase nor to change the core body temperature. They are ineffective to treat circadian rhythm disorders, and should never be attempted as a first-line treatment. Although sleep hygiene can obviously help in other areas, using it as a first-line treatment for circadian rhythm disorders is like advising an alcoholic to eat healthily. Yes it can be a more healthy lifestyle, but this procedure is irrelevant in the context of this clinical entity.

Logically, in accordance with a recently growing body of scientific evidence, another alternative are drugs that increase photosensitivity. Since light therapy affects directly the circadian rhythm and core body temperature, anything that increases the sensitivity to light will also indirectly affect the circadian rhythm, but only when combined with light therapy.

Hence, to summarize, the only drugs that help are those which either directly affect the core body temperature eg melatonin, or sensitivity to light such as antidepressives and ADHD medications. Marijuana and psychedelics cannot manipulate the circadian rhythm. Our body needs a very stable core body temperature to ensure survival, so it's extremely difficult to affect it (humans are endotherm and homeotherm). Manipulating core body temperature is the key to manipulate the cercadian rhythm, but the very safety focused homeostatic processes that safeguard the stability of our core body temperature and hence our survival is also what hinders our ability to manipulate the circadian rhythm.

In practice, this becomes a bit more difficult: how can we know whether a procedure can shift the circadian rhythm? There are mostly two ways:

  • Either look at past academic literature, although there are conflicting results and often false positives, so it requires some training to discern what is viable and what is not.
  • Either test on yourself and measure the effect on your own individual case. There are multiple avenues:
    • The measurement can simply be a sleep diary, but this medium can suffer from high variability so it should be considered as partially unreliable. One way to overcome this is to maintain the sleep diary for a longer period of time (eg, months), to ensure the procedure is consistently effective (and it's not a coincidence with relative coordination - see the section below).
    • A more experimental but more reliable and objective method is to record the core body temperature or wrist skin temperature. See the wearables section for more information.

Accommodations for circadian rhythm disorders including non-24

Disability rights and disability recognition

The very first step to get accommodations with non-24 is to get to learn about your disability rights in your country.

Disabilities recognition and accommodations should be available in most countries in the world, as 164 countries ratified the United Nations' Convention on the Rights of Persons with Disabilities (CRPD), easy read versions are available here and here, and the list of countries that ratified the convention is here. You may choose to use your rights or not, but it is crucial you do the formalities to get acknowledged and to get offered these possibilities if you need them. Do them while you are still able to, because when you will need them, you may be in the incapacity to fulfill the steps or may be in a dire financial situation.

In practice, to get disability recognition is not easy, the eligibility criteria are usually quite harsh, so that only the most debilitating illnesses are eligible (contrary to what the convention states...), and although non24 usually meet them, insurances and clinicians will often fail to recognize that.

First you need to estimate how many days you can (not) work per week, and check your country's eligibility threshold for disability. Usually it's around 2/3rd of disability required at minimum for recognition. There are also othes eligibility criteria you need to check, but the productivity handicap threshold is nearly always the most important. Then you need a medical report / accommodation letter from your sleep specialist describing your difficulties with the illness and how it affect your ability to work, and most important of all, write their (or your) estimation of your productivity handicap, eg, can't work more than 2 days per 7 days due to the illness without accommodations. This doesn't mean that you can't work more with accommodations, in fact the accommodations are there to allow you to be more productive, with an adapted work environment to your condition. Of course, it's necessary first to be medically diagnosed, so if that's not the case yet, check the informations in the Diagnosis section in this document.

Now with the medical accommodation letter, you can check how is the administrative process and the forms needed in your country to ask for a disability recognition. You can also ask for financial help if you need it, but even if you just ask for a disability recognition, this should at least allow you to ask for work accommodations or even financial access to work help (eg, tax reductions for your employer) which would already be tremendously helpful. For insurances benefits, you can remind the ICD code (ICD-10 code is G47.24), which is the basis used in most countries in the world to bill illnesses costs. Note that although non-24 (and other circadian rhythm disorders such as DSPD) are perfectly billable and fit all the criteria of a disability, it may be easier to highlight a comorbidity such as ADHD or autism to open these disabilities rights.

The other sections below describe specific practical accommodations that either you (the patient/employee) or the employer can be reasonably expected to implement. Indeed, the disability rights only guarantee "reasonable accommodations", which is subject to interpretation. It's hence a good idea to check what previous accommodations were implemented for other cases, as this sets a precedent for what is considered reasonable.

Advocacy for the accessibility for people with handicaps

Advocacy, especially for oneself, can sometimes be seen pejoratively, and hence people who could benefit from it, and require it, may avoid doing it. But advocacy is not necessarily selfish, it can be very altruistic, and necessary.

Indeed, people with disabilities have rights in the countries that ratified the UN convention for disabilities rights as explained in the previous section. However, a lot of these people with disabilities are unable to advocate for themselves, for their rights to access facilities and get equal chances than non disabled individuals. Hence, advocating for accessibility of the people with disabilities must necessarily a collective endeavor of the whole society. This includes when you advocate for your own disabilities rights: this also improves the access for others with disabilities who cannot advocate for themselves.

This advocacy culture is currently lacking in most disabilities community, partly because of the self-guilt due to internalized ableism. But inspiration could be taken from the neurodivergent community, especially the autism spectrum community, who have a very developed advocacy culture and numerous publications on the topic.

Furthermore, advocating for disabilities access can also highlight the convergence of other causes, such as costs and ecology footprint reductions.

Indeed, circadian rhythm disorders including non24 and DSPD require accesibility accommodation solutions that actually reduce ecological footprint, such as the direct delivery in a collection point instead of at home which has been made into an official policy the year after, and online meetings (eg, free tools such as Jitsi Meet exist) or even asynchronous communication instead of physical events, which eliminates transportation and hence reduces both the ecological footprint, cost for the attendants, and cost for the hosting institution since they do not have to book a big venue nor food nor hotel. This also reduces viral transmissions risks, another ecological risk. And these accommodations usually require no cost (original survey here), as the american JAN shown.

In summary: We need to take inspiration from autism community's advocacy culture. We need to advocate for oneself's disabilities rights and remind that this also helps for general disabilities inclusion, as solutions for non24 also usually help to include people with other unrelated disabilities. Furthermore, we need to remind that there are also non disabilities related arguments to implementing these accommodations, such as reduced costs and ecological footprints. In other words: nearly all the time, disabilities inclusions involve no cost but actually reduced costs, and so refusing them is often just ideologically motivated but not economically nor ecologically rational. A common example is the mandatory requirement to go back to work physically after covid-19 induced work from home ideological shift. (NB: But in some domains such as research, there are fundings that are given ONLY if physical events are organized - so overall this is still not economically rational, but locally at the scale of the organizers it makes economical sense because otherwise they would not get funding that covers not only the event but also their research - there needs to be a global mindset shift, especially at supranational organizations such as European Union to NOT require ecologically unsustainable practices).

In practice: do not just ask for accommodations for your disability, you may get replies such as "ah yes we would very much like to do so, but we cannot, we will think about it for next time" (even if a simple phone or installing softwares on the presenting computer is enough to make a physical event into a hybrid one...). Instead, ask for your own accommodation, and remind that 1) it also benefits the accessibility for people with other disabilities, illnesses and even pregnant women, 2) it is more ecological, 3) if applicable, that this causes no or negligible cost, or even saves costs.

The book Sleep Misfits: The reality of Delayed Sleep Phase Syndrome & Non-24 by Sally Cat also gives a few other ideas applied by others with circadian rhythm disorders to convince to get accommodations and advocate, such as:

> Nancy Tinney: I once told a medical staffer that I needed an afternoon appointment because I have a circadian rhythm disorder and can't get up before noon. She commented "wow, I wish I could sleep till noon every day!" I told her that saying that to me is like saying to someone in a wheelchair "wow, I wish I could ride everywhere so I didn't have to walk!" she got the point.

Keep in mind that humans cannot comprehend what they did not experience themselves: they can emphathize however, but various levels of explanations are required depending on the recipient's age, background, mindset, mood, etc.

School accommodations for students with the non-24 disorder

Sleep is an essential need for all humans, and is especially crucial for kids, as sleep loss can significantly impair not only their health but also their grades and hence their future. For them to have a fair, equal chance to education and to future work, they are elligible to reasonable accommodations. Reasonable accommodations are accommodations that can be reasonably expected to be implemented by the school, without much cost nor impact on their organization, which is arguably a significant restriction on disabilities rights but nevertheless allows for at least some partial accommodations.

Here are some suggestions of accommodations specifically for students with non-24 that was written by the Sleep Foundation, so you can use that as an official resource to present to the school:

> Students With Non-24-Hour Sleep-Wake Disorder
> As outlined under Section 504 of the 2008 Disabilities Act Amendment Act9, students with disabilities also have the right to an education that meets their needs, whether in elementary, secondary, or post-secondary school. Examples of reasonable accommodation for students might include taking classes online, allowing students to miss some classes and make up the work at another time, or taking a lighter course load.
Source: https://www.sleepfoundation.org/non-24-sleep-wake-disorder/living-managing

In the current document's author's opinion (based on his experience without accommodations), two reasonable accommodations that can significantly improve the fairness of academic training and evaluation of students with non-24 are:

  • Allowing the student to get access to the course content that they not be able to attend, for example by having other students share their course notes, or having handouts of the course by the professor, or online recordings accessible by internet.
  • Not sanctioning the student for their absenteeism, as it is unwillingly caused by their chronic illness. Attendance should not be a limiting factor, the students should be graded based on their academic merit, not their presence. This point is not for comfort, it is a crucial specific accommodation for non-24, since one characteristical effect of this disorder is a chaotic sleep-wake schedule and health status that cannot be planned. A child with non-24 who is sanctioned for missed classes will face the unfair dilemma of either damaging their health and grades by pulling all-nighters repeatedly, or they will face sanctions and potential school exclusion regardless of their academic merit just because of missed attendance. This would be as unacceptable as sanctioning and excluding motor disabled children because they can't participate in most physical exercise classes.

Both of these accommodations cost little to nothing in terms of effort or time (especially the avoiding of sanction of absenteeism) and hence can be considered reasonable accommodations.

The holy grail is asynchronous remote classes, that can be done at home, just as what was organized during the COVID-19 pandemic. But unless such a system is already in place at the school, it can be difficult to consider it a reasonable accommodation if it needs to be completely setup just for one or a few children.

Note that you can also come up with other suggestions, it's not limited to this list. The important thing is that you discuss with the school to find a common ground between your kid's needs and a reasonably implementable accommodation that the school can do without much cost.

See also the rights provided by the United Nations' Convention on the Rights of Persons with Disabilities (CRPD), especially the section "24. Education" in this easy read version.

More ideas of school accommodations: https://web.archive.org/web/20210927021722/https://old.reddit.com/r/N24/comments/ozzqkd/school_accommodations_with_non24/

Hopefully, with increased awareness about (sighted) non-24 in the future, next generation children with non24 will get proper accommodations and won't get unfairly penalized for their unavoidable and unwilling periodic absenteism.

For extreme cases of non-24, parents may consider remote schooling, some countries such as France (CNED) provide official remote schooling curriculum, which would allow the child to sleep and learn according to their biological schedule, but at the expense of reduced sociability and increased time expenditure by the parents as they need to supervise the child.

Note for DSPD: the accommodations are very simple, allow for classes to start later in the day, preferably no earlier than noon. There are plenty of chronobiology researchers and clinicians in several papers already advocating for such a change with later school start times, as it was repeatedly shown to significantly increase the students academic performance.

Example letters of accommodations are available in the members section of the Circadian Sleep Disorders Network website (for those in hardship, membership only costs $5).

Work accommodations with the non-24 disorder

Accomodating the non-24 circadian disorder and its highly variable and mostly unpredictable sleep-wake schedule with a stable work schedule is very challenging, with arguably most individuals with non-24 remaining unemployed most of their lives, regardless of their skillsets.

Indeed, even despite the "Great Resignation" in 2021 following the COVID-19 pandemic's lockdowns and the more widespread use of remote work and teleservices such as telehealth, a job position is still widely seen as a simple equation: presence during clearly delimited hours at work = salary. Even in job positions that are "tasks oriented" such as software development, being absent at the regular office hours is inconducive to developing good relationships with superiors and getting a promotion. Given that individuals with non-24 are fundamentally, technically, biologically incapable of fitting into such constrained work hours for any meaningfully long period of time (ie, less than 6 months), they are fatally predestined to be repeatedly fired and to jump from one job to another, with long periods of unemployment in-between, until at some point most lose any hope or become too old or their skillset too out of fashion to be employable anymore. Anecdotally, this is what happened to the present document's author's father, and despite the current document's author having two masters in profitable industries (artificial intelligence and machine learning ; neurobiology and neuropathology) and running a small company in the past, the same pattern of job jumping and periods of unemployment was experienced, showing how an invasive handicap dwarfs competence.

An often proposed simplistic solution would be to ditch job positions, and to make your own company, or work as a freelance, in other words: to be your own boss. Although this is certainly a more promising path, as there is more latitude to define your own workflow, you are still restricted to delimited working hours that are those of your clients. One solution is to found a company that can provide services or products to international customers, with an online front, so that you can work mostly asynchronously with clients. In other words, to ensure financial safety and independance, an individual with non-24 needs to seek an independent, asynchronous, online and international workflow.

Nevertheless, this path is hard and not achievable without having funds first, so that a standard job position is still required at least at first. Although no definitive solution exists, here are some ideas for accomodations for a standard job position, to optimize the chances of a stable employment and productivity with the non-24 disorder:

  • Get your disorder recognized medically (see the section on diagnosis), then as a disability. This will allow to get "access to employment" helps, including accommodations from your employer and financial help (eg, tax reductions) for your employer or yourself if needed.

  • In terms of practical work scheduling, foremost, seek to strive in an asynchronous workflow. Working remotely is not sufficient: because of the variable sleep-wake schedule, remote appointments at set times will also be as impossible to regularly achieve as in-person meetings. Likewise, flexible hours jobs aren't adequate either, since the variable sleep-wake schedule is unpredictable and makes planning "awake hours" impossible from one day to the next. Hence, the job needs to be achievable with no set hours, it's necessary to be able to accomplish work tasks at anytime of the day and night, whenever you are awake. Hence, prefer e-mails to chats (such as Slack) and (rare) videoconferences. If meetings are necessary, prefer videoconferences rather than in-person meetings, as these will allow you to get back to sleep just after in case they are scheduled in the middle of your circadian night (which is challenging to predict beforehand since the circadian rhythm is always moving with non-24, so usually it's impossible to predict exactly beyond a week before the scheduled date of the meeting). However, keep in mind that any event disrupting your circadian night will affect your sleep and work over the next days and hence your productivity, hence they should be avoided as much as possible when the circadian rhythm is not in phase with the day-night cycle. If possible, ask for recording all videoconferencing sessions so that you can watch them at anytime later at your convenience, and it can be useful for your team for archival purposes.
    • According to a GitLab report "Killing Time At Work" (see also here), remote work should always involve a shift to an asynchronous workflow to be efficient, otherwise a majority of employees will tend to behave with digital presenteeism, ie, being present online at the usual 9-5 office hours even if this is not required by their tasks. They also are dithyrambic in their opinion that the COVID-19 pandemy should have been used more effectively and aggresssively as an opportunity to transition from old less effective productivity theater oriented workflows to more asynchronous and humane workflows. They offer a short cheatsheet of guidance to transition to an asynchronous workflow.

  • Seek a non-scheduled work position with minimal time-fixed events and planning, because: 1) due to non-24, it's often impossible to ascertain whether a time fixed event will happen during a sleep session, 2) it's also often impossible to determine how long and good a sleep session will be, hence it's necessary to take into account that several, if not most (depending on responsiveness to entrainment therapy), days will be spent exhausted, with very little productivity. These two points aren't exclusive, as interrupting a sleep session to meet a time fixed event such as an appointment will cause more exhaustion the next days due to the increased sleep deprivation that will take more time to clear up. The major source of time fixed events is business interpersonal relationships (ie, meetings), hence avoid any work that primarily involves client relationships or interactions with other humans, such as sales. Prefer works that can be done independently from other humans. Freelancing can be a partial solution but unfortunately incomplete as it still requires business client relationships, but it can be managed to your convenience as to reduce (but not eliminate) the impact on your sleep. Only non-scheduled jobs can fully accommodate non24, but flexible schedules are potentially partially possible with non24 although at the cost of some amount of chronic sleep deprivation, so the practical possibility depends on the exact terms of the flexible schedule position.

  • Adopt a task-based agenda instead of date-based or deadlines agenda. As with many chronic illnesses, energy levels can fluctuate a lot and imprevisibly from one day to the next with non-24. Hence, a usual date-based agenda (ie, "Do errands on Tuesday") is likely going to fail and lead to more self-shaming. Instead, adopt a task-based agenda, based on priorities: do first what matters you most, whenever you feel energized enough to do so. If you can't today, try tomorrow, and don't beat yourself meanwhile, allow yourself to rest whenever you need. It's necessary to regularly re-evaluate priorities as time passes. However, avoid a deadline approach, as any fixed date is likely going to be missed, even if it's "only" a personal deadline. Just plan tasks you want to achieve and rank their priorities according to what matters to you most. What matters is that you do what matters to you, not that you meet a specific deadline. It is unfortunately illusory to hope to meet deadlines when you have a chronic illness, especially a chronic illness such as non-24 that specifically impairs our temporal capacities.

  • Learn to rush/botch your work, especially if you are a perfectionnist. As the saying goes: done is better than perfect. With a chronic illness such as non-24, it's necessary to plan to have at least half as less time, and often much less, for any activity than non afflicted individuals. How much can you complete in half the time someone else has? This is what you need to aim for. If then you have time left, you can always further your work, but at least get the most important parts done, the crucial ones, and work on finition much later on if you have time left for that. This doesn't mean you should do work nor good quality work, but you need to significantly lower the bar and focus on fewer items, focus on the primary set of things that needs to be done for the thing to at least be functional/useful/interesting, the rest comes later.

  • The working memory (both verbal and visuospatial) are drastically impaired under sleep deprivation. Although sleep deprivation can be reduced with proper management of non-24, it's unlikely to be completely avoided and will still be a regular occurrence. It's necessary to take into account this impairment to reduce the potential for mistakes or accidents. A workaround is to prefer writing for communication and workflows, rather than oral communications, as the written supports will reduce the need to use your working memory.

  • It's crucial to account for a very prevalent cognitive bias: "out of sight, out of mind". This means that it's necessary to show up to meet your boss and colleagues from time to time to assert your presence and position in the team, otherwise you will be forgotten. Indeed, work quality and completion is not sufficient, humans forget what they do not see, and start acting regardless of the "missing" elements. This is not even specific to circadian rhythm disorders, as this phenomenon can also be observed with night shift workers, whether in the professional or private sphere. Since the workflow of a non-24 is necessarily asynchronous to be healthy and sustainable, this means there will be fewer opportunities to meet and assert one's own presence and position in the team. To optimize, the meetings can be selected: annual meetings, key projects deadline meetings and other key meetings should be attended, as long as it does not impact health too much (ie, these meetings need to be interspesed and rare, if they are weekly occurrences this is unsustainable, max is bimonthly). Any unnecessary meeting that can be done by an asynchronous mean such as e-mail should be done this way. Do not make the usual mistake of considering that work quality and productivity is sufficient: they are not. Even if you are an over-achiever and finish all tasks beyond expectations, you and your achievements will be quickly forgotten or not even accounted for if you do not show up from time to time.

  • Always take into account that you will always have far less opportunities than someone else with same or less abilities or qualifications, just because of the mismatch between your circadian rhythm and the rest of the world. This is a mechanical consequence of the non-24 disorder, as most opportunities are related to the actions of other humans and business networking relationships, so that if you are asleep when they are doing these actions, you miss most of the events, and hence the opportunities. There is no way around this "bad luck". The only thing that can be done is to be aware of this limitation so that to put safeguards in place for when you are asleep, and hence to maximally exploit the few opportunities you get access to.

  • Put your safety first. Do not drive if you are sleep deprived, you will have worse decisional capabilities and slower reaction time, just like as if you were drunk. In fact, sleepiness is the greatest cause of accidents in all modes of transport, far surpassing alcohol. Instead, prefer to plan ahead and use other means of transportation. If you are not sleep deprived but your circadian night will happen during the time you plan to drive, avoid driving as you are more likely to doze off on the wheel, especially for long driving sessions (eg, cross-country). Although not studied, circadian misalignment is very likely to contribute to dozing off while driving, whereas sleep deprivation is a well established factor.

  • To increase your productivity, energy levels and mood/motivation, manipulate light and your sleep pattern to your advantage:
    • Always favor naps/siesta when you can. In terms of productivity, several studies of "assessments of vigilance in monophasic versus polyphasic sleep schedules indicate that performance is comparable given equivalent time in bed (Nicholson et al., 1985; Mollicone et al., 2007; Mollicone, 2008)", which means that what matters is indeed the cumulated total sleep duration of all the sleep periods under a circadian period, including naps, to assess sleep deprivation which is in fine what determines decreases of productivity. In other words, you will be more likely to be productive after napping if you were sleep deprived than by trying to forcefully work instead, as the cognitive fog due to sleep deprivation will drastically decrease productivity (mood and cognitive impairments are curvilinearly correlated with the amount of chronic sleep deprivation). Better to have a few hours of productivity than a day of unproductivity.
    • use light therapy for several hours in the circadian morning and/or day, this greatly increases energy levels and reduces negative mood. This effect of bright light therapy is as beneficial and crucial as its circadian rhythm shifting effect.
    • avoid dark therapy when you are still in your circadian day. Indeed, humans are diurnal animals, so that their behaviors and activities will become more sluggish under darkness even if they are not sleeping. Hence, although dark therapy is a crucial component of circadian rhythm disorders therapies, it is also important to not use it when it is unnecessary. Hence, even if it's night, if your body is still under its circadian day, keeping the room's lighting reasonably bright will significantly bolster productivity. In case of doubt, using a configurable LED bulb such as Yeelight S1 and setting it at a warm yellow or rosé (between yellow and red) with a medium intensity offers a middle ground between bright enough intensity to not hinder activities if it's your circadian day while also being unlikely to significantly suppress melatonin nor delay the circadian phase if it's your circadian night.
    • For individuals with a circadian rhythm disorder such as non-24, having a bifurcated circadian rhythm (achievable using light-dark therapy, see the related section elsewhere in this document) can have significant advantages, such as allowing 2 windows of activity, one during the objective daytime and one during the objective night (whereas nightwalkers such as inversely phased non-24 or extreme DSPD will not have activity opportunities during daytime). For those suffering from chronic fatigue due to chronic circadian misalignment, LDLD allows to multiply by 2 the number of activity periods and rest periods, so this probabilistically increases tremendously the likelihood of experiencing productive activity periods, whereas with a typical schedule the next opportunity is only in 24h, here it can be 12h or even earlier depending on the LDLD scheme used.

  • Keep in mind that sleep deprivation and circadian misalignment will cause increased focus difficulties, more precisely your brain wil prioritize external stimulations over internal actions, and with severe sleep deprivation, only external stimuli will keep you awake. This can sometimes be used to your advantage, by being constantly listening to music (in headphones to not bother your surroundings), although of course use your judgment, as music may not be fit for some situations where it can put you at additional risk. Another trick is to do physical tasks when sleep deprived, as although it will be more painful to you, they do not require much focus (depending on the physical task of course). In summary, anything that can provide external stimuli will keep you awake when sleep deprived, whereas self-generated thoughts are much more difficult to focus on (such as reading).

  • Setup and furnish your work environment to allow for both working and sleeping, as sleep disorders makes wakefulness very fleeting and varying, which makes it necessary to work in an environment accomodating both wakefulness and sleep and everything in-between. For example, having a couch in addition to an ergonomic chair, and a mobile table to move the workstation to either. Such an environment will allow you to nap or to work in a laid down, more comfortable position when you are tired. Although it is usually disadvised to work in a laid down position, this recommendation is made by people who do not have energy issues due to a sleep disorder, for whom it is regularly impossible to work in a usual sitting position. Working in a laid down position allows to reduce physical energy expenditure and hence allow the body to allocate more ressources to cognitive functions. Ergonomic chairs make a real difference, especially when energy levels are low, as they reduce the tiredness from lombar support by transferring the weight onto the chair. Inexpensive ergonomic chairs are available from some manufacturers such as Sihoo or mFavour.

  • The only perennial workspace for non-24 is at home. Due to non-24, the workspace needs to be accessible to work at any time of day and night, to be comfortable and safe for sleeping at any time of day and night, and to be accessible without driving to eliminate the very real risk of car accident due to drowsiness. Realistically, only a home workspace fits with all of these criteria. Dedicate a room for work, separate from the sleep space. Furbish it adequately for both work and impromptu naps/sleep, you can't expect to work to professional standards under an unprofessional environment and with no professional furniture.

  • Expect to work at any time of day and night. If you can't sleep after 30min of laying down, get out of bed and get back to activities, including work if you want. You can't force yourself to sleep, closing your eyes and wishes aren't going to make you sleep. But when you'll feel ready to sleep, go back to take another try, but expect this won't happen before several hours so you have time to work or do other activities meanwhile.

  • Work whenever you have enough energy on the most important/urgent tasks, as you never know when you will get enough energy again (it can be days or weeks from now), and do not wait for full energy level to work, as this will fluctuate a lot from day to day and during the day. Keep a set of tasks you can do with lower energy levels, and try to do what you can. Accept that you may not be able to achieve the tasks, aim to work and progress, not to complete. Far more will be accomplished by working on minor tasks at a slow pace and reduced capacity than not working at all. There are days when cognitive dysfunctions will be so great that you cannot achieve anything (ie, impossible to focus and think), accept these bad days as part of the illness.

  • Find smartphone apps that can be used for your work, so that you can work everywhere at anytime. The lack of a routine in non24 makes it hard to have a defined period at the desk, hence smartphone apps can circumvent partially this lack of physical routine. However be careful not to be overloaded, make sure to disable your smartphone's notifications when you need to sleep.

  • A few tips to organize in practice for appointments:
    • use a chronobiological alarm clock (also called "smart alarm clock"), which monitors the user's sleep stages via actigraphy and vibrate when it detects the user is in a light sleep stage, such as Sleeptracker Pro (discontinued), Fitbit or Sleep as Android (but apps are much less effective than wearables worn on the wrist since it requires actigraphy). Make sure to select the model that offers both a smart alarm and vibration, it's much more effective and with vibration than an auditive signal.
    • for appointments very far in the future, too far for you to predict your circadian phase, try to ask to schedule the same appointment but twice in the same day: one in the morning, and one towards the end of office hours, and that you will call the day before to cancel one or the other. If the office seems reluctant, explain that you have a severe disability, so you cannot know at what time you will be able to go, so having two drastically help improve the odds. This way, by the time the appointment comes, whether you are night walking or day walking, one of the two appointments will likely be during your circadian day.
    • try to stack as many appointments in one day, and leave at least one but preferably "free days" with no appointment in-between days with appointments. This way, you can have some time to recover between days when you have appointments and have to cut on your sleep. The worst is to have appointments at specific times every days, as this will force you to suffer sleep deprivation consecutively with no recovery time, this is very dangerous for health and drastically decrease your productivity. Try to interspece "appointments days" as far as possible, the more recovery/free days the better for your health and productivity. When you have one appointment, it's highly likely you will have to be sleep deprived as it is unlikely that it will be during your circadian day, hence you can as well stack as many appointments during this day so that you can plan to be able to recover the next day (by sleeping/napping whenever needed). Note that one or two days are just barely enough to recover from one day of sleep deprivation, but an all-nighter OR suffering from sleep deprivation over several days/weeks will require many more recovery days, there is some proportionality.

Furthermore, the data on insomnia likely also applies to unmanaged non-24:
> With respect to vocational performance, several studies have found that sleep disturbance and/or chronic insomnia are associated with less job satisfaction, lower performance scores, less productivity, and higher rates of absenteeism.13,14 A study by Leger et al15 found that those with insomnia had more absenteeism compared to good sleepers (31% vs 19%) and made more errors at work in the previous month (15% vs 6%) and that 18% of those with insomnia, versus 8% of good sleepers, reported poor work efficiency in the past month. [...] Individuals with a variety of sleep disorders are thought to be at increased risk for motor vehicle accidents.18 Patients with insomnia in particular have been found to be 2½ times more likely to report car crashes because of feeling tired as compared to those who do not report insomnia.

A 2020 systematic review on sleep disturbances and risk of sick leave found the following:
> Sleep disturbances are risk factors for sick leave. Sleep problems can lead to various health problems that affect the amount of sick leave. Improving sleep quality can have a decisive impact on job performance.

There are several resources to help you navigate how to request work accommodations:

Non-exhaustive list of potential jobs for non24, that would fit the independent asynchronous remote workflow (and online for some):
- content creator for youtube or other on-demand content platforms
- taxi driver (but need enough cath to buy a car)
- artistic works (drawing, photography, literacy, voice acting, etc) with platforms like fiverr to get an async job.
- forex and crypto trading (because these markets are always open, especially crypto, although stock market does influence both and has set hours)
- any work where sales of virtual goods/services are asynchronous and hence can be done while you sleep. Eg, for an artist, an online gallery shop of images you make that visitors can buy online. Or a pro subscription to a software package you develop vs a free one accessible to all but with less features, this example is actually a business i successfully ran for a few years, clients contacted me by e-mail for informations or feature requests, that I then developed at my own pace, and all pro users got notifications and access to the regularly updated software. Can also be an automated web app that provides a service, such as any website with interesting content and ads to generate revenue on web 1.0, platforms that allow users to submit content and others to buy and your platform gets a cut on web 2.0, or crypto defi platforms on web 3.0. In both cases, the platforms offer a service asynchronously even when you are not there. It's a lot if work and stress to maintain, but it can be very prolific. To make sync sales, either need to sell artistic virtual goods, or softwares for professionals, ie, that save them either time or help them gain money.

Some tools may help with organizing setting up and monitoring your own work schedules tailored for non-24:

  • Rotime is a web app available for desktop (Windows, Linux, MacOSX) and mobile (Android, iOS) specifically tailored for people with non-24 and other circadian rhythm disorders. The main demographic is workers with circadian rhythm disorders or shift work, but it can be used by anyone who want to schedule their days on a dynamic non-24 timeframe. You can enter your tasks, their durations, and then the app allows to easily rotate the time you start these tasks. It's a great app for designing a work schedule in general, but not for specific tasks. There is a free version for one day, or an older free version all the time in WebArchive, or a paid version with more features and to support further development.
  • For specific tasks, open-source softwares such as Super Productivity (cross-platform) or OneList/1List (for Android) are great.
  • WarpClock is an open-source alarm clock for Android that calculates when to ring based on how long you want to sleep, so that you don't have to do any math before sleeping. This can also be used during the circadian day to time activities, such as work tasks billing, or set to the individual's non24 period to remind them where they are in their circadian day.
  • FairEmail is an open-source Android e-mail client app that works with most e-mail providers including GMail and provides advanced features such as delayed sending.
  • For programmers, git-privacy is a potentially useful tool to hide commit datetime in git history, a similar idea to delayed sending of e-mails.
  • Try to find mobile apps for most of the tasks you are used to do on computers, so that you are more mobile and can work anywhere. For example, for note-taking, Markor is an awesome open-source Android app, compatible with desktop note-taking apps such as MarkText and Zim Desktop Wiki, and automatic synchronization can be done with open-source tools such as SyncThing.

Additional unorganized information:

  • Expect to often be late if you have appointments. The non-24 makes it difficult to plan ahead of time at what time you will be awake, and so any planning becomes more difficult and productive time during office hours becomes compressed, so that you often end up trying to frantically complete as many tasks as possible under a very tight schedule, which is often impossible. Lower your expectations accordingly, and try to avoid appointments as much as possible, flexible schedules are necessary, so prefer deadline and task based schedules which do not require a completion at a specific time during the day.
  • Sleep deprivation impairs temporal preparation, so this also participates in the higher likelihood of being late as it makes it difficult to adequately prepare on time, every act becomes delayed and rely on automaticity.
  • Since the non-24 disorder makes it hard to maintain a stable employment status, it's necessary to plan to invest part of the earned money during the employed periods to build a safety fund, as is common practice for independent contractors. The first step is to learn how to be more financially literate. The videos of Mark Tilbury are a great start point.
  • When sleep deprived, impairments in thoughts inhibition (ie, running thoughts) can be expected, hence on those days avoid interruptions especially social, as they will be much more disruptive to the workflow than on days with less sleep deprivation.
  • The home environment is also important for work, especially since with non-24 you will live and work mostly at home. It's necessary to choose a home environment that is well exposed to sunlight, especially in the morning, which will reduce the need or duration for bright light therapy, but also can be equipped with blackout opaque curtains to allow you to fully control your exposure to bright light (and avoid it when necessary). Thus, avoid living at the ground/first floor of a building, the higher is better.
  • At school, ask to favor mid term and end of term exams for kids with a circadian rhythm disorder, avoid "continuous exams" (ie, frequent exams done during classes) as these require the students to always be present in class, which is fine and can fit better for some kids, but certainly not for those with circadian rhythm disorders such as DSPD or especially non-24.
  • There are a few initiatives to help signal hidden disabilities and get discreet help or accommodations, such as the Hidden Disabilities Sunflower which is implemented since 2016 by several traveling entities in UK such as airports, railway, supermarkets, etc.
  • When presenting your non24 disorder to work colleagues and superiors, call it a "handicap", not a "disorder". Because what matters work-wise is not what it is, but how it affects your productivity.
  • Here is a list of complaints and tips by individuals suffering from circadian rhythm disorders, demonstrating these issues are common for them, and these resources can provide additional practical advices and ideas for accommodations:

TODO: Add infos about chronic diseases and unemployment:

  • The easiest and most common form of employment is the simple exchange of chronic time expenditure for payment. However, this time expenditure is always depending on the needs of the employer, and in general dependent on commercial aspects such as when clients are mostly present, and hence always entails a predefined schedule (whether fixed or dynamic, it still disregards the individual's sleep needs, especially if out of normal ranges).
  • When presented with the almost insurmountable barriers to employment the disorder entails, interlocutors of individuals with non-24 often suggest to simply run your own company, as the panacea to all scheduling issues. While this is certainly a potentially more successful alternative to employment, this is far from the panacea, as it suffers from a similar issue: an entrepreneur's work schedule is also at least partially if not fully defined by social constraints, such as commercial relationships with clients who will present themselves during regular office hours and rarely at night and even more rarely at a rotating schedule, and the management of employees, who need oversight especially during the starting years of a new company. Some interlocutors will interject that some famous CEOs such as Steve Jobs or Mark Zuckerberg are known to be almost always out of their office, they can work (or not) at anytime and whenever they want. While this is true, this only works for companies that are already very successful and well established, which is a low likelihood, since most companies end in failure.
  • Some interlocuters will suggest to "just grind it out" until you can afford to be such a CEO, and meanwhile just work despite no to little sleep. The only response that can be given is: "would you also be able to grind it out without food / under malnourishment for years before getting paid adequately?", since, just like food, sleep is a necessary and unavoidable need. Planning to forego sleep for years, as is required to grind a company out of the startup phase, is just like trying to grind it out while being malnourished, this drastically reduces performance and the chances of success, over the already low chances of making a new business a viable long-term prospect. Hence, the non-24 is always a severe handicap to employment and entrepreneurship, as it bars from employment and drastically reduces the already low odds of successful entrepreneurship. A practical example: Google products free certifications + fiverr pro, see tutorial: https://youtu.be/Dy1gz4We3Yc

Here are a few ideas of potential jobs for non24 (non-exhaustive list!):

  • content creator for youtube or other on-demand content platforms
  • taxi driver (but need enough cath to buy a car)
  • artistic works (drawing, photography, literacy, voice acting, etc) with platforms like fiverr to get an async job.
  • forex and crypto trading (because markets are always open, especially crypto, although stock market does influence both)
  • any work where sales of virtual goods/services are asynchronous and hence can be done while you sleep. Eg, for an artist, an online gallery shop of images you make that visitors can buy online. Or a pro subscription to a software package you develop vs a free one accessible to all but with less features, this example is actually a business i successfully ran for a few years, clients contacted me by e-mail for informations or feature requests, that I then developed at my own pace, and all pro users got notifications and access to the regularly updated software. Can also be an automated web app that provides a service, such as any website with interesting content and ads to generate revenue on web 1.0, platforms that allow users to submit content and others to buy and your platform gets a cut on web 2.0, or crypto defi platforms on web 3.0. In both cases, the platforms offer a service asynchronously even when you are not there. It's a lot if work and stress to maintain, but it can be very prolific. To make sync sales, either need to sell artistic virtual goods, or softwares for professionals, ie, that save them either time or help them gain money.
  • Online consulting jobs can be a middle ground solution: they aren't fully asynchronous, but you can schedule your clients appointments when you want and potentially around the clock if the job can be offered internationally, and most of the work can be done asynchronously. The big advantage is that there are online consulting jobs in pretty much all segments of the work landscape, eg, typically computer science is the most indicated and it's possible to get free education such as by getting a (free) Google certification for SEO optimization or ads optimization using Google systems, but there are also online consulting jobs in law (eg, legal tech), or even just educating parents to manage their newborn's sleep, there are lots of consultants who do that. All that is required is an expertise in skillset that is often needed and that can be done remotely.

Hence, diagnosing non-24 early in life, especially in childhood, can arguably help the individual pursue early on a career that can lead to a more adequate job for someone with a non-24 disorder. Indeed, when the diagnosis is made later at adulthood, it can be very difficult or impossible to redirect one's career so late in life.

For DSPD, an example letter of accommodations are available in the members section of the Circadian Sleep Disorders Network website (for those in hardship, membership only costs $5).

Home accommodations

Living in an adapted environment is crucial for any individual with a chronic illness, even more for those living in couples or with their family.

Here are some ideas for a home environment adapted to non-24 and other circadian rhythm disorders:

  • Move/choose a home with a separated livingroom, and where each room (including kitchen and sanitary) can be accessed without passing through or close to the bedroom. This is the most important tip, as this allows to make the livingroom the literal living room, where you or your partner/family can wake up and go to to do their activities without bothering those who are asleep. The idea is not to make big noises, but to be able to do the necessary activities without bothering others, such as cooking (carefully to lower noise), going to sanitary, and doing any kind of activity in the livingroom as long as it's not too noisy. For example, talking at a reasonable sound level should be possible at any time of day and night in the livingroom. Anyone should be able to go to the bedroom to sleep at any time, whether day or night, without impacting the activities of others in other rooms. Hence, the best are homes where each room is connected through a corridor, not through other rooms. This tip works for both non-24 and DSPD and is the single biggest improvement that can be made, see for example this New York Times story that was adapted in the Amazon Prime's Modern Love S2.2 episode. This reduces the "walking on eggshells" issue but does not eliminate it, especially not for the individual with the circadian rhythm disorder since they will still have to mind neighbors when they are awake at night (ie, nightwalking).
  • Reduce noise when you sleep, and take it into account as a primary factor when moving to another home. This is crucially important, as noise during sleep, even if heard only unconsciously (ie, no memories of interruptions due to noise at wake-up), it will still greatly impair sleep quality, to the point of feeling permanently exhausted. For example: building works that are common in cities especially in September-November ("back to work" season) and which usually start everyday at 8am and hence can overlap pretty much with a delayed circadian night (DSPD or non-24), relatives or neighbors in a too small flat, etc. Hence, living in cities is likely not a good idea, especially around the arteries or big roads.
  • Given the two points above, the ideal home environment for someone with a circadian rhythm disorder is hence an independent house. Otherwise, there is no other way than to permanently live on eggshells, which is very strenuous and limiting. But this is unfortunately a catch-22, as it is difficult to acquire the financial stability necessary to access the housing market when hindered by a disability.
  • Procure and use as many silent tools as you can find, they can be crucially helpful to improve quality of life and health, by allowing to do activities during night time without bothering neighbors:
    • Buy bluetooth bone conduction headphones. This will allow to use TV and computer at night, without bothering anyone. Usually, multiple headphones can be paired to the same device, so that for example if you have non24 and your kids have too, they can wake up at night, go to the livingroom (see the previous point), and watch TV or use a computer to watch films and anime, and you can even watch with them if you both have headphones! The advantage with bone conduction headphones is that they are very silent to others and also that they do not make the ears become itchy, so they are very comfortable and they do not damage the ear canals. This allows to freeroam and do activities just as if it was day and the speakers were used, but it's a wireless transmission instead that is silent to the environment. You can share some piece of musics and movies with your kids this way, just like you would in the day.
    • Regular physical exercise is necessary for optimal cognitive performance and to improve endurance and hence energy levels. But it can be challenging with circadian rhythm disorders, especially non-24, to go to the gym because of the mismatch with the opening hours or the risk of exercising outside at night, especially for women. An at-home inexpensive but effective alternative is to use resistance bands. Indeed, resistance bands traning was shown by a systematic review to be as effective as conventional resistance training including free weights for muscular and strength gain. Resistance bands allow to do all exercises achievable using free weights (see James Grage tutorials including this excellent beginners tutorial). They can also be used to train cardio in combination with a HIIT or TABATA routine. These can be bought for 30 euros for cheap ones (eg, Decathlon) to 100 euros for the top quality (Undersun Fitness). Prefer to use loop type resistance bands rather than cord-like bands, as the former allow for a broader set of exercises and are more robust over time. Another great advantage is that they are silent, which allows individuals with circadian rhythm disorders the opportunity to train at night without bothering neighbors nor risk going to the gym by night.

Coping and accepting a chronic illness and invisible handicap

Certainly, one of the greatest challenges of acquiring, or discovering, a chronic illness such as non-24 and other circadian rhythm disorders is the necessity to learn how to cope and accept the disease and its chronicity (ie, that the disease is not curable and can only be partially managed with great efforts) and the invisible handicap this causes. Disease acceptance is a lengthy and grueling process spanning years if not decades. Acceptance is more formally called "normalizing" in the academic litterature.

The denial phase is very common and arguably the longest phase. Ignoring the limitations that are inherent to a disability is very different from acknowledging and working around the disability. The former, which is denial, is a sure way to crash into the wall at some point, whereas the latter, acceptance and understanding of the limitations, is the only viable long term solution that can allow to recover a better quality of life to some degree. One very important step to go out of the denial phase is to suppress wishful thinking, which is to believe that the illness can be overcome by willpower, which is a hard fallacy that bit everyone during the COVID-19 pandemic, and is a necessary step to pass through for all individuals with a chronic illness.

It is hence crucial to accept circadian rhythm disorders, and especially non-24, as a debilitating, severe invisible disability. Indeed, they bar from accessing virtually every work positions that exist, whether as employee or as a business owner, due to the severe disruptions they cause in social, cognitive and physical functions. The social disruptions are especially critical, as they cause a physical, logical incompatibility between the person with non24's sleep-wake schedule and the social expectations. Statistics estimate show that contrary to the naive assumptions, 80% of individuals with handicaps have an invisible handicap, whereas only 2% are in a wheelchair. Stigmatisation, as per the works of Erving Goffman, is the major problem individuals with handicaps, invisible or visible, face from society. The stigmatisation of being perceived as lazy is not specific to sleep disorders, but is a common societal mischaracterization of individuals with invisible handicaps, as they are peirceved as lacking the effort to simply willfully fix their handicap that causes them to be incomprehensibly unable to perform simple actions, in this case the ability to sleep at socially acceptable hours at night.

It is important to note that acceptance is here not meant in the usual, idealized form of accepting means that the individual is not affected by the disease anymore and everything gets better and positive. This is unfortunately a widespread ableist view of what acceptance is. Because the disease stays there, it is chronic, it likely does not ever get better for most. There is nothing that can make this soul crushing experience positive. Instead, realistic acceptance consists in accounting for the chronic illness, to acknowledge it really exists and that the individual has it, will likely keep it the rest of their lives, and to plan around it, instead of wishfully thinking it can be powered through via will, as the latter is a sure fire way to head straight into the wall. Acceptance really means to learn how to live with the chronic illness, not despite it, not via its strengths (as usually they provide none), but simply with it. It does not mean to be happy about it, just like accepting the death of a cherished one does not mean it will ever become a positive experience.

Rather than paraphrasing, we will extensively cite extracts from this impressively accurate and fairly exhaustive academic work: The Handbook of Social Studies in Health and Medicine, 2003, chapter Experiencing Chronic Illness, pp 277-292, ISBN: 0761942726, 9780761942726 :

> Chronically ill people seldom want to be invalids; they wish to be accepted as valid adults. Their self-doubts rise if other people imply that they wanted to get sick or harbor questionable motives for seeking care and claiming special needs: 'Are my symptoms real or all in my head?'. Their symptoms may be intermittent or gradually increase until they interfere with everyday life. The person cannot meet obligations, keep up with coworkers, maintain their households, or handle daily child care. Esoteric and invisible illnesses often prove elusive. Then, symptoms may become pronounced before they are recognized as such. Yet, ill people do delay seeking help if it poses risk of further loss. Social purposes rather than health needs take priority. People delay seeking help when they risk losing valued roles, responsibilities, and images of self. For example, a parent who resists relinquishing child-care duties may defer seeking help.
> Recognition of diminished function or inexplicable symptoms spurs a diagnostic search. Stewart and Sullivan (1982) found that patients with multiple sclerosis began their diagnostic search when they could no longer explain their symptoms. However, physicians and relatives typically did not affirm their symptoms as real until after diagnosis more than 2 years later. During this time, ill people live in 'diagnostic limbo' suspended in time. These patients often seek multiple physicians when their complains are discounted and dismissed. Discounting and dismissal also may occur after a problem has been defined as chronic but practitioners cannot ameliorate it, such as chronic back pain.
> Diagnostic shock follows an announcement of serious illness that shows up in testing -- cancer, multiple sclerosis, and diabetes -- before patients either note symptoms or grant them any significance. From the patient's viewpoint, diagnostic shock occurs without warning, such as during a routine physical. Part of the shock means having reality discomfirmed. Not only are the person's suppositions about his body shaken, but also to the extent that a diagnosis has foreboding meaning, prior reality is disconfirmed as this diagnosis is confirmed. Subsequently, prior identities are also disconfirmed. When people do not anticipate bad news, have little knowledge and few symptoms of their confirmed diagnosis, the disparity between diagnosis and self-concept is greatest. Then the person needs time, bodily experiences, social encounters, and self-definitions to redefine self and identity. Meanwhile, the diagnosis confirms being catapulted into a patient role. A new label, a new identity has been applied and given. Yet even the most dreaded and seemingly known diseases such as AIDS, leprosy, and cancer require learning what being ill means.
> Learning what Illness means
> In order to be ill, someone has to feel sick. Merely being informed that one has a disease seldom suffices. Until a person defines changes in bodily feeling or function, she may postpone dealing with a diagnosis, even a serious one, and subsequently ignore medical advice and regimen. Illness does not seem real. Then the person may cleam that the diagnosis is wrong, secondary, or inconsequential, and relations with practitioners suffer accordingly.
> People learn what illness is through their experience of it. Lessons in chronicity come in small everyday experiences such as difficulty in opening a can, bending over to pick up a newspaper, folding bedsheets, and weeding the garden. Comparisons with past effortless performance can be shocking. Such jolts later become measures explicitly sought and then assessed. A man with heart disease who used to stride across a golf course now shuffles half way across the company parking lot. A present reality jolt can be reinvoked as a future measure. Measures include time -- the person can only get through part of the work day, rest requirements become apparent to coworkers, fulfilling work standards takes hours or days longer. Indicators become measures when they are impossible to gloss over or to have someone else camouflage. A person may invoke measures, or other people may supply them. These measures can multiply and form a general standard against which to judge self.
> Historical, cultural, social, and situational contexts influence meanings of illness. Waxler (1981) argues that in every society, the sick person learns to take a role that society expects. [...]

Aparté: this progressive learning through experience of what a chronic illness is like is perfectly illustrated by the "spoon theory" by Christine Miserandino (although this is not a theory at all). This can also be used to explain chronic illnesses to external observers and relatives.

> Normalizing Illness and Regimen
> Normalizing illness and regimen means making them routine, and treating whatever changes and improvisations are created as ordinary. For some people, normalizing means letting past plans and projects go and scaling life down. For others, it means struggling with illness and regimen to make life manageable so a valued future is possible. In both cases, normalizing means adapting to the situation at hand. It also means proceeding with activities 'as if normal'. Normalizing means finding ways to minimize the impact of illness, disability, and regimen on daily life, including their visibility. It constitutes an attempt to contain illness to personal experience and not intrude upon interaction. Thus, chronically ill people cover up limitations and keep up normal appearances and activities. They normalize a certain amount of discomfort when they can still function in ordinary ways. Such strategies become hazardous if a person overextends his capacities and perhabs harms an already compromised body.
> However, when ill people normalize symptom control and regimen, they may increase their capacities and maintain their health. This kind of normalizing means making new routines the norm and the normal. What earlier seemed bizarre becomes customary and comfortable. [...] As innovations and changes become routine and accepted, they feel normal and allow the ill person to view the self as normal and they way of living now as natural.
> Normalization reduces disruption. It softens the impact of frailty and disability. Through normalizing, ill people take their way of being and the changes they have endured for granted. As their lives become more restricted, their world shrivels, frame of reference shrinks, and self contracts.
> Illness Management Strategies
> Chronically ill people learn ways to handle their physical symptoms through various strategies ranging from withdrawal to innovation. Strategies for managing illness also require strategies for effective negotiations. People in lengthy marriages make managing illness a coupled affair. Visible disability drives other adult relatives away. What people need to manage depends on their illness, its progression, and its meaning to them, as well as their situation and their responsibilities.
> [...] Younger and middle-aged people often make concerted efforts to manage their illness. They maintain hopes and plans, reasons, and responsibilities. They have not given up or given in. They become innovators. To do so they listen to their bodies and stay in tune with them in ways that they had not and in ways that Western culture discourages. They make use of indigenous support groups, newsletters, and computer networks independent of professionals. The groups and methods provide collective information and shared community. They may constitute the only community for people who have become isolated in their homes. Members compare stories, gain information, learn about treatment successes and failures, and offer encouragement to continue to struggle with illness and not to sink into invalidism. They may keep daily logs to refine and extend data for working with their professionals.
> Shared comparison give support group members measures of where and who they are now. Certain chronic conditions such as kidney failure and treatment programs such as cardiac rehabilitation bring people into sustained contact with others with similar problems. A collective spirit may develop in these situations that either supports patients remaining involved in prior pursuits, or confirms that the world of illness now dominates their lives.
> Some chronically ill people become so adept at monitoring and managing their illness that they break through textbook definitions, create individualized regimens, and construct new ways of living with their illness; but medical professionals may not welcome their innovations. Alonzo Plough (1986) argues that patients who know too much use medical terms and request specific treatments that anger their practitioners. Practitioners sometimes push these patients back into the sick role when challenged by their growing expertise. Chronically ill patients sometimes find that their practitioners hold an ambivalent stance toward them. Their practitioners want them to take responsibility for themselves but on professionals' terms, not on their own. When these ill people step outside or beyond medical authority, their practitioners resort to medical paternalism and authoritarian demands. Consequently, ill people's strategies for managing illness can require strategies for effective negotiations with professionals to minimize conflict. [...]
> Stigma and Stigma Control
> Experiencing stigma is a common consequence of chronic illness and a constant threat in some ill individuals' view. If so, stigma makes a person vulnerable to negative social identifications and self-definitions. Stigma results from being identified as flowed, discredited, or spoiled. A defined difference from ordinary peers separates a person and confers an actual or potentially devalued identity. That difference often becomes a master status, such as 'disabled person,' 'leper', or 'AIDS victim,' that floods all statuses and identities. The stigmatizing label defines the person and every other defining characteristic she possesses. Thus, a woman who uses a wheelchair because of multiple sclerosis becomes a disabled mother, handicapped driver, disabled worker, and wheelchair dancer. [...] Often other people dissociate the 'understandable' reason for an ill person's difference from his behavior eliciting the stigmatized response. Then blame is turned back upon this person, who is made morally culpable for the stigmatized response itself. In essence, the individual is blamed for the behavior and blamed again for being stigmatized for it. [...]
> Any illness that sets a person apart as different and diminished has stigma potential and thus can affect interaction. The following characteristics increase stigma potential: a high incidence within disparaged groups, compromised adult status, loss of bodily control, sexual transmission, possible pollution, odor, and uncleanliness. [...]
> Davis (1963) argues that efforts toward prior identity preservation fail in direct proportion to the degree and extent of visible disability. Both enacted and felt stigma contribute to difficulties in preserving prior identity. The disability rights movement has made significant recent changes in the lives of its proponents. However, many ill people still find themselves responsible for preserving or reconstructing their identity after losses -- whether their disability is visible or invisible. Concealment of an invisible but potentially stigmatizing mark of difference allows the person to preserve prior identities for a time and under specific conditions. Many disabilities do not remain completely invisible to a discerning observer. Partners or parents may perceive cues more readily than a professional who does not have steady contact. Fatigue, flare-ups, or distress may render symptoms visible. [...]
> When invisible disability undermines fundamental ways of defining self, the person is isolated, and social comparisons are not possible. Then coherence and stability of self-concept is at risk.
> Self and Social Identity
> Stigma can wreak havoc upon the self for it forces unwelcome new ways of conceiving self and situation. Still, serious chronic illness alone can render social identity and self problematic. For months and years, people may try to forestall illness from touching the self. Valued roles and pursuits preserve continuity and coherence of self. People may acknowledge that illness affects their lives but resist its effects upon the self. They conceptualize it as a 'condition, not an illness,' 'just aging,' or 'a spell' and therefore maintain a sense of continuity and coherence of self. They put it into the past by saying they 'had cancer' or 'had lupus' and decree that it will remain in the past. [...]
> People with serious chronic illnesses must repeatedly rethink how they live and who they are becoming. Self and social identities are intertwined in daily actions and endeavors. Chronically ill people seek to reestablish their legitimacy after disruption and devaluation makes them vulnerable. However, they may not go about it in ways of which their practitioners and families approve. As life narrows, the ingredients shrivel for constructing a valued self and legitimate social identity. Their quality of life becomes problematic. Social, economic and psychological resources expand possibilities and options rapidly contract. Using available resources may be fraught with risks and increase vulnerability. Taking sick leave can result in increased scrutiny of an employee's performance. Filing an insurance claim might contribute to raising the business's group insurance rates. Sociale resources mean that commitments, assistance, and back-up are available -- as long as caregivers do not wear out. Concrete assistance smoothes problems and reduces anxieties. Commitments keep the ill person within a web of relationships -- from commitments that permit returning to work to commitments to visit or to run errands. Economic resources allow an individual to purchase objects and services that make life easier -- a car with an automatic shift, a one-story home, household help. The more resources available, the more latitude the person has to take time-outs for illness and then return to earlier pursuits. Identity questions and change of self are muted or occur over long periods of time. As resources dwindle, identity questions and changes of self may be forced much earlier.

Aparté: According to studies, disabled americans need to spend on average 30% more than their non disabled counterparts. This represents about $17K/year.

> Experiencing chronic illness can mean embarking on an odyssey apart from the busyness of other adults' lives. Chronic illness separates the person from the social body, but also gives rise to a story that brings this individual back to reintegrate self on a different level. Someone may leave old identities behind but gain deeper meanings. Long stretches of time allow the person to reflect upon jarring images of self and to make sense of loss. Loss of self and social identity do comprise a fundamental form of suffering among chronically ill people. Still, they may come to believe that facing such losses moves them toward trascending loss. Earlier vulnerability becomes a source of strength as they redefine illness as a time for reflection, reassessment, and redirection.

The reading of the rest of this chapter is highly recommended.

Modernity brought forth a generalized rejection of deities, replacing it with a pervasive and even insidious belief of a meritocracy: those who work hard will reap the fruits of their efforts. But this belief gets logically paired with its inverse: those who struggle or fail are responsible for their own demise. Luck, or the lack of, is no longer considered a factor. Pushed to the extremes, this forms the foundation of the "Just World" hypothesis, whereby this assumption is generalized to be a rule of Nature, and hence applying universally, whereas the universe is fundamentally unjust, unfair and uncaring of humans affairs. For more thoughts on this topic, this excellent talk by Alain de Botton is highly recommended.

A few additional practical tips by the present document's author:

  • Learn to recognize the effects of sleep deprivation and circadian misalignment, and discriminate what is caused by them (and hence by the non24 disorder) from the rest. By recognizing these effects on your health, it's possible to 1) better manage them (either by waiting out or by doing tasks that do not require high functioning and avoid affecting others with one's mood dysregulations — but it's not always possible to manage), 2) not feel guilty or shame for simply being ill, which can significantly decrease the risks of depression, as the illness's "episodes" just become a hassle rather than a pit of despair. If you don't know what are the symptoms, look up jetlag which is the most accurate model, or alcohol hang over since sleep deprivation is similar to alcohol intoxication.
  • Accept that it's likely not possible to fully control the effect of non24 on one's health. Even with the most effective therapies currently available, unproductive days with low mood due to sleep loss for various reasons will still happen regularly. They are part of the disease. Therapies can reduce their frequency, but they will still be relatively frequent (more for non24ers with an extremely long circadian period).
  • Accept that non24, just like any other disability, requires accommodations and prevents from doing some types of jobs. For example, it's unrealistic with non24 to pursue a commercial work position with clients contact, as a strict 9-5 work schedule is required. There are only very few jobs that are adequate for non24, but there are jobs that are sure ways to fail and damage health.
  • Although you may improve your condition a lot with adequate treatments and tools, you must understand and accept that there is no way back to your idealized future. It is impossible to be permanently cured from this chronic illness, and you will have to learn with it, and prioritize what matters to you and what you can do versus what you wished you could do.

Addendum: at some point, you may have a period when you identify yourself with your illness, that it defines you. Although such a chronic illness can certainly explain a lot of previously misunderstood "habits" that were mere consequences of the illness, it does not define you. Your abilities, your passions, your goals do not revolve around the illness, although it is certainly a limiting factor.

Addendum2: it's ludicrous to claim that acceptance of the non24 disorder and follow the natural sleep-wake pattern is acceptable. It drastically impairs quality of life, it is a very invasive disease that disables from doing everuday activies and essential life stages such as raising kids. Of course, without an effective entrainment therapy, there is no acceptable alternative to just following it, and acceptance involves accepting that the disabilities created by the non24 disorder. But chronic disorders induced disabilities do not get any better by acceptance. Hence, "accepting your disorder" is a fallacious mantra. Accepting the limitations and accommodations necessary around the disability is a necessary step, but the idea that accepting the disability will make everything work somehow is ludicrous. Without a stable entrainment, at least either social life, family care or your health will have to be compromised, often all will be in an attempt to juggle between them, and that's considering the best case scenario where your work position is not impacted. But since robustly stable entrainment is not currently achievable, only imperfect solutions are currently available, and hence sleeping in circadian alignment remains a much healthier and viable solution to working and sleeping in circadian misalignment and chronic sleep deprivation.

Additional reading materials on this topic of normalizing are available here, here, here, here and here. Also, the book Sleep Misfits: The reality of Delayed Sleep Phase Syndrome & Non-24 by Sally Cat is highly recommended, being the only book currently written compiling the experience specific to patients living with non-24 and DSPD handicaps.

For relatives and loved ones of people with a chronic illness such as non-24, here are some helpful resources:

Zeitgebers - The circadian rhythm manipulators

Introduction to zeitgebers

What is the circadian rhythm(s)?

The circadian rhythm is an essential biological process that not only regulates sleep but also wakefulness, its purpose is to be in phase with the environment to improve the chances of survival.

Before the circadian rhythm appears, fetuses display an innate, pre-existing ultradian cycle, which alternates wakefulness phases with sleep phases about every 45min, but there is some evidence that fetuses start developing the groundwork for an immature circadian rhythm based on their mother's rythmic secretion of hormones such as melatonin. The pupillary light reflex, which is controlled by the melanopsin photopigment in the eyes' ipRGC cells, the same pigment that controls circadian rhythm shifting (see also here), appears between 6-7 months (30-34 weeks) postmenstrual age (ie, from pregnancy onset, hence age includes fetuses or in preterm infants). The appearance of this reflex demonstrates that fetuses and preterm infants already have a functioning photic non-visual system, ie, that their circadian rhythm and hormonal system can be affected by bright light zeitgeber exposure. Indeed, genetically muting the melanopsin pigment severely impairs both the pupillary light reflex and circadian alignment, and pupil area is proportional to melatonin suppression. Hence, contrary to common assumptions even among sleep specialists, current evidence support the notion that newborns are already responsive to bright light exposure, but not necessarily like adults, since they do not yet have a circadian rhythm.

Newborns continue to sleep exclusively on their ultradian rhythm according to current findings, despite the pupillary light reflex being established, arguably because of light being red-pass filtered by eyelids since 30-98% of environmental light was incident on the eyelids (ie, newborns often have their eyes closed), until they transition into a circadian rhythm very early in the life, the maturation, stabilization and synchronization of the circadian rhythm to the objective day-night cycle happening around 3 months after birth in most babies, although some newborns can have a mature circadian rhythm earlier at 1.5 months especially with early exposure to a rigorous day-night pattern of sunlight and limited to no artificial bright light at night (dark therapy), while others may need a few more weeks (and bear in mind that most babies don't sleep the whole night like adults at this age, they just sleep more often at night than during the day, but still wake up very often according to the ultradian cycles transitions), potentially helped by maternal milk's hormones such as melatonin (night milk) and cortisol (day milk), although the vast majority of artificial milk fed babies also develop a circadian rhythm around the same time as breastfed babies, if not earlier. A fantastic case study of a newborn from the 2nd week of age up to 6 months old elucidated the timeline of appearance of the various components of the circadian rhythm:

> The circadian rhythm of temperature appeared first, soon after birth, and became statistically significant within one week. The wake circadian rhythm appeared second, attaining significance at day 45; approximately the same time that increased melatonin concentration began to occur at sunset. The sleep circadian rhythm appeared last, attaining significance after day 56. Ninety to 120 minute zones of sustained wakefulness first appeared in the second month of life subsequent to awakening and prior to sleep onset. The infant's nocturnal sleep-onset was coupled to sunset before day 60 and subsequently to family bedtime, giving evidence of initial photic entrainment followed by social entrainment. Conclusions: Circadian rhythms appeared much more rapidly in this infant than previously reported; their rapid appearance was probably facilitated by maximal exposure to sunlight, and regular social cues. These lighting conditions replicate universal infant experience prior to the invention of artificial light.

(NB: social interactions have since been disproven as zeitgebers, they do not entrain the circadian rhythm).

This single-case study has since been partially reproduced in a cohort study of 130 full-term infants, demonstrating that cortisol circadian rhythm, cortisol being the hormone of wakefulness, is established at age 1 month and remains throughout life.

Given that body temperature circadian rhythm appears within one week, the time delay it takes for this primordial rhythm to get established may be dependent on when the newborn starts to keep their eyelids open more often than closed, one hypothesis being that the pupillary light reflex and hence the circadian rhythm system coupling with bright light is already established at or before birth, and hence that the only factor to entrain a newborn's circadian rhythm is to expose their eyes to bright light without the red pass filter of the closed eyelids, although previous studies found that medium exposure (1h) to bright light even with eyelids closed can inhibit melatonin in adults, hence future studies may elucidate this point.

The endogenous (ie, baby's) production of sleep-wake regulation hormones such as melatonin and cortisol appears later around the 8th month of life (see also here), although there are conflicting evidence such as the case study above which found an endogenous variation in melatonin as early as 45 days along with the appearance of the wake circadian rhythm. The pineal gland size and melatonin secretion level stabilize around 1 year of age. Circadian sleep patterns during the first two years in life, and later well into adulthood as well, are strongly influenced by genetic factors. The circadian rhythm is a universal biological process observed in all living organisms, from mammals to plants and even bacteria, mitochondria and unicellular organisms, strongly suggesting this is a crucial trait for survival since it was highly conserved throughout evolution.

Sleep graph from a sleep diary of a baby from 3 months old to 17 months, collected by u/jitney86. This shows how the baby's sleep transitions from a somewhat irregular sleep pattern but with already clear night block, into a highly regular biphasic or triphasic sleep pattern. Note this child was breastfed, which is known to slow down the stabilization of the sleep-wake pattern.

Another sleep graph for an even younger infant from 3 days old to 3 months old, showing a completely irregular sleep pattern at first, then slowly transitioning to a more regularly patterned sleep, with a big block of sleep at night and smaller naps blocks during the day. By u/AtmosChemist.

Although in the literature the "circadian rhythm" is commonly employed in the singular form, there are in fact multiple independent but synchronizable molecular clocks throughout the body and down to every cells (see also here), with each organ having its own clock and time of peak performance, including different brain regions (see also this talk by the same author), and this molecular circadian machinery was observed in all mammals. The circadian system is structured as a loop-on-loop architecture with feedbacks, which both ensures persistence of rhythmicity and local adaptations depending on metabolic needs.

The body has 2 major biological processes to regulate sleep, according to the now well demonstrated empirically Borbély's model:

  • the homeostatic sleep pressure process S that relies on adenosine. The homeostatic process S is more like a countdown timer, which tracks how long the individual stayed awake and continues to build up without any limit as long as they stay awake. When this timer reaches beyond a threshold, which means the individual stayed awake for a long period of time, it ensures that individual will feel sleepy enough to get necessary sleep to avoid the risk of dying by prolonged sleep deprivation. In other words, the homeostatic process S is like a failsafe mechanism in case the individual didn't sleep during their circadian night. The more sleep pressure, the more slow wave deep sleep during the sleep session after, without affecting the core body temperature. The process S was discovered in 1984 by Borbély's team.
  • the circadian rhythm process C, most correlated with melatonin although it is more tightly coupled with core body temperature which seems to be the core method circadian rhythm phase changes are propagated throughout all cells in the body. The circadian rhythm (process C) is periodic, it doesn't account if the individual stayed awake for way too long, it's like a 24h clock defining different periods: one of activity (circadian day), one of sleep and rest (circadian night) and transition periods in-between, and it always repeats itself periodically no matter if the individual stayed awake or was asleep. This is the reason why if the individual stay awake beyond the circadian night, they will paradoxically feel less fatigued than during the circadian night, as although the sleep pressure of homeostatic process S will still build up, the pressure of the circadian rhythm will lift off. The circadian rhythm is what maintains all living organisms asleep for long periods of time. For example, if the individual wakes up only after sleeping a short period of time, it means they were sleeping in circadian misalignment, outside of their circadian night, so that their body didn't have the support of the circadian rhythm to maintain them asleep, and so they essentially napped.

Although these are two different systems, they do interact with each other (see also here and here and here and here and here). So using a treatment that affects one will also often affect the other (eg, both light therapy and melatonin have been shown to affect both processes). See this video by Thoughty2 for a nice introduction. It is currently accepted that the effect of each system is minimal on the other, with a lab-controlled study demonstrating that the sleep homeostat S does not alter core body temperature and hence nor the circadian rhythm. Other studies found no effect of the homeostatic process on the circadian rhythm at all when observing the effect of napping versus prolonged sleep deprivation in humans. However, this assertion of independence between these two systems must be tempered by the recent finding from a study screening for molecular circadian shifting molecules which found that adenosine analogs such as cordycepin were the most potent by far. Future studies will hopefully elucidate the conditions of this inter-systems interaction.

Neurologically, although research is still ongoing in this area, it appears that the association cortices, especially in the frontoparietal attention network, are particularly sensitive to sleep pressure, whereas the subcortical thalamic and basal ganglia brain regions are more affected by the circadian rhythm.

Given that the sleep process S has little effect over the circadian rhythm process C apart from amplifying sleep induction (aka sleepiness) when both have aligned troughs, we will mostly focus on the circadian rhythm process C in the rest of this document.

The circadian rhythm is primarily governed by subpopulations of neuronal oscillators in the suprachiasmatic nucleus (SCN), with different subpopulations encoding different times of the day (eg, morning, afternoon, evening, night).

Although the SCN is considered the "master clock" as it synchronizes all other, peripheral clocks throughout all organs and cells in the body, it is not necessary for the circadian rhythm to be expressed. Indeed, astrocytes (cells that feed neurons) arguably play an important role (see also here), and circadian shifting by bright light is not impacted by the destruction of the SCN, with another study showing that the ipRGC cells in the eyes alone were sufficient for circadian rhythm and body temperature shifting without needing the SCN, showing that the non-visual effect of light on the circadian rhythm is independent from the SCN.

One of the major established pathways for the SCN's control of the circadian rhythm is by the cyclical activation of secretion of melatonin by the pineal gland via the retinohypothalamic-pineal (RHP) axis's , a "vestigial eye" that is highly conserved throughout evolution. In some reptiles and amphibians, the pineal gland is even directly visible, forming its own "pineal eye" or "parietal eye" colloquially named a "third eye" smaller than retinal eyes, but it is absent in mammals, endothermic archosaurs such as birds and ectothermic archosaurs such as crocodilians and turtles. However, the vast majority of melatonin is produced outside the brain, with the gastrointestinal tract secreting 2 orders of magnitude (at least 400x!) more melatonin in response to food than the SCN. Furthermore, even after pinealectomy, melatonin levels still increase in a dose-dependent manner (ie, proportionally) to oral intakes of melatonin in animals, just like for animals with their pineal gland, and it even restores an entrained circadian rhythm, showing that extrapineal producers of melatonin, likely the digestive tract, are producing and managing most of the circulating melatonin, not the pineal gland.

Hence, it appears from recent empirical evidence that both the pineal gland and the SCN, the two major brain structures related to circadian rhythm modulation, are not required for circadian rhythm modulation and entrainment.

However, there is one biological phenomenon that is tightly coupled, almost indissociable from the circadian rhythm: the core body temperature. Indeed, core body temperature modulation is the primary way that circadian rhythm changes are signalled across all cellular clocks throughout the body, with the circadian clock and the cell cycles being coupled, which demonstrates that core body temperature modulation is a strong tool the body uses to control cells activity, not just their circadian clock. Humans are homeothermic animals, hence core body temperature plays a crucial role in survival, and it is hence maximally internally regulated and shielded as much as possible from ambient factors. Likewise, the effect of melatonin on the circadian rhythm is mediated by its effect on core body temperature (as suspected since at least 2007), with melatonin being an inhibitor fo temperature (see also here). It hence appears that what matters to control the circadian rhythm is the modulation of core body temperature, the various structures such as the SCN and the pineal gland acting as main controllers, but they are not the only ones that can affect the circadian rhythms of various clocks.


TODO: add figure and rewrite section below to be more intelligible:

There are rules I derived for how much we can sleep in and out of circadian alignment and per 24h. I am still refining them but essentially, you usually can't sleep more than your ideal amount of sleep. For example, on average adult humans need to sleep 7-9h per night, let's say 8h to simplify. This means, if you fit in this average, that you need ideally to sleep 8h per night to feel fully restored and be healthy.

Now, if you sleep twice per day, eg during your circadian night and during the siesta, you will only be able to sleep a cumulative sum of 8h, for example 5h during your circadian night and 2-3h during the siesta. This is called a biphasic sleep pattern. This can even be a triphasic pattern for young children. This is in line with previous studies finding that children who take daytime naps actually have the same total sleep duration as children who don't.

So if you want to sleep a full night at once, you need to avoid the siesta in the 24h preceding the circadian night. But this only works if you can avoid using an alarm clock, and if you know when is your circadian night. Otherwise, it's much healthier to sleep the siesta (biphasic sleep), it's not for nothing that the body devised this failsafe mechanism.

Another rule is that it's only possible to sleep a full night of sleep during the circadian night. The siesta is limited to 1-2 ultradian cycles shorter than the circadian night. For example, if your ideal sleep duration is 8h, 1-2 ultradian cycle less represent 1.5 to 3h less, in other words 5h is the maximum duration of the siesta (ie, the longest nap that you can do). You will never be able to sleep more outside of the circadian night, unless you have a huge sleep pressure buildup (ie, you didn't sleep for 30h+) or acquired an illness that modifies your core body temperature.

Example of how the interplay between the circadian rhythm C and homeostatic process S can produce different sleep-wake patterns:

6 possible scenarios:

  • Monophasic in phase and woke up more than 10h before. Will sleep at maximum the optimal duration (eg, 8h on average for adults) and wake up at the natural wake up time or before when optimal duration is reached. Can only sleep 1 or 2 ultradian cycles earlier than optimal fall asleep time. Can sleep less if slept too late and natural wake up time happens before optimal duration (eg, 6h of sleep = 1 ultradian cycle less).
  • Monophasic out of phase woke up 10h before (will sleep max 5h).
  • Monophasic in phase woke up less than 10h before. Low homeostatic sleep pressure will make it difficult to fall asleep, but if it happens then the circadian rhythm will maintain the body asleep and it should be possible to sleep a full night if in alignment with the circadian night.
  • Biphasic idem 3 item. Then will sleep optimal duration - amount of time slept in the last 10h (eg, if napped for 2h, then can only sleep 6h during the circadian night).

In phase 8h max. Out of phase, 5h30 max incl nap in biphasic, it's the sum over 24h (or freerunning period eg 25h for non-24). We assume no prior sleep deprivation, which could result in increased homeostatic sleep pressure and chaotic circadian rhythm which could make sleep significantly longer or paradoxically shorter.

If we assume the current circadian night is from 2am to 10am:
- if woke up at 3pm, can sleep in phase at 2am, 8h. Wake up around 10am.
- can sleep out of phase 5.5h.
- can sleep partially out of phase between 6am and 8am, resulting in at least one ultradian cycle in phase and hence between 2 and 4h of optimal in phase sleep + 4 or 2h of out of phase sleep respectively totaling about 6 to 7h of sleep. Wake up around 1pm (if slept at 6am) to 2pm (if slept at 8am, we sleep less if sleeping later because more out of phase).
- can sleep biphasic, 2h to 4h before 10pm, then 4h anytime between 2am and 10am, totaling close to 8h (sometimes more up to 9.5h).
- can sleep completely out of phase, 2h before 2am and 3.5h after 10am, totalling 5h30 of sleep.

If woke up at 6am:
- can only sleep 6h from 4am to 10am.

What are zeitgebers?

Zeitgeber literally means "time giver" in german. A zeitgeber is any periodic signal of about 24h (ie, a cycling signal, such as light-dark), which the body can pick up and use to get entrained to (ie, synchronize like a clock to a 24h schedule). Since the circadian rhythm regulates crucial biological processes for health and survival, the periodic signal needs to be reliable (ie, not random) to be a zeitgeber and entrain the circadian rhythm.

Indeed, humans, and all biological systems, have no way to determine exactly the absolute time. Hence, we have biological, chemical and hormonal systems that approximate what can be called a biological clock. But since it's an approximation, it is imperfect: on average, humans follow a 24.2h schedule naturally according to the NIH. The remainder, 0.2h, serves as a margin of error, which is eliminated thanks to external time cues: the zeitgebers. When this margin of error is correctly eliminated, we say that the individual is entrained on a 24h schedule.

Why is the biological clock approximative? Cannot it just run on exactly 24h like mechanical clocks? This is because of synchronization theory. There is no way to design two independent clocks (eg, such as the human biological clock and day-night cycle) that will forever stay synchronized together. Even mechanical clocks end up out of sync after a long enough period of time without being reset manually by the user or automatically by an online system. Indeed, the only way for two clocks (or periodic events) to become and stay synchronized is to link them, to make them dependent with the other in some way, as synchronization theory teaches us.
For example, if you place two metronomes on the same physical support, they will at some point become synchronized with one another. Zeitgebers are the link, the physical support that links our biological clock with the external world, with the sun caused day-night cycle. Without zeitgebers, it would be impossible to be synchronized with the day-night cycle, our clock would just be running on its own time, which is exactly what individuals with non-24 do. Furthermore, since there is no way to design two independent physical clocks with the exact same period, it is hard to see how this could be achievable by biological systems with innumerable SCN neurons with each their own phase and period and hence molecular clock, not to mention peripheral clocks in other organs throughout the body beyond the brain down to each biological cell, and so logically these independent biological clocks must synchronize together, and also with the environmental cycles using external cues, the zeitgebers. And indeed, studies demonstrated that the circadian rhythm emerges as the interaction of populations of clock neurons in the SCN, and in the body (peripheral clocks), with this interaction being tweaked by zeitgebers such as photic inputs (ie, bright light exposure).

Hence, zeitgebers are the essential tool we have to modify the circadian rhythm of humans, and hence potentially to treat circadian rhythm disorders. When something alters the circadian rhythm, it is a zeitgeber (ie, a time cue that alters/synchronizes the biological clock(s)) by definition.

Humans are biologically predetermined to respond more or less intensely to some zeitgebers, which includes the influence on their circadian rhythms. According to the current scientific literature, here is a rough outline of the order of power of zeitgebers on the circadian rhythm:

Light (strongest) > melatonin (strong) ~ food (likely strong) >> exercise (weak) ~ social interactions (weak) ~ sleep behavior (weak)

Light is the strongest zeitgeber by far. Indeed, we have specific photoreceptors, the ipRGC cells, in the eyes which are tailored to react to light to both dilate or contract the pupils and to shift the circadian rhythm. Light is undoubtedly the most potent zeitgeber both for the central clock (SCN in the brain) but also for all peripheral clocks of all the organs throughout the body, and hence bright light is the most potent therapeutic tool for circadian rhythm disorders. Light directly alters core body temperature. Light is also likely the first zeitgeber that the human brain's circadian system is programmed to react to, since there is evidence that ipRGC cells are already mature already at 6-7 months (30-34 weeks) postmenstrual age as shown by the appearance of the pupillary light reflex, which is controlled by the melanopsin photopigment in the eyes' ipRGC cells, the same pigment that controls circadian rhythm shifting (see also here). Note however that it's not just bright light that resets the circadian rhythm phase, but the alternance between high phases and low phases, here the alternance between bright light and darkness, as studies using the constant routine protocol demonstrated that individuals under constant bright light exposure lose entrainment and freerun just like individuals under constant darkness. The alternance between light color (blue versus yellow) also serves as a failsafe mechanism to entrain when light intensity doesn't vary.

Melatonin comes second, as its purpose is to both consolidate sleep and the circadian rhythm (ie, ensure you don't wake up in the second half of your night so you can sleep a full night), and phase advance.

Food is still under research but since the digestive tract produces most melatonin in the body by far, 2 orders of magnitude more than the brain, and also consumes it, food is thus arguably an also very strong zeitgeber. Food is thus an additional source of variation in circadian rhythm.

Other potential zeitgebers such as physical exercise or social interactions are very weak zeitgebers and named zeitnehmer ("time taker" in german) by some authors. Zeitnehmers are weaker than zeitgebers as although they can send rhythmical signals that can help with entrainment, they are also majorly affected by other oscillators through feedback loops. Hence, including them in an entrainment therapy leads to issues as they are often tricky to time appropriately (eg, exercise is more in phase with the circadian rhythm when done in the evening than the morning) and don't provide much circadian shifting or entrainment effects.

Physical exercise produces slight circadian rhythm shifts thanks to muscle contraction which modulates the BMAL1 clock gene in the muscle. The more muscle contraction, the more phase advance is obtained. Although exercise can slightly shift the circadian rhythm (see also here), it does not affect melatonin levels. Furthermore, a systematic review of 23 studies has shown that evening exercise does not affect sleep if done at least 1h before sleep, it instead helps people fall asleep and spend more time in deep sleep, the only exception being high-intensity exercise done under 1h of bedtime, which then caused people to take more time to fall asleep. Hence if you are night-walking (awake during the night and sleeping during the day), it's perfectly fine and actually healthy to do sports during the night, as long as your exercise session is at least 1h before your biological night. The precise effect of physical exercise on the circadian rhythm depends on the minimal core body temperature (CBTmin - can be approximated with wrist skin temperature too):

> When exercise was performed in the period between 4 h before and 1 h after the temperature minimum, there was a phase delay of 1.03 +/- 0.78 h (mean +/- s; n = 6); when performed between 3 and 8 h after the temperature minimum, there was a phase advance of 1.07 +/- 1.23 h (n = 9). [...] Performed at other times, exercise had no significant effect on the phase of the temperature rhythm.

Accordingly, a 2019 systematic review of physical exercise as a therapy for insomnia found only weak objective improvements in sleep parameters, mostly in reduced sleep latency (time to fall asleep), which rather suggests an effect on the sleep homeostat rather than the circadian rhythm, as otherwise it would be the wake up time (dawn marker) that would be modified, since SCN neurons in diurnal animals encode circadian phase in relation to dawn, not dusk like nocturnal animals. Other studies on cohorts found no evidence that physical exercise impaired nor improved sleep, even when done close to bedtime or at night. However, the effect of physical exercise on the circadian appears to be additive with other zeitgebers such as bright light therapy, so they can be combined. Furthermore, an analysis of the PRC curve of physical exercise relatively to the DLMO suggests that exercising in the circadian morning phase advances the phase, whereas exercising in the circadian evening or night delays the phase, which explains why individuals with DSPD who forcefully wake up early to exercise may in fact be delaying their circadian rhythm by exercising during their circadian night. Also, the change in blood pressure due to exercise is greater in the circadian evening than in the circadian morning, which suggests that it may be safer for individuals with DSPD to exercise in the objective evening if this aligns with their circadian morning, instead of the objective morning which may align with their circadian evening or night.
More likely, all potential circadian phase shifting effects of physical exercise are either local (ie, changes clocks in muscle tissues but not the central clock in the SCN), or their effect can only be observed in constant conditions experiments, as otherwise light exposure overrides any small effect obtained from physical exercise. Indeed, a study on mice with a LDLD schedule, which is a way to entrain them to 2 small days in one, found that when physical exercise was prevented during one of the small days by wheel locking, only the intensity of physical increased during the next activity period, but not the phase/timing, which appears to be only defined by the circadian rhythm and not activity/physical exercise.

Social interactions were previously considered to the primary zeitgeber for humans since a 1971 study by Aschoff. However, these results were debated, and it was finally found that this study and others were confounded with uncontrolled light exposure amounts and patterns and furthermore later studies controlling for these factors could not reproduce the effect, so that the current consensus is that social interactions are not zeitgebers, the previously observed effects being due to uncontrolled light therapy:

> Early human entrainment studies led to the belief that the primary entraining agent for humans was not light, but rather social interaction (Wever, 1979; Aschoff & Wever, 1981). However, due to concerns about the design of these experiments (primarily the use of self‐selected lighting schedules) and the subsequent demonstration that light cycles indeed can entrain human circadian rhythms (Czeisler et al. 1981; Wever et al. 1983; Honma et al. 1987a), this belief is now considered unwarranted (Czeisler, 1995).

Nowadays, the well established high prevalence of the non-24 disorder in blind individuals, "in spite of living with strong social cues (e.g., employment, families, alarm clocks and guide dogs) [...] strongly supports the primary role of light in human entrainment" and is another empirical evidence in humans that social cues are not zeitgebers.
It should be noted that social factors can nevertheless affect sleep-wake patterns as demonstrated by the well established social jet lag phenomenon, which is important to distinguish from the inexistent effect on the circadian rhythm, since modifying the sleep-wake pattern does not affect the circadian rhythm.

What about sleep itself (ie, the sleep-wake schedule, which is to schedule a rigorous sleep and wake time)? Past studies found that the sleep-wake schedule may feed back to the circadian rhythm but weakly, and hence more likely qualifiable as a zeitnehmer. However, this and other past studies were biased by uncontrolled factors such as posture, as the participants are usually told to lay down to sleep at the same time as lights are switched off, with posture decreasing core body temperature for at least 2h and lights off also increasing melatonin levels and hence decreasing core body temperature. Indeed, later more stringently controlled studies found no effect: a an excellently designed lab-controlled study showed no effect of sleep (naps) and sleep pressure (complete sleep deprivation) on the core body temperature and hence the circadian rhythm of humans. On the other hand, they confirmed that the core body temperature and distal skin temperature showed great coupling with circadian factors such as the lighting pattern. Likewise, sleep deprivation did not demonstrate any incidence on core body temperature whether in a comfortable ambient temperature nor after cold air exposure (see also here and here). Note however that sleep deprivation does mask proximal skin temperature, but not core body temperature.. In other words, the sleep schedule does not affect at all the circadian rhythm, hence why chronotherapies and cognitive behavioral therapies (CBT) have shown low to no efficacy so far. In fact, it was already observed since 1987 that locomotor activity nor sleep had any effect on the circadian rhythm.

Relatively recently, it was discovered that the lunar cycle influences humans' sleep and melatonin rhythms, with a reduction of 30% of deep sleep during full moon, according to a well designed in-lab controlled human study.

Since we have multiple clocks throughout the body and down to every cells (see also here), we ideally need to entrain a maximum of them for successful robust entrainment. The VLiDACMel protocol attempts to do that with a combination of light/dark therapy, melatonin and food (composition and timing) control.

To achieve greater circadian phase shifting, it is possible to combine multiple zeitgebers, which makes their effects additive, which means that a combination therapy produces more phase shift than any of the components alone. For example, light therapy's effect is additive with melatonin (see also here and here and here and here) and with physical exercise.

When used for therapeutic purposes, especially to treat DSPD and non-24, zeitgebers are also called chronobiotics.

Can changing timezone help?

No it wouldn't work. But if you live in a latitude where there's not long enough sunlight such as closer to the arctica, then moving south can help.

What matters in different world regions is light exposure, not the timezone.

If light therapy doesn't work for you, it won't work better in another timezone of similar latitude or with a similar light exposure. And if light therapy does work for you, you don't need to move to a new latitude, you can just buy a lightbox or light therapy glasses.

As to why it wouldn't work, there is no absolute time, time is always relative (as demonstrated by Einstein's relativity theory). To know when it's day time or night time (and hence sleep time), our bodies use external time cues, formally called "zeitgebers". These include various things such as light, temperature, etc. These are more intense in the day, and lower in the evening and night, and is what hints our body to know the difference between day and night. So our body's rhythm always works relatively to these external cues.

To make an analogy, it's like navigation, when you're lost, you use points of interests to know where you are such as recognizable buildings in the distance and then you can deduce where you should head to to reach your destination, or you can use a compass to indicate the north. Without external tools, you have no way to know where to go, you will randomly walk and just get more lost.

Zeitgebers are the external compass that our body naturally uses to synchronize the circadian rhythm with the day night cycle. When you move to another timezone, the timing of these zeitgebers change, and so your body adapts. But it will adapt the same wherever you go. So after some time you will sleep and wake up at the same times as in your old timezone, but just shifted to the new timezone. The issue with DSPD, non-24 and other circadian rhythm disorders is likely not that they do not adapt to zeitgebers, it's that they adapt incorrectly, it's like having a miscalibrated compass that indicates an offset north pole.

The relative effect of zeitgebers

Every zeitgeber can be good (phase advance) or bad (phase delay) depending on the timing. Phase advance means that the circadian rhythm period is shortened, whereas phase delay lengthen it. This time-dependent effect, which is on top of the dose-dependent effect (eg, intensity of light or dosage of melatonin), is summarized in the Phase Response Curve (PRC) of the target treatment.

Zeitgebers are double-edged swords: since PRC is an intrinsic and universal property of all zeitgebers, present in all animals and even unicellular organisms, this means that when a factor can phase delay, it can also phase advance if exposure happens at another time. For example, if you suspect getting exposed to screens light in the evening phase delays your circadian rhythm, then the same screens light can be used at wake-up to phase advance.

All PRC curves have a tipping point, where the zeitgeber's effect on the circadian rhythm will completely reverse, from maximal phase delay to maximal phase advance or the opposite. Hence, the exact appropriate timing for phase advance or phase delaying depends on the zeitgeber, it's not necessarily at wake up for phase advance or at evening for phase delay (eg, for melatonin the PRC is inversed with the light PRC). For light therapy, this tipping point is the minimal core body temperature CBTmin (with more phase advance after), whereas for melatonin it's the DLMO (with more phase advance before DLMO or more delay after) (see also here). The CBTmin matters for light therapy but not for melatonin, for which only DLMO matters. For physical exercise, the CBTmin is also the tipping point. Thus, adequate timing of zeitgebers is critical to get phase advance effects, otherwise a mistimed zeitgeber can not only be ineffective but even further worsen the delay and hence the circadian rhythm disorder condition.

Here are the simplified PRC curves for light and melatonin effect on humans (image from Wikipedia):

Citing Lewy (1985) explanation on bright light zeitgeber:

> In both diurnal and nocturnal species, certain features of PRCs appear to be universal. When the pulse of light occurs during the animal’s subjective day (based on the activity-rest cycle), hardly any effect is noted. When the pulse of light occurs during the beginning of the animal’s subjective night, the animal will delay the phase position of its subsequent activity-rest cycles. When the pulse of light occurs during the end of the animal’s subjective night, the animal will advance the phase position of its subsequent activity-rest cycles.

The relative effect of zeitgebers on the circadian rhythm can be confusing. We can make the following analogy: it's a bit like a boat, naturally you will float with the river (your natural circadian rhythm), but you can use paddles (light therapy) to row against the river (waking up earlier and earlier when used in the biological morning) or faster along the river (being exposed to bright light in the biological evening because you don't do dark therapy). But you can't just stick the paddles in the water to precisely stay where you are in the river, it doesn't work like that, you have to row in one direction or the other, even if just to stay in place (maintaining a stable wake up time), and where you will end up (your wake up time) won't be super exact and will change with the flow, but you can ensure what direction you go (against or with the river's flow = natural phase of the circadian rhythm). How much earlier you wake up is defined by how strong you row (light intensity), how aerodynamic your boat and paddles are (blue light color and ergonomic form factor to optimize delivery such as light therapy glasses instead of lamps), and how long you row (how long you do light therapy).

The relative effect of zeitgebers is crucial and fundamental for the synchronization of multiple independent clocks, whether the host's circadian clock with an environmental zeitgeber, or down to the synchronization of SCN's clock neurons together. Indeed, if there was no relative effect, in other words no PRC curve, there would be no synchronization.

There are in theory two types of zeitgebers: the type-0 resetters, which theoretically can reset at the time you target regardless of your current circadian rhythm, versus type-1 resetters, which effect is dependent on the intake/exposure time relatively to your current circadian rhythm. In practice, all currently known zeitgebers (and hence treatments) are type-1 resetters. Hence, it's crucial to time all treatments relatively to your current sleep and wake up times, not the target/wished ones. This is true not only for melatonin (see also here), but also light therapy and food. It's not specific to treatments for circadian rhythm disorders, in fact there are now chronotherapeutics as coined by Smolensky et al, an emerging field of scientific and medical study which is finding that virtually all drugs have a time-dependent effect relative to the circadian rhythm, such as antibiotics, with adequate timing of administration during the circadian day both increasing efficacy and reducing adverse effects. For more informations, see the following papers about chronopharmacokinetics and chronotherapeutics: here, here, here, here, here, here, here, here, here, here, here, here and Smolensky, Labrecque, Chronotherapeutics Pharmaceut News 1997:4: 10-7. This makes sense, as it was discovered that nearly half of protein-coding genes are rhythmically expressed in at least one part (tissue) of the human body. This time-dependent effect of zeitgebers is also what makes research about them difficult, as it is easy for scientists, working at usual office hours, to miss time-dependent effects.

So far, we have mentioned only the temporal aspect of zeitgebers (ie, shifting the circadian rhythm). But zeitgebers also modulate the amplitude/magnitude of the circadian rhythm. In fact, both the amplitude and synchronization are simultaneously modulated in a non-linear and non-trivial way as shown experimentally, which can explain the asymmetrical response to bright light, with dimmer lights sufficient to shift the circadian rhythm at (circadian) night but brighter light necessary in the (circadian) day for the same effect.

Is it necessary to use multiple zeitgebers, even if we only have a slightly bigger circadian rhythm than the average, let's say 24.5h? Yes, because not only having multiple zeitgebers allows to have a failsafe in case you miss one of the zeitgebers (eg, forget to take the melatonin pill one day, then at least the light therapy will still help), and also because the body has multiple circadian clocks: the most famous one is the "master clock" in the brain, more formally known as the photoneuroendocrine system, which consists of the suprachiasmatic nucleus (SCN) in the hypothalamus, which is photoreceptive (respond to the photic signal from the ipRGC cells in the eyes) and communicates bidirectionally with the pineal gland which regulates melatonin (side-note: only in mammals did the pineal gland lose its photoreceptive capacity) , but there are also lots of peripheral clocks in other organs (liver, intestines, muscles) down to every cells (mitochondria produce and metabolize melatonin, see the Melatonin section). If a zeitgeber entrains one but not the others (such light not entraining the digestive clock), then the body may still continue to freerun because of the mismatch between the various body clocks and hence prevent whole body entrainment.

Since the industrial era, most zeitgebers are weakened in our daily lives, foremost light due to officies deprived from direct exposure to sunlight and artificial lighting in the evening, which led and is still leading to a widening and delaying of the chronotype distribution except for the very early morning larks, ultimately causing social jet lag for nearly everyone.

A few studies indicate that likely all zeitgebers work by ultimately modulate body temperature: body temperature modulation is the universal signal to reset the biological clocks throughout the body (see also here for a more easy to read article). This is further demonstrated by the fact that light therapy does not need the suprachiasmatic nucleus (SCN) to affect the circadian rhythm, only the ipRGC cells. Since light therapy modulates melatonin levels, and that one of the core melatonin activities is to modulate the body temperature, and given the widespread availability of melatonin receptors throughout the body, it appears likely that light therapy shifts the circadian rhythm by modulating melatonin levels which itself modulates the circadian rhythm clocks over both the central and peripheral systems.

(TODO: add the proposition of an evolutionarily derived algorithm for circadian rhythm entrainment to zeitgebers: https://archive.is/AvoPl )

Seasonal variations in zeitgebers

Or why Bedtime and wake up time are independent (dual-oscillator model)

A common assumption is that human sleep schedule is flexible and can be manipulated by varying - or maintaining stable - the bedtime: an earlier bedtime will lead to an earlier wake up time, and a later bedtime to a later wake up time. This is however contradicted by the evidence.

Although this is commonly studied in seasonal animals such as migrating birds, a lesser known fact is that the circadian rhythm of humans also has seasonal variations, although artificial lighting can eliminate these variations. What is interesting with these seasonal variations is that they allow to observe how the human's circadian rhythm naturally fluctuates in typical sleepers with varying zeitgebers exposure: later, shorter and weaker zeitgebers such as sunlight during winter, versus stronger, longer and earlier sunlight during summer.

This figure (from this review on seasonal variations of the circadian rhythm and melatonin in humans) shows the changes in melatonin secretion start time (onset-time, left graph) and stop time (offset-time, right graph) relatively to the duration of melatonin secretion and season.

What this figure shows is that the start time of melatonin secretion (associated with the fall asleep time), on the left, doesn't change much with the season, despite the melatonin secretion duration (associated with the sleep duration) increasing in general during winter. But on the right, it's shown that the melatonin secretion stop time (associated with the wake up time) changes linearly with the melatonin secretion duration across seasons! So it's the melatonin secretion that stops later during winter, likely due to progressively later sunrise time and hence later start of exposure to bright light, resulting in a longer melatonin secretion. In other words, during the winter, humans sleep longer on average, and we have a longer melatonin secretion that goes well into the morning as the melatonin secretion stop time and wake up time get delayed later according to sunrise time, but not the fall asleep time which remains constant. This is the same phenomenon that underlies the relative coordination phenomenon (see the dedicated section below).

This is a crucial observation, as this is a very compelling evidence that the wake up time is decoupled/independent from sleep onset (fall asleep) time. Indeed, since sunlight is both rising later and setting earlier during winter compared to summer, we could assume that to sleep longer, humans would both sleep earlier and wake up later, with their circadian rhythm being recalibrated to fit the sunlight exposure. But this is not the case, since only the wake up time varies with season and sunlight exposure (onset and duration) but not the falling asleep time. This shows that sunlight (and hence light therapy) primary modulates the wake up time, but not the fall asleep time.

There is a model of the circadian rhythm that is founded on this sleep offset-onset decoupling: the Dual-Oscillator Model of Regulation of Human Melatonin Secretion : "the nocturnal period of melatonin secretion are governed by the mutual phase relationship of two circadian oscillators: one (E) that is entrained to sunset and controls the evening onset of activity and melatonin secretion, and another (M) that is entrained to sunrise and controls the morning offset of activity and melatonin secretion. In this way, when the interval between sunset and sunrise becomes longer, the duration of the nocturnal period of activity and melatonin secretion becomes longer. Results of our research suggest that this model can be extended to humans."

This model is quite old, and is based on findings on animals: "Studies examining the profile of melatonin secretion in rodents following phase shifts to light stimuli have indicated that the onset and offset of melatonin secretion do not always phase shift in a parallel manner. Accordingly, the hypothesis has been suggested that there may be two coupled oscillators, an evening or E oscillator associated with melatonin onset, and a morning or M oscillator associated with melatonin offset (Pittendrigh & Daan, 1976; Illnerová & Vanecek, 1982; Elliott & Tamarkin, 1994; Illnerová & Sumová, 1997). [...] In contrast to the pattern of light-induced phase delays noted in rats above, Elliott & Tamarkin (1994) have reported a tendency for the melatonin offset in hamsters to shift before that of the melatonin onset following phase-delaying light pulses. However, their results following phase-advancing light stimuli concurred with those of Illnerova & Sumová (1997), with the shift in melatonin offset occurring immediately, whereas the shift in melatonin onset advances only after several days of transient adjustment."

Computational modeling revealed that the EM model better predicts the 2 key behavioral phenomena observed with skeleton photoperiods: activity psi-jumps and photoperiod-induced changes in activity phase duration. Although the biological basis is debated, one potential culprit may lie in the SCN neural subpopulations: indeed, it can be schematically separated into two kinds of subpopulations, with the ventral/core SCN subpopulation being more reactive to the phase (timing) of bright light exposure and which expresses period1 gene with a bimodal waveform with two peaks at dawn and at dusk which assumedly tracks day-to-day entrainment, whereas the dorsal/shell SCN subpopulation only expresses period1 gene with a unimodal profile with one peak locked to dusk. The EM model can be seen as the first theory of the circadian rhythm being comprised of multi-oscillators, although we now know that it is an oversimplification, it still allows to predict observed key behavioral phenomena. As a 2011 review nicely summarizes:

> While both photic entrainment and seasonal adaptation arise from a redistribution of SCN oscillatory activity patterns, different neuronal coupling mechanisms are employed, which are reviewed in the present paper.

Although the EM model is based on animals findings, the above results on humans seasonal variations show this is applicable to humans too.

Furthermore, there is evidence from human newborns that the wake circadian rhythm appears earlier than the sleep circadian rhythm, which further supports the hypothesis of distinct circadian pacemakers (oscillators) for the wake up times and the sleep times.

Another evidence in humans are the community studies to delay the college schools start time, to adapt to adolescents biologically induced transient circadian phase delay: when the schools start later, most teenagers will still sleep at about the same time, but will wake up later (TODO: add refs). This is in line with what can be expected if the evening (sleep) and morning (wake up) oscillators are distinct and mostly decoupled.

This is especially interesting as this indicates, by transitivity, that both the wake up time, bright light exposure, minimal core body temperature and melatonin offset (stop of endogenous melatonin secretion) are coupled, whereas the onset of melatonin secretion (DLMOn) seems to be decoupled and may be affected or play a role in photic history, and potentially be more controllable via other means such as with exogenous melatonin pills. Hence, it's no wonder the wake up time is a more reliable estimator of the circadian rhythm than the bedtime or the fall asleep time! Indeed, it was found that the wake-up time is a reliable predictor of the DLMO and the circadian rhythm similarly to the sleep midpoint, whereas the bedtime is not.

Interestingly, this means that the melatonin levels are independent (decoupled) from circadian phase shifting, and indeed that's the case as was later demonstrated (see also here and here and here). In fact, this was first discovered in 1985 by Lewy et al, as they found in humans that there is indeed a delayed effect of bright light on melatonin onset, concluding that bright light both entrained and suppressed melatonin, which prompted them to conceive the clock-gate model integrating this dual effect of bright light on melatonin. The dim light melatonin onset (DLMO) sampling method of the circadian rhythm phase was also orginally devised for this study (see also here). Combined with the fact that the melatonin onset is always delayed of several days after the circadian phase shift, this shows that the start of melatonin secretion (aka melatonin onset or DLMO or DLMOn) is a very unreliable proxy of the circadian rhythm, studies should prefer to measure the core body temperature or at least the wake up time instead.

However, this model assumed that melatonin is the underlying circadian rhythm signalling hormone, whereas recent evidence demonstrated that it's only a relay to modulate core body temperature, the latter being the core signalling pathway for circadian clocks throughout the body. Hence, this model is still valid if we simply replace the assumptions about melatonin secretion by the core body temperature pathway.

This hypothesis that the sleep offset (wake up time) is governed by the circadian rhythm with the sleep offset being delayed, dependent adjustment variable was already advanced by Krauchi et al in 1998:

> Does the SCN regulate heat production, heat loss, or both together? There are only few data available at present to answer this question. Czeisler (1978) has shown that the daily rhythm of heat loss from the extremities (as indicated by wrist skin temperature) is mainly coupled to sleep onset, and can be dissociated from the CBT rhythm when subjects internally desynchronize under free-running conditions. Thus, the heat loss rhythm cannot be the major circadian input of the CBT rhythm, but is rather the dominant contributor to the sleep-evoked component. One preliminary conclusion is that heat production seems to be driven by the SCN, and heat loss is rather the dependent variable which adjusts for heat balance.

This also suggest that any therapy aiming at controlling the bedtime, such as sleep hygiene and chronotherapy, is inappropriate to shift the circadian rhythm, as effective therapies should target the wake up time, such as light therapy.

In summary, the age old assumption that humans can control when they fall asleep is a core idea we got wrong about sleep. Instead, we cannot control when we sleep, but we can indirectly control when we wake up via zeitgebers (such as bright light therapy), which in turns will drag the fall asleep time along with some delay.

(TODO: Distinct Components of Photoperiodic Light Are Differentially Encoded by the Mammalian Circadian Clock, 2020 https://doi.org/10.1177%2F0748730420929217 )

Circadian waveform manipulation: shorter light and bifurcated exposure makes all parameters of the circadian rhythm more flexible

WORK-IN-PROGRESS: this section is subject to vast changes in the future.

Another very important effect of seasonal variations in zeitgebers, especially in sunlight exposure, is the shorter duration of daylight: the days get shorter during winter and longer during summer. The key takeaway is that photoperiod (day length, duration of bright light exposure) affects phase response. But both phase shifting and period plasticity (ie, lengthening/shortening the day length) are themselves just a few subtypes of circadian waveform manipulation, as shortening happens naturally with seasons, but circadian waveform can also be artificially manipulated to cause interesting circadian patterns, such as light-dark-light-dark (LDLD), with interesting properties, such as allowing for very fast (<3 days) phase resetting (ie, 12h phase shift) or stable biphasic circadian alignment.

The SCN is split into two kinds of subpopulations of neurons, ventral/core SCN and dorsal/shell SCN, with ventral SCN adapting faster to bright light input, and dorsal SCN being slower to adapt as it relies on feedbacks from the ventral SCN. The synchronization between subpopulations of SCN neurons is what is thought to underlie the ability to track seasonality, with previous studies finding that individual neurons do not encode short or long days information, but the neural activity at the population level (ie, of a lot of neurons) does encode this information, however newer studies found otherwise, that the dorsomedial SCN does indeed encode period length and is sensitive to retinal inputs. This was found to modulate circadian clock gene expressions, especially period1 which is modulated in ventral SCN in long days to encode both dawn and dusk, whereas the dorsal SCN only encodes dusk in both short and long days (for nocturnal rodents, or dawn in diurnal animals). The slower synchronization (several hours) of the dorsal SCN to zeitgebers compared to ventromedial SCN (under a hour) is likely what allows the SCN to continue to maintain entrainment temporarily in the absence of zeitgebers. Furthermore, a very well designed ex-vivo 2021 study found that the core/ventrolateral SCN network is more susceptible to phase shifts, whereas the shell/dorsomedial SCN network more to period changes: it appears that the ventrolateral SCN responsible for daily entrainment is made to be more sensitive to the timing/phase of bright light exposure and less to period lengthening and is affected under less than a hour, whereas the dorsomedial SCN which encodes seasonal entrainment (long vs short days) is more sensitive to the duration/period of bright light exposure and less to phase shifts and takes several hours to adjust, causing what is termed an after-effects to stimulation such as bright light exposure, also called photic history. These findings suggest that contrary to what was previously thought, circadian plasticity, of both phase shifting and period lengthening/shortening, is also observed at the SCN neuronal scale, not just as an emergent property of networks coupling. In addition, this study demonstrated that clock genes express a sinusoidal waveform in free-running conditions, but a highly asymmetrical waveform with a shorter phase advance portion and a longer phase delay portion when entrained ; and it was also observed that daily waveform changes were observed under entrainment to long days, short days and non-24 periods. Finally, and contrary to what was supposed before, a previous study observed that "ipRGC cells have retinal projections that are widespread across the entire SCN and neuronal activation following light exposure was ubiquitous", which shows that both the ventrolateral and dorsomedial SCN networks equally receive photic inputs, but they just have different intrinsic responses as shown by this 2021 ex-vivo study. The authors further suggest the following: "As the VIP and AVP neurons are respectively located in the ventral and dorsal SCN, this suggests that regionally differential phase and period responses in the SCN might be derived from intrinsic differences between the VIP and AVP neuronal clocks. The period response, inversely correlated with the phase response, could serve to help the SCN recover back to its baseline network phase state from decreased synchrony following phase shifts."

The day length, also called photoperiod and is equivalent to the duration of bright light exposure, is very significant, as it was found to modulate other aspects of the circadian rhythm, such as the phase shift response to bright light exposure, with shorter days (of rodents, hence longer active phase) increasing phase shifts to the same photic input comparing to longer days (ie, longer sleep phases). Shorter days were further found to be associated with a greater synchronization in the SCN subpopulations, especially between the ventral and dorsal SCN, whereas longer days produce a more desynchronized and spread out profile encoding multiple times of the day.
More precisely, short days concentrate the distribution profile of the phase response curves of each clock neuron in the SCN to a shorter timespan in the day (when there is the short bright light exposure), so that they are more easily synchronized and hence a phase shift in the photic input induces a bigger phase shift in the neuronal population since they 1) receive the photic input at the same point of their PRC since they are synchronized, so they get the same phase shift, 2) they echo together with the feedback loops especially using GABA inhibitory and excitatory connections. Whereas in longer days (longer bright light exposure), the clock neurons phase response curves profile distribution is more spread out throughout the day, so that the synchronization is reduced and the phase shift differs greatly between each neuron, leading to a reduced compounded phase shift at the population level.

Shorter total bright light exposure induces a more flexible circadian rhythm. Which is the opposite of what we want to treat non24, as the therapeutic goal is to stabilize the circadian phase. This explains why during winter it's even more difficult to freeze freerunning with non24 compared to summer. But the silver lining is that this may be used advantageously to shift faster to a desirable phase, as a phase reversal (ie, 12h shift) takes much less time when mice have been exposed to a short days compared to a long days. Biphasic days (LDLD) allow for an even faster adaptation to a phase reversal than shorter days. However, these findings were only observed in nocturnal rodents for the moment, more studies are needed to observe whether this also applies to humans and other diurnal animals.

Short days are one example of natural circadian waveform manipulation. Another, but artificial, circadian waveform manipulation is light-dark-light-dark (LDLD).

LDLD days are composed of two blocks of one photophase followed by one scotophase. In other words, two small days in one. For example, LDLD(7:5:7:5) denominates a day comprised of 2 subdays with 7h of bright light exposure and 5h of darkness. Non-24 periods entrainments are called T-cycles, examples: T15 means an entrainment to a 15h day, T30 to a 30h day.

Although short days allows for a significantly faster entrainment to a new bright light schedule than long days, under about 4 days instead of 7 days, LDLD provides additional benefits: not only is it much faster to entrain from long days to LDLD than to short days (1 day vs 1 week), LDLD also allows to entrain to a full phase reversal under just 3 days, hence the total time between the initiation of LDLD and the end of phase reversal is 4 days. Furthermore, LDLD is a highly stable entrainment pattern, so that it can not only serve as a fast resetting method, but also as an alternative sleep-wake schedule for a circadian aligned biphasic sleep, which has potential applications for shift work.

However, LDLD has some limitations: first, it is highly artificial, and although it is resilient to temporary perturbations in the photophases and scotophases, it requires to shield/manipulate one's exposure to sunlight and artificial light therapy to create two distinct photophases and scotophases. Secondly, this biphasic pattern of the circadian rhythm naturally reverts to a monophasic pattern, with the two scotophases joining together, when exposed to constant conditions (either always dark or always bright light), so that for LDLD to be maintained, the distinction between the two subdays is necessary. Thirdly, not all animals could entrain to LDLD, with 3/36 rodents just freerunning with an underlying long day entrained circadian rhythm, and similarly in another study 1/18 hamsters failed to entrain.

Time to adapt to a shifted phase compared to the original phase, per bright light exposure pattern. Long day and short day here refer to objective days (ie, length of photoperiods) not the subjective day, which is the inverse for nocturnal animals (ie, short subjective day for long objective day, and long subjective day for short objective day). Excerpt from Figure 2 of this study.

Now it is important to note that short objective days (short photoperiods) for nocturnal rodents imply longer active periods (longer subjective days), whereas for diurnal animals, for which the retinal-SCN pathway is inverted, short days imply a shorter active period (see also here). Indeed, melatonin and bright light are wired inversely to the noradrenergic vasoconstrictor system in nocturnal animals compared to diurnal animals, so that melatonin signals wakefulness periods and bright light exposure induces sleep, but the circadian rhythm and its linear coupling with core body temperature remain the same as in diurnal animals, with high phases associated with wakefulness periods and low phases with sleep periods. Since the basis of greater phase shifts and greater period lengthening/shortening stem from a greater synchronization of the SCN neuronal ensemble, and that it's the bright light input that projects and affects the SCN neuronal ensemble, then to translate these results from nocturnal onto diurnal animals such as humans, a short photoperiod implying a shorter subjective day (ie, shorter active period) can be expected to produce similar results of increased circadian plasticity. In other words, whereas short days imply shorter sleep periods and longer active periods for rodents, we infer that they translate as shorter active periods and longer sleep periods for humans, similarly to what both rodents and humans naturally experience with seasonal variations in bright light exposure.
This is in contrast to the hypotheses other authors offer, and if ours is correct, then this put into question the practicability and usefulness of short days and LDLD interventions for shift-working humans: whereas short days and LDLD imply longer active periods for rodents while allowing them to obtain wider phase shifts to realign with zeitgebers faster, humans would have to (forcefully) experience shorter less productive active periods and longer sleep periods, with sleep induction and maintenance being known as more difficult to achieve than wakefulness induction and maintenance (ie, it's easier to stay awake longer than to sleep earlier and longer).

Is LDLD producing a really biphasic circadian rhythm, or is it only a masking effect of behavioral activity? According to this early paper, by Gorman et al, original discoverers of LDLD, the observed phenomena cannot be explained by masking. More recent evidence using objective markers of the circadian rhythm, such as body temperature in mice, also observed a bimodal waveform, hence demonstrating that it's not just activity but the circadian rhythm itself that is bifurcated by LDLD.

Phase shifting and period shortening/lengthening are just two kinds of circadian waveform manipulations, but there are several other parameters that were found to be modifiable as an after-effect through light-dark manipulations, with an after-effect being the description of an effect that both appears after and hence as a result of a circadian waveform manipulation, and stays after discontinuation of the manipulation:

TYPES OF CIRCADIAN AFTER-EFFECTS: PERIOD, WAVEFORM, ENTRAINMENT, PHASE-SHIFTING: "The effects of previous states of entrainment on properties of the biological clock are termed aftereffects. Best known are period after-effects—lengthened and shortened free-running period in constant darkness following entrainment to long versus short light cycles (Pittendrigh and Daan 1976) and waveform after-effects—lengthened and shorted active period (alpha) in free-run after short versus long photoperiod. Less well known are after-effects on entrainment—different patterns of entrainment in identical conditions in T22 depending on lighting history (Chiesa et al. 2006) and after-effects on phase resetting—larger light-induced phase shifts in hamsters entrained to short compared with long photoperiods (Pittendrigh et al. 1984; Evans et al. 2004; Glickman et al. 2012; Glickman et al. 2014). The ability to entrain to 30-h LDLD cycles following bifurcation, but not other conditions, represents another type of circadian entrainment after-effect." Ref: https://pubmed.ncbi.nlm.nih.gov/28770653/

  • In addition: shorter photoperiod (longer subjective day) for the same total light cycle (same day duration) leads to lengthened freerunning period: "Under constant conditions, animals previously entrained to LD5:19 had significantly longer freerunning periods than those from LD9:15 (Fig. 4C)." https://pubmed.ncbi.nlm.nih.gov/16731659/
  • "after-effects on entrainment" refers to photic history. Which includes dim light at night effect of increasing phase shifting and entrainment bounds!

A few practical aspects to implement circadian bifurcation (LDLD):

Although it is currently (as of 2022) unknown whether artificial temporal reorganization manipulations of the circadian waveform such as LDLD would work on humans, scientists suggest it is possible and already see potential applications to improve the health, wellbeing, safety and productivity of shift workers, with some tentative schematics of how such protocols would be done in practice.
For individuals with a circadian rhythm disorder such as non-24, having a bifurcated circadian rhythm can have significant advantages, such as allowing 2 windows of activity, one during the objective daytime and one during the objective night (whereas nightwalkers such as inversely phased non-24 or extreme DSPD will not have activity opportunities during daytime). For those suffering from chronic fatigue due to chronic circadian misalignment, LDLD allows to multiply by 2 the number of activity periods and rest periods, so this probabilistically increases tremendously the likelihood of experiencing productive activity periods, whereas with a typical schedule the next opportunity is only in 24h, here it can be 12h or even earlier depending on the LDLD scheme used.
For individuals with DSPD and shift work disorder, the benefits are obvious, as a LDLD pattern is essentially a robustly circadian aligned biphasic sleep, where the napping sleep period is replaced by a "true" second night sleep, with melatonin production and other circadian night processes that are not activated during naps of non-LDLD biphasic sleep patterns.

The 2021 optogenetics study already mentioned above also found something very interesting: all the effects are reproducible with just short light-dark transitions, as with skeleton photoperiods, but replaced by neuronal stimulation that mimics it. Hence, it appears that to trigger phase shifts and period shortening/lengthening, all that is needed is to apply a contrast to the neurons, this is all they detect. Furthermore, by default, when there is an ambiguity, the SCN networks seem to revert to a shorter day. Finally, it was found that non-24h light-dark schedules (T-cycles) cause SCN desynchrony, similarly to long days, and hence reduced responsiveness to phase shifts. This may explain why individuals with non-24 are usually more treatment-resistant to light therapy, and require longer and more intense light therapy, than other circadian rhythm disorders.

Another particularly interesting finding is that it appears that the period plasticity has an after-effects, with long days causing mice to keep a longer freerunning period after being moved to constant conditions compared to short days ("under constant conditions, animals previously entrained to LD5:19 had significantly longer freerunning periods than those from LD9:15.").

It's worth noting that now that there is unequivocal evidence of the circadian rhythm being composed of multiple oscillators, and that it can be dynamically reprogrammed (ie, high neuronal plasticity), there is nothing that indicate that bifurcation should be limited to a split in two: it may very well be possible to bifurcate the circadian rhythm into 3 or 4 functionally independent oscillators, since this simply implies a SCN neuronal connectivity reorganization, with subcommunities of neurons getting assigned to track specific photoperiods (see also the Balanced Networks model for how neuronal networks can specialize in an unsupervised way based only on stimuli). For those interested in history of science, it seems that one of the earliest if not the earliest evidence of the circadian rhythm being composed of multiple oscillators in humans come from a 1983 study which used a sort of early LDLD-like design, although an earlier work by Wever in 1975 appears to document the circadian rhythm in humans as a multi-oscillatory system (but inaccessible online, could not read content).

These findings on circadian waveform manipulation, especially the greater synchronization for shorter bright light exposure compared to longer light exposure, may imply that there may be a sweet spot for entrainment, with a long enough bright light exposure to synchronize but not too long to remain synchronized to the zeitgeber robustly, but at the same time it's worth considering that longer bright light exposure causing desynchronization shields against unwanted phase shifts since the effect will be distributed across multiple populations of SCN neurons with different PRC phase profiles. Anecdotally, when the present document's author experimented with LDLD, this indeed allowed to produce 2 short days of high attention and productivity under 24h, with entrainment achieved under 2 days, but lost after only 2 days, which caused the circadian rhythm to freerun much faster than even before (about 3h/day of phase delay over the next 3 days under constant conditions - artificial bright light and sunlight were excluded - following loss of entrainment to LDLD and bright light therapy discontinuation). Hence, LDLD can have serious adverse effects in case of entrainment failure. Nevertheless, using 3-4h/daily of standard bright light entrainment (using the VLiDACMel protocol) allowed to reduce the freerunning speed back to its original state under a few days, even after discontinuing bright light therapy. Nevertheless, a longer lasting after effect (ie, longthened circadian period) can not be excluded after LDLD entrainment failure in case the circadian period was not instantly reduced by a VLiDACMel manipulation.

Another field worth investigating is the study of military and commercial submarines personnels, as they are regularly forced to rotate on artificial non-24 T-cycles (eg, 18 hours days) or even split cycles, with or without exposure to zeitgebers depending on submergence.

Synergistic effect of multiple zeitgebers

WORK-IN-PROGRESS: this section is subject to vast changes in the future.

A study has demonstrated a synergistic effect of using multiple zeitgebers, by observing the induction of period genes by light together "with modulations of nuclear receptor activities by drugs and metabolism" and hence "medical treatment strategies which aim for stable circadian rhythms should consider interactions of multiple zeitgebers". More precisely, they found that "the entrainment of a circadian rhythm to two coexisting zeitgebers depends strongly on the phase difference between the two zeitgebers".

Light and dark therapy

Circadian rhythm disorder management involves maximal control of the pattern of exposure to light, which for diurnal animals such as humans includes being exposed to bright light during the circadian morning and day, and avoiding bright light exposure during the circadian evening and night. Furthermore, all zeitgebers work only when they have a periodic component, which is an alternance between high and low phases, for light it's composed of bright blue light phases versus dimly lit/dark reddish phases, as without such alternance, participants lose entrainment (ie, constant routine protocol). Hence, bright light therapy should always be complemented with dark therapy, and both therapies should really be considered a single therapy, a light exposure control therapy or, more prosaically, light and dark therapy.

The next subsections will cover the various parameters and findings about bright light therapy and dark therapy on the circadian rhythm.

Brief history of bright light therapy

Heliotherapy, which is bright light therapy using sunlight (or sunlight therapy nowadays), can be traced back to 15 centuries BC. Renewed interest by pre-modern medicine emerged with the discovery of the importance of UV light for the human body to produce the essential vitamin D during the mid nineteenth century, which led to the UV therapy craze and its excesses. Modern light therapy seems to have emerged around in the late 1970s to 1980s, with research on insomnia and on depression uncovering the previously unknown effects of bright light therapy on the human circadian rhythm and on mood. Indeed, until the early 1980s, it was assumed by chronobiologists that social cues were the main zeitgebers for the human circadian rhythm, with bright light having little importance, despite being the main zeitgeber for animals, until this assumption was disproven first by a review in 1981 by Czeisler et al and then by empirical data in 1986 and in 1989 demonstrating the vast underestimation of the magnitude of bright light circadian resetting effect. The existence of the ipRGC cells in the eyes, the cells that allow circadian rhythm shifting from bright light ocular exposure, was discovered in frogs and mice in 2000 and later in humans, in 2003 by Panda et al.

Norman E. Rosenthal is often credited as the first scientist to have coined the term Seasonal Affective Disorder (SAD) for seasonally-dependent depression, and the use of bright light therapy to treat it, in 1984, from a case study on a depressive patient admitted in 1980. However, Rosenthal is actually not the first to have used bright light therapy to treat depression. Indeed, there is another study published 1979 by Wehr which used bright light therapy to treat depression in a group of human patients. Wehr went on to become a principal investigator and led the study that Rosenthal worked on and which defined the SAD disorder.

The effect of bright light on the circadian rhythm is known since at least before 1966, thanks to the groundbreaking works of Kleitman in 1949 and later by the invention of the free-running protocol of Aschoff and Wever in 1962 inspired by the De Candolle experiments in 1832 successfully making the Mimosa Pudica (nicknamed the "Sensitive plant") free-run under constant dark conditions, which experiment was itself inspired from de Mairan precursory discovery of the existence of the circadian rhythm using the same plant. In 1971, K. Hoffman appear to have been the first to discover the photic history effect as well as the splitting effect on syrian hamster, which he named "hysteresis" at the time. Hence, the knowledge that bright light influenced not only the circadian rhythm of animals and plants but also humans was well established much before 1979 when the effect of bright light on mood was discovered with Wehr's work. A review published in 1983 concludes that there was sufficient evidence of an effect of bright light on humans circadian rhythm similar to animals that this warranted further investigations into the use of bright light as a therapy for circadian rhythm disorders. Another review in 1983 specifically focuses on DSPD as a primary target of bright light therapy intervention. A group study was conducted in 1985 on healthy volunteers. Hence, light therapy was investigated for circadian rhythm shifting and potentially sleep disorders treatment directly subsequently to its use for depression.

In conclusion, the effect of bright light on the circadian rhythm was first discovered before its effect on mood. The first case studies investigating the use of bright light as a therapy were done first for mood disorders (depression, SAD), and then for circadian rhythm shifting on healthy volunteers, before starting trials for sleep disorders the next decade. However, it's important to note that the rationale for using bright light therapy for depression always involved the hypothesis of a circadian dysregulations underlying depression (the critical photosensitive period hypothesis, see also here, later renamed to circadian phase shift hypothesis, or also the phase advance hypothesis) and that properly timed bright light could be an effective treatment to affect both the circadian and mood systems.

Hence, the circadian shifting effects of bright light exposure were amusingly enough discovered more than 40 years before the biological pathway was found, since the ipRGC cells existence was discovered only in the 2010s.

It's worth noting psychiatry (eg, Lewy, Krauchi) and psychology significantly contributed to the early research on circadian rhythm science, core body temperature, and bright light therapy to treat depression and sleep disorders, with both disorders being at the time considered to be of nonorganic cause and hence belonging to these specialties. Kleitman, another psychologist who used physiological tools and designs, explained this peculiarity (studying a purely biological phenomenon like sleep by psychological researchers) by the lack of biological technologies which prevented physiologists to study sleep processes, who implicitly delegated this task to psychologists. These pioneers nevertheless did not restrict themselves to their field but also versed in a variety of other fields such as biology, physics and mathematics, just like Piéron before them.

Artificial light is also intimately related to the modern society's economical and labour organization. The essay "The Biopolitics of Melanopic Illuminance, Magnus Eriksson and Geraldine Juárez, Scapegoat (10), 2017" describes how labour laws are a direct consequence of the invention of artificial lighting, how the 24/7 consumerist society is a byproduct of earlier military experimentations to create sleepless soldiers inspired from migratory birds and hence how not surprising it is that the "sleep is for losers" mindset is systematically implemented in the military up to this day, and how artificial lighting is still used as a torture tool in Guantanamo. Note that "biopolitics" is a term coined by Michel Foucault, a philosopher who studied the history of modern medicine and its sociopolitical use as a tool of power to control populations.

Nowadays, artificial bright light therapy is not only investigated for the treatment of circadian rhythm disorders and insomnia, but also for major depression, Alzheimer, delirium and ADHD.

The medical consensus for the use of artificial bright light therapy in the treatment of circadian rhythm disorders varies as of 2022: considered as an option but without sufficient evidence to be systematically recommended by the American Academy of Sleep Medicine, except for ASPD for which it is the treatment of choice, and it is however a recommended treatment for the french sleep medicine institution SFRMS since 2017, with french experts considering bright light therapy as being "amply validated" for the treatment of circadian rhythm disorders.

Bright light therapy parameters, Luminette and photic history

Light therapy, or phototherapy, is a therapy that consists in being exposed to bright light on a precise timing relative to the user's circadian rhythm. The therapy is usually repeated everyday in practice, although studies demonstrated effects with a single exposure.

Light is without a doubt the most powerful tool we have to manipulate the circadian rhythm. Indeed, in case of conflicting inputs between clocks, light always has precedence over other clocks according to Aschoff, and it entrains all central and peripheral clocks throughout the body. Light is the main modulator of circadian rhythms, sleep and mood. Bright light even affects DNA transcription in the process of genes expression through CREB, which is phosphorylated in response to photic stimuli. Hence, light is the number 1 tool anyone with a (sighted) circadian rhythm disorder needs to try. All other currently available treatments (including melatonin) provide much less circadian shifts than light can (but they can be combined for greater effect).

The medical use of light therapy started in the 1900s with UV therapies which awarded its author a Nobel prize. However, modern bright light therapy only came up later, after the 1950s. The effect of bright light on the human circadian rhythm and its interaction with other vital signs such as core body temperature and heart rate was pioneered by the extensive works of Kleitman before 1966. The discovery of the biological pathway for the circadian shifting effects of bright light came even later, first named the "pre-optic area of the anterior hypothalamus" as it was assumed to be a yet to be discovered neurological structure, until the discovery of the ipRGC cells in the eyes in the 2010s.

However, as the french sleep medicine institution SFRMS stated: "The biological clock can only be synchronized to 24h if the received photic inputs during the day are sufficient in length and intensity and if exposure happens at adequate timings", hence bright light therapy needs to be used in a specific manner to ensure efficacy. It is hence crucial for circadian rhythm sleep medicine to identify the parameters effecting bright light therapy efficacy.

Bright light, including artificial light therapy, affects the circadian rhythm by stimulating the intrinsically photoreceptive retinal ganglion cells (ipRGC) receptor cells (that can be connected to S-Cone cells) mostly present in the parafovea of the macula and nasal regions of the retina in humans (see also here), not the inferior nor superior nor temporal regions of the retina, but according to an animal study, each ipRGC cells in fact axonally innervates bilaterally the suprachiasmatic nucleus (SCN), with ipRGC cells located in the dorsal-temporal region of the retina primarily targeting the dorsal part of the SCN, and those located in the ventral-nasal region targeting the ventro-medial parts of the SCN, although studies on humans so far found no evidence of a dorsal-ventral gradient in ipRGC cells placement in humans, contrary to other animals. The ipRGC (also called mRGC cells or melanopsin O