SleepDisordersPsychoRebuttal

Créée le mardi 02 mars 2021
Last update: November 2023
DRAFT

Intro

Please consider the following as an opinionated work-in-progress review of the evidence basis of the psychological approach to sleep disorders, and of all disorders in general, as the same approach is used for several diseases for similar rationales, refuting one inevitably requires and leads to refuting the others.

Rough overview

Glucocorticoid hypothesis claims that emotional stress applies to all inflammatory diseases. So it seems like at least there is a restriction on what kind of diseases chronic emotional stress can apply to. But then the proponents also claim that emotional stress applies to psychological disorders, which includes arguably the only kinds of non-inflammatory diseases. So in the end, to what diseases emotional stress does not apply? It seems that none, according to the proponents.

Did you ever see a medical concept that can cause, and cure, all diseases? There is only chronic psychological stress. If true, that would be the only omnipotent and ubiquitous medical ailment. A quite extraordinary claim that requires as extraordinary proofs.

Running thoughts as a cause of insomnia is the cognitive hyperactivity of insomnia. But it's easy to disprove, because patients with ADHD, a disorder characterized by hyperactivity, who are properly managed with a therapy for ADHD still have insomnia, which for the vast majority is DSPD.

All behavioral therapies, except for CBT-i, lack follow-up studies, which is worrying given these therapies are commonly prescribed since decades or centuries for some like sleep hygiene or sleep restriction. This strongly suggests a publication bias, where these follow-up data are not published because they are negative results. This is strengthened by the lack of drop-out rate. These two parameters are crucial to assess the efficacy of therapies, and they remain largely unreported for behavioral therapies despite their widespread use.

The psychiatric assumption that sleep is just a psychological habit even led some to use classical conditioning to try to treat insomnia. Pavlok is a bracelet that induces a painful but allegedly non dangerous electrical shock to the user when it's time to wake up. Not only is this literally a torture, it's not even studied scientifically as there is no mention in meta-analyses on behavioral therapies. It's not a recognized medical therapy for insomnia at all. And yet, a non-24 patient reported (private communications) that a sleep clinic prescribed this item to treat their circadian rhythm disorder when light therapy and melatonin failed. In other words, sleep medicine professionals sometimes recommend clearly pseudomedical therapies that have not been previously vetted by any study, an unarguably unethical act. It is truly appalling and even horrifying that in 2020 (time of the diagnosis and intervention) there are still some medical professionals who can prescribe this kind of painful and ineffective treatments to their desperate patients.

Here is an excerpt from the non-24 patient's testimony (private communications with authorization to publish anonymously) explaining the medical professionals rationale for using this inhuman procedure:

> The shock bracelet as explained to me was not strong enough to cause harm, and was a try to literally shock my system into a 24h rhythm again, was a last resort for them also as all treatment failed up to this one. A week later i had my n24 diagnosis.

The worst part being that the sleep clinic held hostage the patient by conditioning their non-24 diagnosis to the failure of such an extreme pseudomedical therapy, while there is NO requirement of being treatment resistant for a non-24 diagnosis, and even if there were, they had no right to use an unnecessarily painful pseudomedical procedure that is not recommended in any modern medicine guideline for any ailment.
https://www.youtube.com/watch?v=eoovqtyQ1UE
https://pavlok.com/

Intensive sleep retraining is literally a torture: "After a night wherein the patient limits time in bed to no more than 5 hours, the treatment includes a 24-hour laboratory protocol in which the patient is given an opportunity to fall asleep every 30 minutes in sleep-conducive conditions. If sleep occurs, then the patient is awakened after 3 minutes and remains awake until the subsequent 30-minute trial. For each sleep opportunity, the patient is given feedback as to whether or not sleep occurred."

there is no evidence that treating depression can treat a comorbid insomnia, and no evidence that antidepressants can improve insomnia,

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. 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:

> For several decades beginning in the 1970s, insomnia was considered a “symptom” not a “disorder.” To the extent that insomnia was considered just a symptom of medical or psychiatric disease, it was believed that treatment of the parent disorder was sufficient and would result in the resolution of the insomnia. More recently, this perspective has given way to the position that, when chronic, insomnia should be characterized as a primary disorder, which, when it co-occurs with other medical and psychiatric illness, should be designated a comorbid condition (as opposed to a secondary symptom). These nosologic designations carry with them the clear implication that chronic insomnia merits targeted treatment. This perspective, however, has yet to influence the standard of practice. More often than not, insomnia continues to be undiagnosed and/or untreated.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882812/

This is also stated in Hitchens's razor, which declares that "what may be asserted without evidence, may be dismissed without evidence." https://en.wikipedia.org/wiki/Burden_of_proof_(philosophy)
We are here in the second case, an evidence of absence:

• "A proof of impossibility or an evidence of absence argument are typical methods to fulfill the burden of proof for a negative claim." https://en.wikipedia.org/wiki/Burden_of_proof_(philosophy)#Proving_a_negative
  • We are here in the second case, evidence of absence: https://en.wikipedia.org/wiki/Evidence_of_absence
  • "Per the traditional aphorism, "Absence of evidence is not evidence of absence", positive evidence of this kind is distinct from a lack of evidence or ignorance[1] of that which should have been found already, had it existed."
  • "The difference between evidence that something is absent (e.g., an observation that suggests there were no dragons here today) and simple absence of evidence (e.g., no careful research has been done) can be nuanced. Indeed, scientists will often debate whether an experiment's result should be considered evidence of absence, or if it remains absence of evidence. The debate regards whether the experiment would have detected the phenomenon of interest if it were there."

why it's so important that we focus on what works, so that we can improve these approaches and increase their benefits instead of losing our time and effort on things that have been clearly demonstrated to not work, time and time again.

Anyway, although there is a prevalent view that the mind can affect the body, this new age thought school is not supported by evidence (how surprising). There is a Cochrane Systematic Review on the placebo effect, which found that the only significant effect of placebo is on the subjective perception (of pain or other factors). But not on any objective parameter. In other words, the placebo effect never improves any condition objectively, it can only make you feel better about it.

> Title: Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment
>
> Conclusion: We found little evidence in general that placebos had powerful clinical effects. Although placebos had no significant effects on objective or binary outcomes, they had possible small benefits in studies with continuous subjective outcomes and for the treatment of pain. Outside the setting of clinical trials, there is no justification for the use of placebos.

New England Journal Of Medicine with Cochrane, 2001 https://pubmed.ncbi.nlm.nih.gov/11372012/

So no, nocebo nor placebo have any powerful effect except maybe modulating slightly the subjective perception of pain. No objective effect whatsoever otherwise.

A later Cochrane systematic review confirmed this finding, and further suggests that the purpoted small effect of placebo in very rare instances (pain, nausea) may rather be due to biased patients reporting, and specifically found no evidence that placebo effect could affect insomnia: https://doi.org/10.1002/14651858.CD003974.pub3

But as usual, psychologists and psychotherapists are theorizing that the nocebo effect may be the cause of COVID-19 induced POTS and depression, without, again, any evidence, and despite previous reviews finding no evidence... But why would they check out past research literature, that's not their job, is it? https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7661580/

The issue with insomnia is that the detrimental effects of chronic sleep deprivation on health are very, biologically real. Changing perception doesn't change the fact that insomniacs are much more likely to die by a car/work accident or by a stroke or by cancer.

• The APA itself recognizes that most psychological therapies are ineffective! Or at least not sufficiently validated! https://www.apa.org/ptsd-guideline/patients-and-families/cognitive-behavioral
  • "It is important to emphasize that advances in CBT have been made on the basis of both research and clinical practice. Indeed, CBT is an approach for which there is ample scientific evidence that the methods that have been developed actually produce change. In this manner, CBT differs from many other forms of psychological treatment."
    • See also: https://doi.org/10.1038/d41586-020-00922-8 — mentions that randomizing mental diagnosis and psychological therapy provided same results for all groups, so that it shows that both the psychological diagnoses and treatments are unspecific!
  • Plus CBT premisse is faulty, there is NO reason to apply it for sleep! Because it targets psychological issues. But sleep is NOT a psychological issue!
  • "CBT is based on several core principles, including:

Interestingly, the meta-analysis notes that it was "found that both Z drugs and placebo statistically significantly reduced sleep latency", demonstrating that an intervention reduces sleep latency is not sufficient to prove efficacy if not properly controlled against a placebo.

• Another argument: insomnia and circadian rhythm disorders are most likely genetically inherited. Psy behavioral interventions cannot change genes. See van someren q and a: https://www.sleepmeeting.org/wp-content/uploads/2021/06/SLEEP2021_VirtualGuide-1.pdf

Can psychological disorders such as depression or anxiety cause sleep issues and insomnia

In medical terms, we say that insomnia is secondary to psychological disorders. Is this true?

No. That's a myth.

Several reviews of studies have amply demonstrated that, contrary to previous assumptions of psychology theorists, insomnia does not appear to be caused by psychological disorders, and rarely resolve when the psychological disorder is treated.

In the case of circadian rhythm disorders, a clear biological basis is well established, with objectively measurable melatonin and core body temperature dysregulations, which are inconscious, automatic processes that are crucial for human's (and other mammals) survival (see homeothermy and endothermy), which means that psychological factors are very unlikely to play any role. (Unless for believers of Voodoo Death, see the next sections).

• Read this for a gentle intro: https://www.independent.co.uk/life-style/health-and-families/why-lack-sleep-makes-us-depressed-insomnia-and-what-we-can-do-about-it-a7371786.html
• https://doi.org/10.1016/S0272-7358(00)00083-0
• https://dx.doi.org/10.1136/bmjopen-2017-016873
• https://doi.org/10.1016/S2215-0366(20)30136-X
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882812/
• https://pubmed.ncbi.nlm.nih.gov/31108433/

I even found [a historical review](https://doi.org/10.1098/rsfs.2019.0094) finding the root of this misconception, which dates back to middle age's superstitions:

> While the concept of ‘stress' in the modern sense is a twentieth-century innovation, many of the symptoms we associate with the modern condition appear in historical materials going back many centuries. But how did premodern people understand and experience these symptoms and their relation to sleep? This study focuses on the rich materials from the central middle ages in Western Europe, a period during which understandings of the body, mind, emotions and sleep were radically different from the present. It analyses two examples, nightmares and insomnia, disease categories which illustrate medieval views of the impact of worries and anguish on sleep. Medical and other sources identified a number of ways in which the mind and body interacted with one another in complex ways which disrupted the humoral and mental balance of the individual.

This misconception is even recognized by [the AASM](https://doi.org/10.5664/jcsm.8988) nowadays:

> some treatments (eg, biofeedback, relaxation therapy) emerged decades ago and thus reflect clinical conventions of those times, such as a focus on sleep-onset insomnia and conceptualization of most insomnia as a symptom of another disorder; therefore, they do not reflect current diagnostic or assessment standards.

Furthermore, antistress and antianxiety therapies have shown no efficacy compared to placebo to improve insomnia on objective parameters (TODO: add sources, see section "Anxiety and circadian rhythm disorders are NEVER secondary to psychiatric disorders, they are independent, and their basis is certainly not psychiatric" and https://pubmed.ncbi.nlm.nih.gov/11584515/ , search "stress management therapy").

Interesting that we are still hailing a medieval belief as if it was a medical evidence despite proof of the contrary, [don't you think](https://en.wikipedia.org/wiki/Psychology#Contemporary_issues_in_methodology_and_practice)?

Furthermore, there a now widely recognized dogma in the practice of clinicians, especially psy, who systematically disregard sleep issues (TODO add ref).

That said, it recently appeared that several antidepressants and stimulants could help treat circadian rhythm disorders. Indeed, effective antidepressants are also those that can shift the circadian rhythm, likely by making the patient more sensitive to photic inputs, and hence more responsive to bright (sun)light therapy.
Another reason why is because of serotonin. One theory of depression pathogenesis is that it may be caused by a deficiency in serotonin secretion. Hence, the efficacy of serotonin reuptake inhibitors (SSRI). However, this is only a partial picture. Serotonin is also a precursor of melatonin, so that serotonin deficiency may logically cause a melatonin deficiency. Increasing the levels of serotonin secretion may in turn increase the levels of endogenous melatonin secretion, hence consolidating sleep and entraining the circadian rhythm phase. It is hence arguable whether serotonin deficiency is actually a cause of depression, or actually a cause of sleep disorders which in turn cause depression and other mood disorders via chronic sleep deprivation. In any case, it seems clear that serotonin dysregulation also impacts the circadian rhythm, and hence that this is as much a sign of depression as it can be of a (concurrent) circadian rhythm sleep disorder. This is also a confounding factor in psychotherapeutical theories of depression, as sleep is often not accounted for in the studies designs, despite sharing many common pathways, especially serotonin and the HPA (cortisol) axis.

Although there is no evidence for psychological disorders causing sleep disorders, there is ample evidence that sleep disorders, or even just acute sleep deprivation, can cause depressive symptoms. (More in health section about anhedonia).

In summary, although evidence shows insomnia is not caused by psychological disorders or factors, and circadian rhythm disorders even less given their biological basis is well established, neurological drugs are currently investigated for being repurposed to complement light therapy to treat circadian rhythm disorders.

---
TODO:

sleep disorders cause depression, but not the other way around
the view that depression can cause sleep disorders is a very old view that was thoroughly disproven by lots of well designed studies

there is indeed a link between depression and circadian rhythm disorders
there are actually strong evidences that circadian dysregulation accompanies depression
and even that effective antidepressants are actually effective circadian rhythm regulator (likely because they increase photosensitivity)
same for light therapy: it's effective for both circadian rhythm disorders AND depression
as much as antidepressants in fact
and even more when combined
the current hypothesis is that circadian rhythm disorders precede depression
so actually, it's rather more likely that your non24 is contributing, or even causing, your depression
treating non24 can likely improve your depression
but treating depression isn't likely to improve your non24
although indirectly you will get more motivation to try stuff and comply rigorously if you treat depression, so this increase in motivation can indirectly help with non24, but not directly. It's not like you are going to treat depression and it's going to improve non24 just with depression treatment
I am quite sure of that because, as the review I linked above states, treating depression doesn't improve insomnia
the review isn't even talking about circadian rhythm disorders, which have a much more determined biological basis, insomnia is much more multiform, we don't know what is causing insomnia in most cases, it may very well be psychological in some cases, but the review shows that's not the case since psychological treatments, whether antidepressive, antistress or bipolar or others, often do not improve insomnia at all. In fact, there are antidepressive drugs that worsen insomnia.
For circadian rhythm disorders, we know it's a dysregulations in hormones such as melatonin and in core body temperature (both are in fact linked), so there is a clear biological basis for these disorders.
In this case, it's very highly unlikely antidepressive treatments can help. EXCEPT if they are increasing photosensitivity, but then you also need to combine the treatment with light therapy
so you see it's a bit of a mixed bag, the answer to your question is literally "yes and no" ;-)
no, it's pretty sure that depression doesn't cause circadian rhythm disorders such as non24, but yes, treating depression may indirectly or even directly help with non24, but only if you have the adequate antidepressive drug and you use light therapy too
about the antidepressants being effective only when they also shift the circadian rhythm, this stems from this Nature review: https://doi.org/10.1038/s41398-020-0694-0

• Testimonial: Even when other health issues including psychological disorders are treated, non24 still remains a hard cap for employment: https://web.archive.org/web/20210922180241/https://old.reddit.com/r/N24/comments/psw8od/overcame_severe_and_persistent_problems_lasting/

Can psychological disorders worsen sleep issues and insomnia

A weakened argument that stems from the previous one is that even though insomnia is not caused by psychological disorders, it may be worsened by psychological disorders, or mental states for the boldest claims. Although this claim is weaker than claiming that insomnia can be caused by psychological disorder, it's harder to disprove, as it would require to show that under any circumstances and out of all mental states and disorders, none can affect sleep significantly. This would nevertheless be a reversal of the burden of proof, as rather the claim needs to be substantiated first, not its disproval. Nevertheless, we will attempt the latter here.

It's not (emotional) stress, it's the chronic sleep deprivation that directly causes your issues.
Studies on stress are often (always?) confounded with sleep deprivation. Stress researchers almost never measure nor control the sleep of their participants.
A landmark 2020 study found that prolonged sleep deprivation causes death by the accumulation of reactive oxydative species, in other words a buildup of cellular damage.
But oxydative/cellular stress != emotional/psychological stress (the latter is the one I was referring to). It's obvious why if you don't control for sleep deprivation, which causes oxydative stress, any result about emotional stress correlating with oxydative stress will be confounded.

See also what I wrote: https://www.reddit.com/r/DSPD/comments/ogz068/scientists_have_found_that_three_consecutive/h4r3yc3/ (mirror: https://archive.is/ynT7U )

Are sleep patterns due to sleep habits?

Qualifying sleep patterns, and especially insomnia, as sleep habits implies these patterns are by choice. This is as inaccurate as qualifying paraplegia as a "walking habit".

Cognitive hyperactivity

Having racing thoughts is not a sign of being too awake, it's a sign of being sleep deprived, as sleep deprivation causes racing thoughts by reducing the ability to suppress unwanted thoughts, in other words a dysregulation in conscious thoughts (spontaneous brain activations) control and especially inhibition.

Furthermore, if the hypothesis of racing thoughts as a contributor of insomnia was true, then people with ADHD, a disorder characterized by hyperactivity including racing thoughts, who have full control over their hyperactivity thanks to pharmacological treatments should see an improvement in their sleep issues, which is not the case. On the contrary, a vast majority (78%) of people with ADHD also suffer from the DSPD circadian rhythm disorder.

In other words, the cognitive hyperactivity theory of insomnia is not supported by evidence, as 1) cognitive hyperactivity does not cause insomnia, but insomnia or just sleep deprivation causes cognitive hyperactivity, 2) treating cognitive hyperactivity does not improve the sleep disturbances.

On the other hand, racing thought are actually a quite reliable signal of sleep deprivation, with the author of the present document actively using it to assess if the recent sleep sessions happened in circadian misalignment.

Some people would argue that intellectual stimulation before sleep can worsen sleep. Although certainly mental stimulation is counter-productive, there is no evidence that this can shift nor entrain the circadian rhythm (and there is no biological reason to think it can happen), hence even if we assume mental stimulation may affect sleep, it would only affect sleep quality (and this remains to be proved), not the circadian rhythm. Actually, there is some evidence that racing thoughts are in fact a consequence of chronic sleep deprivation rather than a cause.

BEST CRITICAL: it's useless to stay in bed or laid down or to avoid doing activities, because most of core body temperature variation is due to the circadian rhythm, strongly suggesting it's mostly unaffected by activities even physical! "Body temperature depends on the balance between heat production and loss. Heat production usually varies circadianly, since a major source of variation is muscular rest and activity; but even in subjects at strict rest and fasting this circadian variation persists, with the lowest values in the small hours of the morning (25), in fair correspondence with the familiar rhythm of body temperature. This rhythm in metabolic rate is, however, unlikely to contribute significantly to the temperature rhythm, since the amplitude of the temperature rhythm is commonly as large in people confined to bed, and even in the paralyzed, as in those with much larger metabolic swings due to diurnal activity.‘The rhythm in metabolism is therefore more likely to be a consequence than a cause of the temperature rhythm, especially as the quoted amplitude of the metabolic rhythm is that which the van’t Hoff-Arrhenius equation would predict from a circadian temperature oscillation of around 1°C. The cause of the rhythm of body temperature probably lies in variations in the heat-loss mechanisms, such as cutaneous blood flow; in fact, the diurnal rhythm of finger or skin temperature is nearly a mirror image of that of rectal temperature (94, I I I). However, the amplitude of the internal temperature rhythm is very similar in a temperate or in a humid tropical climate (I) ; it seems, then, that the rhythm is in the temperature-regulating mechanism, rather than in any single contribution to it, such as metabolic rate or cutaneous blood flow (9). The ease of measuring body temperature must have contributed to the enormous accumulation of data, both by assiduous workers in this field such as Kleitman, and by people who in the course of easterly or westerly journeys have taken the opportunity to make personal observations." https://doi.org/10.1152/physrev.1966.46.1.128

Hence, if physical activity doesn't even contribute majorly to the core body temperature, how could we even assume that cognitive activity would? The major contributor of core body temperature modulations is the endogenous circadian rhythm, it is a homeostatic process, it's its purpose to be independent from external factors.

Furthermore, several studies have demonstrated that "alertness does not determine core body temperature", in other words cognitive (hyper)activity has no effect on the circadian rhythm.

BEST CRITICAL: cognitive hyperactivity is arguably an example of the introspection illusion: the individual think their will were responsible for their sleep patterns, when their sleep patterns (and especially the circadian rhythm) are responsible for their actions and their late sleep time.

There is a lack of evidence in particular for the following sleep hygiene items in regard to the treatment of insomnia: "more comfortable mattress, removing bedroom clocks, not worrying, and limiting liquids" from wikipedia sleep hygiene and https://www.elsevier.com/books/therapy-in-sleep-medicine/9781437717037

Sleep restriction

TODO: rewrite from: https://www.reddit.com/r/insomnia/comments/mbww58/i_found_a_doctor_who_listened_who_took_my/gs3gxo4?utm_source=share&utm_medium=web2x&context=3 (mirror: https://archive.fo/s2wik )
Indeed I'm very surprised you can be cured with sleep restriction therapy given the 2021 AASM meta-analysis on behavioral therapies could not find definitive evidence that SRT can treat insomnia, despite numerous studies. Even theoretically, SRT doesn't make sense: how could sleep deprivation treat insomnia? Nobody would suggest to treat malnutritioned people with food restriction, that would be ludicrous. The same goes for SRT.

Yes, what you do temporarily modifies your circadian rhythm, but as I said it's not due to restricting your sleep, but because of you waking up earlier and getting exposed to bright light. You can probably achieve the same results without sleep restriction by simply using a bright light therapy device at wake up.

Anyway, your experience is very common in the r/DSPD community. If the same happens to you, you'll feel more and more tired doing SRT. We all think at first that we solved the issue, but the truth is that everytime you do SRT, you are depleting your "sleep reserve" or rather increasing your sleep debt. At some point, you'll be exhausted, even more than before with "just" your insomnia. It can take months, it can take years, it can even take decades for some (like me), but at some point it always happens.

If this happens for you too, come to r/DSPD, you're not alone and we are actively looking for ways to improve our condition, and several of our members have gotten encouraging results. No complete cure, but significant improvements in both our health and sleep patterns.

I certainly hope I am wrong and that you will strive with this treatment, but as I explained, I cannot see how this can have any benefit to your health or sleep, it logically can only increase your sleep deprivation and deteriorate your health over time, just as food restriction can only worsen malnutrition.

Unspecificity and limited clinical significance of psychological therapies

Can use CBT on any psychological diagnosis and even switch diagnosis between multiple individuals and the end result is the same, which shows that CBT is unspecific: https://doi.org/10.1038/d41586-020-00922-8

Simplistic nature of psychological therapies

Sleep restriction for insomnia.

Most psychological therapies demonstrate the very simplistic view of reality of their authors. Instead of targeting the cause, which is often complex, psychological therapies target the symptoms:

• One common approach, still accepted by modern medicine, to treat sleep disorders is to prescribe sleep restriction. This is as logical as to prescribe food restriction to treat malnutrition. People with sleep disorders often suffer from a lot of chronic sleep deprivation, and sleep restriction only adds to this. Restriction is never a solution to the chronic lack of a vital need.
• Another is to focus on sleep onset (bedtime), disregarding the circadian rhythm altogether or the cause of this inadequate sleep onset.
• Memory training for Alzheimer. Several authors tried to do memory training exercises to people affect with the Alzheimer disease. Several papers were published, and still are. Although this may be worth trying, it is obviously naive to think that just doing memory exercises can overcome the progress of the physiological neurodegenerative disorder.

But psychology also significantly contributed to the understanding of how the human brain works, when it focused on practical models that could be simulated or tested. https://en.wikipedia.org/wiki/Frank_Rosenblatt
"I agree that this view may seem too extreme—but sometimes, to explore new ideas, we need to set our old ones aside, at least temporarily. " Marvin Minsky https://web.media.mit.edu/~minsky/Introduction.html

Cortisol theory

Cortisol blood tester: https://www.sciencealert.com/stress-hormones-can-now-be-detected-in-real-time-from-a-single-drop-of-blood

12 blood biomarkers of mood disorders: https://doi.org/10.1038/s41380-021-01061-w and https://www.sciencealert.com/scientists-develop-new-blood-test-that-can-diagnose-your-level-of-depression

BEST: instead of just explaining away diseases as induced by stress or anxiety, this hypothesis can actually be tested although imperfectly, by monitoring the cortisol levels, but this must be done relatively to the circadian rhythm, one hour after natural wake up, otherwise the data will be biased according to an operator. Otherwise, such an explanation has no medical value, it is only an opinion if not backed by objective data.

Hans Selye authored the concept of different "energies" of stress, with eustress being the positive stress, and ... the "negative energy" stress. Sounds like a woo-woo theory. This was later more modernly transposed into acute stress, which is assumed to be positive, and chronic stress, assumed to be negative. And all of this relies on the HPA axis.

HPA axis often used as a biological explanation to justify the universality of emotional stress on all illnesses, but it's confounded by the circadian rhythm, both are using the same axis! Hence we need studies to assess the effect of both conditions independently, as it may very well be the case that what is causing the observed worsening (or causing) of illnesses is in fact not the induced stress but the sleep disturbances induced by the stressful experimental conditions.

BEST CRITICAL: 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.

Somatoform disorders

Medically Unexplained Symptoms are often conflated with somatoform disorders "that are all in your head"

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7488826/
  • It is about somatization and how it does NOT fit nor is supported by empirical findings! And they push even more when the patient rejects the psychological assumption! And that they change name to come back later!
  • "There are strong indications of a move towards such strategies in the sample, in the form of assumptions that unexplained physical symptoms are really symptoms of mental distress (e.g. Jutel, 2010). Such assumptions are criticized in the sample (e.g. 5-3) but not nearly as often as they are taken for granted. They come to the fore, for instance, in the conviction that psychiatric therapy is appropriate for but hampered by uncooperative patients (e.g. 6-5; 11-7) or in the fact that only two articles in the sample actually investigate new hypotheses that MUS have somatic causes (7-9; 8-5). As indicated in the analysis, the connection with somatization is one way this assumption seeps through. Other ways are through concepts that carry similar psychogenic assumptions – such as ‘alexithymia’ (2-3), ‘illness perceptions’ (9-10), and ‘somatovisceral illusions’ (1-16), each indicating that the patients have misunderstood the nature of their symptoms. As such, psychogenic assumptions are part of the biomedical doxa and the commitment to make MUS ‘fit in’. They may be interpreted as a form of monster-adjustment, pushing for the resolution of the anomalous character of present symptoms without signs.

• + Note they say they blame ineffectiveness on uncooperative patients. Unfortunately seemingly common in psychotherapy practice, which stems from the inversion of the burden of proof.
• In the end, MUS and somatoform disorders are of course empty misdiagnoses, as they are based on the logical fallacy that the abscence of evidence is evidence of absence.

Voodoo Death, or the origin of mental stress theory and the belief that thoughts can kill or make ill

BEST CRITICAL: the origins of psychosomatic medicine and the field of psychophysiology. All because of WB Cannon who sloppily confused dehydration for emotionally induced death, aka Voodoo Death! (ref: Eastwell, Harry D. "Voodoo Death and the Mechanism for Dispatch of the Dying in East Arnhem, Australia." pp. 5–18)
There are even some researchers who hypothesized the possibility of VR-induced psychogenic death, if the VR simulation is sufficiently realistic, WTF???? https://www.researchgate.net/profile/Ben-Peterson-6/publication/332290012_Preventing_VR-Induced_Psychogenic_Death/links/5cac3759a6fdcca26d08ea00/Preventing-VR-Induced-Psychogenic-Death.pdf
This may have been the Takotsubo syndrome, which we now know is not caused by emotions but by biological pathologies! It's just that the technology wasn't sufficiently advanced to detect them before! https://doi.org/10.1093/eurheartj/ehab198
Takotsubo cardiomyopathy is even dubbed stress cardiomyopathy! https://doi.org/10.1016/j.amjmed.2018.01.001 (a letter to the editor which hilariously starts with a biblical quote), or broken heart syndrome https://doi.org/10.1080/10253890.2018.1561847
Dehydration again: https://doi.org/10.2190%2FOM.59.1.a

In other words: proponents of psychosomatic medicine are convinced that the mind can cause the body to die! Literally! Of course, by the same logic, then mental stress can cause any illness!

> Fear is not merely an emotion or state of mind. In 1942, Cannon’s research into “Voodoo death” a sudden, unexplained death resulting from a Voodoo curse formed the basis for much of our modern understanding of the physiological response fight-or-flight systems linking emotions, such as fear, with illness.75 Sympathetic activation and the subsequent catecholamine release brought on by emotional distress is implicated in the pathophysiology of the “broken heart syndrome.” 76 Thus, a state of fear and panic can potentially worsen clinical outcomes through sympathetic activation, the HPA axis, or other, yet unexplained mechanisms. https://doi.org/10.1016/j.mayocp.2020.08.028

• Another link between Hans Selye's stress theory and WB Cannon's Voodoo Death works: "Les travaux de Cannon ont exercé une grande influence sur Hans Selye." https://www.biusante.parisdescartes.fr/sfhm/hsm/HSMx1977x011x003/HSMx1977x011x003x0135.pdf

Voodoo death theorized to be an extreme form of nocebo? https://pubmed.ncbi.nlm.nih.gov/17484949/

Voodoo Death and stress as a generic cause of all illnesses is still carried by modern authors: In 2018, a "systematic" review "suggests" that acute stress can cause sudden death. Of course published in "Stress" journal. It's a perfect illustration of Ioannidis criticism of improperly conducted and biased systematic reviews. Indeed, this review is only systematic in its exploration of the diseases but not in its "suggestion" that there is a common causal factor, nor of the selection of these diseases to clump them together, all of which are personal choices by the authors and are not systematic at all. A systematic review which ends with a "suggestion" is quite uncommon.

Pediatric concussion due to violent sports is unproven according to the authors, it's all due to the nocebo effect! https://doi.org/10.1123/jsr.2020-0519

Mental healing movement

TODO: it seems this movement preceeded Voodoo Death and the modern concept of stress by Hans Selye?

> Wattles' "Certain Way" descended from the "mental healing movement" that had started earlier with Phineas P. Quimby in the mid-19th century. As Horowitz explained to a reporter from the Washington Post, after experiencing relief from physical symptoms of discomfort or illness through Quimby's mental strategies, people began to wonder, "If my state of mind seems to have a positive influence over how I feel physically, what other things can it do? Can it lead to prosperity? Can it lead to happiness in my home? Can it lead to finding love and romance?" One result of such questioning was Wattles's application of Quimbian "mental healing" strategies to financial as well as physiological situations.
https://en.wikipedia.org/wiki/The_Science_of_Getting_Rich and https://www.washingtonpost.com/wp-dyn/content/article/2007/06/23/AR2007062300646.html

Takotsubo syndrome

Medicine is not necessarily scientific. There is a lot of procedures for which the benefits are not necessarily verified by empirical data. Indeed, not all of medicine is evidence-based. Evidence-based medicine, which was to be initially called scientific medicine, is a relatively recent movement that is seeing more adoption over time but is not the de facto standard. This is arguably rooted in genuine care for the patients, that the physicians want to provide the best treatments for their patients even if it means using approaches that are known to work or help in practice but have not yet verified. It is indeed true that a lot of procedures lack evidence simply because they have not been studied. But the unintended consequence is that some medical procedures are used despite not knowing whether they are beneficial, neutral or even counter-productive including potential harm.

All medical practices and even sciences have culturally rooted ideologies, what is sometimes termed traditional medicine. In chinese practices, it's acupuncture, chinese medicinal herbs and Feng Shui. In indian cultures, it's breathing and sun, including the inedist ideology on the extreme of the continuum. In germany, the freudian psychosomatic school of thoughts that originated from psychananalytics has now permeated across nearly all modern medical disciplines, including in cardiology under the name of psychocardiology.

Takotsubo is a perfect example of this. The Takotsubo syndrome, also called stress cardiomyopathy or "broken heart disease" (in a hilarious letter to the editor starting with a biblical quote), is a cardiac disease that is thought to be mainly triggered by emotional stress. This syndrome disproportionately affects women, about 90% of women for only 10% of men. This alone, combined with the assumption that this syndrome is triggered mainly by emotion, should already be enough to ring all red alarms in the minds of those who remember how epilepsy was misdiagnosed as hysteria for a very long time, including the very first diagnosis of hysteria by Freud. It was also formerly assumed to be mostly affecting postmenopausal women, but recent evidence show it also affects younger women and with more severity.

The contribution of stress as a primary trigger for this syndrome is only currently accepted in Europe guidelines, showing a cultural disparity with other medical practices worldwide, likely under the pressure of the german school of psychocardiology: "only European guidelines for cardiovascular disease prevention acknowledge stress as a clinically meaningful risk factor in individuals with a high overall risk of cardiovascular disease or with established cardiovascular disease".

Nevertheless, empirical evidence contradict the assumed etiology of the Takotsubo syndrome: one review reports that about 1/3rd of cases have no clear causal link with stress. Another review criticizes several of the assumptions behind the Takotsubo syndrome and especially that it is a benign disease nor is it chronic:

> Overall, a misconception of the disease has evolved: TS is still widely considered a benign, transient, “self-healing” disease with an emotional trigger and “clean” coronary arteries, but without relevant complications. In clinical routine one can even hear opinions such as, “I suspected my patient was suffering from acute myocardial infarction, but after all it was only Takotsubo,” reflecting a significant underestimation. Already the title of the first official description (“Takotsubo-type cardiomyopathy due to multivessel spasm”) [1] contained the term “cardiomyopathy,” suggesting a rather chronic condition, for which no robust evidence exists. In contrast, TS is not a benign disease [9], is not uniformly preceded by an emotional trigger [4], and does not require “clean” coronary arteries (see below).

Another review discusses how the assumptions of the stress pathway underlying the Takotsubo syndrome have not been empirically verified and is likely insufficient to cause the syndrome, that associations should not be considered sufficient (ie, correlation is not causation), that there is likely a selection bias where individuals with a prior history of emotional stress are more readily identified with a Takotsubo syndrome in hospital registries but the proportions are much reduced (only 30%) with independent and unbiased selection:

> In early years, the disease was considered to be typically preceded by an emotional trigger; however, recent studies demonstrate that physical triggers are equally important and that TTS may frequently occur without an evident trigger 1, 3. A hallmark of TTS patients is the predominant prevalence of neuropsychiatric comorbidities 1, 4, 5. However, despite many efforts, the exact pathophysiological mechanism behind TTS remains elusive and primarily relies on assumptions (6).
> [...] A hallmark of TTS is the proposed association with catecholamines, stress, and the autonomic nervous system. From early years on, the disease was believed to be induced by a spillover of catecholamines and to be precipitated by a trigger. Indeed, there are several arguments for a role of the catecholaminergic system in the onset of TTS (20). However, following the famous work of Robert Koch (21), unequivocal evidence is required to prove the relation between cause and effect. We should not be satisfied with associations. For instance, it is true that many patients develop TTS with a stressful trigger. However, about 30% of patients spontaneously develop TTS without any identifiable trigger. Do these patients have a different “TTS-like” syndrome? Probably not. If we also include histories of ACS patients, we would discover lots of “triggers”; thus, there is obviously a relevant awareness bias. On the other hand, TTS research underlines the need for reversion to the classical medical skill of history taking. In a previous study, we could demonstrate a high prevalence of neurological and psychiatric disease in TTS patients, which outnumbered that of ACS patients (1). The present study found a much lower prevalence (about one-third of our numbers). As also stated by the authors, the value of registries critically depends on careful maintenance, and thus, data obtained from registries may significantly differ between studies.
> [...] In summary, pathogenesis of TTS appears to be multifactorial. Catecholamine levels, beta-agonist use, triggers, hormone status, and microvascular dysfunction are all true, but probably not sufficient per se to induce TTS. The present study adds to previous data, emphasizing that TTS carries a substantial risk of morbidity and mortality. However, prospective studies are now needed to elucidate pathogenesis and management of this peculiar disease.

This non-evidence-based psychosomatic conception of the Takotsubo syndrome is not innocuous, it is not just a matter of labels, it has real consequences that have been undoubtedly harmful for innumerous patients who suffered from delayed treatment or non-treatment at all (eg, those who died eventually of the syndrome). Anyone who would prescribe an antistress therapy to cure cancer would be labelled as a pseudomedical fraud and promptly stripped from any medical certification. And yet, this was precisely what the well respected author of the modern concept of stress Pr Hans Selye did. But prescribing an antistress therapy to cure a substantially fatal cardiac condition is an accepted practice, but only in Europe and when it mostly affects women. This looks very much like a moving the goalpost situation, especially given that empirical evidence disprove the hypothesis that emotions often trigger this syndrome. Unfortunately, the misconceptions about the Takotsubo syndrome, such that it is nearly always caused by emotional stress, is permeating into the general public, which further risks stigmatization of women with serious cardiac issues.

Indeed, Takotsubo is a modern variant of the Voodoo Death translated into (psycho)cardiology, both likely descending from the medieval concept of heartache/anguish. As we will see in the next section, some authors have recently tried to lump the Takotsubo syndrome together with other potentially fatal condition to "suggest" in a modern variant the concept of Voodoo Death that acute stress can be fatal and underlies all these conditions.

Stress, anxiety and the p-factor

A little bit of history to start.

The concept of the mind having power on the body to the extent of causing ailments or even death is an old romantic idea that can be traced back to at least the medieval concept of anguish. Hence, anguish was one of the first concept of a universal cause of death, that could happen to anyone at anytime, regardless of their health and environment. All that mattered was their thought, and no treatment could cure them.

The "stress" word began being used in english in the 14th century, signifying at the time any event bringing difficulty, adversity or misfortune. It began being used more commonly in English during the 17th century in physics and chemistry, when forces deform physical or alter chemical objects. Progressively, the term begins to be used in medicine in its modern sense, to refer to the concept that the harshness of life or strenuous work can lead to physical consequences for the individual, such as by Osler in 1910 to explain the prevalence of the angor pectoris condition in the jewish community. Hence, the old concept of anguish was revived in the form of stress by the medical community, based on assumptions, lacking evidence based hypothesis testing.
Since 1914, WB Cannon then later tried to scientifically reformulate the stress medical concept as reaction to an external threat, and devised a theory of emotional and physiological reactions, which later went on to influence Hans Selye's concepts of chronic and acute stress, and physiological and psychological/mental/emotional stress, and also devised his famous Voodoo Death concept based on poor documentation of dehydration: the supposed phenomenon by which tribespeople's death can be caused by their own beliefs, when later scientific scrutiny found them to be most likely caused by dehydration. A more prosaic, but less impressive finding.

Hans Selye, an admirer of Cannon and admittedly inspired by his works on stress, later discovered oxydative stress, a biological phenomenon that is triggered when the body suffer from damages. Emotional stress was later discovered, again by Selye, as a response to both physiological or psychological damage. The existence of these two phenomena are well documented. However, Hans Selye couldn't be content with these discoveries that brought him a nobel prize, he seeked a universal discovery. Hence, he posited that stress was not only the generic response caused by nearly any ailment and in turn causing the set of similar symptoms that can be observed in almost all ill patients, but also the cause of these ailments: he conceived stress as the generic gateway, the essential hidden factor that mediated any effect of any ailment, from benign ailments to cancer. There, Hans Selye defined the first biologically plausible mechanism for what was assumed intuitively since ages by Humanity, and observed by his inspiration WB Cannon.

Both Cannon's voodoo death, and Selye's stress, led to the inception of the psychophysiology research domain and psychosomatic medicine. This has pervaded throughout medicine, with side-branches of classical medicine created to integrate psychophysiological theories, such as psychodermatology (specific to germany but with ideas pervading the global medical knowledge, such as eczema being caused by stress when it may rather be caused by sweat with an imbalanced composition), psychocardiology (also pioneered by germany) or even classical cardiology notably with the Takotsubo syndrome, TODO... It's worth mentioning that germany is the only country fully covering psycho* therapies, and that "only European guidelines for cardiovascular disease prevention acknowledge stress as a clinically meaningful risk factor in individuals with a high overall risk of cardiovascular disease or with established cardiovascular disease", likely under the impulse of german psychocardiology clinicians.

In recent years, the field of psychopathology has come back to its root, with the formulation of the p-factor, an universal factor that is conceptually posited to be represent the common part among all psychopathologies (archive). An extension is to use genome-wise sampling (GWAS) to find support for this p-factor, what is termed the genetic p-factor, which is hailed as "the pinnacle of the hierarchical genetic architecture of psychopathology".

That's the history of this concept of the mind power over the body.

But once we take a closer look, cracks begin to appear systematically.

First, the elephant in the room: if we accept that the mind can have power over the body, under all the currently accepted frameworks, we then have to accept that humans can die by thoughts alone. Indeed, voodoo death is still accepted by modern medicine as a valid theory.

Second elephant in the room, is that although it is not here disputed that stress is a common response to aggressor factors, the assumption of Hans Selye that stress is also the cause for the deleterious effects of any disease is much more dubious and not supported by any evidence but a leap of faith and inversion of causal reasoning. It is also obviously against the findings of modern evidence-based medicine, as we would not need evidence-based medicine if there was only one cause to treat all diseases. Finally, this means that accepting the original concept of stress by its discovered/author Hans Selye means believing in this one cause to treat all diseases, which is nowadays a minor thought school of modern medicine although it can still be found in the propositions of some authors in a lessened form to move the goalpost, such as the supposed p-factor as the cause of all psychological disorders, or by the german school of psychocardiologists proposing that cardiac disorders such as Takotsubo cardiac disease is rooted in emotional stress when the evidence show that most are not preceded by emotional stress at all but by physiological accidents, or that stress can worsen diseases but not cause them, or that stress can cause some minor diseases but not major ones such as cancer (contrary to what Hans Selye declared). This seems similar to the moving the goalpost that happened with the Freudian theory of hysteria.

It's worth noting that Hans Selye worked with the Tobacco Industry to help them avoid or reduce public health regulations that could unfavor them. This was at a time when suspicions grew around the dangerosity of cigarettes, a product that the Tobacco Industry continued to publicly market as innocuous despite their internal research clearly demonstrating a high dangerosity. Hans Selye is also an author of many a dozen books, all around stress and how some tips can change one's life by better controlling stress.

The p-factor can be seen as a variant of the concept of stress as a universal cause of diseases. Some researchers even argue that the both are robustly linked, with past severely stressful events reliably predicting a high p-factor. We can even go further: stress is the p-factor. It is at least a very good candidate, given how they share the attribute of universality, p-factor is clearly a variant with reduced range of the stress concept.

Recently, this concept of a common generic psychogenic cause to several, or even all, illnesses have started to resurface in tangential domains to the german psychanalytical school, such as psychocardiology, with a 2018 "systematic" review trying to convince their readers that they can "suggest" that "acute stress can be fatal" to explain several potentially fatal conditions including the Takotsubo cardiac syndrome.

In summary, the story of the invention of stress is a story of a quest for a universal cause for all psychological and physiological ailments. Whether this is to be considered naive or plausible is left up to the reader.

TOREAD: integrating all 3 axes of p-factor: https://doi.org/10.1038/s41380-021-01031-2

• BEST CRITICAL TOADD STRESS: There is strong evidence sleep issues cause anxiety, and modest evidence circadian rhythm disturbances can cause anxiety: https://www.nature.com/articles/s41398-020-0694-0

• 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. https://doi.org/10.1177%2F1948550613488952
• "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." https://pubmed.ncbi.nlm.nih.gov/28579842/
• While burnout has and is still mostly considered a psychological stress-related issue, there is accumulating empirical evidence that burnout is rather caused by chronic sleep deprivation, and a 2017 systematic review on potential interventions to reduce burnout rates in resident physicians found that a reduction of work hours, potentially mediating a reduction in sleep deprivation, led to a significant reduction of burnout scores and emotional exhaustion, with no impact on performance. There are hence calls to further study this promising lead, about the involvement of sleep deprivation and circadian misalignment in the pathogenesis of burnout, since both burnout and sleep deprivation involve "(1) a chronic depletion of energy stores; or (2) activation of the hypothalamic-pituitary-adrenal axis and increasing levels of bodily stress", and hence share the same pathways of action and similar physiological consequences. This 2019 review further notes that "although sleep deprivation is associated with clinical burnout, direct studies showing that sleep extension can improve burnout recovery are lacking", and that "early detection and early intervention to improve both sleep deprivation and burnout are warranted in health-care professionals", with "interventions [that] should be directed not only at individuals but also at the entire health system".

• 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.

• Specialists of fertility are also voicing their doubts over the supposed impact of stress and psychosomatic theories on female fertility: https://youtu.be/6q2dGcrJaU0?si=3R5uJEOS9aiQ-Gdj&t=1003 (Dr Joelle Belaisch Allart)

Stimulus control

> A set of instructions designed to (1) extinguish the association between the bed/bedroom and wakefulness to restore the association of bed/bedroom with sleep, and (2) establish a consistent wake-time. Stimulus control instructions: (1) go to bed only when sleepy, (2) get out of bed when unable to sleep, (3) use the bed/bedroom for sleep and sex only (eg, no reading or watching television in bed), (4) wake up at the same time every morning, and (5) refrain from daytime napping. https://jcsm.aasm.org/doi/10.5664/jcsm.8988

Stimulus control is essentially what most laymen and medical practitioners think about when they mention sleep hygiene. And in fact, most of these items originate from the original set of sleep hygiene tips. Stimulus control is based on the assumption that behavioral association of bed/bedroom with other activities than sleep will prevent sleeping (behavior). This is again likely an inversion of cause and effect: people who spend longer time in bed do so because they are insomniac, they are utterly tired and hence have difficulties with their (very low) energy expenditure. In other words, treating the sleep disorder will likely naturally reduce the length of time spent in bed, whereas there is little evidence that reducing time in bed improves sleep.

No positive finding of efficacy according to this meta-analysis: https://www.reddit.com/r/DSPD/comments/ljjcxc/ignorant_doctors/gsx6l18?utm_source=share&utm_medium=web2x&context=3

Behavioral assessments of sleep are unreliable

"A recent systematic review including 45 articles and demonstrated the heterogeneous dimensionality of PSQI in both clinical and community-dwelling populations (31). A cross-sectional study including 17 comparative factor structures explored the fitness of different PSQI factor scoring models (32). Moreover, some studies also reported conflicting results in older adults (33–35)." https://www.frontiersin.org/articles/10.3389/fpsyt.2020.573530/full

Refuttal of all psycho theories for sleep disorders

Major argument ME: Sleep is inambiguously accepted as a physiological process, even vital, similarly to eating and drinking. So why is modern medicine considering that the vast majority of causes of sleep disorders are psychogenic? Current theories and models of sleep disorders do not offer any explanation as to this leap of faith, nearly every authors except Harvey 2001 (who criticized current views on insomnia as psychogenic) do not even attempt to produce an explanation as to why a profoundly physiological process such as sleep would be mostly dysregulated by psychogenic factors, very much unlike other physiological vital processes such as cardiac function and drinking. It is interesting to note that historically, cardiac disorders suffered a similar fate, until modern cardiology (mostly) replaced the medieval misconceptions of cardiac disorders being related to emotional distress (although there is still some leftovers, see the concept of anguish, voodoo death, eustress, takotsubo syndrome, etc). But it's not the only one: epilepsy, multiple sclerosis, me/cfs (another demyelination disease similar to multiple sclerosis), parkinson, alzheimer, and more, all started as being labelled as disorders of psychogenic causes, before scientific and medical progress allowed to identify their physiological causes. Hence, I argue that current sleep medicine guidelines about sleep disorders and insomnia management are mostly incorrect, based on non evidence-based hypotheses and unsupported, unproven conjectures, as we can safely assume that most sleep disorders should be of physiological causes, not psychogenic, given this is a physiological process that is affected, and a vital one only strengthen the case that we could even argue that only physiological causes can impair such a vital biological function. Instead of psychogenic by default, these causes should be considered of cryptogenic origin.

Some people can't see, some people can't walk, some people can't do physical activities because of cardiac or metabolic dysfunctions, some people can't sleep. This has nothing to do with will or an unhygienic lifestyle, it's just that these people were unluckily born or unluckily acquired these impairments. Why would it be so different for sleep?

2 major evidence-based points:

• fall asleep time is not correlated with the wake up time, the latter being tightly coupled with the circadian rhythm. Hence all therapies targeting the fall asleep time fail.
  • Can reject:
    • sleep hygiene
    • bedtime procrastination
    • chronotherapy
  • Easy to test, even for typical sleepers: try to sleep 5h later than your usual ideal fall asleep time. Now check how long you slept. You will notice you likely only slept less than 2/3rd of what an average adult human needs (eg, less than 5h30 instead of 8h). This demonstrates that moving the fall asleep time does not affect the wake up time, and hence the circadian rhythm remains unaffected. If the circadian rhythm was shifted along with the fall asleep time, we should be able to sleep as long as we need to be in optimal shape, whatever time we fall asleep (eg, wake up 8h later than the fall asleep time, but this simple experiment shows that this is not what happens, rather we sleep less, only the minimum necessary for survival / cognitive function minimal maintenance thanks to adenosine build up / the homeostatic sleep pressure process, which allows us to sleep even when we sleep out of phase with our circadian rhythm). We can sleep at anytime but only using adenosine buildup then and hence have a short sleep, or we can sleep a long session only during the circadian night when both the circadian rhythm and adenosine buildup are in phase.
    • TODO: make graphic: sleep during circadian night 8h, sleep anywhere one single session only 5h outside of circadian night, or sleep 2 short sleep sessions of 3/4h during circadian night + anytime elsewhere such as during the siesta. In the latter case, the lack of adenosine buildup prevents sleeping a full night. This illustrates the possible mismatches between both C and S processes and how these can affect sleep.
  • Even the AASM 2021 meta-analysis on behavioral therapies states that focusing on sleep-onset insomnia does not follow current consensus, since insomnia is not just a sleep-onset issue as was previously thought but clearly encompasses sleep-offset and maintenance/consolidation: "some treatments (eg, biofeedback, relaxation therapy) emerged decades ago and thus reflect clinical conventions of those times, such as a focus on sleep-onset insomnia and conceptualization of most insomnia as a symptom of another disorder; therefore, they do not reflect current diagnostic or assessment standards."
• psycho tendency to inverse cause and effect, eg mind wandering and cognitive hyperactivity theory of insomnia
• humans are homeothermic. The circadian rhythm is mediated by core body temperature changes. The body temperature governed by completely automatic unconscious processes because it is crucial for our survival. It is by design inaccessible to mind states, it even resists robustly against environmental ambient temperature changes. It is IMPOSSIBLE for mind states to modify the core body temperature. Unless a procedure can demonstrate it can change the core body temperature, the procedure should be deemed useless for circadian rhythm shifting. Hence psychology is BS and our mindset or psychological disorders cannot be the cause of circadian rhythm disorders. Just like we can learn to ignore thirst but cannot learn to not FEEL thirsty, we can learn to ignore our circadian rhythm signals of optimal time to sleep but we can not learn to shift our circadian rhythm, and in both cases ignoring essential needs always have detrimental consequences. Hence, if an objective test can show that you have a circadian rhythm disorder, you can discard all learn based and mind states based approaches. Core body temperature is one such test.

More arguments:

• sleep-wake schedule is only a weak zeitnehmer, not a zeitgeber. Hence, targeting the wake up time such as with sleep restriction will only provide little effect.
  • But sleep restriction can increase adenosine / sleep pressure. But that's not sufficient.
• insomnia is not secondary to psychiatric disorders
• lack of robust evidence on critical outcomes for insomnia (as defined by the AASM) despite the therapy being old enough to have had enough time for controlled studies to be conducted

• Anxiety has nothing to do with sleep. Nothing. Don't lose your time and kid's health on this dead end, this was the prevalent hypothesis for decades and insomnia is still an ever growing disease affecting now about 10% of the population, demonstrating this approach utterly failed. See the list of references I have posted here for more details: https://www.reddit.com/r/N24/comments/n5yg9f/hello_new_here_do_n24_people_suffer_mental/gxa91qc?utm_source=share&utm_medium=web2x&context=3

It's simply not how the circadian rhythm works, it can't be modified by the sleep-wake schedule, because it is tied to core body temperature and our body is programmed to ensure your core body temperature does not get affected by environmental factors, otherwise we would die. It's this very protection that is also what is preventing us from effectively manipulating our circadian rhythm easily.

---

Co-morbidity is high, because sleep disruption and circadian rhythm disruptions both independently increase the likelihood of psychological disorders (and also health issues especially cardiometabolic). Treating the sleep disorder usually improves the co-morbid psychological disorder(s). But not the other way around, improving psychological disorders does not improve the sleep disorder.

For more infos:

• Walker WH 2nd, Walton JC, DeVries AC, Nelson RJ. Circadian rhythm disruption and mental health. Transl Psychiatry. 2020 Jan 23;10(1):28. doi: 10.1038/s41398-020-0694-0. PMID: 32066704; PMCID: PMC7026420. https://pubmed.ncbi.nlm.nih.gov/32066704/
• Harvey AG. Insomnia: symptom or diagnosis? Clin Psychol Rev. 2001 Oct;21(7):1037-59. doi: 10.1016/s0272-7358(00)00083-0. PMID: 11584515. https://pubmed.ncbi.nlm.nih.gov/11584515/
• Faulkner SM, Bee PE, Meyer N, Dijk DJ, Drake RJ. Light therapies to improve sleep in intrinsic circadian rhythm sleep disorders and neuro-psychiatric illness: A systematic review and meta-analysis. Sleep Med Rev. 2019 Aug;46:108-123. doi: 10.1016/j.smrv.2019.04.012. Epub 2019 Apr 30. PMID: 31108433. https://pubmed.ncbi.nlm.nih.gov/31108433/
• Matteson-Rusby SE, Pigeon WR, Gehrman P, Perlis ML. Why treat insomnia? Prim Care Companion J Clin Psychiatry. 2010;12(1):PCC.08r00743. doi: 10.4088/PCC.08r00743bro. PMID: 20582296; PMCID: PMC2882812. https://pubmed.ncbi.nlm.nih.gov/20582296/

See also my summary [here](https://circadiaware.github.io/VLiDACMel-entrainment-therapy-non24/SleepNon24VLiDACMel.html#depression,-anhedonia,-running-thoughts-and-social-isolation) and [here](https://circadiaware.github.io/VLiDACMel-entrainment-therapy-non24/SleepNon24VLiDACMel.html#comorbidities-with-other-disorders-mood,-neuroatypism,-motor,-addictions).

Keep in mind that in the vast majority of studies on sleep, the metrics used are subjective (usually a simple questionnaire). Only studies using reliable objective metrics such as actigraphy or at least sleep diaries should be accounted for, otherwise you'll find LOTS of contradictory results (really, you can find everything and the contrary - when it's subjective, it's up to anyone's opinions, not facts ;-) ).

https://www.reddit.com/r/Nightshift/comments/n9kmw6/more_prone_to_anxious_sleep_when_sleeping_during/?utm_medium=android_app&utm_source=share

https://www.reddit.com/r/ChronicIllness/comments/n9k93k/i_never_anticipated_how_isolating_developing_a/?utm_medium=android_app&utm_source=share

Need to accept life is deeply unfair. Not just you but also your relatives need to understand that. There are often no way back from a chronic illness, it's a different life that opens in place of the old, standard one thrt closes down.

"Relaxation response" by Herbert Benson, another crazy charlatan who thinks that praying for someone will cure them from their terminal illness and that hypothermia can be medited out! https://en.wikipedia.org/wiki/Herbert_Benson and https://www.reddit.com/r/insomnia/comments/nawiyh/i_cant_make_friends_or_date_anyone_because_i_have/gy13rgh?utm_source=share&utm_medium=web2x&context=3

• ME: Chronotherapy and sleep hygiene disproven by the existence of jet lag
  • even theoretically chronotherapy and sleep hygiene do not make any biological sense. If sleep could be controlled by the sleep wake pattern, then jet lag wouldn't exist. The very existence of jet lag demonstrates that sleep is regulated by hidden processes (eg circadian rhythm) that we cannot modify just by choosing a stringent sleep schedule. Jet lag affects everyone, it only depends on the number of timezones that are crossed.

• ME: instructing a patient with a circadian rhythm disorder to just sleep is analogous to instructing a tetraplegic patient to just walk, in both cases it's a physical impossibility.

• A systematic review on traumatic brain injury survivors found that methylphenidate was the only therapy that provided an improvement of the depressive symptoms, whereas all other tested therapies (including numerous forms of cognitive behavioral therapy, but not including bright light therapy) yielded no significant result. → even for depression, CBT is not effective!!!!

• BEST CRITICAL: link between circadian rhythm disorders and insomnia, Czeisler et al 1987: https://doi.org/10.1152/ajpregu.1987.253.1.R172

• Why it's important to assess this question of the potential impact of mind states on sleep, because of this: https://youtu.be/y1Ui4weUSlE?t=165

The main issue of psychological diagnoses: the lack of falsiability

A far reaching core issue of psychological diagnoses is that they most often rely on conceptual theories rather than data-driven findings. This lack of grounding makes them more susceptible to lack the definition of criteria to be proved wrong, which is necessary for any theory to be scientific. Indeed, Karl Popper, in a famous accusation of psychoanalysis as being a pseudo-science, devised the falsifiability criterion: if a theory cannot be proven wrong, then it is a truism that cannot be scientifically validated. Obviously, psychiatrists replied in support of psychoanalysis by... claiming that Popper's arguments were ill-founded. Nevertheless, Popper's falsifiability criterion has since been a well established staple of modern science, and is regarded as an evidently necessary part of any robust and serious scientific theory.

However, due to this denial, this widespread failure among psychological theories to meet the fasifiability criterion has over time led to several crises that even reached the public opinion due to the magnitude of their implications. This was highlighted by the psychologist David Rosenhan, who devised two renowned field experiments.

In the first one, dubbed the "pseudopatients experiment", he and several volunteers went to several different psychiatric hospitals to be admitted while faking mental symptoms that were not associated with any known mental illness in the literature, but once admitted, they were instructed to just act normally as they would usually while taking notes about how the hospital's staff and other patients' behaviors. The goal was twofold: first, to observe how the psychiatric screening process was robust to fake patients (ie, the reliability of mental diagnosis), secondly to observe how long it would take for the psychiatric staff to realize the fake patients were not ill and booted out (ie, falsifiability of a mental diagnosis). To his dismay, the results were much worse than he expected, especially for himself. All fake patients were accepted, and they all spent at least weeks or even months, whereas he expected them to be detected only after a few days at most. He himself could only get released after 2 months and while being forced to agree, like other pseudo-patients, to recognize they were mentally ill and to take psychiatric medication. All pseudo-patients were diagnosed as "in remission", indicating that the hospitals psychiatrists did not detect they were pseudo-patients but rather considered they would always be mentally ill (they were almost all diagnosed with schizophrenia).

This sparked a lot of criticism in the psychiatric and psychological fields, so Rosenhan devised a second field experiment: he notified several hospitals among those where he went, that he would send a new batch of pseudo-patients, and the goal of the study would be to count how many they correctly detected. In the upcoming weeks and months, all of these hospitals reported they successfully detected several pseudo-patients. But Rosenhan sent none.

These experiments were reproduced over the years in various forms, with similar results.

The unreliability of mental disorders diagnosis is still an issue nowadays and pertinent for sleep disorders, as most cases of insomnia used to be misdiagnosed and mistreated as secondary insomnia to a mental disorder less than a decade earlier, which depended on the clinical institutions, with institutions either overdiagnosing secondary insomnia, and others diagnosing mostly with primary insomnia (see figure 1.2) (mirror).

Both of these studies further fuelled the anti-psychiatry movement, which contested the power given to mental institutions, as they were able to wrongfully involuntary commit anyone against their will at the time, and they could be instrumentalized for political purposes and games of power, since psychiatry is intrinsically more prone to be abused than other fields of medicine, one historical example being king Ludwig II of Bavaria , and another the Duplessis Orphans.

This lack of falsifiability led to more recent crises, such as the reproducibility crisis notably in psychology (but not only). Variability and poor definition and lack of evidence support of mental disorders diagnostic items is another related issue.

Psychology studies target metrics are biased towards psychogenic causes

A model is only as good as the data used to make it. The same applies to any scientific and medical theory. One major criterion for new psychogenic disorders to be accepted by standards such as the DSM-V is that there is enough evidence that they can be reliably detected, such as with a scale designed for this purpose, with studies showing high inter-raters reproducibility. This is very fine. However, issue arises when these scales are not only used for detection, but also in studies investigating the efficacy of psychological therapies, in which a decrease of severity in these scales is interpreted as evidence of efficacy. This is a clear case of circular reasoning and inadequate target metric: if we measure both identification and improvement with a subjective scale, then where is the evidence that the disorder really exists at all? Any scale can be created for any target, hence scales need to be assessed in regards to empirical data. And therapies efficacy even more so. A counter-argument would be that there is no other way to assess a psychological disorder, since by definition it is not assumed to be of physiological causes, there is no physiological metric. But there are objective independent metrics, such as behavioral, socioeconomics, performance/productivity-related, etc. that can be used to objectively assess the correlation between improvement in these metrics with the use of a therapy, without relying at all on the identification scale, and hence avoiding entirely the circular reasoning pitfall. Alas, as Karl Popper already noticed in his time and which is still cause for a lot of concern (see Replication crisis in psychology), methodological issues are still very common in medical psychology, and I would argue that this is one of the most common, if not the most common, instance of such issues.

This is further compounded by the fact that most psychological studies do not adequately test for the objectives they state, and do not support the conclusions they draw, which is due to insufficient statistical training as noted already by Chris Chambers in 2017.

Common inversion of cause and effect, or overinterpretation

There is a common issue in modern science, despite being well known by now and taught as an easy red flag to avoid in most doctoral programs, is the inversion of cause and effect, or simply the overinterpretation of causation from simple associative relationships, which can be spurious. This is often used as a mean to make ordinary results extraordinary and worth publishing. The issue is not so that there is a possibility of such an extraordinary causation, but that this is the main argument to make the results worth publishing, as otherwise the results would be too ordinary to be considered. That this happens is not surprising, but what is surprising is that even well established world renowned journals that are the leaders in their respective domains regularly accept such kinds of papers. And it seems it is even more commonly accepted in psychological studies than elsewhere, since it is easy to find associations between subjectively designed scales and behaviors.

What follows is a non exhaustive list of such studies:

• https://www.ladepeche.fr/2023/04/29/vrai-ou-faux-manger-des-frites-serait-il-vraiment-source-de-depression-et-danxiete-11164506.php and https://www.pnas.org/doi/10.1073/pnas.2221097120

Contagion of mental illnesses such as chronic anxiety

Origin: Dr Cameron, president of the american psy association and canadian one of his time, and also led horrible MK Ultra experiments by putting unwitting patients with just minor mental disorders into prolonged coma via anesthetics, for months at times, which debilitated them permanently: https://en.wikipedia.org/wiki/Donald_Ewen_Cameron#Mental_illness_as_a_social_contagion

Behaviorism and conditioning

Behaviorism father is John B Watson, who is infamous for his Little Albert experiment, with which he allegedly created ex nihilo using conditioning a fear of mice in a newborn. Unfortunately, the experiment went out of hand, as often with psychological experiments at the time due to a lack of ethical scrutiny, and it was discovered the baby acquired fear of not only mice, but any anything with fur, including Santa Claus apparatus. Furthermore, the validity of the experiment is now in question, for several reasons: first, Watson was unable to decondition the fear, which raises doubts about how much control he had over the whole process; secondly, later studies tried to trace back who was the Little Albert subject, and although there are two possible leads, one involves a baby with congenital hydrocephalus, which increases sensitivity to sound, which is the method Watson chose for his conditioning, and which would bias the entire experiment obviously if this was indeed the real subject. Finally, Watson applied behaviorism to the education of his three children, who all attempted suicide, with two succeeding.

Behaviorism has since then been applied to try to "treat" various conditions including sleep disorders including insomnia.

Voir aussi: https://www.youtube.com/watch?v=sa6qj1w8f8A

Classical psy researchers work by first crafting a theory for how they think a phenomenon works, and then they design an experiment to see if this is the case. In theory, that's not that bad, but this approach to the scientific method is fraught with biases, so it must be very rigorously designed and controlled. The last part is what psy researchers often fail at. They are often insufficiently trained in study designs, and in statistical tests. (Both points are also what was criticized in this very influential 2022 paper and also in Chris Chambers 2017 book)

"Reality is that which, when you stop believing in it, doesn't go away." - Philip K. Dick, science fiction writer (16 Dec 1928 – 1982)

Placebo

> Title: Is the placebo powerless? An analysis of clinical trials comparing placebo with no treatment
>
> Conclusion: We found little evidence in general that placebos had powerful clinical effects. Although placebos had no significant effects on objective or binary outcomes, they had possible small benefits in studies with continuous subjective outcomes and for the treatment of pain. Outside the setting of clinical trials, there is no justification for the use of placebos.
>
New England Journal Of Medicine with Cochrane, 2001 https://pubmed.ncbi.nlm.nih.gov/11372012/

So no, nocebo nor placebo have any powerful effect except maybe modulating slightly the subjective perception of pain. No objective effect whatsoever otherwise.

A later Cochrane systematic review confirmed this finding, and further suggests that the purpoted small effect of placebo in very rare instances (pain, nausea) may rather be due to biased patients reporting: https://doi.org/10.1002/14651858.CD003974.pub3

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Other notes to integrate

• BEST TOADD ME: anxiety confounded with sleep for two reasons: 1) because insomnia is used as a diagnostic item for anxiety, whereas it should be considered a comorbidity (eg, DSM-V); 2) even objective metrics of anxiety and psychological stress are confounded with the same biological structures as for sleep deprivation.
  • BEST REVIEW: Rodent models of insomnia: A review of experimental procedures that induce sleep disturbances, 2009 https://doi.org/10.1016/j.neubiorev.2009.03.002
    • Also: "However, the reciprocal relationship between sleep and the activity of the HPA axis is problematic when investigating sleep using traditional sleep-deprivation protocols that can induce stress per se. This is especially true in studies using rodents in which sleep deprivation is achieved by exogenous, and potentially stressful, sensory–motor stimulations that can undoubtedly confuse their conclusions. While more research is needed to explore the mechanisms underlying sleep loss and health, avoiding stress as a confounding factor in sleep-deprivation studies is therefore crucial." https://doi.org/10.1098/rsfs.2019.0092

• Depression:
  • A highly critical paper on the research on the pathogenesis of depression: https://doi.org/10.1186/1741-7015-11-79
  • Excerpts (includes a mention of the HPA axis):
    • "Nowhere is the loss of confidence in the diagnostic processes in psychiatry more acute than it is in relation to the major depressive disorders [1, 2]. This is reflected not only in the acrimonious debate about proposed changes to the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 [3], but also in the degree of professional discord [4] and the sustained social critique of the current concepts [5, 6]. More profoundly from a therapeutic perspective, it has contributed to the withdrawal of major pharmaceutical industry support for new drug development [7].

• Generalizability crisis, and related commentaries: Yarkoni, T. (2022). The generalizability crisis. Behavioral and Brain Sciences, 45, E1. doi:10.1017/S0140525X20001685 https://www.cambridge.org/core/journals/behavioral-and-brain-sciences/article/abs/generalizability-crisis/AD386115BA539A759ACB3093760F4824#related-commentaries https://doi.org/10.1017/S0140525X20001685 (see related comments too)
  • "Most theories and hypotheses in psychology are verbal in nature, yet their evaluation overwhelmingly relies on inferential statistical procedures. The validity of the move from qualitative to quantitative analysis depends on the verbal and statistical expressions of a hypothesis being closely aligned – that is, that the two must refer to roughly the same set of hypothetical observations. Here, I argue that many applications of statistical inference in psychology fail to meet this basic condition. Focusing on the most widely used class of model in psychology – the linear mixed model – I explore the consequences of failing to statistically operationalize verbal hypotheses in a way that respects researchers' actual generalization intentions. I demonstrate that although the “random effect” formalism is used pervasively in psychology to model intersubject variability, few researchers accord the same treatment to other variables they clearly intend to generalize over (e.g., stimuli, tasks, or research sites)."
• The Seven Deadly Sins of Psychology: A Manifesto for Reforming the Culture of Scientific Practice, 2017, Chris Chambers https://doi.org/10.2307/j.ctvc779w5
  • "Why psychology is in peril as a scientific discipline—and how to save it" https://press.princeton.edu/books/paperback/9780691192277/the-seven-deadly-sins-of-psychology
  • "Psychological science has made extraordinary discoveries about the human mind, but can we trust everything its practitioners are telling us? In recent years, it has become increasingly apparent that a lot of research in psychology is based on weak evidence, questionable practices, and sometimes even fraud. The Seven Deadly Sins of Psychology diagnoses the ills besetting the discipline today and proposes sensible, practical solutions to ensure that it remains a legitimate and reliable science in the years ahead. In this unflinchingly candid manifesto, Chris Chambers shows how practitioners are vulnerable to powerful biases that undercut the scientific method, how they routinely torture data until it produces outcomes that can be published in prestigious journals, and how studies are much less reliable than advertised. Left unchecked, these and other problems threaten the very future of psychology as a science—but help is here."
  • "History may look back on 2011 as the year that changed psychology forever. It all began when the Journal of Personality and Social Psychology published an article called “Feeling the Future: Experimental Evidence for Anomalous Retroactive Influences on Cognition and Affect.”¹ The paper, written by Daryl Bem of Cornell University, reported a series of experiments on psi or “precognition,” a supernatural phenomenon that supposedly enables people to see events in the future. Bem, himself a reputable psychologist, took an innovative approach to studying psi."
• Improbable Science Journal https://www.latimes.com/archives/la-xpm-2009-oct-02-sci-ignobels2-story.html
  • https://www.semanticscholar.org/paper/The-seven-deadly-sins-of-psychology-a-manifesto-for-Kaplan-Sowman/f531b840e6ae8febdaa2fc6840b00ac1a7cb90d5

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Well before the works of Rosenthal birthing the anti-psychiatry movement and later the reproducibility crisis with contributions from Popper's falsifiability criterion and criticism, psychological medicine, which originates in Germany, was already weaponized since the very beginning, including towards prominent figures such as Ludwig II. Stress is in line with this history. Its creator Hans Selye was commissioned to weaponized it to defend the Big Tobacco industry against planned governmental health regulations. This weaponization never really stopped, to the contrary, it only expanded to become an easy and lazy universal band aid explanation conveniently superceeding medico-physiological and socio-economical factors, much more embarassing to acknowledge for decision makers. High insatisfaction and very low quality of life at work place? Promote meditation and yoga classes for a stress-free workforce, as it can certainly not be due to degrading work conditions and galloping precariousness in the workforce due to the globalized ultraliberal economical conditions. Women presenting with chronic vertigo and fainting? That must be hysteria/somatization, certainly not chronic carbon monoxide exposure. A child unable to fall asleep at the societally acceptable time with mood dysregulations and studying difficulties? This must be stress and schizophrenia and a whole lot of other very severe and socially unacceptable uncurable mental disorders, certainly not chronic sleep deprivation due to a non-24 circadian rhythm disorder... This concept was so weaponized that these proponents even truly believe it can cause death (see Voodoo Death and Takotsubo syndrome).

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References to integrate in the sections above

Anxiety and circadian rhythm disorders are NEVER secondary to psychiatric disorders, they are independent, and their basis is certainly not psychiatric

• SUMMARY ME: psychosomatic theory is from psychoanalysis and its first use can be traced by to Freud, the father of psychoanalysis, when he misdiagnosis epilepsy in a woman as the non existent and mysogynistic hysteria pseudopathology.
  • anxiety disorder diagnosis is so unspecific that it can be applied to literally half of the population, this clearly shows an overdiagnosis problem and the medicalization of normal human states.
  • stress was conceived by Hans Selye, a proponent of the psychoanalysis and psychosomatic school of thoughts, using pseudoscientific mystical concepts such as "stress energy levels reservoir". And he was corrupted, he used the concept of stress to defend Big Tobacco against Canadian's governement attempt to instate anti-smoking ads (and of course he was plentily paid). Also by definition stress was conceived as the common set of symptoms of people afflicted with chronic diseases, so it's a tautology to assess that anyone with a chronic disease is stressed.
  • Treating psychological disorders (including depression and anxiety) never help insomnia nor circadian rhythm disorders. And in fact sleep issues often precede psychological disorders.
  • The common unfounded assumption of all psychoanalysis related theories is that psychological states can affect biological tissues. But the placebo and nocebo effect (Cochrane Systematic Review) only affect subjective measures, no objective biological measure or state.
    • Also psychoanalytical related studies always suffer from huge biases: small sample size, use of subjective measures (eg, quality of life assessments) instead of objective measures, and inversion of causality or confusion with correlation (eg, stress is commonly associated with chronic diseases or acute severe life changing events, which intuitively is very obvious that these situations can create stress, but psychoanalytical proponents will do a leap of faith to reach the more extravagant and extraordinary claim that it's rather stress that is causing these diseases, because extraordinary claims allows to publish, not ordinarily intuitive and obvious claims). Not to mention selection bias as shown in the scottish prospective study etc
  • We can call psychoanalysis as a pseudoscience as Karl Popper, one of the founders of modern science thanks to his falsifiability criterion, himself used psychoanalysis as an example of pseudoscience that doesn't meet the falsifiability criterion.
  • Finally, look at the success rate for psychanalytical and psychological treatments: none for CBT-i and insomnia (see below), none for stress management and coronary heart diseases (see Cochrane Systematic Review). Even for eczema there is no solid evidence, only widespread assumptions!

• BEST CRITICAL: same for insomnia: INSOMNIA: SYMPTOM OR DIAGNOSIS? 2001 Harvey https://doi.org/10.1016/S0272-7358(00)00083-0 and https://www.independent.co.uk/life-style/health-and-families/why-lack-sleep-makes-us-depressed-insomnia-and-what-we-can-do-about-it-a7371786.html
  • "Is insomnia a clinical entity in its own right or is it simply a symptom of an underlying medical or psychological disorder? The widely held view among many clinicians and researchers is that insomnia is secondary to or an epiphenomenon of a ‘primary’ medical or psychological disorder. Consequently, insomnia ‘symptoms’ have tended to be trivialized or ignored. [...] It is concluded that viewing insomnia as a symptom or epiphenomenon of other disorders can be unfounded. This view may deprive many patients of treatment, which might not only cure their insomnia, but may also reduce symptoms associated with the assumed ‘primary’ disorder."
  • BEST CRITICAL TOADD HISTORICAL ROOTS OF STRESS AND ANXIETY CAUSAL ASSUMPTION ON INSOMNIA: combine with historical review of the assumption of the links between insomnia and stress, which is of course unfounded: https://royalsocietypublishing.org/toc/rsfs/2020/10/3 and especially https://doi.org/10.1098/rsfs.2019.0094
    • "While the concept of ‘stress' in the modern sense is a twentieth-century innovation, many of the symptoms we associate with the modern condition appear in historical materials going back many centuries. But how did premodern people understand and experience these symptoms and their relation to sleep? This study focuses on the rich materials from the central middle ages in Western Europe, a period during which understandings of the body, mind, emotions and sleep were radically different from the present. It analyses two examples, nightmares and insomnia, disease categories which illustrate medieval views of the impact of worries and anguish on sleep. Medical and other sources identified a number of ways in which the mind and body interacted with one another in complex ways which disrupted the humoral and mental balance of the individual." → stress is an archaic concept.
    • ME: I even found [a historical review](https://doi.org/10.1098/rsfs.2019.0094) finding the root of this misconception, which dates back to middle age
    • BEST CONFIRMATION: historically, they link the concept of stress with anxiety.
    • (keep in mind this is a historical review, they do not necessarily reflect accurately modern day knowledge, especially the "humoral imbalance" part which is quite outdated)
    • See also WB Cannon formalization of the already prevalent use of the medical concept of stress and then Hans Selye's later conceptualization: https://doi.org/10.3917/dunod.chape.2018.01.0007
  • BEST CRITICAL: The same is stated in the AASM 2021 systematic review of behavioral therapies for insomnia, insomnia should be considered as primary, not secondary to a psychological disorder: https://doi.org/10.5664/jcsm.8988
    • "some treatments (eg, biofeedback, relaxation therapy) emerged decades ago and thus reflect clinical conventions of those times, such as a focus on sleep-onset insomnia and conceptualization of most insomnia as a symptom of another disorder; therefore, they do not reflect current diagnostic or assessment standards." → they also reject relaxation therapy and biofeedback!
  • Anxiety and depression are genetically inherited and explained at 74% and 58% by shared genes between twins! https://doi.org/10.1016/j.jpsychores.2011.03.011 And heritability of insomnia is 30.7% in young (8-16 yo) individuals! https://www.ncbi.nlm.nih.gov/pubmed/22131600 - great summary of both in https://www.independent.co.uk/life-style/health-and-families/why-lack-sleep-makes-us-depressed-insomnia-and-what-we-can-do-about-it-a7371786.html
  • LOL: insomnia is comorbid because it's PART of the diagnostic items of lots of psychological disorders! It is partially a diagnostic artifact! "The evidence reviewed in this section indicates that insomnia has a high rate of comorbidity with a range of psychological disorders, particularly depression and anxiety. However, consideration must be given to the fact that insomnia is a part of the diagnostic criteria for several psychological disorders (as evident in Table 2). It is therefore possible that some of the comorbidity observed may be attributed to a artifact of measurement (van Moffaert, 1994). Greater specificity in diagnostic criteria would assist in reducing false-positive insomnia diagnoses. Nonetheless, insomnia clearly is commonly comorbid with other disorders."
    • "Clearly, high comorbidity with another disorder is a feature of many psychological disorders."
    • " Further, the clinical implication of the primary/secondary distinction is that treatment should be targeted at the ‘primary disorder’ (because it is assumed that the ‘secondary’ disorder will remit with successful treatment of the primary disorder). Recommendations along these lines have often been made in the literature. For example, Lopez-Ibor (1996, p. 33) advises treating the ‘primary’ disorder first on the basis that the insomnia will remit. "
    • INTERESTING: even if we consider insomnia as secondary, it should not be left untreated! "Obviously, interventions for PTSD involve treating comorbid depression (Bryant & Harvey, 2000) and when treating substance abuse that occurs in the presence of an anxiety disorder, the intervention targets the substance use and the anxiety (Beeder & Millman, 1996). Taken together, the precedent set by comorbidity between other psychological disorders does not provide a mandate for regarding insomnia as ‘secondary’ on the basis of comorbidity."
    • BEST CRITICAL: Precedence, indicating insomnia is more likely the causal parent to anxiety, not the other way around: "A robust finding in the literature is that sleep disturbance precedes the development of depression. [...] Further, other studies have found that insomnia also precedes the development of anxiety disorder (Breslau et al., 1997; Ford & Kamerow, 1989) and alcohol abuse (Weissman, Greenwald, Nino-Murcia, & Dement, 1997). Taken together, if the disorder that develops first and heralds in the second disorder is a marker of a ‘primary’ disorder, it would appear that there is little reason to regard insomnia as the ‘secondary’ disorder. On the contrary, insomnia is a clear antecedent to the development of depression and a likely antecedent to the development of anxiety and alcohol abuse."
    • Treatment outcome: "It is widely held that ‘The first step toward insomnia management is a correct diagnosis and treatment of possible underlying or concomitant conditions, especially those of a psychiatric nature’ (Lopez-Ibor, 1996, p. 33). In other words, if the ‘primary’ disorder is targeted in treatment, it is assumed that the insomnia will remit. There are several studies indicating this not to be the case. "
    • Insomnia as a risk (causal) factor: "Determining cause, often referred to as ‘the chicken and the egg’ dilemma (van Moffaert, 1994), is notoriously difficult in the context of psychological disorders. However, clues to solving the dilemma are discernible from studies where data are collected longitudinally."
    • SUMMARY: "Contrary to the widely held belief, insomnia was not found to be ‘secondary’ in that (1) it develops first, (2) it can be treated without concurrent treatment of the comorbid disorder, and in the sense that (3) it is a risk (potentially causal) factor for the development of the comorbid disorder."
    • A significant proportion of insomnia occurs without a co-morbid disorder and increases the likelihood of later onset of physiological and psychiatric disorder: "Evidence that a significant proportion of insomnia cases occur in the absence of comorbidity would further strengthen the case against insomnia being the ‘secondary’ disorder and conversely, would strengthen the case for it being an important clinical entity in its own right. Several studies have reported high rates of insomnia without any comorbidity. The rate of insomnia in the absence of another psychological disorder is 10% in a community adult sample (Ford & Kamerow, 1989), 54% of a sample of young adults (Vollrath et al., 1989), 30% in patients presenting with a sleep complaint (Zorick, Roth, Hartze, Piccione, & Stepanski, 1981), and 31% of clinician or self-referrals to a sleep disorders center (Morin, Stone, McDonald, & Jones, 1994). Importantly, Weissman et al. (1997) found insomnia in the absence of a comorbid psychological disorder to be associated with increased use of general medical and psychiatric services. Further, it was a predictor of a first-onset psychological disorder. These findings attest to the frequency of insomnia as a ‘stand-alone’ diagnosis and constitute further evidence that insomnia not be regarded as the secondary disorder."
    • Research is biased: "With some exceptions (Weissman et al., 1997), the literature has been dominated by an almost exclusive focus on comorbidity between mood disorders and insomnia."
    • BIASES IN RESEARCH:
      • No question about the effect of sleep, and whether symptoms are due to sleep deprivation or the co-morbid psychological disorder: "One particularly salient gap in the literature relates to information about the level of disability, distress, and dysfunction caused by insomnia relative to comorbid disorders. Such information could be obtained with a simple addendum to the structured interviews employed in epidemiologic studies, which asks patients to order the problems identified during the interview according to the level of disability, distress, and dysfunction caused. Self-report information of this kind would provide a crucial angle on the standing of insomnia relative to the comorbid disorder. Process research is required to illuminate the interplay between sleep disorder and psychological disorder. Specifically, longitudinal and experimental studies should be conducted to delineate the cause and maintenance of the comorbid disorders. For example, the documented effects of sleep deprivation include increased irritability, increased pain perception, decreased memory, increased autonomic activity, and increased anxiety and depression (see Ware & Morin, 1997). Future research should explore the possibility that sleep deprivation may be one mechanism by which insomnia relates to psychopathology."
      • Insomniacs with a co-morbid psychological disorder have been (historically) excluded! "In the past, treatment outcome studies for insomnia have typically excluded patients diagnosed with a comorbid psychological disorder. This decision has been driven by the assumption that an insomnia-focused intervention would not be helpful because it would not tackle the ‘primary’ disorder. [...] To be thorough, treatment trials should test the differential efficacy of all permutations; treatments targeting both disorders concurrently, treatments just targeting the insomnia, and treatments just targeting the comorbid disorder."
        • Luckily in AASM 2021 review now they do not, they make subgroups but they do not exclude anymore it seems!
    • BEST CRITICAL: it mentions sleep disorders as causes for insomnia, and mentions DSPD as being a particularly common cause of insomnia! It's largely underdiagnosed! "Insomnia is often caused by sleep disorders such as sleep-related respiratory disturbance, periodic leg movements, restless legs syndrome (tightness or drawing in the calf or thigh), obstructive sleep apnea, narcolepsy, periodic limb disorder, and idiopathic hypersomnia (Spielman & Glovinsky, 1997; White & Mitler, 1997). Delayed sleep phase syndrome is a particularly common cause of insomnia (Regestein & Monk, 1995). This is a disorder in which sleep is delayed in relation to the clock time, resulting in difficulty falling asleep and waking up in the morning at the desired time."
    • BEST CRITICAL: supports the wearables and criticize psychological approaches on insomnia and anxiety/stress which are based on assumptions: "The first fundamental step is to standardize diagnostic criteria for insomnia and develop an effective and widely available measurement tool to diagnose insomnia. To echo the bidding of Chambers and Keller (1993, p. 662) in relation to a different aspect of the field of insomnia ‘understanding should be the result of science, not supposition.’"
    • BEST Confirmation it worked, now the distinction between primary and secondary insomnia was removed in the DSM-V: "It is important to note that despite sleep disturbance sometimes being considered a symptom of another disorder, there has been a shift away from simply considering sleep disturbances as a symptom of other problems – and ‘primary’ insomnia was removed from the most recent version of the DSM (DSM‐5, American Psychiatric Association, 2013) reflecting the current thinking that insomnia should not be dismissed as secondary to other disorders where comorbidity occurs (for a comprehensive discussion, see Harvey, 2001)." https://doi.org/10.1111/jcpp.12469
      • BEST CONFIRMATION: same root (genetic) cause causing both some sleep disorders and psychological co-morbid disorders. And that sleep disorders may have similar symptoms but totally different causes that require different approaches.
        • "An alternative view is that shared risks of different types (e.g. genetic, environmental, hormonal, neural and psychological) may underlie associations between sleep disturbances and other psychopathologies. For example, there is increasing support for the ‘generalist genes hypothesis’ which proposes that genes may explain the cooccurrence of traits and the persistence of disorders over time – with environmental factors more likely to be time and phenotype specific (e.g. Eley, 1997). Such explanations could explain why those suffering from sleep disturbances are also more likely than others to display signs of other psychopathologies."
        • "Finally, it is possible that for certain sleep and sleep‐related problems (e.g. nightmares; sleep onset delay; poor sleep efficiency) the same mechanism (i.e. a general disruption to sleep) could underlie seemingly disparate associations (see Peterman et al., 2014). Nonetheless, explanations should be tailored for specific associations. For example, recent research suggests that impaired cortical processing may explain associations between sleep‐disordered breathing and behavioural disorders."
        • See also circiatric review
    • Good overview saying the same (also including same genetic root causing both sleep disorder and psychological disorders): Why we sleep? By Russell Foster, TED, Aug 2013. https://www.youtube.com/watch?v=LWULB9Aoopc
    • BEST CONFIRMATION NOT SECONDARY: also uses assessment of interventions improving sleep and mental health to see if there is a link (but results unavailable - file drawer bias?): "Sleep and mental health go hand-in-hand, with many, if not all, mental health problems being associated with problems sleeping. Although sleep has been traditionally conceptualised as a secondary consequence of mental health problems, contemporary views prescribe a more influential, causal role of sleep in the formation and maintenance of mental health problems. One way to evaluate this assertion is to examine the extent to which interventions that improve sleep also improve mental health." https://dx.doi.org/10.1136/bmjopen-2017-016873 — can provide more insights when published
    • BEST CONFIRMATION NOT SECONDARY: "It is argued that insomnia and other mental health conditions not only share common causes but also show a bidirectional relationship, with typically the strongest pathway being disrupted sleep as a causal factor in the occurrence of other psychiatric problems. Treating insomnia lessens other mental health problems. Intervening on sleep at an early stage might be a preventive strategy for the onset of clinical disorders. Our recommendations are that insomnia is assessed routinely in the occurrence of mental health disorders; that sleep disturbance is treated in services as a problem in its own right, yet also recognised as a pathway to reduce other mental health difficulties; and that access to evidence-based treatment for sleep difficulties is expanded in mental health services." Sleep disturbance and psychiatric disorders, review, 2020 https://doi.org/10.1016/S2215-0366(20)30136-X
      • "Signs of mental ill health that cut across psychiatric diagnostic categories at high rates are typically viewed as non-specific occurrences, downgraded in importance and disregarded. However, problems not associated with particular diagnoses should be expected if there is shared causation across mental health conditions. If dynamic networks of interacting symptoms are the reality of mental health presentations, then particularly disruptive and highly connected problems should be especially common. The non-specific occurrence might be highly consequential. One non-specific occurrence that is often overlooked is patients' chronic difficulty in getting good sleep. In this Review, we consider whether disrupted sleep might be a contributory causal factor in the occurrence of major types of mental health disorders. It is argued that insomnia and other mental health conditions not only share common causes but also show a bidirectional relationship, with typically the strongest pathway being disrupted sleep as a causal factor in the occurrence of other psychiatric problems. Treating insomnia lessens other mental health problems." → it's the opposite for stress!
  • Another similar article: Why treat insomnia? https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2882812/
    • HISTORY + BEST CONFIRMATION NOT SECONDARY: "For several decades beginning in the 1970s, insomnia was considered a “symptom” not a “disorder.” To the extent that insomnia was considered just a symptom of medical or psychiatric disease, it was believed that treatment of the parent disorder was sufficient and would result in the resolution of the insomnia. More recently, this perspective has given way to the position that, when chronic, insomnia should be characterized as a primary disorder, which, when it co-occurs with other medical and psychiatric illness, should be designated a comorbid condition (as opposed to a secondary symptom). These nosologic designations carry with them the clear implication that chronic insomnia merits targeted treatment. This perspective, however, has yet to influence the standard of practice. More often than not, insomnia continues to be undiagnosed and/or untreated."
    • Insomnia is a long-term disease: "There are very few studies on the natural history of insomnia. To our knowledge, there are a handful of such investigations.1–5 In general, these studies find that chronic insomnia does not spontaneously resolve,1,3,5 and the presenting form of insomnia (ie, initial, middle, or late) tends to be unstable or variable over time. With respect to spontaneous remission, Mendelson1 found that subjects who reported difficulty sleeping at their initial assessment (average chronicity of 10 years) continued to report insomnia at 2 follow-up intervals (70% at 40 months and 88% at 64 months) (Figure 1)."
    • INSOMNIA IS DISABLING
    • "This said, neuropsychological evaluations of patients with chronic insomnia have not yielded reliable data regarding specific cognitive deficits.10 This discrepancy between perceived and measured impairment may be reflective of several things. First, there may be an attentional bias toward negative performance, which nevertheless occurs at a normal rate.11,12 Second, a neurotic preoccupation with poor performance irrespective of whether or not it occurs may be present. Third, and finally, the perception of performance deficits may not be related to actual poor performance, or altered self-monitoring, but rather to the patient's real appreciation of the fact that extra effort is required to maintain normal or near-normal performance.10"
    • "With respect to social functioning, patients with chronic insomnia reliably report decreased interest in, facility with, and satisfaction from interpersonal relationships and social interactions. For example, in patients being seen in a primary care practice, chronic insomnia is associated with decreased ability to handle minor irritations, decreased ability to enjoy family/social life, and poorer interpersonal relationships with spouses.8"
    • COST: "In the United States alone, the direct and indirect costs attributable to insomnia exceed $100 billion annually.16 Direct costs, including physician visits, prescriptions, and procedures, equal or exceed $13 billion per annum.17 These costs are, in part, related to the increased tendency of patients with insomnia to use health care resources and to the costs of pharmacotherapy.15 The estimated cost of physician visits is over $600 million per year, and the cost of prescription medications is estimated to be over $800 million per year.17 Indirect costs associated with motor vehicle and workplace accidents, reduced productivity, and absenteeism are thought to account for the majority of the economic consequences of insomnia with cost estimates between $77 and $92 billion per annum. 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.19 One study in an Australian cohort estimated the cost of sleep-related motor vehicle accidents to be in excess of $180 million per year (Australian $).20 Patients with insomnia are also thought to be at increased risk for workplace accidents (industrial accidents). In the Australian cohort, it was found that patients with insomnia were approximately 8 times more likely to have such accidents as compared to good sleepers. In this instance, the annual cost of work place accidents was estimated to be in excess of $1.9 billion (Australian $).20 Finally, as noted above, insomnia is associated with reduced productivity and absenteeism. These costs have been estimated to exceed 1.3 billion per annum (Australian $)."
    • "Insomnia is best conceptualized as a disorder (as opposed to a symptom)"
    • "The primary barrier to successful treatment of insomnia is the relative unavailability of CBT-I providers" - WTF
    • Insomnia is pervasive:
      • "As stated in the 2005 National Institutes of Health (NIH) State-of-the-Science Conference Statement on Manifestations and Management of Chronic Insomnia in Adults … chronic insomnia is known to be common. Population-based studies suggest that about 30% of the general population complains of sleep disruption, while approximately 10% has associated symptoms of daytime functional impairment consistent with the diagnosis of insomnia, although it is unclear what proportion of that 10% suffers from chronic insomnia. Not surprisingly, higher prevalence rates are found in clinical practices, wherein about half of respondents report symptoms of sleep disruption."
    • READ CONCLUSION about veracity of secondary insomnia, has been questioned! CBT-i does NOT improve more primary or secondary insomnia, work the same! But BZRAs work better for secondary insomnia, not primary! But the debate has been reduced to "Which is better of CBT-i and BZRAs?". That's how little therapies there are available. And the available treatments for insomnia didn't change since at least 2006.
• BEST CRITICAL CONFIRMATION NOT SECONDARY: Same as for insomnia but for circadian rhythm disorders in addition to insomnia, both should not be considered secondary but be treated independently of other diseases: https://pubmed.ncbi.nlm.nih.gov/31108433/
  • BEST CRITICAL CONFIRMATION that primary/secondary insomnia distinction was removed from DSM-5 and ICSD-3: "Historically sleep problems have been neglected in groups with neuropsychiatric disorders due to diagnostic overshadowing [23], 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 [24], [25]. 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 [26]. 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 [6], [9], [24], but usually CRSD terminology is not applied."
  • "Effects of light on sleep and circadian outcomes have received limited attention in studies in psychiatric disorders, but results were promising in these groups. [...] Historically sleep problems have been neglected in groups with neuropsychiatric disorders due to diagnostic overshadowing [23], 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 [24], [25]. 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 [26]. 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 [6], [9], [24], but usually CRSD terminology is not applied."
  • BEST CRITICAL: TOADD in light therapy section? It's a systematic review! More updated than the AASM since it's 2019
  • BEST CRITICAL: ample evidence that circadian disruption may underlie several psychological disorders such as major depression disorder, since all effective therapies and drugs also affect the circadian rhythm. https://doi.org/10.1038/s41398-020-0694-0
    • BEST CRITICAL: Circadian rhythm disruption and anxiety. Although several studies have suggested that night shift work and persistent jet lag provoke anxiety, more recent analyses suggest that the mood changes may reflect disturbed sleep, rather than disturbed circadian rhythms per se.
• BEST CRITICAL: Positive affect and sleep: A systematic review 2017 https://doi.org/10.1016/j.smrv.2016.07.006
  • No strong evidence for now that mood affects sleep, as all studies finding a significant effect are at high risk of bias, but sleep affects mood for sure!
• BEST CRITICAL: Overdiagnosis of psychological disorders especially anxiety: https://doi.org/10.1007/978-1-4614-5583-7_435 and https://www.psychiatrictimes.com/view/normality-endangered-species-psychiatric-fads-and-overdiagnosis
• BEST CRITICAL: DSM shows it's the same sleep disturbances symptoms for all sleep disorders, and clearly state that insomnia is a diagnosis by elimination of all known possible causes, hence insomnia is a diagnosis of sleep disturbances of unknown origin. Hence, being diagnosed with insomnia without a thorough examination and consideration of other potential sleep disorders, including circadian rhythm disorders and sleep apnea, goes against the current clinical guidelines, and constitute a misdiagnosis due to medical negligence, a medical error. One common sign of an insomnia misdiagnosis is the failure to require a sleep diary over at least 2 weeks but preferably for as long as the sleep disturbances continue or reoccur, as the sleep diary is not only the gold standard assessment method for insomnia, it's also the only one for circadian rhythm disorders, although actigraphy is an optional complement (but not replacement!). https://www.ncbi.nlm.nih.gov/books/NBK519704/table/ch3.t36/ and https://www.psychiatrictimes.com/view/review-changes-dsm-5-sleep-wake-disorders
• short explanation: https://www.reddit.com/r/insomnia/comments/lmfh4h/longterm_sleep_deprivation_is_inevitable_rantvent/gnyxows?utm_source=share&utm_medium=web2x&context=3
• BEST REVIEW: Rodent models of insomnia: A review of experimental procedures that induce sleep disturbances, 2009 https://doi.org/10.1016/j.neubiorev.2009.03.002
  • Also: "However, the reciprocal relationship between sleep and the activity of the HPA axis is problematic when investigating sleep using traditional sleep-deprivation protocols that can induce stress per se. This is especially true in studies using rodents in which sleep deprivation is achieved by exogenous, and potentially stressful, sensory–motor stimulations that can undoubtedly confuse their conclusions. While more research is needed to explore the mechanisms underlying sleep loss and health, avoiding stress as a confounding factor in sleep-deprivation studies is therefore crucial." https://doi.org/10.1098/rsfs.2019.0092
  • and "Sleep is highly conserved across evolution, suggesting vital biological functions that are yet to be fully understood. Animals and humans experiencing partial sleep restriction usually exhibit detrimental physiological responses, while total and prolonged sleep loss could lead to death."
  • BEST CRITICAL TOADD ME SUMMARY: There are many more things to say on this topic, such as the big confound of the HPA axis with sleep as both stress/mood disorders and sleep deprivation interact with this axis, so since most (all?) studies on stress lack a control of sleep deprivation, they are confounded, the effect may very well be caused by sleep deprivation instead of stress or mood disorders. That's why I would like to write a full section about this issue, but it's going to be a lot of work, I have the data already though.
• Effects of antipsychotics on circadian rhythms in humans: a systematic review and meta-analysis, 2020 https://doi.org/10.1016/j.pnpbp.2020.110162
• BEST: This may be due to the fact that medicine is on average 17 years behind translational research. https://geneticgenie.org/2019/12/15/where-do-i-get-whole-genome-sequencing/ and https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241518/
• Some psy researchers in 2021 even deny the circadian rhythm as the foundational cause of jet lag, because they made a behavioral experiment and a regression curve that finds expectation to be more predictive than circadian rhythm parameters! https://doi.org/10.1101/2021.04.23.441149 Nevermind that there are tons of studies on CELLS showing that we can jetlag them and how long it takes to resynchronize them in either direction of phase delay or advance. https://doi.org/10.1101/lm.038877.115 And how do you think they measured the circadian rhythm parameters? Via a sleep diary! Nevermind that there are objective metrics such as at minimum actigraphy (although not a direct metric of the circadian rhythm) and core body temperature!
• BEST TOADD: "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." http://dx.doi.org/10.1038/nrn.2017.55
• BEST: confirmation that CBT-i does not include bright light therapy, it's used as an "adjunct" here: Cognitive Behavioral Therapy as an Adjunct Treatment to Light Therapy for Delayed Sleep Phase Disorder in Young Adults: A Randomized Controlled Feasibility Study, 2014 https://doi.org/10.1080/15402002.2014.981817
  • they found better results for depression and anxiety when using both light therapy and cbt-i than light therapy alone.
• BEST CRITICAL TOADD: The 2021 AASM guidelines on behavioral therapies: they recognize that in current standards, insomnia is seen as a primary disorder, not secondary to psychological disorders, which fits with previous reviews (see here and here): "some treatments (eg, biofeedback, relaxation therapy) emerged decades ago and thus reflect clinical conventions of those times, such as a focus on sleep-onset insomnia and conceptualization of most insomnia as a symptom of another disorder; therefore, they do not reflect current diagnostic or assessment standards." https://doi.org/10.5664/jcsm.8986

NO COPIES: One sighted non24 misdiagnosed as a conversion syndrome (aka hysteria or "stress") who was finally correctly treated with melatonin. An adolescent with DSPD was misdiagnosed as ADHD. Psychologists misdiagnosis is not uncommon unfortunately, in particular with anything stemming from freudian psychotherapeutic approaches such as the conversion syndrome with nearly all non-organic diagnoses being reevaluated as an organic disease in follow-up studies (see here), and these misdiagnosis are more frequent in vulnerable populations such as women and children, delaying and interfering with adequate treatments and undermining patients trust towards healthcare. Historically, this tendency towards misdiagnosis was particularly marked with movement disorders as epilepsy was diagnosed by psychologists as a conversion syndrome (=hysteria) and 40% of Parkinson were misdiagnosed with a psychiatric disorder instead, until technology caught up and shown that both of these disorders are organic, which obviously did not help and dangerously delayed the appropriate treatment, since untreated epilepsy can cause death. To overcome these misdiagnosis issues, the strategy chosen by successive generations of psychiatrists and psychotherapists including the current ones is to regularly rename this "non-organic disorder" and its criteria.

Psychological treatment based on cognitive-behavioural therapy principles for managing medically unexplained somatic complaints. https://www.who.int/mental_health/mhgap/evidence/other_disorders/q1/en/

Although it was hypothesized more than 50 years ago by Franz Halberg that non-24 may be associated with the bipolar disorder, a study found little to no evidence.

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.

BEST: Sleep deprivation causes depression-like symptoms in healthy individuals without any depressive symptom prior to the experiment: https://www.ncbi.nlm.nih.gov/pubmed/20231014

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. Misdiagnosis and medication errors are frequent and the most common types of medical errors. A psychological misdiagnosis (such as 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. 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 in 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.

"Behavioral and psychiatric conditions are also frequently associated with CRSD (Dagan et al., 1996, 1998)."

• "Attempts by patients with CRSD to adjust to daily activity often results in mild to severe sleep deprivation, which in children frequently leads to symptoms of inattention, irritability, distractibility, impulsivity (Dahl, 1995), and decrements in performance (e.g., Randazzo et al., 1998)."

• BEST CRITICAL DONE: many antidepressants worsen sleep: https://www.ncbi.nlm.nih.gov/pubmed/28791566 and https://pubmed.ncbi.nlm.nih.gov/22681161/

• From the book DSM-5: Handbook of Differential Diagnosis, p. 17:

• Immutable psychiatric labels make psychiatric misdiagnosis especially harmful, and hence people who suspect they have a sleep disorder or a circadian rhythm disorder should avoid consulting psychiatrists.
• Anxiety is over-represented in chronic illnesses subpopulation and women!
  • A systematic review of reviews on the prevalence of anxiety disorders in adult populations https://doi.org/10.1002/brb3.497
    • "Despite the high heterogeneity of prevalence estimates across primary studies, there was emerging and compelling evidence of substantial prevalence of anxiety disorders generally (3.8–25%), and particularly in women (5.2–8.7%); young adults (2.5–9.1%); people with chronic diseases (1.4–70%); and individuals from Euro/Anglo cultures (3.8–10.4%) versus individuals from Indo/Asian (2.8%), African (4.4%), Central/Eastern European (3.2%), North African/Middle Eastern (4.9%), and Ibero/Latin cultures (6.2%)."
    • "Women are almost twice as likely to be affected as men (female:male ratio of 1.9:1), with sex differences persisting over time and across high and low resource settings (Somers et al. 2006; Baxter et al. 2013; Steel et al. 2014). Irrespective of culture, individuals under the age of 35 years are disproportionately affected by anxiety disorders (Baxter et al. 2013, 2014) with the exception of Pakistan, where midlife represents a period of high burden (Mirza and Jenkins 2004)."
    • Clearly state that anxiety can be a consequence of the chronic illness, no the cause! "Vulnerable population subgroups refer to individuals at high risk for poor health, who may experience stigma, marginalization, or health service access barriers."
    • Nearly ALL chronic illnesses are associated with higher rates of anxiety, so it's certainly NOT a specific diagnosis: "The only chronic condition that has failed to show a link with anxiety is age‐related macular degeneration; while this review recruited patients from clinics, it was largely based on US studies (Dawson et al. 2014)."
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4964851/
• BEST CRITICAL: Overdiagnosis of psychological disorders especially anxiety: https://doi.org/10.1007/978-1-4614-5583-7_435 and https://www.psychiatrictimes.com/view/normality-endangered-species-psychiatric-fads-and-overdiagnosis
  • "The overdiagnosis of mental disorder has been the subject of much scholarly examination and public debate over the past several decades. Since the introduction of fluoxetine in 1987, the “Decade of the Brain” (1990–1999), and the introduction of blockbuster atypical antipsychotics and “mood stabilizers” by the pharmaceutical industry (1990s–present), the estimated prevalence of many mental disorders has skyrocketed. This led psychiatrist Allen Frances, chair of the DSM-IV Task Force, to summarize the issue of overdiagnosis by writing, “The NIMH estimates that, in any given year, twenty-five percent of the population (that’s almost sixty million people) has a diagnosable mental disorder. A prospective study found that, by age thirty two, fifty percent of the general population had qualified for an anxiety disorder, forty percent for a depression, and thirty percent for alcohol abuse or dependence... In this brave new world of psychiatric overdiagnosis, will anyone get through life without a mental disorder?” (Frances, 2010)."
  • Fads in psy are a staple...
  • "Overdiagnosis in general medicine is often generated through overuse of biological testing for disease (e.g., PSA testing for prostate cancer, blood tests for high cholesterol, or flowmeter tests for asthma). In contrast, there are no valid biological tests for mental disorders. Such diagnoses are made based on the clinical judgment of mental health providers, by performing clinical interviews while referring to the Diagnostic and Statistical Manual of Mental Disorders (DSM). There is no compelling research demonstrating that clinicians reliably diagnose mental disorders in routine practice (Kutchins & Kirk, 1997). It has been argued that this subjective process of diagnosis is shaped by bias, in terms of both the psychiatric definitions of mental disorder used and their clinical implementation. Many types of potential bias have been identified, ranging from sexism to pharmaceutical company influence (Caplan & Cosgrove, 2004) to pseudoscientific bioreductionism (Lacasse & Leo, 2006). Clearly, the most overarching type of bias in Western societies is the increasing trend towards labeling and classification of disturbed and disturbing behaviors as mental disorders (Kutchins & Kirk, 1997). In the absence of objective, reliable, and valid tests for mental disorder, this can lead to overdiagnosis."
    • pseudoscientific bioreductionism → confusion between physiological stress and psychological stress!
  • "While it is argued that many different mental disorders are overdiagnosed, given the lack of objective tests, there is often no rigorous way to settle the issue." → ME: I disagree, there is one objective and universal test: whether this diagnosis can lead to a treatment that can improve the disease's symptoms and the patient's quality of life. Since most disorders diagnosed by psy and the psy therapies do not help apart from subjective measures but not objective measures, this is a clear sign that a lot of psy diagnoses are useless and potentially flawed as they can prevent further investigations into other potential causes for the symptoms the patient expresses a wish to treat, one example being the overdiagnosis of anxiety and depression instead of chronic sleep deprivation (by a sleep or circadian rhythm disorder), the latter being effectively treated by light therapy and melatoninergic therapy while the former leads to CBT which has no proven benefits for these conditions (whereas treating the sleep disorder also improves these other symptoms).
  • "The overdiagnosis rate for ADHD was thus 37 % in this study, illustrating the point that the DSM criteria are biased towards overdiagnosis of ADHD. It is unknown whether clinicians are aware of this diagnostic inaccuracy embedded within the ADHD definition or whether parents are informed of this when their children are assessed."
  • "The DSM-5 was released in May of 2013, and Frances (2010) has cautioned that several categories may lead to overdiagnosis: Binge eating, hypersexuality, minor neurocognitive disorder, and mixed anxiety/depression are all arguably “normal” experiences which may be medicalized by their inclusion in the DSM-5. Similarly, the bereavement exclusion will be removed from DSM-5. This means that in contrast to the DSM-IV, recently bereaved clients will be eligible for a diagnosis of Major Depression if they have clinical symptoms more than 2 weeks after the death of a loved one. Thus, it is likely that the overdiagnosis of mental disorder will increase in the DSM-5 era."
  • "In recent years the pace has picked up and false “epidemics” have come in bunches involving an ever-increasing proportion of the population. We are now in the midst of at least 3 such epidemics-of autism, attention deficit, and childhood bipolar disorder. And unless it comes to its senses, DSM-5 threatens to provoke several more (hypersexuality, binge eating, mixed anxiety depression, minor neurocognitive, and others)."
  • ME: sleep-induced autism? Autism phenotype induced by sleep deprivation, and resolving when sleep is recovered?
  • "The “epidemics” in psychiatry are caused by changing diagnostic fashions-the people don’t change, the labels do. There are no objective tests in psychiatry-no X-ray, laboratory, or exam that says definitively that someone does or does not have a mental disorder. What is diagnosed as mental disorder is very sensitive to professional and social contextual forces. Rates of disorder rise easily because mental disorder has such fluid boundaries with normality."
  • "8. We live in a society that is perfectionistic in its expectations and intolerant of what were previously considered to be normal and expectable distress and individual difference. What was once accepted as the aches and pains of everyday life is now frequently labeled a mental disorder and treated with a pill. Eccentrics who would have been accepted on their own terms are now labeled as sick (with Asperger's) and in need of therapeutic intervention. Mental disorder labels can provide cover for societal problems. Criminal behavior has been medicalized (eg, rape as a psychiatric disorder) because prison sentences are too short and such labeling allows for indefinite psychiatric commitment."
  • "What makes something a psychiatric fad is that a psychiatric label seems to explain some common, nonspecific, problematic symptom or behavior, and that label is suddenly given to everyone. The fact that everyone is doing it reduces the stigma of the diagnosis and leads to more people getting the diagnosis. Then, like the old adage that if you have a hammer, everything looks like a nail, the new label gets twisted to fit cases which really don’t fit it simply because the label itself is popular and accepted."
  • "The DSM-5 bias to thrust open the diagnostic floodgates is supported only by flimsy evidence that does not come close to warranting its great risks of harmful unintended consequences. It is too bad that there is no advocacy group for normality that could effectively push back against all the forces aligned to expand the reach of mental disorders."
• bioreductionism of antidepressants advertising: https://doi.org/10.1371/journal.pmed.0030321 "Regarding unipolar depression, we recently argued [5] that antidepressant manufacturers commonly advertise their products by claiming that depression is caused by a lack of serotonin and that selective serotonin reuptake inhibitors normalize this deficiency, a claim not congruent with the peer-reviewed literature or FDA-approved product information. We have not received any academic objections to our article, but several prominent psychiatrists have affirmed our conclusions. For instance, Wayne Goodman, Chair of the FDA Psychopharmacological Advisory Committee, admitted that the serotonergic theory of depression is a “useful metaphor”—and one that he never uses within his own psychiatric practice [6]."
• ME: First off, i disbelieve that functional neurologic disorders exist, if we look [at the history of other such disorders such as epilepsy](https://doi.org/10.1111/j.1528-1167.2011.03051.x), the ratio of non organic diagnoses over organic diagnoses decreases over time as the precision of our neuroimaging tools and scientific knowledge progress, and nowadays for epilepsy the consensus is that these is almost always an organic cause.
• BEST: concrete example: high dose carbon monoxide poisoning was misdiagnosed as anxiety TWICE in a woman: https://www.reddit.com/r/TwoXChromosomes/comments/khk6wd/i_23f_was_admitted_to_the_hospital_2_days_in_a/
  • If such an obvious physical affliction as carbon monoxide could be misdiagnosed twice as anxiety, imagine the misdiagnosis rates of less obvious organic afflictions!
  • https://www.reddit.com/r/subredditcancer/comments/awvg9w/twoxchromosomes_appears_to_be_implementing_some/
  • https://www.reddit.com/r/saskatoon/comments/eaw1be/when_3_doctors_failed_to_recogniz_my_symptoms/
• In search of "non-disease", BMJ, 2002 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1122831/
  • In the 80s, 80% of the "non-medical academics, medical academics, general practitioners, and secondary school students" thought that lead poisoning and carbon monoxide poisoning were not diseases! But their point that this shows that the definition of what is a disease is vague is moot, because they lumped together the non-medical public! At a time without internet! So they were really testing here medical literacy rather than the informed consensual definition of what is a disease, most of these people arguably didn't know what exactly these diseases referred to.
  • “There is no disease that you either have or don't have—except perhaps sudden death and rabies. All other diseases you either have a little or a lot of.”
  • Starvation and drowning not classified as diseases. But they are conditions that need (urgent) medical treatment nevertheless.
  • They have an interesting discussion about non-diseases: diseases for which the outcome would be generally better without treatment. BUT this makes a HUGE implicit assumption: that this improvement of outcome with no treatment is because there is no illness, where in fact it can be that there IS an illness but current medical treatments can not help (ie, medical science has not progressed enough). There are a few diseases that obviously fit the latter case, and which would be labelled as non-diseases: Alzheimer, Parkinson, and several forms of epilepsy. A much better measure is whether this affliction, or set of symptoms, is generally associated with reduced life expectancy, then it is a disease, whatever treatments there is (not). Founding the definition of diseases on the availability of medical treatments is a slippery slope, more than the definition of disease itself. It would be wiser to consider these as afflictions of cryptogenic cause when no treatment is available but epidemiological data show reduced life expectancy or major hindrances to quality of life.
• Idiopathic disease, MUS, anxiety, hysteria, somatic, etc.
• CBT-i ME criticism and analogy with a money therapy: I agree! I think CBT-I is nothing more than placebo. The only measure that is improved in all the academic papers I could find was that subjectively some of the patients feel better after CBT-i. No improvement in objective sleep metrics whatsoever.
  • I know another therapy that is much more effective than CBT-i to make any patient feel better, 100% guaranteed: I give them 1000 euros/dollars. They will instantly feel better. This won't treat or improve their disease whatsoever, but I'm 200% certain that when I'll hand them a quality of life assessment to fill in, there will be a very significant increase in various dimensions after they receive 1000 free euros/dollars.
  • Can I then claim that my "money therapy" is effective to treat insomnia and virtually any disease? Of course not. I can't see why CBT-i should be considered any different.
• Normal sleepers don't need sleep hygiene and other things, insomnia and sleep disorders are not psychological but physiological: https://www.reddit.com/r/insomnia/comments/lkq6e6/normal_sleepers/

• AASM latest guidelines on Insomnia of 2008: https://doi.org/10.5664/jcsm.27286
  • Sleep diary over 2 weeks is a standard for insomnia too, so for ALL sleep disorders consultations, a sleep diary is required according to guidelines: "A two-week sleep log to identify general patterns of sleep-wake times and day-to-day variability."
  • Actigraphy optional, for circadian rhythm disorders assessment: "Actigraphy is indicated as a method to characterize circadian rhythm patterns or sleep disturbances in individuals with insomnia, including insomnia associated with depression."
  • "Regardless of the therapy type, primary treatment goals are: (1) to improve sleep quality and quantity and (2) to improve insomnia related daytime impairments. (Consensus)" → well CBT-i fails at that...
  • BEST CONFIRMATION: sleep diary should ALWAYS be maintained, it's our primary management tool! "Sleep diary data should be collected prior to and during the course of active treatment and in the case of relapse or reevaluation in the long term (every 6 months). (Consensus)"
  • But still the old view of insomnia being potentially secondary to psychological disorder: "Psychological and behavioral interventions are effective and recommended in the treatment of chronic primary and comorbid (secondary) insomnia. (Standard)"
  • "Although all patients with chronic insomnia should adhere to rules of good sleep hygiene, there is insufficient evidence to indicate that sleep hygiene alone is effective in the treatment of chronic insomnia. It should be used in combination with other therapies. (Consensus)"
  • "When an initial psychological/ behavioral treatment has been ineffective, other psychological/ behavioral therapies, combination CBT-I therapies, combined treatments (see below), or occult comorbid disorders may next be considered. (Consensus)"
  • Hypnotics (sleeping pills) should only be used short-term!!! "Short-term hypnotic treatment should be supplemented with behavioral and cognitive therapies when possible. (Consensus)"
  • Ramelteon recommended? It's a melatoninergic agent!
  • But they recommend sedating agents... "Sedating antidepressants, especially when used in conjunction with treating comorbid depression/anxiety: examples of these include trazodone, amitriptyline, doxepin, and mirtazapine"
    • "These medications may only be suitable for patients with comorbid insomnia who may benefit from the primary action of these drugs as well as from the sedating effect."
  • "Over-the-counter antihistamine or antihistamine/analgesic type drugs (OTC “sleep aids”) as well as herbal and nutritional substances (e.g., valerian and melatonin) are not recommended in the treatment of chronic insomnia due to the relative lack of efficacy and safety data. (Consensus)"
  • "Older approved drugs for insomnia including barbiturates, barbiturate-type drugs and chloral hydrate are not recommended for the treatment of insomnia. (Consensus)"
  • Ah yes they are ok with long-term use of sleeping pills... BS! "Chronic hypnotic medication may be indicated for long-term use in those with severe or refractory insomnia or chronic comorbid illness. Whenever possible, patients should receive an adequate trial of cognitive behavioral treatment during long-term pharmacotherapy."
  • Evidence for pharmacological treatments is weak, for ALL treatments: https://doi.org/10.5664/jcsm.6470
    • "BzRAs were found effective for short-term use, although degradation of improvement following discontinuation of hypnotic was noted to be of concern. Limited evidence and toxicity concerns were cited for other prescription and non-prescription agents, although prolonged-release melatonin was recommended as a first-line treatment for insomnia in persons over 55 years."
    • Insomniacs with co-morbid disorders are STILL excluded! "Subjects in each study met criteria for primary insomnia or insomnia associated with nonpsychotic mental disorder by either DSM-III-R or DSM-IV criteria"
    • "To reduce the uncertainty resulting from the possibility of publication bias, increased nonindustry-sponsored research will be needed. Improvement in the standardization of assessing sleep outcomes and reporting of adverse effects will be essential for future clinical practice guidelines. Finally, there continues to be uncertainty regarding the appropriate metrics for assessing the efficacy of a treatment intervention in the management of chronic insomnia. Further research may lead to an understanding of nonconventional measures such as improvement or resolution of the “insomnia syndrome,” which suggests a more patient-centered approach. This could include metrics of improved daytime cognitive, emotional, and psychomotor function." https://doi.org/10.5664/jcsm.6428
• Insomnia epidemiology: https://pubmed.ncbi.nlm.nih.gov/16686591/
  • "Epidemiologic studies show that abnormal sleep patterns predict lower life expectancy, and that people with insomnia are more likely to develop affective disorders, substance abuse, and other adverse health outcomes."
  • "The 2005 NIH State-of-the-Science statement, however, has suggested the use of the term comorbid insomnia, instead of secondary insomnia, based on a limited level of understanding of the causal relationships which may exist between insomnia and coexisting disorders. Conceivably, primary insomnia could coexist as an independent entity in the context of another disorder, as opposed to being caused by it."
• Review of 2003 about psy theories of insomnia, they are mostly based on activity induced arousal... They found consistent association of running thoughts but they assumed that it's the running thoughts which caused sleep disorders... https://doi.org/10.1146/annurev.psych.53.100901.135243
  • presleep cognitive activity: "Harvey (2001b) has explored the effects of suppressing presleep cognitive activity on sleep-onset latency. A cohort of insomniacs and good sleepers were allocated to either a suppression condition (“suppress the thought most likely to dominate your thinking as you get into bed”) or nonsuppression condition (“think about anything as you get into bed, including the thought you would most likely think about as you go to sleep”). Suppress participants reported longer sleep latencies and poorer sleep quality, regardless of whether they were insomniac or not. Harvey concluded that thought suppression appeared to have the opposite effect in that it prevented sleep-onset, in a manner consistent with Wegner’s theory of ironic mental control."
  • "There are parallels between Wegner’s theory and the performance anxiety model that gave rise to the adaptation of paradoxical intention from the work of Frankl (1960). Indeed, Ansfield et al. (1996) propose that their results are consistent with theories of cyclic escalation of anxiety disorders (Ascher 1981) and worry about sleep (Borkovec 1982)."
• History again: "Nonetheless, historically, researchers with an interest in developmental psychopathology have largely ignored a possible role for atypical sleep. Recently, however, there has been a surge of interest in this area, perhaps reflecting increased evidence that disturbed or insufficient sleep can result in poor functioning in numerous domains." — that's why sleep disorders have been largely disregarded in children! https://doi.org/10.1111/jcpp.12469
• Anxiety is built from the inability to sleep and the apprehension born from the expectation the patient has that they will likely not be able to sleep enough or even at all before they have to wake up for their appointments. This apprehension built from past experiences of insomnia leads to anxiety via learned selfhelplessness. This can be demonstrated empirically quite easily: just take a typical sleeper with no sleep disturbances, and warn them that they will have to wake up 2h only after they fall asleep. Every time. After a few iterations, I can guarantee they will become anxious about sleeping.

• Heart rate and stress?
  • functional somatic disorder: "We conclude that current available evidence is not adequate to firmly reject or accept a role of ANS dysfunction in FSD." https://doi.org/10.1016/j.biopsycho.2009.05.002
  • Nonlinear Analysis of Heart Rate Variability: A Comprehensive Review, 2016 http://96.126.98.199/index.php/jct/article/view/1724
    • "It can be concluded that the analysis of HRV in the nonlinear domain provides very useful information to characterize the appropriate autonomic balance and is a more reliable marker of complications and mortality in patients with cardiovascular disease."
  • BEST METHODS: A Quantitative Systematic Review of Normal Values for Short‐Term Heart Rate Variability in Healthy Adults, 2010 https://doi.org/10.1111/j.1540-8159.2010.02841.x

• BEST: Clinical review: A review and analysis of heart rate variability and the diagnosis and prognosis of infection, 2009 https://doi.org/10.1186/cc8132
• BEST CRITICAL TOADD ME: It's normal to become anxious of sleep when you are unable to sleep when you'd like to and you know you'll have to wake up utterly sleep deprived, literally suffering the rest of the day (yes studies have shown that sleep deprivation is literally painful). More formally, sleep anxiety is an instance of learned helplessness due to your inability to sleep when you can and the apprehension of the unavoidable pain and suffering of the sleep deprivation you'll have to unwillingly endure.

• TOSEE: 20% very suggestible to placebo (search morphine): https://www.huxley.net/bnw-revisited/
• Introspection illusion, why most people rationalize their disease as being caused by their own mental states, convinced they are in control.
• Placebo effect not always additive with drug effects: Hall KT, Loscalzo J. Drug-Placebo Additivity in Randomized Clinical Trials. Clin Pharmacol Ther. 2019 Dec;106(6):1191-1197. doi: 10.1002/cpt.1626. Epub 2019 Oct 26. PMID: 31502253; PMCID: PMC7168700. https://pubmed.ncbi.nlm.nih.gov/31502253/
  • "In randomized clinical trials (RCTs), it is assumed that nonspecific effects beyond action of pharmacological agents are roughly equivalent in drug and placebo treatment groups. Hence, since the inception of RCTs, drug efficacy is determined by comparing outcomes in active to those in placebo control arms. However, quantitation of efficacy is based on an unproven assumption, that drug and placebo responses are always additive. Response to treatment in RCTs can be differentially influenced by the perturbing effects of patient expectations, side effects, and pharmacogenomic interactions in both drug and placebo arms. Ability to control for these effects requires understanding of when and where they arise, how to mitigate, analyze, and even leverage their impact. Here, we examine three factors that influence additivity: expectation, side effects, and pharmacogenomics. Furthermore, to provide novel insights into nonadditivity and solutions for managing it, we introduce systems pharmacogenomics, a network approach to integrating and analyzing the effects of the numerous interacting perturbations to which a patient is exposed in RCTs."

• BEST confirmation sleep quality is often a subjective measure in psychology studies: https://pubmed.ncbi.nlm.nih.gov/27663102/
  • "However, sleep quality, including depth of sleep, general satisfaction with sleep, etc., is usually investigated by subjective sleep quality indexes [14]. Take Pittsburgh Sleep Quality Index for example, sleep quality is defined as a composite score of seven subcategories: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction."

• ME: the issue with psychology is that it is founded on a simplistic and dualistic view of reality and especially of human biology. For example Alzheimer. This is a disease that causes significant impairments in memory. So what is the logical conclusion for psychologists to derive an effective therapy? To train memory! But this is exactly what is impaired by the disease! The disease is not caused by a lack of use of memory, and it impairs memories formation and recall, and yet they assume that using this impaired function can improve it. At no point did they think that diet can be a major factor that can be controlled to much more effectively manage Alzheimer as is currently the experts' consensus. The time lost by the patients in trying to train their memory, a painful process full of expectable failures and with very few improvement just like asking a tetraplegic to try to walk, could have been much better used in educating the patients to modify and manage their diets, a process that does not involve memory and hence is much less painful. Psychology's therapies basically focuses on forcing the disabled to use their disabilities to their limits, in the hope the disabilities will magically disappear. Hence, the approach of psychology to design therapies is fundamentally flawed by these two core ideologies.
  • https://www.medicalnewstoday.com/articles/324357
  • BS: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5674674/ — dementia group high education, n=10 !!! Vs n=47 for lower education! LMAO! Clearly underpowered and super biased! I can't even understand how this was published!
  • BS again, as noted in the BS study above which reviewed previous results, this could not be reproduced: "While better-educated people may be diagnosed with Alzheimer’s later than people with less education, it appears they have suffered brain damage but their “cognitive reserve” was able to hide and delay the effects, the researchers said." https://www.reuters.com/article/us-alzheimers-education-idINN2245872920071022
  • bias because more people with lower education than higher education so it's an imbalanced class problem and they do not account for this statistical bias and variability.
  • "Education has long been thought to protect against the ravages of brain diseases like Alzheimer’s. Numerous studies seemed to suggest that the more educated were less likely to develop dementia." https://www.nbcnews.com/health/aging/higher-education-won-t-prevent-mental-decline-study-finds-n968531
  • ME SUMMARY: training memory and education have NO relationship whatsoever with the development nor the improvement of Alzheimer.
  • Dualism is reflected in two fundamental assumptions pervasive throughout psy practice and research: that the body does not affect the brain states, and that the mental states can have an effect on the body. Dualism is obviously pseudoscientific, and psychology, if they were to state clearly their assumptions, would also be considered as pseudoscientific.
  • BEST ME: The domain of subjectivity is where psychology reigns supreme. But sleep is anything but subjective: it is a real biological phenomenon that is objectively measurable as well as the consequences of its deprivation.

• The idea that autism and ADHD can both be present may be due to a HUGE bias that sleep deprivation can cause ADHD-like symptoms and behaviors, including irritability, increased forgetfulness, trouble focusing or sitting still, difficulty controlling emotions. https://www.healthline.com/health/adhd/caffeine#stimulation
  • BEST CRITICAL TOADD VLIDACMEL: can switch between diagnoses and psychological therapies work the same!!! https://www.reddit.com/r/ItsAllInYourGenes/comments/m4ftns/the_hidden_links_between_mental_disorders/ (mirror: https://web.archive.org/web/20210706161646/https://old.reddit.com/r/ItsAllInYourGenes/comments/m4ftns/the_hidden_links_between_mental_disorders/ ) and https://doi.org/10.1038/d41586-020-00922-8
• BEST CRITICAL: BS! P factor (p-factor) and other veiled polite criticisms on psychological methods and classification and diagnosis: https://www.reddit.com/r/ItsAllInYourGenes/comments/m4ftns/the_hidden_links_between_mental_disorders/ and https://doi.org/10.1038/d41586-020-00922-8

• The best medical proof is a proof of therapeutic efficacy. If a therapy is significantly improving the individual's symptoms, it means that the diagnosis was at least pertinent enough to explain some of the theoretical underpinnings of the disease and derive a clinically useful therapy, whether or not the diagnosis is completely accurate. For example, ADHD is still diagnosed with unspecific items that do not really reflect the primary characteristics of the disease, but the diagnosis was specific enough to derive a pathogenesis theory and effectivy therapies.

• Long-Term Pharmacological Treatments of Anxiety Disorders: An Updated Systematic Review, 2016 (agabeptin and agomelatin seem good for GAD) https://doi.org/10.1007/s11920-016-0668-3

• Best toadd: dsmdv and icd are not empirically based! An Empirically Based Prototype Diagnostic System for DSM-V and ICD-11 https://psycnet.apa.org/record/2010-13146-020
  • "Despite these criticisms of the current diagnostic procedures, the majority of research and work directed at reining successive editions of the DSM has focused not on the process through which disorders are diagnosed, but instead on which diagnostic categories should be included, excluded, or modified."
• BEST CONFIRMATION: Sleep duration and social jetlag are independently associated with anxious symptoms in adolescents https://doi.org/10.1080/07420528.2018.1509079
  • Their conclusion is that the maintenance of emotional support is the key point. But NO! Social jet lag implies circadian misalignment, potentially even a circadian rhythm disorder.

• BEST CRITICAL TOADD: study showing a causal link between genetical chronotype and circadian misalignment on generalized anxiety disorder symptoms (and depression): https://doi.org/10.1038/s41380-021-01157-3 and https://www.sciencedaily.com/releases/2021/06/210607202226.htm
  • "Circadian misalignment is a potential explanation for the link between diurnal preference and mental health and wellbeing, with evening people tending to be more misaligned [13, 49]. The actigraphy data in UK Biobank provided a unique opportunity to quantitatively test the role of misalignment in mental health and wellbeing. We provided evidence that a genetic liability to morningness had a nominal effect on CPD; morning people were more aligned. Observationally, we demonstrated that more misaligned individuals (i.e., higher CPD) were more likely to report depression, anxiety and have lower wellbeing. This was true when several sensitivity analyses were performed including stratification by sex, age, diurnal preference, relevant medication usage and shift worker status. These analyses strengthen the evidence that circadian misalignment has adverse effects on mental health and may partially explain the links between diurnal preference and mental health although reverse causation (depression disrupting sleep patterns and causing misalignment) can not be ruled out and should be tested in future work."
  • "Our findings fit with previous evidence that evening people may experience more circadian misalignment, as their chronotype is often mismatched with diurnal (9–5) schedules, which are the societal norm [16]. Individuals with a physiological tendency towards delayed sleep and circadian timing are especially prone to further delay by modern schedules and lighting, resulting in greater social jet-lag [50]. Our findings also build on existing evidence of circadian misalignment in shift workers, who often work against their diurnal preference, with some studies suggesting that these individuals have a higher prevalence of depression and lower wellbeing [51, 52]."

• Isn't it ironic that studies on the placebo effect suffered themselves from the very bias this effect and protocol was designed to excluse, which is the effect of chance?
• sleep hygiene and stress catch-22: if you do all sleep hygiene tips which are very restricting and constraining, the blame for ineffectiveness will be on your "stress levels"....

• Again a testimonial of anxiety used as a hysteria-like misdiagnosis of a very real and life threatening physiological pathology: https://archive.is/GwPCH

• BEST CRITICAL TOADD: CBT does have adverse effects, for example for CFS/ME!
  • "Randomized controlled trials have shown that CBT is beneficial in the treatment of chronic fatigue,181 however, this is conflicted by findings from a reanalysis of a Cochrane review which question its effectiveness and show a high incidence of adverse events. This re-analysis study states that if a trial of a drug or surgical procedure demonstrated similarly high rates of adverse effects, then it would not be accepted as a safe treatment option, therefore CBT should have to adhere to the same level of scrutiny." Long covid—mechanisms, risk factors, and management, 2021 https://doi.org/10.1136/bmj.n1648
  • "Sleep disturbances may be managed by following relevant guidelines on insomnia,193 and a range of treatment strategies can be considered.1"

Stress and its pseudoscientific psychoanalysis roots

• BEST CRITICAL TOADD: my own comments and analysis on why stress is only a symptom and why it's an inversion of reasoning that isn't founded to try to treat it as a medical illness: https://archive.is/6nX5t

• Something else:

> Here is an older study that finds a causal link between stress and skin cell changes in rat cells.
>
> https://www.sciencedirect.com/science/article/abs/pii/S0889159198905414

Nice study! It's a nice preliminary result, but it needs confirmation, as it has some serious limitations:

• The most obvious is the sample size and statistical thresholds. Although the methods seem fine to me since they are non-parametric (but you know better than me), having n=5 animals in the intervention group and n=4 in the control is not super robust.
• [Asphyxia may cause mast degeneration](https://pubmed.ncbi.nlm.nih.gov/26062756/), although [there is conflicting data](https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0012360).
• A more arguable but interesting thing to consider is the method to induce stress in animals. Commonly, it's done by restraining physically the animal, in this study they put the animal in a plexiglass box for 30min. Are other factors such as inactivity influencing the results, and not just emotional stress? That's always trick to say with animal studies. An interesting thing to see is what other studies with other methods found, and indeed it's possible to induce stress without restraint by social isolation. In this study, this is what they did, and [they found no significant MC degranulation (although they found significant MC reduction)](https://doi.org/10.1007/BF02007774). They interestingly also did not find significant increases in histamines levels, which should be the case if the glucocorticoid cascade hypothesis is correct, but this may be because the effect is too small and the study not powered enough.
• Finally, and most importantly, this study only shows that a link between stress and mast cells degranulation. But [mast cells degranulation is not necessarily involved in atopic dermatitis](https://pubmed.ncbi.nlm.nih.gov/14698841/).

In both cases, note these studies are quite old. It doesn't mean their results aren't valid, but I would be careful, as there are lots of studies from that era which were proven wrong. And I tried to find more up-to-date confirmation or reproduction studies, but couldn't yet.

BUT I have found this interesting lead: [psychological stress via the downregulation of mast cells may decrease the skin barrier and increase its propensity to be infected](https://dx.doi.org/10.1172%2FJCI31726). In other words, psychological stress increases the risk of being infected, it's not just triggering rashes per se, it just opens the gates for an infectious agent, so that there is something else to treat.
And interestingly the antimicrobial barrier can also be broken by overuse of antimicrobial soap as is common during the pandemic.

To me, it makes much more sense for psychological stress to reduce the skin barrier for an infectious agent to contaminate or further propagate, than directly trigger or cause flares of a skin disease.

> Here’s a study showing the same relationship in humans:
>
> https://link.springer.com/article/10.1007/s11882-008-0050-6

Could you please give a relevant excerpt? I skipped through it quickly admittedly but did not find a reproduction of the finding on animals. Also it's not a study per se but a reports that is kinda a review? It's a bit weird how this was categorized by the journal.

> Here’s a study that finds a link between stress after natural disasters and eczema:
>
> https://www.sciencedirect.com/science/article/abs/pii/S0091674999701302

Interesting indeed, but only an association. There are lots of other factors that are not accounted for, foremost sleep deprivation, as we can assume that people in more damaged areas had less opportunities to sleep since their home was at least partially destroyed... And that's just one counter-hypothesis, I'm sure there are plenty of other potential factors at play here.

In fact, when you look at their multiple logistic regression results, table IV, we can see that clearly their conclusion is biased. All factors can explain the increases in atopic dermatitis symptoms. Yes, subjective distress has a higher odds ratio, but it can be a statistical artifact, or, and that's my hypothesis but I think it's HIGHLY plausible, it's the most inclusive factor to model the general impact of the earthquake on the individual. All the other variables are much more specific, but this, it's almost like asking: "how much worse your life is now after the earthquake compared to before?". And I bet that such a question would have similar or an even better odds ratio.

> This paper talks about the direct hormonal impacts of stress on eczema:
>
> https://link.springer.com/article/10.1007%2Fs00105-003-0609-z

Interesting theoretical paper but no evidence. The only concrete evidence they present are studies showing an association between stress and atopic dermatitis. Which I can totally conceive: for most people, having hands or feet not only look like an inhumane lizard but also be so itchy it wakes you up when you sleep can be quite stressful, especially if your daily life involves frequent social contacts (eg, commercial activities).

But jumping from this association to assuming that stress is causing atopic dermatitis flares is quite a leap of faith. They present just one study that could have given strong evidence, which is a study on 2 individuals who were monitored for 50 days, and they could see that acute emotional stress preceded atopic dermatitis symptoms. Temporal precedence is a huge hint of causality. But it's on 2 patients only! We need a similar longitudinal study but better controlled for other factors and with an acceptable sample size to draw statistical inference.

The rest of this review is about preclinical findings that could support this hypothesis so I won't dwelve further as it's not my specialty. But I note that the authors make no secret of their apriori bias, since in the first sentence they state: "As for other chronic diseases, there is no clinical doubt with atopic dermatitis that patient experience and stress management have an impact on the aggravation or maintenance of the disease". But they give no proof, and I did not find a single solid review showing that stress management improves the management of acute dermatitis...

> Here’s a paper showing a significant association with stress/family life and eczema in children:
>
> https://scholar.google.com/scholar?hl=en&as_sdt=0%2C5&q=stress+atopic+dermatitis&oq=stress+ato#d=gs_qabs&u=%23p%3DT7csAaTSM_QJ

Given the new infos, I would like to modify my statement and position: [emotional stress may reduce skin's antimicrobial barrier and hence open it to infectious agent](https://dx.doi.org/10.1172%2FJCI31726), although it doesn't appear emotional stress can trigger eczema flares since it appears [it does not significantly elevate histamine levels](https://doi.org/10.1007/BF02007774). This only pertains to skin, as it is indeed nerved much like the guts and with direct communication pathways to the brain.

----

However, after some additional background search, I would still argue that this is NOT stress, what was observed here in this study may very well be real but not due to what we conceive as stress but to another, potentially neurologic but maybe not, phenomenon. And even more, I would still argue that the concept of stress is pseudoscientific.

Here's why I say that: the concept of stress is flawed from its very root. And here is the proof.

Hans Selye is the father of the concept of stress, and it is indeed a child theory from the parent psychosomatic theory of psychoanalysis, which first incarnation was in the diagnosis of an epileptic female patient as hysteria, by Freud himself.

Rather than paraphrasing, let me show some excerpts, and you can make your own opinion about how the stress theory was conceived by Selye:

> Selye's interest in stress began when he was in medical school; he had observed that patients with various chronic illnesses like tuberculosis and cancer appeared to display a common set of symptoms that he attributed to what is now commonly called stress.
> [..]
> Selye defined general adaptation syndrome (GAS) as the sum of all nonspecific systemic reactions that occur in response to an extended and continued exposure to stress.14
> [...]
> His last inspiration for general adaptation syndrome (GAS, a theory of stress) came from an endocrinological experiment in which he injected mice with extracts of various organs. He at first believed he had discovered a new hormone, but was proved wrong when every irritating substance he injected produced the same symptoms (swelling of the adrenal cortex, atrophy of the thymus, gastric and duodenal ulcers).[9] This, paired with his observation that people with different diseases exhibit similar symptoms, led to his description of the effects of "noxious agents" as he at first called it. He later coined the term "stress", which has been accepted into the lexicon of most other languages.[10]
> [...]
> Selye has acknowledged the influence of Claude Bernard (who developed the idea of milieu intérieur) and Walter Cannon's "homeostasis". Selye conceptualized the physiology of stress as having two components: a set of responses which he called the "general adaptation syndrome", and the development of a pathological state from ongoing, unrelieved stress.
> [...]
> Selye discovered and documented that stress differs from other physical responses in that stress is stressful whether one receives good or bad news, whether the impulse is positive or negative. He called negative stress "distress" and positive stress "eustress". The system whereby the body copes with stress, the hypothalamic-pituitary-adrenal axis (HPA axis) system, was also first described by Selye. He also pointed to an "alarm state", a "resistance state", and an "exhaustion state", largely referring to glandular states. Later he developed the idea of two "reservoirs" of stress resistance, or alternatively stress energy.

Quite interesting isn't it? But there's more:

> Although it was not widely known at the time, Selye began consulting for the tobacco industry starting in 1958; [...] The companies wanted Selye's help in arguing that the recognized correlation between smoking and cancer was not proof of causality. [...] One lawyer advised him to "comment on the unlikelihood of there being a mechanism by which smoking could cause cardiovascular disease” and to emphasize the “stressful” effect that anti-smoking messages had on the US population.[13]
>
> Publicly, Selye never declared his consultancy work for the tobacco industry. In a 1967 letter to "Medical Opinion and Review," he argued against government over-regulation of science and public health, implying that his views on smoking were objective [...]. In June 1969, Selye (then director of the Institute of Experimental Pathology, University of Montreal) testified before the Canadian House of Commons Health Committee against anti-smoking legislation, opposing advertising restrictions, health warnings, and restrictions on tar and nicotine. [...]
>
> In 1999, the US Department of Justice brought an anti-racketeering case against 7 tobacco companies (British American Tobacco, Brown & Williamson, Philip Morris, Liggett, American Tobacco Company, RJ Reynolds, and Lorillard), the CTR, and the Tobacco Institute. As a result, the industry's influence on stress research was revealed.[15]

I guess you didn't expect how close your random example with smoke and lungs cancer was to the topic of stress! ;-) So if we assume Selye was right, cigarettes do not kill people and do not cause lung cancers, it's the stress that does. Good to know!

Sources: [This review](https://doi.org/10.1111/bjd.13084) and [Wikipedia](https://en.wikipedia.org/w/index.php?title=Hans_Selye&oldid=997686551#Controversy_and_Involvement_with_the_Tobacco_Industry) (sourced from Selye's book The Stress Of Life)

----

• BEST ME: the two diseases categories where stress is most commonly researched, intuitively applied and used to dismiss treatment are cardiac (Tatsumo...) and skin diseases (atopic dermatitis/eczema, same thing). And for both, there is no evidence!!! It's crazy! In fact there even starts to be evidence accumulating that stress is NOT the sole or even sufficient culprit, especially for cardiac!!!

• BEST CRITICAL ME: Here's how to create sleep anxiety ex nihilo for anybody: warn someone that they will be awakened 2h after their usual bedtime, and that no matter what, they will have to wake up and go on with their day. Alternatively, tell them that for the night, they will be forcefully awakened 2h exactly after everytime they fall asleep. They will then experience sleep anxiety, with an inability to sleep or at least a very long time to fall asleep, despite being able to fall asleep easily at their usual bedtime usually. This shows that sleep anxiety is not a cause but a consequence of insomnia and anticipation of (painful) sleep deprivation. Sleep anxiety can indeed worsen insomnia, but treating sleep anxiety will likely not improve insomnia, it would make more sense to rather treat the insomnia which will likely clear up the sleep anxiety along the way.
• Even for fungal infections! "Often, stress is cited. Stress is a false enemy. Bad eating, too much sugar, not sleeping, and stress hormones like Cortisol, and other physical factors of stress probably encourage Candida to morph into its mycelial form. But the root cause always seems to be due to some hormonal/steroidal change. 1:2:2015 edit: ALWAYS! Stress is NEVER THE ROOT CAUSE. I am fed-up with patients and their GPs insisting that stress is the cause. It is not. A pathogenic microbe upsetting the immune system is the cause." http://www.dyshidrosis.co.uk/
• BEST CRITICAL TOADD: TIL there is such a strong correlation between circadian rhythm issues and psychological disorders that scientists suggest calling them "circiatric" disorders. https://doi.org/10.1172/JCI135500 and https://www.reddit.com/r/DSPD/comments/krdzu9/til_there_is_such_a_strong_correlation_between/
• BEST CRITICAL TOADD ME: about stress, and alternative explanation of chronic or extreme acute sleep deprivation as a trigger for symptoms of other diseases:

Stress is often touted as a cause or trigger for virtually any disease. So far i haven't found any scientific proof or even a solid theoretical founding (i exclude psychotherapy, i can't place any trust on a practice which is founded by the confusion between epilepsy with the non existent mysogynistic hysteria).

Stress is a particularly vicious explanation as it can be applied to virtually anybody at anytime, even if you don't feel stressed, well maybe you were but you didn't realize it? There is no objective measure of stress (at least not widely recognized). For instance here you say it's stress. Is it really the time you've got the most stressed lately? There was no other time you were more stressed and didn't get a dyshidrotic reaction? If there was, how can you explain that you got more stressed in the past and had no issue, but now you have while being less stressed in comparison to the most stressful event?

Rather than stress, i argue that often (but not always) such kind of issues are due to sleep deprivation. Aren't you lacking sleep lately? Stress and anxiety and all kinds of emotional dysregulations are drastically increased by sleep deprivation, so it's easy to confuse the effect (stress, depression) for the cause (sleep deprivation). Biologically this would make much more sense, as sleep deprivation is well known for basically disabling temporarily your immunological system.

If sleep deprivation is the culprit, then the fix is simple and actionable: avoid situations where you could get (too much) sleep deprived. That's something testable and even measurable, the amount of sleep you get and its relationship with your dyshidrosis appearances.

Whereas for stress, well this explanation doesn't bring anything actionable or verifiable/measurable objectively.

UPDATE: with the works of S. Cohen, the medical concept of psychological/emotion stress as a clinical entity to treat evolved, now the bad stress (distress) is the chronic stress (whereas eustress = good stress = acute stress), and it's now supposed that chronic stress can worsen or cause any inflammatory disease, not just any disease. Although the dif

• BIG HINT: psychological stress interventions have not been found to have a positive impact beyond doubt on CARDIOVASCULAR OUTCOMES by Cochrane Systematic Reviews. Like, if there is ONE disease that is considered the most prone to have worse outcome because of psychological stress, it's cardiac issues. Psychological interventions did not help at all, so how could they help for other diseases? https://doi.org/10.1002/14651858.CD002902.pub4
  • "This updated Cochrane Review found that for people with CHD, there was no evidence that psychological treatments had an effect on total mortality, the risk of revascularisation procedures, or on the rate of non‐fatal MI, although the rate of cardiac mortality was reduced and psychological symptoms (depression, anxiety, or stress) were alleviated; however, the GRADE assessments suggest considerable uncertainty surrounding these effects."
    • This CRUSHES the Coronary Personality hypothesis! https://pubmed.ncbi.nlm.nih.gov/6040635/
  • BEST CRITICAL ME: The concept of psychological stress has no clinical utility. Neither for outcome prediction nor therapeutic management. In line with: https://pubmed.ncbi.nlm.nih.gov/10553729/
  • "Stress-management interventions improve the quality of life of patients with advanced coronary heart disease, but effects on disease prognosis have been inconsistent" → Translation: subjectively, using a subjective scale measure of perceived quality of life by the patient, they think that stress-management interventions improved their lives, while objectively they didn't. https://doi.org/10.1038/nrcardio.2012.45
  • The dogma is strong, someone else tried to do a counter Cochrane Systematic Review trying to modify the conclusion that yes psychological stress interventions improve CVD but it's not published on Cochrane LOL https://doi.org/10.1177%2F2047487317739978
  • ME: Finally, psychological stress interventions have not been found to have a positive impact beyond doubt on CARDIOVASCULAR OUTCOMES by a Cochrane Systematic Review of 2017. Like, if there is ONE disease that is considered the most prone to have worse outcome because of psychological stress, it's cardiac issues. Psychological interventions did not provide benefits beyond doubt, so how could we assume they could help for other diseases given the current lack of evidence?
• Not even proof of increased histamines because of psychological stress: https://doi.org/10.1007/BF02007774
  • "Isolation stress substantially, though not significantly, increased the hypothalamic histamine content. The serum corticosterone levels in isolated rats did not significantly differ from the control levels." → they needed to mention a non-significant result in the abstract... I don't even know how this got published, but it was in 1994, the statistical crisis in medical and psychological sciences did not exist yet.
• Arguments FOR and theory behind psychological stress affecting the immune system, see figure 1, it's ridiculous! It's indeed confusing psychological stress with physiological stress (ie, reactive oxydant species): https://journals.sagepub.com/doi/pdf/10.1111/1467-8721.ep10772808?casa_token=qJsajGGwBu8AAAAA%3A4kGzfxOG5UouNjQeeyXUTCmxHvCADSi9sB9Y23-zCXoRCViPltPBfgc6gisrRzuE-RkAE7ajp2XKdg&
• 2020 review arguing emotional stress can cause cardiac injuries (but it's more theoretic than anything else): https://link.springer.com/article/10.1007/s11886-020-01406-x
• Typical: increased emotional stress associated with worse outcomes and diseases. So the authors argue it's stress that is causing the disease. It can't just be that people with a worse disease are more stressed, so that the stress has nothing to do with the outcome but is just an associated variable? Typical association=cause confusion by psychology proponents: https://doi.org/10.1016/j.psyneuen.2020.104599
• A study showing there is a systemic bias in these stress and cardiac studies: "The relation between higher stress, angina, and some categories of hospital admissions probably resulted from the tendency of participants reporting higher stress to also report more symptoms. The lack of a corresponding relation with objective indices of heart disease suggests that these symptoms did not reflect physical disease. The data suggest that associations between psychosocial measures and disease outcomes reported from some other studies may be spurious." https://doi.org/10.1136/bmj.324.7348.1247
• "Although stressors trigger events, it is less clear that stress “causes” the events. There is nonetheless overwhelming evidence both for the deleterious effects of stress on the heart and for the fact that vulnerability and resilience factors play a role in amplifying or dampening those effects." https://www.jacc.org/doi/full/10.1016/j.jacc.2007.12.024
• Again, only subjective measures improved: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0073459
• "The association of anxiety with adverse outcome in patients with existing CHD is similarly mixed. For example, in some studies generalized anxiety disorder is associated with increased risk for recurrent events and mortality (HRs = 1.7–1.9),71,72 but others have found no association,73 or even a protective effect for this anxiety disorder." https://doi.org/10.1093/ajh/hpv047
• Heart rate variability as a measure of autonomic regulation of cardiac activity for assessing stress and welfare in farm animals — A review https://doi.org/10.1016/j.physbeh.2007.01.007
• Stress and Heart Rate Variability: A Meta-Analysis and Review of the Literature, 2018 https://dx.doi.org/10.30773%2Fpi.2017.08.17
• Persistent Long-Term Structural, Functional, and Metabolic Changes After Stress-Induced (Takotsubo) Cardiomyopathy https://doi.org/10.1161/CIRCULATIONAHA.117.031841
  • Syndrome de Takotsubo : mythe ou réalité ? 2009 https://www.revmed.ch/RMS/2009/RMS-205-1/Syndrome-de-Takotsubo-mythe-ou-realite
    • "L’étiologie et la physiopathologie du ST sont sujettes à de nombreuses hypothèses parfois contradictoires. Toutefois, des stresseurs émotionnels, physiologiques, voire environnementaux seraient impliqués dans sa genèse."
    • "Actuellement, aux Etats-Unis, le chiffre avoisine les 1,5-2,2% de tous les SCA et 6-12% chez les femmes chez lesquelles on suspecte un SCA.3 En Suisse, Eshtehardi P. et coll.4 ont étudié une population de 2459 SCA dont la coronarographie a objectivé 41 ST, soit une incidence de 1,7% par an."
    • "La cause exacte du syndrome de ballooning apical transitoire du ventricule gauche n’est à l’heure actuelle pas clairement établie." → donc on va dire que c'est le stress!
    • "Dans un tiers des cas, cependant, le stress causal n'est pas identifié7." https://fr.wikipedia.org/wiki/Syndrome_de_tako-tsubo
    • Stress always used as a vague explanation for diseases of unclear origin (cryptogenic).
  • BEST: Takotsubo syndrome: between evidence, myths, and misunderstandings https://www.ncbi.nlm.nih.gov/pubmed/32206851
    • "Overall, a misconception of the disease has evolved: TS is still widely considered a benign, transient, “self-healing” disease with an emotional trigger and “clean” coronary arteries, but without relevant complications. In clinical routine one can even hear opinions such as, “I suspected my patient was suffering from acute myocardial infarction, but after all it was only Takotsubo,” reflecting a significant underestimation. Already the title of the first official description (“Takotsubo-type cardiomyopathy due to multivessel spasm”) [1] contained the term “cardiomyopathy,” suggesting a rather chronic condition, for which no robust evidence exists. In contrast, TS is not a benign disease [9], is not uniformly preceded by an emotional trigger [4], and does not require “clean” coronary arteries (see below). Based on the available evidence on TS, the present review focuses on pitfalls, misinterpretations, and knowledge gaps considered important during diagnosis and management of the disease."
  • BEST: starting to shift: Takotsubo Syndrome: Underdiagnosed, Underestimated, but Understood? https://doi.org/10.1016/j.jacc.2016.03.006
    • "In early years, the disease was considered to be typically preceded by an emotional trigger; however, recent studies demonstrate that physical triggers are equally important and that TTS may frequently occur without an evident trigger 1, 3. A hallmark of TTS patients is the predominant prevalence of neuropsychiatric comorbidities 1, 4, 5. However, despite many efforts, the exact pathophysiological mechanism behind TTS remains elusive and primarily relies on assumptions (6)."
    • "A hallmark of TTS is the proposed association with catecholamines, stress, and the autonomic nervous system. From early years on, the disease was believed to be induced by a spillover of catecholamines and to be precipitated by a trigger. Indeed, there are several arguments for a role of the catecholaminergic system in the onset of TTS (20). However, following the famous work of Robert Koch (21), unequivocal evidence is required to prove the relation between cause and effect. We should not be satisfied with associations. For instance, it is true that many patients develop TTS with a stressful trigger. However, about 30% of patients spontaneously develop TTS without any identifiable trigger. Do these patients have a different “TTS-like” syndrome? Probably not. If we also include histories of ACS patients, we would discover lots of “triggers”; thus, there is obviously a relevant awareness bias. On the other hand, TTS research underlines the need for reversion to the classical medical skill of history taking. In a previous study, we could demonstrate a high prevalence of neurological and psychiatric disease in TTS patients, which outnumbered that of ACS patients (1). The present study found a much lower prevalence (about one-third of our numbers). As also stated by the authors, the value of registries critically depends on careful maintenance, and thus, data obtained from registries may significantly differ between studies."
    • "In summary, pathogenesis of TTS appears to be multifactorial. Catecholamine levels, beta-agonist use, triggers, hormone status, and microvascular dysfunction are all true, but probably not sufficient per se to induce TTS. The present study adds to previous data, emphasizing that TTS carries a substantial risk of morbidity and mortality. However, prospective studies are now needed to elucidate pathogenesis and management of this peculiar disease."
• BEST CRITICAL: "Only European guidelines for cardiovascular disease prevention acknowledge stress as a clinically meaningful risk factor in individuals with a high overall risk of cardiovascular disease or with established cardiovascular disease" https://doi.org/10.1038/nrcardio.2017.189 → likely because of the german practice of psychocardiology...
• Review on stress epidemiological studies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5422316/

• Recent trends in the incidence of anxiety and prescription of anxiolytics and hypnotics in children and young people: An e-cohort study https://doi.org/10.1016/j.jad.2015.05.002
  • "Concerns have been raised relating to the medicalisation of stress and unhappiness."
  • send by gmail on Thursday 3 December 2020
• Stress and circadian rhythm SCN:
  • https://www.reddit.com/r/DSPD/comments/k3tkyb/how_many_of_you_have_anxiety_issues_as_well/gebbia5?utm_medium=android_app&utm_source=share&context=3
  • https://medicalxpress.com/news/2020-11-stress-circadian-clock-affect.html
  • https://medicalxpress.com/news/2017-07-secret-anxiety.html
  • https://medicalxpress.com/news/2017-05-wake-promoting-compound-validatedthe-magic-bullet.html
  • https://medicalxpress.com/news/2013-06-role-orexin-neuropeptides.html
  • https://phys.org/news/2019-08-role-gaba-neurons-central-circadian.html
  • https://medicalxpress.com/news/2020-08-rem-tunes-behaviour.html
  • * [Stress hormone helps control the circadian rhythm of brain cells -- ScienceDaily](chrome-extension://klbibkeccnjlkjkiokjodocebajanakg/suspended.html#ttl=Stress hormone helps control the circadian rhythm of brain cells -- ScienceDaily&pos=0&uri=https://www.sciencedaily.com/releases/2019/11/191108102850.htm) and http://dx.doi.org/10.1159/000503720
  • Meditation Training Reduces Long-Term Stress, Hair Analysis Shows https://www.sciencedaily.com/releases/2021/10/211007122203.htm

• TOSEE: Multilevel Interactions of Stress and Circadian System: Implications for Traumatic Stress on Pubmed
• [Circadian rhythm changes in core temperature over the menstrual cycle: method for noninvasive monitoring | American Journal of Physiology-Regulatory, Integrative and Comparative Physiology](chrome-extension://klbibkeccnjlkjkiokjodocebajanakg/suspended.html#ttl=Circadian rhythm changes in core temperature over the menstrual cycle%3A method for noninvasive monitoring %7C American Journal of Physiology-Regulatory%2C Integrative and Comparative Physiology&pos=0&uri=https://journals.physiology.org/doi/full/10.1152/ajpregu.2000.279.4.R1316)
• Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies, 2011 https://doi.org/10.1093/eurheartj/ehr007
• BEST CRITICAL TOADD: review on the theory underlying psychological stress in diseases causing, the glucocorticoid cascade hypothesis, not yet proven in humans, it's still an assumption: How does the brain deal with cumulative stress? A review with focus on developmental stress, HPA axis function and hippocampal structure in humans, 2013 https://doi.org/10.1016/j.nbd.2012.03.012
  • "There is evidence that excessive stress exposure of the brain, mediated through the neurotoxic effects of cortisol and possibly neuroinflammation, causes damage to brain structure and function: the glucocorticoid cascade hypothesis. Functional changes of hypothalamic–pituitary–adrenal (HPA) axis as well as alterations in brain structures like the hippocampus have been consistently reported in major depression. [...] Finally, we have to conclude that the cascade hypothesis, mainly based on preclinical studies, has not been translated enough into humans. While there is evidence that early life maltreatment results in structural hippocampal changes and these are in turn more prominent in subjects with higher continuous cortisol secretion it is less clear which role early life maltreatment plays in HPA axis alteration."
• ME again: https://www.reddit.com/r/Dyshidrosis/comments/kt826d/stress_sometimes_there_is_nothing_you_can_do/giqseal?utm_source=share&utm_medium=web2x&context=3

• Scientists consensus is to limit the use of systemic corticosteroids for atopic dermatitis and prefer steroid-free therapies, as there is little benefits and there are lots of serious side effects:

"There was general consensus in the literature to limit the use of systemic steroids to short courses as a bridge to steroid-sparing therapies. Systemic side effects include growth suppression in children, osteoporosis, osteonecrosis, adrenal insufficiency, Cushing syndrome, hypertension, glucose intolerance, diabetes, gastritis, gastroesophageal reflux, peptic ulcer disease, weight gain, emotional lability, behavioral changes, opportunistic infections, cataracts, glaucoma, myopathy, myalgia, dysaesthesia, pseudotumor cerebri, hyperlipidemia, malignancy, thrombosis, skin atrophy, sleep disturbance, and rebound flaring."
https://doi.org/10.1016/j.jaad.2017.09.074

• When does atopic dermatitis warrant systemic therapy? Recommendations from an expert panel of the International Eczema Council, 2017 https://doi.org/10.1016/j.jaad.2017.06.042

• Micronutrients in Atopic Dermatitis: A Systematic Review https://doi.org/10.1089/acm.2018.0363
• The role of oral vitamins and supplements in the management of atopic dermatitis: a systematic review https://doi.org/10.1111/ijd.14404

• Atopic dermatitis is associated with depression, anxiety and suicidal ideation https://doi.org/10.1016/j.jaad.2018.03.017

• Frequency and Management of Sleep Disturbance in Adults with Atopic Dermatitis: A Systematic Review, 2017 https://doi.org/10.1007/s13555-017-0192-3

• "In 1978, Griesemer published a study involving 4576 patients, which addressed the incidence of emotional triggering of common dermatoses.8 Stressful life events preceding the onset of itching were found in > 70% of the patients with AD.9" https://doi.org/10.1111/bjd.13084
  • But the latest findings about the Takotsubo Syndrome should make us wary to draw premature conclusions about this associations, as it's now known that acute emotional stress is not sufficient nor always present in individuals who acquire the Taotsubo Syndrome despite being previously assumed given similar epidemiological data (and is still widely believed - see the wikipedia page). https://www.ncbi.nlm.nih.gov/pubmed/32206851 and https://doi.org/10.1016/j.jacc.2016.03.006

• The stress hypothesis for dermatitis (eczema) is even contradicting itself: "Acute stressors are known to enhance immunity, but chronic stress has an adverse effect on health.13" https://doi.org/10.1111/bjd.13084
  • this review about glucocorticoid cascade hypothesis also acknowledge that there are contradicting evidence: https://doi.org/10.1016/j.nbd.2012.03.012

• BEST CRITICAL REVIEW ORIGIN OF THE PSYCHOLOGICAL STRESS INFLUENCING BIOLOGY HYPOTHESIS from a 1946 paper by Selye, general adaptation syndrome (GAS): "Selye defined general adaptation syndrome (GAS) as the sum of all nonspecific systemic reactions that occur in response to an extended and continued exposure to stress.14 He divided GAS into three phases, with the first being the alarm phase (stress perception), after which additional physiological systems are activated; the second phase is resistance, when the body tries to adapt to the stressor; and the third, chronicity, leads to exhaustion, distress and disease. Also included in this list is the flare up of pre‐existing dermatosis. Since this initial definition, research into stress and immunity has challenged the traditional concept of stress playing a central role in inducing/enhancing allergies, and studies now suggest that certain types of stress induction could alter the stress response and instead lead to the induction of tolerance.15, 16

The neuroendocrine basis of stress is well known. Both physical and psychological stressors induce neuroendocrine responses that can affect several aspects of skin physiology.11, 13 The systemic stress response affects two biological systems: the hypothalamic–pituitary–adrenal axis, which regulates the release of adrenocorticotropin, β‐endorphin and cortisol; and the sympathoadrenal medullary system, which regulates the release of epinephrine and norepinephrine.11 Catecholamines and cortisol have potent effects on the immune system. They mediate the differentiation of T‐helper (Th) cells to Th2 cells, to the detriment of the development of Th1 cells and, as a consequence, an increased allergic inflammatory response.17 Nerve terminals in cutaneous sensory nerves release neuropeptides, such as calcitonin gene‐related peptide and substance P, which have a variety of effects on the local inflammatory response.15, 18 Mast cells – which, once activated, release further proinflammatory mediators that contribute to this response – also play a central role in neurogenic inflammation.19

Cortisol acts as a negative feedback mediator in the hypothalamus and inhibits the further release of corticotrophin. A recent study showed that patients with AD may have an inherited deficiency in the function of their hypothalamus: when exposed to experimental stressors they respond with a blunted production of cortisol, which could help explain flares in the presence of stressors.17" --> always sum of nonspecific symptoms, that's convenient!

• In addition to the (more modern?) glucocorticoid cascade hypothesis: https://doi.org/10.1016/j.nbd.2012.03.012
• Link with sleep deprivation: "Acute psychosocial and sleep deprivation stress may actually decrease skin barrier function in women and may be related to stress‐induced changes in cytokine secretion.21"
• And this review confirms its author believes in the psychotherapy's psychosomatic theory, which has no ground and no evidence so far: see section "Trauma and atopic dermatitis" https://doi.org/10.1111/bjd.13084
• BEST REVIEW on physiological stress: The concepts of stress and stress system disorders. Overview of physical and behavioral homeostasis https://pubmed.ncbi.nlm.nih.gov/1538563/
• BEST CRITICAL: yes Selye is the father of the concept of stress, and it is indeed a children of the psychosomatic theory of psychoanalysis: "Il explique que « le changement brutal survenant dans les habitudes d'une personne, jusque-là bien équilibrée, est susceptible de déclencher un bouleversement dans sa structure psychique et même somatique »13. C'est dans ce contexte qu'il développe sa théorie du syndrome général d'adaptation." https://fr.wikipedia.org/w/index.php?title=Hans_Selye&oldid=173944799#Le_p%C3%A8re_du_concept_du_stress
  • Original source: Hans Selye, The Stress of life, 1956
  • "Selye s'est intéressé au stress après avoir observé, lors de son internat à l'Université de Prague, que les patients présentaient tous le même syndrome : ils avaient tous l'air malade14." --> non mauvaise translation de l'anglais qui dit plutot "he observed a common set of symptoms, a pattern, common to nearly all people with chronic disorders, which he termed stress".
    • BEST CRITICAL: hence by definition and since its inception, stress is ALWAYS associated with chronic disorder! Hence, diagnosing a patient with stress when he has a chronic disorder is a useless oxymoron!
    • by definition, the concept of stress models the common pattern of symptoms displayed by individuals afflicted with various chronic disorders. Hence, it's a tautology to qualify any chronic sufferer as being stressed.
  • Il a même créé le concept de bon et de mauvais stress! "Selye met de l'avant le concept d'Eustress qui signifierait bon stress. Selon lui, il existerait un stress positif et un stress négatif. Un stress négatif ne permettrait pas un retour à l'équilibre, mais alimenterait l'état de détresse de l'organisme causé par les stimuli. Il est cependant possible de changer un stress négatif en stress positif10."
  • "Selye has acknowledged the influence of Claude Bernard (who developed the idea of milieu intérieur) and Walter Cannon's "homeostasis". Selye conceptualized the physiology of stress as having two components: a set of responses which he called the "general adaptation syndrome", and the development of a pathological state from ongoing, unrelieved stress."
  • CRITICAL: "Selye discovered and documented that stress differs from other physical responses in that stress is stressful whether one receives good or bad news, whether the impulse is positive or negative. He called negative stress "distress" and positive stress "eustress". The system whereby the body copes with stress, the hypothalamic-pituitary-adrenal axis (HPA axis) system, was also first described by Selye. He also pointed to an "alarm state", a "resistance state", and an "exhaustion state", largely referring to glandular states. Later he developed the idea of two "reservoirs" of stress resistance, or alternatively stress energy." --> stress resistance and stress energy??? WTF! Isn't that pseudoscientific?
  • AND CRITICAL he was also corrupted by Tobacco Industry. The Tobacco Industry paid Selye, the father of the concept of stress, to claim that cigarettes weren't harmful but it was the stress! That's where the stress theory comes from! Cigarettes don't kill, it's stress! Or maybe cigarettes smokers don't have a big enough stress energy reservoir! https://en.wikipedia.org/w/index.php?title=Hans_Selye&oldid=997686551#Controversy_and_Involvement_with_the_Tobacco_Industry
  • BEST CRITICAL: "His last inspiration for general adaptation syndrome (GAS, a theory of stress) came from an endocrinological experiment in which he injected mice with extracts of various organs. He at first believed he had discovered a new hormone, but was proved wrong when every irritating substance he injected produced the same symptoms (swelling of the adrenal cortex, atrophy of the thymus, gastric and duodenal ulcers).[9] This, paired with his observation that people with different diseases exhibit similar symptoms, led to his description of the effects of "noxious agents" as he at first called it. He later coined the term "stress", which has been accepted into the lexicon of most other languages.[10]" --> PROOF that he confused oxydative stress with emotional stress during his animal experiments!
    • "Selye has acknowledged the influence of Claude Bernard (who developed the idea of milieu intérieur) and Walter Cannon's "homeostasis". Selye conceptualized the physiology of stress as having two components: a set of responses which he called the "general adaptation syndrome", and the development of a pathological state from ongoing, unrelieved stress." --> without any proof! It's an assumption that is still yet unproven 70 years later!
• BEST CRITICAL ME: Also something I did not mention but that I always keep in mind is that the [placebo and nocebo effect were not demonstrated to have any effect on biology, but only on subjective measures](https://www.cochrane.org/CD003974/COMMUN_placebo-interventions-for-all-clinical-conditions). The claim that psychological states can affect biological tissues is a staple of psychoanalysis and psychosomatic proponents, and that's why whenever there is a similar claim, I suspect that psychoanalysis is behind, and for stress this is in fact the case. Small world for frauds. And yes, I do not have an issue to be so decisive when Karl Popper was as much, I (try to) require the same amount of evidence as he does to accept the scientific validity of a claim.
• BEST CRITICAL academic source: The “Father of Stress” Meets “Big Tobacco”: Hans Selye and the Tobacco Industry, 2011 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3036703/
  • "The concept of stress remains prominent in public health and owes much to the work of Hans Selye (1907–1982), the “father of stress.” One of his main allies in this work has never been discussed as such: the tobacco industry.

• Stress and adrenaline got popularized by both Hans Selye, the father of the concept of stress, and then Archibald Hart, another psychologist with no peer-reviewed research: https://books.google.be/books?id=KwLQ_9BYBZcC&pg=PT103&dq=%22many+get+a+second+wind+late%22&redir_esc=y#v=onepage&q=%22many get a second wind late%22&f=false

• TOSSEARCH: mast cells degranulation is really proven to cause dermatitis? NO!
  • Finally, and most importantly, this study only shows that a link between stress and mast cells degranulation. But [mast cells degranulation is not necessarily involved in atopic dermatitis](https://pubmed.ncbi.nlm.nih.gov/14698841/).

• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3422784/ (already in VliDacMEl)
  • BEST REVIEW: Mast cells and histamines production biology: "Histamine is produced not only by mast cells but also by other cells of epidermis and dermis and acts locally in the epidermis and dermis by binding to H1-H4 receptors. Histamine targets not only endothelium and smooth muscles of blood vessels but also modulates function of keratinocytes, melanocytes and cells of skin immune system. It affects intracellular signaling cascades, cell proliferation and melanogenesis. Histamine is upregulated in melanoma cells. It signals mainly via H4 receptor on the cells of the immune system and affects their migration and cytokine secretion patterns. Moreover, it modulates Th2 type immune responses and antimicrobial peptide expression. Thus, histamine is an important part of the neuro-immunoendocrine system of the skin (Slominski and Wortsman, 2000) with local and systemic effects (Figs. 1, ​,22)."
  • but mast cells degranulation not involved in these diseases? "These facts can help us better understand a variety of sterile inflammatory conditions, such as multiple sclerosis (MS), migraines, inflammatory arthritis, atopic dermatitis, coronary inflammation, interstitial cystitis and irritable bowel syndrome, in which mast cells are activated without allergic degranulation." https://pubmed.ncbi.nlm.nih.gov/14698841/

• Great Lead: psychological stress via the downregulation of mast cells may decrease the skin barrier and increase its propensity to be infected. In other words, psychological stress increases the risk of being infected, it's not just triggering rashes per se, it just opens the gates for an infectious agent, so that there is something else to treat. https://dx.doi.org/10.1172%2FJCI31726
  • And interestingly the antimicrobial barrier can also be broken by overuse of antimicrobial soap as is common during the pandemic.
  • BEST CRITICAL ME: Given the new infos, I would like to modify my statement and position: [emotional stress may reduce skin's antimicrobial barrier and hence open it to infectious agent](https://dx.doi.org/10.1172%2FJCI31726), although it doesn't appear emotional stress can trigger eczema flares since it appears [it does not significantly elevate histamine levels](https://doi.org/10.1007/BF02007774). And this only applies to skin as its links to the hypothalamic–pituitary–adrenal axis and mast cells are well established.

• Placebo response in phase 2 and 3 trials of systemic and biological therapies for atopic dermatitis — a systematic review and meta-analysis, 2019 https://doi.org/10.1111/jdv.16163

• Atopic dermatitis = eczema: https://doi.org/10.1007/s00403-020-02165-z

• Confirmation stress management = psychosomatic theory: "Psychosomatic counselling is recommended especially in stress‐induced exacerbations.", in European guidelines: https://doi.org/10.1111/jdv.14888
  • Consensus‐based European guidelines for treatment of atopic eczema (atopic dermatitis) in adults and children: part II, 2018 https://doi.org/10.1111/jdv.14888
  • Totally biased by the prevalence of psychodermatology field in Germany! They want to protect their jobs! Proof: the whole Psychosomatic intervention section and guidelines. First they recommend it for emotional stress, but then provide no evidence (the closest one being that relaxation techniques MAY be more effective than discussion only, which in itself is likely not helpful at all to reduce symptoms). Then in their guidelines they state that relaxation techniques are recommended! WTF! Where's the GRADE system? This guideline is a shame for this field!
  • Also note that nearly ALL psychosomatic therapies results are on CHILDREN! Of course, children are super malleable and suggestible, it's super easy to get improvements with them by doing almost anything!

• Atopic dermatitis (eczema) is SUPER prevalent and flares are SUPER often: https://pubmed.ncbi.nlm.nih.gov/16815160/
  • "Atopic dermatitis (AD) is increasingly common, with a point prevalence of more than 30% in some countries, and is characterized by visible skin lesions and intense itching."
  • "During each year, patients spend, on average, 1 of 3 days in flare."
  • "On average, patients and caregivers delay initiating treatment for 7 days after onset of a flare. Only 24% of patients and caregivers feel confident they can manage AD flares adequately. Seventy-five percent of caregivers and patients feel that being able to effectively control AD would be the single most important improvement to their or their child's quality of life."

• Toread: Stress vague word for complex diseases + assumed it was both the cause and effects of all those diseases https://amp.theguardian.com/society/2016/feb/14/workplace-stress-hans-selye
  • "What he needed, he decided, was a name for all those diverse agents and the apparently nonspecific effects they produced, effects that he by now had hypothesised – he was not a cautious man – were a root cause of “high blood pressure, angina, disorders of the digestive system, kidney diseases, diabetes, rheumatism, certain cancers and most nervous and mental disorders”. By 1946 he had landed on the single word he needed to get his idea across. He called his syndrome, both cause and effect, “stress”. Selye never looked back."
• Stress heart history: https://www.scielo.br/scielo.php?pid=S0102-79722016000104301&script=sci_abstract
• Stress in gastroenterology https://f1000research.com/articles/6-2149
• BEST CRITICAL: extreme idea that stress was causing all the observed diseases! It's Selye himself who did this leap of faith! https://brainconnection.brainhq.com/2013/04/05/hans-selye-the-discovery-of-stress/

• Reorganize psycho section by adding subsections: the roots of the psychological arguments: the psychosomatic theory etc. Plus conclusion
• Conclusion:
  • The widespread misconception that the "mind" can affect the body's biological tissues and processes is rooted in the psychosomatic theory of psychoanalysis. Despite being conceived centuries ago and lots of practitionners attempts, this has yet to be solidly demonstrated, and should is currently unproven despite a widespread common misconception, including by clinical staff, very much like homeopathy. Mind states can affect other mind states, the body can affect the mind states, the environment can affect the mind states, but the mind states cannot affect the body or the environment. This concept is also sometimes marketed as "neural rewiring", which is the idea that training to reach a different mind state can modify the brain and body. This is not how the brain nor neurology works. A common thread is that all these concepts are promoted with very little and very vague descriptions of their theoretical pathways, or when they are detailed, they always involve some kind of "energy" without defining what this mystical energy is (eg, Selye's concept of stress).
  • The problem is not with the existence of stress, as stress reaction to nocious event for the body or mental state indeed exists and can be biologically observed (adrenal glands, HPA axis etc). The issue is to assume that stress is the CAUSE of virtually all diseases: cancer, cardiac, gastric, etc. It's inversing the cause and consequence! Ie, the causality inversion and the universality of the stress response as a cause instead of a symptom. And the major issue is that it's not just some random people who started this wild assumption, but Hans Selye, the author of the concept of stress himself! He was so much into marketing his discovery that he made a logical leap of faith!

• BEST ME CRITICAL: medicine is plagued by the existence of "bullshit diagnoses", diagnoses that are so nondescript that they can be applicable to virtually anyone and have no clinical utility, as they are so nondescript they cannot help with the proper treatment of the underlying cause of the disease. Eg, psychological/emotional stress, eczema, insomnia, psychosomatic disorder, hysteria, idiopathic diseases, etc... All these empty diagnoses share at least one of three logic cardinal sins: 1. they define a disease by the absence of a measurable cause, which is a non sequitur as the existence of something cannot be inferred from the non existence of something else, 2. the range of applicable cases, and the extent to which treating it would improve the person's wellbeing or other afflictions, is largely extrapolated (eg, reducing stress would cure cancer, as Hans Selye himself assumed after a logical leap of faith), 3. their "empirical" proof of existence often relies on subjective measures.
  • Sources for eczema: https://doi.org/10.1007/bf00509073 and https://pubmed.ncbi.nlm.nih.gov/7802166/

• Post-traumatic stress disorder and dissociative disorders are NOT due to stress, that's just "conventional wisdom" that is NOT supported by empirical evidence. Instead, everything points rather to sleep dysregulations and deprivation as the cause for these dissociative symptoms. https://doi.org/10.1177%2F0963721411429457 and https://doi.org/10.3389/fpsyg.2017.02248

• OBSERVATION (and could do a paper on it quite easily): virtually ALL diseases can supposedly be caused by stress. Look at publications or just wikipedia.
  • BEST REF: Sheldon Cohen's glucocorticoid resistance theory is the root of this research line trying to link stress as a direct causation factor of ALL illnesses: https://www.bbc.com/future/article/20120619-how-stress-could-cause-illness and https://pubmed.ncbi.nlm.nih.gov/22474371/
    • "Cohen has been working on stress for 30 years, and despite a fair amount of epidemiological evidence accumulated during this time, he and other professionals have been cautious about accepting a link without firm evidence about a possible mechanism. In a 2007 review of psychological stress published in the Journal of the American Medical Association, Cohen said: “Despite widespread public belief that psychological stress leads to disease, the biomedical community remains [sceptical] of this conclusion.” But speaking now, little more than half a decade later, he takes a rather more positive view. There’s been a shift, he says. A plausible mechanism to explain the effects stress will reinforce it."
    • "While this work confirmed the association between stress and illness, it left Cohen little wiser about the mediating influence. Part of the explanation is quite likely behavioural. Stressed people smoke and drink more. They sleep badly and often take less exercise. All these things have detrimental consequences on your health. But Cohen worked on the assumption that as well as lifestyle issues there are also specific biochemical pathways linking stress and health." → So he IS aware that sleep and lifestyle can mediate this increase in risk but he did not care to test them in his studies!!! LOL
    • "One of the key molecular players in these pathways is also among the most familiar of the body’s signalling chemicals: cortisol, a steroid commonly referred to as a “stress hormone”. Produced by the adrenal gland in response to stress, the original view of cortisol was straightforward: more stress prompts your body to make more cortisol, and the higher the level of cortisol in your circulation, the worse the outlook for your health.

• Lol idem, he started with the flu and then went on to test cancer.
• "Colds may be unpleasant but, in the scheme of things, they’re hardly a big deal. So what of more serious disease? The real importance of the work, says Cohen, lies in its relevance to the many other conditions in which inflammation is a factor. “It’s a model that can be applied to many diseases. Cardiovascular disease, asthma, autoimmune disease, diabetes…The regulation of inflammation plays a big role in the progression of all of them.”
• "Steptoe agrees. “People are already interested in inflammation in relation to chronic diseases such as diabetes and coronary heart disease,” he says. And Phil Evans too joins the chorus of acceptance. Cohen’s conclusions, he says, are “potentially generalisable to a range of other inflammatory illnesses”.

• "After thirty years of exploration, Cohen says he remains undaunted by the prospect that definitive experiment might elude him, and he laughs off any suggestion of frustration. “When you work in chronic stress,” he says, “you don’t expect to be able to do experiments like that.”"
• The problem is that even if we assume that the glucocorticoid resistance theory is true, these experiments do NOT show that it's emotional/psychological stress that is producing glucocorticoid resistance! It may very well be sleep or risky lifestyle behaviors, with stress only being a proxy to indirectly measure these! Also this very much sounds like the astroglial cells removal mistake of the past, before it was understood they were actually helping. So he also does not demonstrate a causal link between glucocorticoid resistance and worsening of symptoms, it may very well be the opposite and this would actually be MUCH more intuitively valid: that more severe diseases are accompanied with greater inflammation and hence more cortisol production to try to reduce it. He did NOT demonstrate that cortisol is worsening inflammation.
• Again, he's using subjective measures of health, and publishing in... a psychosomatic journal! LOL! https://pubmed.ncbi.nlm.nih.gov/26397938/
• LOL PROFESSOR OF PSYCHOLOGY! LMAO! It's NOT biology!
• LOL he is not the first! Before, the SAME theory was applied on depression! https://doi.org/10.1192/bjp.164.3.365
• "In recent years the classic view that glucocorticoids, the adrenal steroids secreted during stress, are universally anti-inflammatory has been challenged at a variety of levels. It was first observed that under some circumstances, acute GC exposure could have pro-inflammatory effects on the peripheral immune response. More recently, chronic exposure to GCs has been found to have pro-inflammatory effects on the specialized immune response to injury in the central nervous system. Here we review the evidence that in some cases, glucocorticoids can increase pro-inflammatory cell migration, cytokine production, and even transcription factor activity in the brain. We consider how these unexpected effects of glucocorticoids can co-exist with their well-established anti-inflammatory properties, as well as the considerable clinical implications of these findings." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1997278/
  • Also mentions Selye lol: "The pioneering physiological investigations of Walter Cannon and Hans Selye in the early 20th century began to define precisely what is involved in the stress- response. “Fight or flight,” as described by Cannon, reflects the actions of both catecholamines and GCs (although the latter were unknown until the work of Selye, some years later) to immediately increase cardiovascular output and blood flow to the brain and skeletal muscles. This is predominately mediated by catecholamines, although GCs potentiate their effects."
  • "Hans Selye in the 1930’s obtained the first evidence for GCs being anti-inflammatory, noting that sustained stress or GC exposure caused involution of the thymus."
  • Stress pro-inflammatory response = immunity reduction. So you don't want to use corticosteroids on top if you think it's due to stress!!! WTF!
  • "These well-characterized anti-inflammatory effects of GCs make it seem likely that stress is also anti-inflammatory. However, as discussed next, the effects of stress are not that simple and in many cases can be divided based on the duration of the stressor."
  • stress and eustress (bad and good stress) now are qualified scientifically as acute stress and chronic stress.
• BEST CRITICAL: immune system and glucocorticoid secretion (cortisol) are also regulated by the circadian and ultradian rhythms, and disturbances affect locomotor and other health aspects! So it's not necessarily stress but simply a result of circadian dysregulation! So another confound S. Cohen and others did not account for! https://doi.org/10.1016/j.ynstr.2014.10.008
  • "These effects are mediated in part by glucocorticoids, which are released from the adrenal gland in response to a stressor and also oscillate in synchrony with diurnal rhythms."
  • Journal Neurobiology of Stress
  • "We conclude by considering how disrupted glucocorticoid oscillations may contribute to the pathophysiology of depression and PTSD in vulnerable individuals, and how circadian rhythm disturbances may affect non-psychiatric populations, including frequent travelers, shift workers, and patients undergoing treatment for autoimmune disorders." → links with PTSD and depression
  • "circadian glucocorticoid oscillations"
  • "In a recent meta-analysis of 8521 subjects across 107 independent studies, the most consistent findings were that chronic stress increases the total daily output of cortisol (the principal glucocorticoid in humans), flattens the diurnal rhythm, and reduces the amplitude of the circadian peak (Miller et al., 2007)." WTF???
    • LOL not at all, that's a misquoting: "For stress that evokes feelings of loss, a flattened cortisol profile may reflect social isolation or a withdrawal from regular social activities. Social contact with others programs many of the body’s circadian rhythms, including those regulating the secretion of hormones like cortisol (Stetler, Dickerson, & Miller, 2004; Stetler & Miller, 2005). Thus if major losses significantly alter an individual’s social activities, this could result in a dysregulated cortisol rhythm that remains flat across the day, rather than a diurnal profile that is regulated by social contact. A major difficulty with the emotion findings is that they were not robust across outcomes." https://pubmed.ncbi.nlm.nih.gov/17201569/
    • BEST CONFIRMATION: same question raised about circadian dysregulation confounding results about chronic stress: "The same issues pertain to biological mechanisms that are more proximal to the HPA axis. Little theory exists to specify what goes awry in the system when it faces chronic stress. Is the high, flat pattern of cortisol secretion across the day a result of dysregulation in the suprachiasmatic nucleus, the endogenous circadian pacemaker that regulates HPA rhythms? Or does chronic stress leave the suprachiasmatic nucleus’s functions intact, and instead modify downstream structures like the pituitary and/or adrenal glands?"
  • Circadian rhythm disturbance has similar effects to chronic stress, MAYBE BECAUSE IT'S THE SAME ROOT CAUSE: SLEEP DEPRIVATION! But circadian rhythm disturbance produces sleep deprivation, whereas chronic stress is induced by sleep deprivation. "And in an environmentally induced model of circadian rhythm disruption, mice that were housed on a shortened 20-h light–dark cycle exhibited learning and structural connectivity deficits comparable to those seen in chronic stress states, including apical dendritic atrophy in mPFC pyramidal cells and PFC-dependent cognitive deficits (Karatsoreos et al., 2011)."
  • But at least they recognize that it's only correlative, not causative (but you need to read to the very end): "Perhaps most importantly, many of these links remain purely correlative, and it will be critical to test whether and how changes in synaptic remodeling directly affect the function of cortical microcircuits, the integration of information across neuroanatomically distributed networks, and the emergence of behavioral effects and psychiatric symptoms."
• Neurobiological links between stress and anxiety https://doi.org/10.1016/j.ynstr.2019.100191
• LOL even COVID-19: https://doi.org/10.1016/j.ynstr.2021.100296
• ALL inflammatory diseases are caused by stress according to this journal: https://www.sciencedirect.com/journal/neurobiology-of-stress
• Roadmap for optimizing the clinical utility of emotional stress paradigms in human neuroimaging research https://doi.org/10.1016/j.ynstr.2018.05.001
• Syndromes of Glucocorticoid Resistance, 1993 https://doi.org/10.7326/0003-4819-119-11-199312010-00009
• BEST CRITICAL REF: systematic reviews finds "no evident positive correlation between glucocorticoid resistance and inflammation" https://doi.org/10.3389/fpsyt.2019.00423
• BEST REF: another systematic review on clinical value of anti-stress therapies, they improve only subjective measures of stress but not physiological stress! "However, reappraisal intervention groups did not outperform control groups on measures of physiological stress, with standard differences of -0.084 (SE = 0.135, 95% CI = -0.349 to 0.180; z = -0.627, p = .531)." https://doi.org/10.1371/journal.pone.0212854
• BEST REF: "Despite widespread public belief that psychological stress leads to disease, the biomedical community remains skeptical of this conclusion." https://doi.org/10.1001/jama.298.14.1685
• Terminology was defined by Selye + polysemy of (emotional) stress: Confusion and controversy in the stress field, 1975 "The continued use of the word "stress" for the nonspecific response to any demand is deemed most desirable. The once vague term can now be applied in a well-defined sense and is accepted in all foreign languages as well, including those in which no such word existed previously in any sense. Subdivision of the stress concept has become necessary as more recent work has led to such notions as "eustress," "distress," "systemic stress" and "local stress." Confusion between stress as both an agent and a result can be avoided only by the distinction between "stress" and "stressor". It is explained that the stress syndrome is--by definition--nonspecific in its causation. However, depending upon conditioning factors, which can selectively influence the reactivity of certain organs, the same stressor can elicit different manifestations in different individuals." https://pubmed.ncbi.nlm.nih.gov/1235113/
  • BEST REF CONFIRMATION: ambiguity and vagueness of the concept of medical stress and its lexicon: "The terminology relating to 'psychological stress' is so confused and ambiguous that research in this field - and application of its results - must surely be hampered. Relevant words with conflicting usages and scientific definitions include 'stress' itself, 'stressor', 'strain', 'challenge', 'demand', 'threat', 'resource', 'coping' and 'mental load'. 'Stress' and 'anxiety' are often confounded. Because of this confusion it can be hard to decide how closely one view of stress matches another and to integrate the variety of published conceptual frameworks. The word 'stress' is therefore useful only as a deliberately vague umbrella term. Nevertheless there is moderate consensus in the literature that the mental state characterizing 'stress' (which, to avoid ambiguity, we call 'psystress') results from awareness that one is not coping with something, a perceived stressor, that relates to a need that is deemed personally important. Other definitions and models of 'stress' are compared. 'Stress' is often applied to situations that actually cause pleasurable excitement. We propose the unambiguous term 'euchallenge' for such enjoyable demands, because 'eustress' and 'challenge' also have other meanings. Supposedly adverse stress responses are sometimes studied using tasks or situations, which are assumed to be stressors, but which for some individuals might be euchallenges or in others produce apathy through perceived irrelevance to personal needs. Much research utilizes self-report stress questionnaires and many of these are composed with poor regard to theory. Some, for example, mix psystress causation with a variety of response factors or pay inadequate attention to 'chronic' and 'acute' time scales. Testees may even be required to interpret words on which psychologists themselves disagree - notably 'stress' itself. It is important, therefore, to evaluate carefully every test in the context of its purpose, but, most importantly for scientific advance, to relate it to a comprehensive testable theoretical model." https://pubmed.ncbi.nlm.nih.gov/19932940/
    • BEST CRITICAL ME: LIMITATION OF STRESS STUDIES: so this review shows and even states it clearly that the terminology used in questionnaires is not even precise enough to study stress!
  • Review 1975 A historical view of the stress field "An analysis is presented of selected aspects of stress theory and research in biology and medicine, both before and after the introduction of Selye's stress formulations, which have been of major importance in the development and popularity of this research area. An attempt is made to explore some possible sources of present confusion and controversy in the stress field, with a view to the development of new research strategies that may enable us to clarify, update, and revise stress concepts and to facilitate future progress. In particular, it is suggested that an experimental reevaluation of the concept of the non-specificity of pituitary-adrenal cortical response is a matter of particular strategic importance, if we are to move out of the present prolonged period of stalemate and confusion over stress theory and terminology. Recent experimental studies which suggest that the nonspecificity concept may have been applied erroneously to lower level physiological mechanisms, rather than to higher level psychological processes, are reviewed. The possible implications of this development are discussed in terms of clarifying current concepts and providing guidelines for future lines of approach in stress research." https://pubmed.ncbi.nlm.nih.gov/798012/
• TOSEE REVIEW: Physiological and psychological conceptions of stress have evolved independently within their respective fields. https://pubmed.ncbi.nlm.nih.gov/7264287/
• "Selye then developed his theory of general adaptive syndrome (GAS) in 1936, known today as "stress response". He concluded that humans exposed to prolonged stress could also experience hormonal system breakdown and subsequently develop conditions such as heart disease and elevated blood pressure.[3] Selye considered these conditions to be "diseases of adaptation", or the effects of chronic stress caused by heightened hormonal and chemical levels.[2] His research on acute and chronic stress responses introduced stress to the medical field.[2]" https://en.wikipedia.org/wiki/Chronic_stress
• Critique de la mesure du stress https://hal.archives-ouvertes.fr/hal-00755690

• Horton: Psy and biomedical reproducibility issues and 50% of medical research is false, fashionable trends https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572812/
  • To find real results, it's important to collaborate rather than compete in the medical field: "He concludes that scientists have incentives to be productive and innovative but no incentives to be right. He muses on removal of incentives, emphasizing collaboration rather than competition, improving research training and mentorship, funding studies that attempt to replicate published data. Horton ended by noting that it is a good first step to recognize the problems but no one seems ready to begin the task of reversing the trends."
• Critique of PTSD in DSM-V: https://doi.org/10.1111/j.1749-6632.2010.05699.x and https://doi.org/10.1177%2F0022167805280265
• Critique of work stress (chronique stress): https://doi.org/10.1111/j.1744-6570.1984.tb00528.x
• The diagnosis of acute stress disorder has no clinical value: https://pubmed.ncbi.nlm.nih.gov/10553729/

---

MY WRITING ABOUT STRESS:
https://www.reddit.com/r/N24/comments/ljdint/dissociative_disorders_as_observed_post_trauma/gndzdr4/?context=8&depth=9 and https://archive.is/W16Ed

I'm not sure I understand your question, so please forgive me and precise your thoughts if I missed the point in my reply below.

If your question is whether dissociative disorders are currently assumed to stem from stress, that's the case, and this is what this paper (and other works of the same author but also a few others) challenge.

If your question is whether this is pertinent to N24, yes I think so. There are several individuals with N24 and a dissociative disorder, and I would argue the prevalence may be bigger than in the general population. This would not be surprising, as it's known that patients with [DID also have "complex sleep disorders"](https://www.isst-d.org/wp-content/uploads/2019/02/GUIDELINES_REVISED2011.pdf). And I bet that these "complex sleep disorders" are for a good chunk undiagnosed circadian rhythm disorders.

If your question is whether the medical concept of stress is pertinent for N24: heck yeah. When you go to a specialist to treat your circadian rhythm disorder, you are guaranteed to hear about "managing your stress" at some point. And this is utterly useless, and I would say even detrimental as the patient then spend their effort on something that has no chance of providing any relief for their disorder. Furthermore, if your therapy fails, this will be "because you're too stressed". The medical concept of emotional/psychological stress is I am convinced the biggest pseudomedical scam of this century. But more on that later, elsewhere, in the rest of the series ;-)

*(meanwhile you can read the [Wikipedia page on the creator of emotional/psychological stress](https://en.wikipedia.org/wiki/Hans_Selye), that's already enough to raise huge red flags!)*

No! I mean the very concept of medical stress is a scam! It does not exist! Oxydative stress and physiological stress as a generic adrenergic response to any kind of attack are real, but the very concept that stress is a medical entity in and of itself that should be treated is a scam!

To make an analogy: all patients with a pulmonary disease cough. So if we treat the cough with syrup, they should be cured and live a long happy life, right? Of course not. This inversion of reasoning is exactly what Hans Selye did with stress.

Indeed, he took a real response of the body and turned it upside down to serve his benefits and career. Both kinds of stress are universal responses (oxydative stress at the molecular/chemical level, physiological stress at the biological level). But they are just that: responses. Treating the response is NOT going to cure the root illness that caused the response.

Hans Selye firmly believed that stress was not just a response but also the root cause of ALL diseases, including cancer! Not just some forms of cancer, ALL cancers! And ALL other diseases! That's how much delusional he was! He convinced himself that curing stress was THE miraculous treatment to end ALL diseases.

Beyond the logical fallacy of his reasoning, I did my due diligence, and found no empirical evidence for this claim. Which says a LOT. Because stress is over-investigated, it's a so well known concept there are lots of fundings and lots of studies done on it. Yet, none found any significant effect on objective metrics when properly controlled (check out the systematic reviews). Even for cardiac illnesses! It's just a medical scam with no evidence supporting it despite hundreds of scientific teams trying to research it for the past century.

Despite what you seem to think, my very skeptical position is in fact quite common in my field, as I am a biomedical researcher:

> Despite widespread public belief that psychological stress leads to disease, the biomedical community remains skeptical of this conclusion.
https://doi.org/10.1001/jama.298.14.1685

Why is that so? At the conceptual level, emotional/psychological stress is flawed, it's so vague that it has no clinical value:

> The terminology relating to 'psychological stress' is so confused and ambiguous that research in this field - and application of its results - must surely be hampered. [...] 'Stress' and 'anxiety' are often confounded. Because of this confusion it can be hard to decide how closely one view of stress matches another and to integrate the variety of published conceptual frameworks. The word 'stress' is therefore useful only as a deliberately vague umbrella term.
https://pubmed.ncbi.nlm.nih.gov/19932940/

Which can be seen in practice, as upon scrutiny of a systematic review, only subjective measures of stress (the same ones used to diagnose stress and claim its existence - see the circular reasoning?) are improved with anti-stress therapies, but not objective measures of physiological stress, for which anti-stress therapies do not perform better than control groups who did not get any therapy.

> However, reappraisal intervention groups did not outperform control groups on measures of physiological stress
https://doi.org/10.1371/journal.pone.0212854

Surely, if stress is really a medical entity, anti-stress therapy would have measurable improvement effects on the patient. But that's not the case. The very therapies that were designed to treat stress aren't improving even the objective measures of stress, and we are not even talking here about other outcomes, such as cardiovascular diseases where stress is considered since a long time to be a BIG factor, [some psychologists even claiming in the past that there was a "coronary personality" that predisposed to CVDs](https://pubmed.ncbi.nlm.nih.gov/6040635/).

But here's what a Cochrane systematic review found:
> This updated Cochrane Review found that for people with CHD [coronary heart diseases], there was no evidence that psychological treatments had an effect on total mortality, the risk of revascularisation procedures, or on the rate of non‐fatal MI, although the rate of cardiac mortality was reduced and psychological symptoms (depression, anxiety, or stress) were alleviated; however, the GRADE assessments suggest considerable uncertainty surrounding these effects.
https://doi.org/10.1002/14651858.CD002902.pub4

Idem for anxiety, which is often mixed up with stress by psychologists:
> The association of anxiety with adverse outcome in patients with existing CHD is similarly mixed. For example, in some studies generalized anxiety disorder is associated with increased risk for recurrent events and mortality (HRs = 1.7–1.9),71,72 but others have found no association,73 or even a protective effect for this anxiety disorder.
https://doi.org/10.1093/ajh/hpv047

So why are some studies finding significant results (often unproperly controlled and with subjective scales though)? Because of bias:
> The relation between higher stress, angina, and some categories of hospital admissions probably resulted from the tendency of participants reporting higher stress to also report more symptoms. The lack of a corresponding relation with objective indices of heart disease suggests that these symptoms did not reflect physical disease. The data suggest that associations between psychosocial measures and disease outcomes reported from some other studies may be spurious.
https://doi.org/10.1136/bmj.324.7348.1247

In other words: the psychology researchers find what they are looking for, by making the tools to ensure that. Even if there is nothing to find.

This issue is not new and not even limited to stress/anxiety, or even to psychology for that matter. [Psychology is well know for its huge array of biases, casting huge doubts over ALL results from this field of study](https://en.wikipedia.org/wiki/Psychology#Contemporary_issues_in_methodology_and_practice) (which is unfortunate since there are some really great true results from this field!). But the same applies for medical research, where [some very established scientists state they believe that up to 50% of all medical research results are... plainly false](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4572812/). One of the stated reasons is the seeking of fashionable research trends, and the lack of incentive to produce true results, the only incentives are to produce more results and to be innovative. The results from meta-scientific studies support this claim, with [empirical estimates ranging from 20% to 75% of all medical science research being false or unreproduced, including therapies](https://en.wikipedia.org/wiki/Replication_crisis#In_medicine).

In the end, for the issue at hand, the lack of empirical findings support the claim that the medical concept of stress has no clinical value. This is for example the conclusion of [this review about acute stress disorder](https://pubmed.ncbi.nlm.nih.gov/10553729/).

---

So the above lays out a critique of psychological stress as a clinical, medical entity to treat, based on methodogical issues (in additional to the logical issues I have outlined in my above replies).

But beyond that, [Hans Selye, the author of the concept of stress, was corrupted](https://doi.org/10.1111/bjd.13084). He lied in his national hearings in Canada to protect Big Tobacco, who paid him for counselling. How did he protect them? By claiming that regulating, or banning, cigarettes would "increase the stress of the population" and hence be detrimental to the public health.

So I guess that settles it: we should all smoke to reduce our stress levels, we will certainly live longer thanks to the stress reducing effect of cigarettes, as Hans Selye himself stated ;-)

(PS: I was not always skeptical. I only became such a fierce opponent of the medicalization of stress since I started to investigate it as a potential factor to control and target to improve the management of non-24. But I only found lack of evidence and pseudoscientific, sometimes mystical claims, such as Hans Selye's claims of positive stress energy and negative stress energy - note the term energy, typical of pseudomedical theories)

----

• I'm not on a mission to prove that stress is a scam, it's just that it was necessary for me to know whether stress (and other psychological conditions) was something that was necessary to be accounted for in an effective therapy for circadian rhythm disorders. From my literature review, they are not, and so the circadian rhythm disorder can be treated independently from any comorbid psychological disorder.
• BEST CRITICAL REF: clinical practice lags behind research for decades for most topics, and up to centuries in some cases: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3241518/
• Plan:
  • generic response to any insult, whether physiological or mental, finding by Hans Selye
  • emotional stress = psychological stress, surprisingly, not only physiological insults such as cancer and cardiac arrests elicited the stress response, but also mental threats and insults. This is where emotional stress, also called psychological stress, born.
  • it must be differenciated from oxidative stress which is simply another word for the chemical reaction that is oxidation.
  • hypothesized eustress and distress (positive stress energy and negative stress energy). Unclear what he meant by "stress energy" although energy is always a sign of pseudomedical procedures.
  • went further by doing a leap of faith in his logical reasoning, by starting to claim that stress was not only a generic response found in all diseases: it was also the cause. Cancer, diabetes, epilepsy, cardiovascular diseases, you name it: they can all be cured by treating stress, according to Hans Selye. One has to wonder if the near hundred of books he published, among which several best sellers, played a role in his advocacy of his own "star theory".
  • found that the HPA axis and cortisol were the key pathway and hormone biologically characterizing the stress response. The other guy made the glucocorticoid theory.
  • But empirical experiments shown that cortisol was in fact a strong antioxydant! It was repairing the body and allow it to be more resilient to insults. Where was the negative stress energy, were wondering the stress proponents? Well, maybe a little bit of stress is good, but too much stress is bad? That's the basic premisse for the rebranding of eustress and distress energies as the more scientifically acceptable acute stress and chronic stress, where acute stress is good, but chronic stress is bad because of cortisol overload.
  • Unfortunately, the stress proponents have a hard to to scramble together some empirical evidence. They only present non controlled studies, or are using subjective behavioral assessment scales even when objective methods exist, and rely only on correlational studies since causational is either difficult or provides no significant result, or are using small effect sizes. Often, several or multiple of these flaws are present, despite being known flaws to avoid in any scientific research and part of any graduate program of any university.
  • claim diseases which involve HPA in their pathogenesis can be caused by stress and treated with antistress therapies. The issue with that reasoning is that, by definition, ALL diseases involve the HPA, since stress is a generic response to any insult. Hence, this is yet another example of circular reasoning: we know that all diseases involve the HPA, and if a disease involve the HPA then it can be treated by stress, then all diseases can be treated by stress. The problem is the middle proposition, although all diseases do indeed involve the HPA, this remains a response, there is no proof to this day that 1) the HPA and cortisol, whether acute or chronic, has any effect other than protective for the biological system, 2) switching off the HPA and cortisol would improve the disease, as this would imply that stress participate in the pathogenesis of the disease rather than being a (generic) epiphenomenon, the latter being amply demonstrated, contrary to the former.
  • Proponents will often use the example of tobacco: although it is nowadays well accepted that tobacco can cause lungs cancer, there is no way to prove that causally as we have to rely on epidemiology, since we can't subject a human to tobacco to see if they develop a lung cancer, we cannot do a RCT study. This is only partially correct, and hence factually incorrect. Although we cannot test on humans, we can subject human lungs cells to tobacco smoking and see what happens: of course they develop a carcinomic mutation. We can also subject animals to tobacco smoking, whether rats but also primates (although this is ethically unacceptable for obvious reasons, but it wasn't so in the past). Hence, we can and have already perfectly well tested and verified that tobacco can indeed cause lungs cancer.
    • But emotional stress cannot be tested on cells, as it involves psychology. But it can be tested on animals, although it's more difficult: how do you assess whether an animal is stressed? How do you cause an animal to be stressed?
    • A common approach is to disturb the animal during their sleep. Which works wonderfully to produce significant results. But of course, the sleep disturbances are never taken into account.
  • Best evidence is that antistress therapies do not work. Which suggest that stress is not a factor for effective therapies, and that the causal factor(s) is(are) elsewhere. (TOFIND SOURCE).
    • Studies finding that antistress therapies work are often uncontrolled. The few that are controlled find counter-intuitive or even antiresults, such as a RCT on gratitude meditation showing participants in this group became actually less altruistic after the intervention compared to controls: https://doi.org/10.1371/journal.pone.0207765
  • The author is convinced that all the significant results for stress actually stem from unaccounted sleep disturbances due to the study's design or observed population, and that if sleep disturbances were taken into account, emotional stress would have no correlation with any affliction apart from occurring, but not predicting anything. In other words, that every significant results about sleep actually qualify effects of sleep deprivation. A great clue is that antistress therapies have never been shown to be effective to treat any non-psychological condition, and even for psychological conditions it remains controversial whether antistress and antianxiety therapies actually do anything apart from changing the subjective perception. Sources:
    • 2020 review arguing emotional stress can cause cardiac injuries (but it's more theoretic than anything else): https://link.springer.com/article/10.1007/s11886-020-01406-x → this is just one example of how prevalent is the belief that stress can cause cardiac issues. Indeed, since the stress concept, or even anguish, were coined, the most obvious disease category associated is heart disorders.
    • "Only European guidelines for cardiovascular disease prevention acknowledge stress as a clinically meaningful risk factor in individuals with a high overall risk of cardiovascular disease or with established cardiovascular disease" https://doi.org/10.1038/nrcardio.2017.189
    • > This updated Cochrane Review found that for people with CHD [coronary heart diseases], there was no evidence that psychological treatments had an effect on total mortality, the risk of revascularisation procedures, or on the rate of non‐fatal MI, although the rate of cardiac mortality was reduced and psychological symptoms (depression, anxiety, or stress) were alleviated; however, the GRADE assessments suggest considerable uncertainty surrounding these effects. https://doi.org/10.1002/14651858.CD002902.pub4
    • Idem for anxiety, which is often mixed up with stress by psychologists:
      • > The association of anxiety with adverse outcome in patients with existing CHD is similarly mixed. For example, in some studies generalized anxiety disorder is associated with increased risk for recurrent events and mortality (HRs = 1.7–1.9),71,72 but others have found no association,73 or even a protective effect for this anxiety disorder. https://doi.org/10.1093/ajh/hpv047
    • "Stress-management interventions improve the quality of life of patients with advanced coronary heart disease, but effects on disease prognosis have been inconsistent" → Translation: subjectively, using a subjective scale measure of perceived quality of life by the patient, they think that stress-management interventions improved their lives, while objectively they didn't. https://doi.org/10.1038/nrcardio.2012.45
    • "The relation between higher stress, angina, and some categories of hospital admissions probably resulted from the tendency of participants reporting higher stress to also report more symptoms. The lack of a corresponding relation with objective indices of heart disease suggests that these symptoms did not reflect physical disease. The data suggest that associations between psychosocial measures and disease outcomes reported from some other studies may be spurious." https://doi.org/10.1136/bmj.324.7348.1247
    • In the end, for the issue at hand, the lack of empirical findings support the claim that the medical concept of stress has no clinical value. This is for example the conclusion of [this review about acute stress disorder](https://pubmed.ncbi.nlm.nih.gov/10553729/).
    • Takotsubo syndrome: between evidence, myths, and misunderstandings https://www.ncbi.nlm.nih.gov/pubmed/32206851
      • "Overall, a misconception of the disease has evolved: TS is still widely considered a benign, transient, “self-healing” disease with an emotional trigger and “clean” coronary arteries, but without relevant complications. In clinical routine one can even hear opinions such as, “I suspected my patient was suffering from acute myocardial infarction, but after all it was only Takotsubo,” reflecting a significant underestimation. Already the title of the first official description (“Takotsubo-type cardiomyopathy due to multivessel spasm”) [1] contained the term “cardiomyopathy,” suggesting a rather chronic condition, for which no robust evidence exists. In contrast, TS is not a benign disease [9], is not uniformly preceded by an emotional trigger [4], and does not require “clean” coronary arteries (see below). Based on the available evidence on TS, the present review focuses on pitfalls, misinterpretations, and knowledge gaps considered important during diagnosis and management of the disease."
    • starting to shift: Takotsubo Syndrome: Underdiagnosed, Underestimated, but Understood? https://doi.org/10.1016/j.jacc.2016.03.006
      • "In early years, the disease was considered to be typically preceded by an emotional trigger; however, recent studies demonstrate that physical triggers are equally important and that TTS may frequently occur without an evident trigger 1, 3. A hallmark of TTS patients is the predominant prevalence of neuropsychiatric comorbidities 1, 4, 5. However, despite many efforts, the exact pathophysiological mechanism behind TTS remains elusive and primarily relies on assumptions (6)."
      • "A hallmark of TTS is the proposed association with catecholamines, stress, and the autonomic nervous system. From early years on, the disease was believed to be induced by a spillover of catecholamines and to be precipitated by a trigger. Indeed, there are several arguments for a role of the catecholaminergic system in the onset of TTS (20). However, following the famous work of Robert Koch (21), unequivocal evidence is required to prove the relation between cause and effect. We should not be satisfied with associations. For instance, it is true that many patients develop TTS with a stressful trigger. However, about 30% of patients spontaneously develop TTS without any identifiable trigger. Do these patients have a different “TTS-like” syndrome? Probably not. If we also include histories of ACS patients, we would discover lots of “triggers”; thus, there is obviously a relevant awareness bias. On the other hand, TTS research underlines the need for reversion to the classical medical skill of history taking. In a previous study, we could demonstrate a high prevalence of neurological and psychiatric disease in TTS patients, which outnumbered that of ACS patients (1). The present study found a much lower prevalence (about one-third of our numbers). As also stated by the authors, the value of registries critically depends on careful maintenance, and thus, data obtained from registries may significantly differ between studies."
      • "In summary, pathogenesis of TTS appears to be multifactorial. Catecholamine levels, beta-agonist use, triggers, hormone status, and microvascular dysfunction are all true, but probably not sufficient per se to induce TTS. The present study adds to previous data, emphasizing that TTS carries a substantial risk of morbidity and mortality. However, prospective studies are now needed to elucidate pathogenesis and management of this peculiar disease."

Video on Freud Ted animated?

• It's likely again an [introspection illusion](https://en.wikipedia.org/wiki/Introspection_illusion), a cognitive bias we are prone to which makes us confuse cause and effect...
• TOADD: keto diet for psychiatric disorders: https://doi.org/10.3389/fpsyt.2017.00043
• BEST CRITICAL TOADD: evidence that keto diet stabilizes brain networks, which may explain mood stabilization and focus improvement: Diet modulates brain network stability, a biomarker for brain aging, in young adults, 2020 https://doi.org/10.1073/pnas.1913042117
  • "Targeted experiments show that this biomarker for brain aging is reliably modulated with consumption of different fuel sources: Glucose decreases, and ketones increase the stability of brain networks. This effect replicated across both changes to total diet as well as fuel-specific calorie-matched bolus, producing changes in overall brain activity that suggest that network “switching” may reflect the brain’s adaptive response to conserve energy under resource constraint."
  • This confirms a previous hypothesis that ketones "attenuate brain network excitability" and hence further explain their anti-seizure action when used as a treatment for severe epilepsy: https://doi.org/10.1007/s11064-017-2253-5
• TOADD: keto diet, too much protein is not going to get converted to carbs, they contribute very little to glucose it seems contrary to common wisdom:
  • http://journal.diabetes.org/diabetesspectrum/00v13n3/pg132.htm
    • A daily intake of 2,500 calories contributes ~100 g of protein—about twice what is needed to replace protein lost on a daily basis. Excess amino acids must be converted into other storage products or oxidized as fuel. Therefore, in theory, the excess ingested protein could, through the process of gluconeogenesis, produce glucose. This would mean that 100 g of protein could produce ~50 g of glucose. This has been the basis of the statement that if about half of ingested protein is converted to glucose, protein will have one-half the effect of carbohydrate on blood glucose levels. However, this belief has been challenged.
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3636601/
    • "Our results show that the total postprandial contribution of dietary AA to EGP was small in humans habituated to a diet medium-rich in proteins, even after an overnight fast and in the absence of carbohydrates from the meal. These findings question the respective roles of dietary proteins and endogenous sources in generating significant amounts of glucose in order to maintain blood glucose levels in healthy subjects."
• ME: Studies on stress are often (always?) confounded with sleep deprivation. Stress researchers almost never measure nor control the sleep of their participants.

---

> The current rhetoric of stress combined with busy lives and over-burdened jobs encourage people to make sense of their bodily sensations in alternative ways. However, taken out of the context, it might seem that the person denies real and serious symptoms.
https://books.google.be/books?id=YISsqYc72FoC&lpg=PA277&ots=Is6f9uAE1D&dq=chronic+illness,+shame&lr=&pg=PA283&redir_esc=y#v=onepage&q=chronic illness%2C shame&f=false

• Stress studies on insomnia and circadian rhythm disorders are confounded by cortisol being increased by circadian dysregulation! "Chronic jet lag lasting several years decreases cognitive performance in flight crews compared with flight crews routinely crossing less than three time zones (Cho et al. 2000). Moreover, these cognitive decrements were accompanied by higher cortisol levels and temporal lobe atrophy (Cho 2001)." http://learnmem.cshlp.org/content/22/9/426.full
  • The increase in cortisol is dose-dependent on the amount of circadian disruption: http://dx.doi.org/10.1038/88384

• LMAO: study so biased that it's cringey: https://med.stanford.edu/news/all-news/2021/07/mindfulness-training-helps-kids-sleep-better--stanford-medicine-
  • The control and study groups had at baseline very different sleep durations (and likely sleep patterns) and the researchers have no explanation. They still conducted the study and report their results as significant, despite the fact that the baseline condition shows that many uncontrolled factors can explain the resulting difference after intervention, since the groups were already different at baseline.
  • "The researchers hypothesized that children might experience improvements in sleep via reductions in stress. However, the children who gained the most sleep during the study also reported increases in stress, perhaps because the curriculum helped them understand what stress was. Nevertheless, they slept better."
    • LMAO: the children who report increased stress actually sleep better. Nevermind let's ignore that and just claim that the improvement is due to reduction in stress.

My analysis:
The authors contradict themselves at several key points:

1. The difference after intervention is of a similar magnitude as the difference at baseline, so it's unclear whether the end result is due to intervention or simply variability by unaccounted factors:

> At the start of the study, researchers found that children in the control group slept 54 minutes more, on average, and had 15 minutes more REM sleep per night than children in the group that later received the training: Children in the control group were sleeping about 7.5 hours per night, and those in the curriculum group about 6.6 hours per night. The researchers don’t know why children in the two communities, despite similarities in income level and other demographics, had different average sleep times.
>
> But the two group’s sleep patterns evolved differently. Over the two-year study period, among the children in the control group, total sleep declined by 63 minutes per night while the minutes of REM sleep remained steady, in line with sleep reductions typically seen in later childhood and early adolescence. In contrast, the children who participated in the curriculum gained 74 minutes of total sleep and 24 minutes of REM sleep.

2. Their hypothesis of a stress-induced reduction in sleep was contradicted in the end, since children with the highest reported stress also had the best sleep after intervention (and the authors just shave it off...):

> The researchers hypothesized that children might experience improvements in sleep via reductions in stress. However, the children who gained the most sleep during the study also reported increases in stress, perhaps because the curriculum helped them understand what stress was. Nevertheless, they slept better.

In addition, there are two serious limitations:

• Only a very small subset of children were selected (58+57 out of 1000 students).

• The sleep study was done at baseline, 1 year and 2 year after intervention. That's a lot of time during which a lot of other factors can change the children' sleeps:

> From the more than 1,000 third- and fifth-graders taking part in the study, the researchers recruited 58 children who received the curriculum and 57 children from the control group for three in-home sleep assessments, conducted before the curriculum began, after one year and after two years.

This study doesn't seem very convincing, it lacks necessary explanations for the violation of assumptions and why the difference at the end point should be considered more significant than the difference at baseline. Maybe it's because of the too low sample size to robustly demonstrate an effect, or maybe it's a false positive since a lot of factors were left uncontrolled during such a long timeframe.

• Objective stress monitoring based on wearable sensors in everyday settings, 2020 https://doi.org/10.1080/03091902.2020.1759707
  • Using Shimmer 3 and Empathica wearables 24/7 ! More precisely the ECG and PPG and GSR galvanic skin response!

• Interventions for sleep problems during pregnancy: A systematic review, 2020 https://doi.org/10.1016/j.smrv.2019.101234
• Chapter 10 - Sleep and sleep disorders in pregnancy, 2020 https://doi.org/10.1016/B978-0-444-64240-0.00010-6

Burnout and heart rate and stress

• ME: what about the objective effects of psychological stress on the heart rhythm? Well, physical exercise also increases the heart rate, but it's not detrimental to health. Although stress may be modulating the heart rhythm, that does not mean it's harmful.
• Burnout due to stress or sleep deprivation?
  • How does burnout affect physician productivity? A systematic literature review, 2014 https://doi.org/10.1186/1472-6963-14-325
  • BEST CRITICAL: sleep deprivation increases cynicism for medical doctors https://doi.org/10.1007/s40596-014-0093-z
  • "Finally, in 2004 Thomas49 reviewed the literature and showed that the intensity of the workday and its interference with the resident's home life plays a more influential role in burnout than inadequate sleep." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931238/
  • ME: sleep deprivation also affects medical doctors and their empathy... They have a too huge workload. Does not excuse everything but still.
  • "The literature reveals that burnout is prevalent during medical school, with major US multi-institutional studies estimating that at least half of all medical students may be affected by burnout during their medical education. Studies show that burnout may persist beyond medical school, and is, at times, associated with psychiatric disorders and suicidal ideation." https://pubmed.ncbi.nlm.nih.gov/23834570/
  • BEST: also program directors: "Burnout and distress among internal medicine program directors: results of a national survey" 30% report burnout! https://pubmed.ncbi.nlm.nih.gov/23595924/
  • BEST: burnout in medical field is an epidemic, it's the norm: "All US medical students, physicians in training, and practicing physicians are at significant risk of burnout. Its prevalence now exceeds 50%. Burnout is the unintended net result of multiple, highly disruptive changes in society at large, the medical profession, and the healthcare system. Both individual and organizational strategies have been only partially successful in mitigating burnout and in developing resiliency and well-being among physicians. Two highly effective strategies are aligning personal and organizational values and enabling physicians to devote 20% of their work activities to the part of their medical practice that is especially meaningful to them. More research is needed." 2017 systematic review: https://pubmed.ncbi.nlm.nih.gov/28481850/
  • RESULT OF REDUCED WORK HOURS: less burnout and no impact on performance! "Work hour reductions were associated with score decrease (mean difference, −2.73; 95% confidence interval (CI) −4.12 to −1.34; P < .001) and lower odds ratio (OR) for residents reporting emotional exhaustion (42%; OR = 0.58; 95% CI 0.43–0.77; P < .001);" https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5476377/ Systematic review 2017
  • BEST CONFIRMATION: sleep deprivation and circadian misalignment is not sufficiently explored for burnout: "The relation between sleep deprivation and burnout is not only suggested in hypothetical models but also confirmed in observational studies of workers of all types. Models describing the relation between burnout and sleep suggest as potential causative mechanisms of sleep disturbances the following: (1) a chronic depletion of energy stores; or (2) activation of the hypothalamic-pituitary-adrenal axis and increasing levels of bodily stress. Sleep deprivation and burnout are widespread in health-care workers, affecting not only nurses but also medical students, physicians-in-training, and practicing physicians. Although sleep deprivation is associated with clinical burnout, direct studies showing that sleep extension can improve burnout recovery are lacking. Early detection and early intervention to improve both sleep deprivation and burnout are warranted in health-care professionals. Interventions should be directed not only at individuals but also at the entire health system. This review highlights the latest developments and emerging concepts concerning the role of sleep and circadian disorders in physician burnout." The Impact of Sleep and Circadian Disorders on Physician Burnout, 2019, https://doi.org/10.1016/j.chest.2019.07.008
  • Correlated progression of sleep deprivation and emotional disturbances and burnout/physical exhaustion along the years of medical school: "The prevalence of chronic sleep deprivation, depression, burnout, and empathy increased from baseline to year end. Specifically, the prevalence of "high" scores changed for chronic sleep deprivation (9% to 43%, p = .0001). The prevalence of moderate depression increased from 4.3% to 29.8% (p = .0002). Only 4.3% reported a high level of burnout initially compared with 55.3% at year end (p < .0001). Scores that were originally more favorable than general population norms (p < .001) approached norms at the end of the year for empathic concern (p = .15). There was an association between becoming chronically sleep deprived and becoming depressed (OR = 7, p = .014). Conclusions: Given the association between chronic sleep deprivation and mood disturbances during internship, outcome assessment is warranted to see if duty-hour reform will translate into more hours slept or fewer hours worked, coincident with improved mood." https://pubmed.ncbi.nlm.nih.gov/16377826/
  • Surgeries safety and sleep deprivation and burnout... https://doi.org/10.1016/j.jsurg.2019.07.002
  • BEST CRITICAL CONFIRMATION: that sleep disturbances are likely the ROOT CAUSE of burnout, not stress! "The results indicate that exhaustion disorder (ED), as described in the Swedish version of the International Classification of Diseases, seems to be the most valid clinical equivalent of burnout. The data supports the notion that sleep impairments are causative and maintaining factors for this condition. Patients with clinical burnout/ED suffer from cognitive impairments in the areas of memory and executive functioning. The studies on neuro‐biological mechanisms have reported functional uncoupling of networks relating the limbic system to the pre‐frontal cortex, and decreased volumes of structures within the basal ganglia. Although there is a growing body of literature on the physiological correlates of clinical burnout/ED, there is to date no biomarker for this condition." Stress‐related exhaustion disorder – clinical manifestation of burnout? A review of assessment methods, sleep impairments, cognitive disturbances, and neuro‐biological and physiological changes in clinical burnout, 2015 https://doi.org/10.1111/sjop.12251
    • PLUS: burnout = exhaustion = épuisement
  • Les médecins sont victimes de leur propre idéologie du sommeil! How ironic! Epidemy of burnout and suicidal ideation in medical doctors, and they think it's stress, whereas it's sleep deprivation (due to too heavy work schedule and shift work).
  • no biomarkers of burnout found because of too much heterogeneity in studies: https://doi.org/10.1016/j.jpsychores.2010.10.012
  • BEST: burnout leads to a load of health issues, strikingly similar to those of chronic sleep deprivation: "Burnout was a significant predictor of the following physical consequences: hypercholesterolemia, type 2 diabetes, coronary heart disease, hospitalization due to cardiovascular disorder, musculoskeletal pain, changes in pain experiences, prolonged fatigue, headaches, gastrointestinal issues, respiratory problems, severe injuries and mortality below the age of 45 years. The psychological effects were insomnia, depressive symptoms, use of psychotropic and antidepressant medications, hospitalization for mental disorders and psychological ill-health symptoms. Job dissatisfaction, absenteeism, new disability pension, job demands, job resources and presenteeism were identified as professional outcomes. Conflicting findings were observed. In conclusion, several prospective and high-quality studies showed physical, psychological and occupational consequences of job burnout. The individual and social impacts of burnout highlight the need for preventive interventions and early identification of this health condition in the work environment." Physical, psychological and occupational consequences of job burnout: A systematic review of prospective studies, 2017 https://doi.org/10.1371/journal.pone.0185781
  • Burnout in Belgian physicians and nurses, 2017 https://pubmed.ncbi.nlm.nih.gov/29016982/
  • Causes and Adverse Impact of Physician Burnout: A Systematic Review, 2017 https://pubmed.ncbi.nlm.nih.gov/28903843/
  • Workplace bullying and subsequent sleep problems - the Helsinki Health Study https://www.jstor.org/stable/41151544
  • Burnout and risk of cardiovascular disease: Evidence, possible causal paths, and promising research directions, 2006 https://doi.apa.org/doi/10.1037/0033-2909.132.3.327
    • shows that burnout is associated with increased risk of type 2 diabetes, infections and cardiovascular diseases.
  • Psycho again...
    • "Vital exhaustion (VE), a psychological concept that originates from clinical work with cardiovascular patients, is closely related to the burnout syndrome and was originally identified as an independent risk factor for coronary artery disease (for reviews see Kop, 1999, Appels, 2004). VE is thought to be a potential consequence of long-term stress or chronic BO, resulting in excessive fatigue, loss of mental and physical energy, increased irritability, and feelings of demoralization." https://doi.org/10.1016/j.biopsycho.2008.01.006
  • BEST CRITICAL: Sleep deprivation leads to burnout and cardiothoracic surgeons have to deal with its consequences, 2014 https://pubmed.ncbi.nlm.nih.gov/25464417/
    • BEST CRITICAL: depersonalization is "treating patients and colleagues as objects rather than human beings (depersonalization)"!!! So this explains a LOT actually!
    • "Sleep deprivation (SD) increases risk of human error related accidents, as optimal performance and learning of new skills requires activation of the circadian wakefulness circuitry and maintenance of sleep hemostasis [4].

• "Over the years, there has also been a paradigm shift, with many unwilling to make huge sacrifices in their lifestyle for a successful surgical career. A guiding principle of the Hippocratic oath is to ensure the ‘welfare of the patient’, even above and often at the expense of the doctor. This is probably now an outdated concept, which has advanced to one that takes into account not only the patient, but also the doctor as professional stakeholders and the healthcare system as a whole."
• "Firstly, training program directors and residents feel a reduction in hours will hinder continuity of care, professionalism, education and hinder the degree of ‘stress-training’. "
• BEST: it's known with medical night shift staff that sleeping in circadian misalignment causes a decreased and more fragmented sleep : "The adoption of ‘night-float’ systems to comply with ACGME regulations may have led to more fatigue due to disruption of normal circadian physiology. Such shift patterns are seen as more tiring by some compared with an on-call system, due to decreased and more fragmented sleep [14]."
• "Of 4047 consecutive procedures performed by six surgeons, there was no significant interaction between hours of sleep and outcomes. [19]. The authors hypothesized that well developed compensatory mechanisms must develop in cardiac surgeons to combat the effect of SD. Perhaps, SD induced reduction in higher executive functioning has a minimal effect as experienced cardiac surgeons have reached a stage of automaticity for complex decision-making and manual dexterity." → LOL, yeah of course surgeons are superhumans, they aren't affected by sleep deprivation...
• "The findings from these studies are challenged by more abundant research in to other surgical specialties. Haynes et al. retrospectively reviewed 6,371 general surgical procedures and found the highest rate of complications in those who had been performed by individuals on call in the last 24 hours [22]. Engleman et al. evaluated the impact of intraoperative 5 minute breaks every half an hour(similar to in air traffic controllers) during complex laparoscopic surgery and demonstrated that this did not prolong operations, reduced cortisol levels and led to fewer intraoperative adverse events [23]."
• "Fatigue has become more prominent with the ACGME requiring residents and faculty members to be educated in recognizing signs of fatigue. The ACS division of education has created a ‘committee to enhance peak performance in surgery through recognition and mitigation of the impact of fatigue’. The Royal Australasian College of Surgeons have organized ‘Beating Burnout’ workshops, with the aim of teaching surgeons to identify and manage stress."
• BEST: independently from burnout, sleep deprivation increases by 50% to 97% the rate of medical errors by physicians depending on the severity of the sleep deprivation! https://doi.org/10.1001/jamanetworkopen.2020.28111

• Connection between circadian rhythm and cortisol (and stress, they share a lot of pathways allegedly): https://doi.org/10.1016/j.slsci.2015.09.002
  • "The secretory activity of the HPA axis follows a distinct 24 h pattern. CRH is released in a circadian-dependent and pulsatile manner from the parvocellular cells of the PVN [3]."
  • "In fact, the circadian rhythm of cortisol secretion derives from the connection between the PVN and the central pacemaker, the suprachiasmatic nucleus (SCN) [4].
  • BEST CORTISOL timeline: "Typically, the nadir (time point with the lowest concentration) for cortisol occurs near midnight. Then, cortisol levels increase 2–3 h after sleep onset, and keep rising into to the waking hours. The peak happens in the morning at about 9 a.m. [4]. Along the day, there is a progressive decline that is potentiated by sleep, until it reaches the nadir and the quiescent period (Fig. 1)." Original source: https://doi.org/10.1210/jc.2004-1056
  • "In general, 3 main pathways are essential for biological clock function: the input (zeitgebers, retina) → SCN circadian pacemaker (as clock genes, neurotransmitters, peptides) → output (pineal melatonin synthesis, thermoregulation, hormones). Then, these factors interact with the sleep–wake cycle to modulate, for example, sleep propensity and sleep architecture, and influence behavior, performance or hormonal output such as cortisol [4]." Idem: https://doi.org/10.1210/jc.2004-1056
  • BEST CRITICAL: theory that most/all sleep and circadian rhythm disorders, including insomnia, share a dysregulation in the hypothalamic-pituitary-adrenal (HPA) axis and hence are at least partially caused by stress! On the Interactions of the Hypothalamic-Pituitary-Adrenal (HPA) Axis and Sleep: Normal HPA Axis Activity and Circadian Rhythm, Exemplary Sleep Disorders, Buckley and Schatzberg, 2005 https://doi.org/10.1210/jc.2004-1056
    • It's the same axis allegedly for stress, hence the assumption of interaction.
    • "We focus on a dose-response relationship of the effects of cortisol activity on sleep, emphasizing relative activation of specific glucocorticoid receptors (GRs) with the resultant effects on CRH and subsequently on ACTH and cortisol."
    • "Cortisol, though widely known as the body's stress hormone, has a variety of effects on different functions throughout the body. It is the main glucocorticoid released from the zona fasciculata layer of the adrenal cortex." https://www.ncbi.nlm.nih.gov/books/NBK538239/
      • BEST CRITICAL: "Cortisol, a steroid hormone, is synthesized from cholesterol." → so need enough cholesterol consumption to improve vigilance! This combined with light therapy to boost its production could improve daytime functioning and wakefulness! If no cholesterol then cannot work!
      • BEST CRITICAL: The effect of diet components on the level of cortisol, 2016, review https://doi.org/10.1007/s00217-016-2772-3
        • BEST: Cortisol is NOT the stress hormone, as it's not causing stress, rather it PREPARES the body to fight off stress! "Cortisol (hydrocortisone) is in human body the prevailing hormone from glucocorticoids group. By multidirectional acting within the physiological processes, it prepares body to physical and mental stress. It affects the metabolism of proteins, carbohydrates and fats and also participates in the regulation of water and electrolyte balance, blood pressure, body temperature, mineralization of the bones and the immune response. Additionally, it acts on mood and behavior, appetite and pain perception [1, 2].
        • BEST: "Cortisol mobilizes organism to fight stress, by affecting functioning of many organs and systems. It regulates the usage of diet nutrients through increasing gluconeogenesis and increasing lipolysis in adipose tissue. In addition, it increases protein synthesis in the liver and restricts their formation in muscles and skin cells. Furthermore, it increases retention of water and sodium, controls production of adrenaline in adrenal medulla, inhibits inflammatory processes and also affects the psyche, often provoking euphoria or depression [3]."
        • "The aim of the study is to present the current scientific views on the role of dietary components and way of nourishment on production of cortisol in the body of physically active person."
        • "A number of dietary and endogenous factors affect on maintaining an appropriate level of glucose in human blood. Cortisol acts on glucose amount by activating hepatic glycogen stores, reducing the oxidation of glucose, stimulation of lipolysis and intensification of gluconeogenesis from amino acid severity. Persisting high levels of this hormone contributes to the development of insulin resistance, dyslipidemia, hypertension and obesity. Mobilization of glucose reserves is particularly important in case of rapid stress situations like endurance training due to prolonged effort [2, 7–9]."
        • "Furthermore, cortisol affects the appetite [7]. De Sa et al. demonstrated that oral administration on this substance amplified startle responsiveness during presentation of pictures of food with high glycemic index. There was not such an effect in case of normal and pleasant non-food images [10]. It was shown that injection of ghrelin, the hormone that stimulates hunger, increases levels of cortisol, ACTH and growth hormone but does not affect leptin [11]."
        • "Cortisol also acts on thermal regulation of body, to prevent overheating of organism [7]."
        • "Hydrocortisone affects the immune system, showing anti-inflammatory and immunosuppressive effects by reducing secretion of proinflammatory cytokines, by decreasing migration of white blood cells to sites of inflammation and by inducting cell apoptosis. This stimulates the body’s defensive responses to injuries, including those occurring during training and sport starts [9, 12, 13]."
        • "Cortisol influences neuronal plasticity and neurodegenerative processes by acting on neurons and glial cells within the central nervous system. In addition, it modifies mood and behavior, as well as perception of pain, which is particularly important in mobilizing player in time of starts [7]."
        • "Cortisol, which is called hormone of fight with stress, prepares athlete to increase effort. However, its excess leads to catabolic reactions, negatively affecting the organism. The concentration of cortisol, as a catabolic hormone, stays in dynamic equilibrium with anabolic hormones. It has been shown that high levels of cortisol (C) inhibit synthesis of testosterone (T) in body, contributing to disorders in quantity ratio of these hormones. Estimated C/T is an indicator that reveals the exhaustion and overtraining of athlete [8, 14]."
        • "The content and type of carbohydrates in diet have a significant affect on endocrine system of active person. It was observed that the level of cortisol increases, by counteregulatory way, in response to hypoglycemia."
        • "In case of supplementation of certain amino acids such as tryptophan, which is a precursor of serotonin, may lead to a reduction in cortisol level increase, inducted by exercise [39]."
        • "Further nutrients, which may affect the levels of cortisol, are phospholipids: phosphatidylserine and phosphatidic acid. It has been shown that supplementation of their complex in a dose of 400 mg/day for 6 weeks resulted in reducing secretion of cortisol, caused by exercise, but a dose of 200 mg did not give a similar effect [41, 42]. Natural source of phosphatidylserine is egg yolk and of serine is protein-rich products. Serine is an endogenous amino acid and can be synthesized by organism from other amino acids. This is another reason why to maintain sufficient amounts of protein in diet of an athlete is very important [43]."
        • Caffeine reduces cortisol levels!
        • "Consumption of caffeine before a workout leads to a dose-dependent increase in both cortisol (K) and testosterone (T) concentrations. Supplementation with caffeine before workout can improve the T/K ratio, regardless of the duration of the night’s rest [76–80]."
        • "The studies concerning consumption of drinks containing carbohydrates and caffeine during workout have shown that the highest increase in cortisol levels were achieved in the group that supplemented caffeine without carbohydrates [81, 82]."
    • BEST ME TOSEE: if cortisol is considered the stress hormone, and it affects sleep, do we have to account for it? Does this mean that stress can impact sleep through cortisol? But it's regulated by the SCN too! AND can check this hypothesis by checking if studies found increased / mistimed / dysregulated cortisol levels in insomnia and circadian rhythm disorders!
• Emotional stress to cause diabetes, WTF! https://youtu.be/LWULB9Aoopc?t=808 — very dangerous, as even good researchers are prone to believe these claims without adequate proofs!
  • BEST CONFIRMATION: that emotional stress studies are maybe biased by publication bias: "It is important to emphasize that publication-bias may have occurred, resulting from "fishing-expeditions," where authors search their data for significant associations. Publication bias may also be caused by the tendency of reviewers and Editors to reject manuscripts with negative results for publication. It is therefore essential that research groups, who aim to conduct a new epidemiological cohort study, prospectively describe and publish the design of their study. Future research should focus on identifying mechanisms linking different forms of stress and incident type 2 diabetes." Does Emotional Stress Cause Type 2 Diabetes Mellitus? A Review from the European Depression in Diabetes (EDID) Research Consortium, 2010 https://www.discoverymedicine.com/Frans-Pouwer/2010/02/11/does-emotional-stress-cause-type-2-diabetes-mellitus-a-review-from-the-european-depression-in-diabetes-edid-research-consortium/
  • "Effects of Hypnotically Induced Acute Emotional Stress on Carbohydrate and Lipid Metabolism in Patients with Diabetes Mellitus" https://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.560.6153&rep=rep1&type=pdf
  • Study explicitly hypothesizing a link between emotional stress and oxidative (physiological) stress: https://doi.org/10.1089/ars.2017.7257
  • "Furthermore, regulation of these stress hormones may be abnormal in diabetes. However, evidence characterizing the effects of stress in type I diabetes is contradictory. Although some retrospective human studies have suggested that stress can precipitate type I diabetes, animal studies have shown that stressors of various kinds can precipitate—or prevent—various experimental models of the disease. Human studies have shown that stress can stimulate hyperglycemia, hypoglycemia, or have no affect at all on glycemic status in established diabetes. Much of this confusion may be attributable to the presence of autonomic neuropathy, common in type I diabetes. In contrast, more consistent evidence supports the role of stress in type II diabetes. Although human studies on the role of stress in the onset and course of type II diabetes are few, a large body of animal study supports the notion that stress reliably produces hyperglycemia in this form of the disease. Furthermore, there is mounting evidence of autonomic contributions to the pathophysiology of this condition in both animals and humans." https://doi.org/10.2337/diacare.15.10.1413
  • BEST: "Controversy exists over the role of stress and depression in the pathophysiology of type 2 diabetes mellitus. Depression has been shown to increase the risk for progressive insulin resistance and incident type 2 diabetes mellitus in multiple studies, whereas the association of stress with diabetes is less clear, owing to differences in study designs and in forms and ascertainment of stress. The biological systems involved in adaptation that mediate the link between stress and physiological functions include the hypothalamic–pituitary–adrenal axis and the autonomic nervous and immune systems. The hypothalamic–pituitary–adrenal axis is a tightly regulated system that represents one of the body’s mechanisms for responding to acute and chronic stress." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5334212/
  • LOL example of a biased review: "The review found an increased risk for T2D in people: exposed to stressful working conditions or traumatic events; with depression; with personality traits or mental health problems that put them in conflict with others; of low SES, either currently or in childhood; and in racial/ethnic minority populations, independent of current SES. " https://doi.org/10.1146/annurev-publhealth-031914-122921
  • This makes more sense: "When knowing is not enough: Emotional distress and depression reduce the positive effects of health literacy on diabetes self-management" https://doi.org/10.1016/j.pec.2017.08.006
    • "Both, depression and diabetes-related distress reduce the positive impact of health literacy on diabetes self-management."
  • My writing: https://www.reddit.com/r/DSPD/comments/lu8lnp/for_those_of_you_who_have_asked_about_mental/gp8m38x?utm_source=share&utm_medium=web2x&context=3

• Stress causes cynicism? NO, measures do not "survive confounders correction"! Why? Well according to the author, this is because a more fine grained analysis is more informative. LOL. If the results don't please you, turn them upside down until they do! That's basically what they admit lol. This is a very poor explanation and amply demonstrates the lack of basic methodological rigor by the authors. "However, in the current study, analyses utilizing total hostility did not survive full adjustment for covariates, further revealing that examination of hostility utilizing the separate subscales may be more informative." https://doi.org/10.1111/psyp.13681
• ME/CFS psychological theory criticism by a psychology researcher Brian Hughes. Himself working on stress and cardiovascular system, but at least he's honest with his findings (he finds links but he doesn't know if causal nor if clinically pertinent). He particularly criticizes the concept of medical malingering. https://thesciencebit.net/2019/03/21/if-you-spend-20-years-gaslighting-your-patients-perhaps-you-should-think-twice-before-accusing-them-of-trolling-you/ and https://doi.org/10.1016/j.ijpsycho.2018.02.003
  • "However, as yet, there is no prospective evidence to confirm that patterns of adaptation predict adverse health, despite there being strong reasonable and logical grounds to suspect so. We suggest how existing studies may offer a means to fill this gap in prospective evidence, and outline four potential typologies in cardiovascular reactivity patterns that fit within and extend the classic reactivity hypothesis."
  • All anxiety is dysautonomia? https://www.reddit.com/r/ChronicIllness/comments/nj80hy/damn_skippy/gz6x3gr?utm_source=share&utm_medium=web2x&context=3 and http://www.virology.ws/mecfs/

• ME about stress again: https://archive.is/hGpTG
  • ./u_lrq3000 - stress etc etc.pdf

• Example of extreme harmful consequences of the misuse of stress and anxiety as a clinical diagnosis instead of symptoms: https://archive.is/Smg3P
  • ME: Your story is exactly why I decry stress and anxiety as a clinical diagnosis. This misuse does more harm than good. Stress and anxiety are symptoms, not causes of diseases. You are unfortunately not a isolated case, although yours is an extreme example of how harmful this misuse can be.

• another way to see anhedonia: as a lack of emotional range. Hence, CBT can't work then, as it can only work to "control" the direction in the emotional range, but if the emotional range is near 0 (ie, there is no emotion), then it cannot do anything: https://archive.is/CNiKR

Opposite (positive results) studies on stress and its effects on the circadian rhythm

TODO: need to read studies in this section, none were processed.

• [Influence of circadian disruption on neurotransmitter levels, physiological indexes, and behaviour in rats: Chronobiology International: Vol 32, No 10](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Influence of circadian disruption on neurotransmitter levels%2C physiological indexes%2C and behaviour in rats%3A Chronobiology International%3A Vol 32%2C No 10&pos=0&uri=https://www.tandfonline.com/doi/full/10.3109/07420528.2015.1105250?casa_token=JGLV6dZvUiwAAAAA%3AbPMFDUtRhJhtum5EtSVRIyhCBpRcT3Zf6tR5qMUvhyYdnQch4FBO83F_QSRE4F47F5ZNBN0h1LzqqBI)
• [Increased core body temperature in astronauts during long-duration space missions | Scientific Reports](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Increased core body temperature in astronauts during long-duration space missions %7C Scientific Reports&pos=0&uri=https://www.nature.com/articles/s41598-017-15560-w?source=post_page---------------------------)
• [Full article: The effect of stress on core and peripheral body temperature in humans](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Full article%3A The effect of stress on core and peripheral body temperature in humans&pos=0&uri=https://www.tandfonline.com/doi/full/10.3109/10253890.2013.807243?casa_token=cSUkqf1i2B4AAAAA%3AzRrKXZLsKMpjniwiOghaQYxqmNTqfODrjybxSnYKCgEaZbMmTG2dO5TcRafsHlqbz_YQ2uX2wz75j04)
• [Alterations in core body temperature, locomotor activity, and corticosterone following acute and repeated social defeat of male NMRI mice - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Alterations in core body temperature%2C locomotor activity%2C and corticosterone following acute and repeated social defeat of male NMRI mice - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/pii/S0031938401005418?casa_token=cHgjYLwVsoIAAAAA:uuT_taxskk0kLS6_9kljklCOwqzaKtvCG0-cid5OoEVFxMWsJwwHNnCJ7TGKROpdfKBZgZZ93srp)
• [Normal body temperature of rats: the setpoint controversy - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Normal body temperature of rats%3A the setpoint controversy - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/pii/S0149763497000511?casa_token=J9JYJBF-AN4AAAAA:DBnlNPbV7O_LE8gsL5qDRA33_BPHMHcDcXNxAKWFqJxeSa2hyj-sT2QdoROpiYLg3_znxHEBUTsM)
• [emotional stress circadian rhythm core body temperature - Google Scholar](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=emotional stress circadian rhythm core body temperature - Google Scholar&pos=0&uri=https://scholar.google.com/scholar?start=60&q=emotional+stress+circadian+rhythm+core+body+temperature&hl=fr&as_sdt=0,5)
• [Full article: Psychogenic fever: how psychological stress affects body temperature in the clinical population](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Full article%3A Psychogenic fever%3A how psychological stress affects body temperature in the clinical population&pos=0&uri=https://www.tandfonline.com/doi/full/10.1080/23328940.2015.1056907)
• [Impact of mental stress, the circadian system and their interaction on human cardiovascular function - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Impact of mental stress%2C the circadian system and their interaction on human cardiovascular function - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/pii/S0306453018310448?casa_token=Ime3rVhRQgMAAAAA:b5lSKBgU4j35DkT0mI1Fq1VaEBptsuZzQ1phcMcCZCKjkQPRZD0ymea5Ss8Em1LE59Rokl00et0A)
• ["Regulation of core body temperature and the immune system determines s" by Ian J. Martins](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=%22Regulation of core body temperature and the immune system determines s%22 by Ian J. Martins&pos=0&uri=https://ro.ecu.edu.au/ecuworkspost2013/4855/)
• [Effects of Chronic Social Defeat Stress on Sleep and Circadian Rhythms Are Mitigated by Kappa-Opioid Receptor Antagonism | Journal of Neuroscience](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Effects of Chronic Social Defeat Stress on Sleep and Circadian Rhythms Are Mitigated by Kappa-Opioid Receptor Antagonism %7C Journal of Neuroscience&pos=0&uri=https://www.jneurosci.org/content/37/32/7656.abstract)
• [Homeostatic versus Circadian Effects of Melatonin on Core Body Temperature in Humans - Angelo Cagnacci, Kurt Kräuchi, Anna Wirz-Justice, Annibale Volpe, 1997](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Homeostatic versus Circadian Effects of Melatonin on Core Body Temperature in Humans - Angelo Cagnacci%2C Kurt Kräuchi%2C Anna Wirz-Justice%2C Annibale Volpe%2C 1997&pos=0&uri=https://journals.sagepub.com/doi/abs/10.1177/074873049701200604)
• [Axillary and Thoracic Skin Temperatures Poorly Comparable to Core Body Temperature Circadian Rhythm: Results from 2 Adult Populations - Karen A. Thomas, Robert Burr, Shu-Yuann Wang, Martha J. Lentz, Joan Shaver, 2004](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Axillary and Thoracic Skin Temperatures Poorly Comparable to Core Body Temperature Circadian Rhythm%3A Results from 2 Adult Populations - Karen A. Thomas%2C Robert Burr%2C Shu-Yuann Wang%2C Martha J. Lentz%2C Joan Shaver%2C 2004&pos=0&uri=https://journals.sagepub.com/doi/abs/10.1177/1099800403260620?casa_token=MAANgq1cfoQAAAAA:3Cf42ApnOAqhvtSmPplMNfcKRT-X0u5cYMvTIoTOXGZssPt9pSSiwRhRTeJYbUEpT4FpkwpWrGjl4FM)
• [Disturbances in Melatonin, Cortisol and Core Body Temperature Rhythms after Major Surgery | SpringerLink](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Disturbances in Melatonin%2C Cortisol and Core Body Temperature Rhythms after Major Surgery %7C SpringerLink&pos=0&uri=https://link.springer.com/article/10.1007/s00268-006-0256-5)
• [The circadian rhythm of core temperature: Effects of physical activity and aging - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=The circadian rhythm of core temperature%3A Effects of physical activity and aging - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/pii/S003193840600388X?casa_token=3fiUFRn8j2QAAAAA:m_5YZZdAYoI9LxRMBCP4NfTbCQHO6Z53owUcvmImq7XP39AAqd0vD6VB_DHWoHUDdtePt4PzOu9g)
• [Dissociation of body‐temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome - Williams - 1996 - Clinical Physiology - Wiley Online Library](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Dissociation of body‐temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome - Williams - 1996 - Clinical Physiology - Wiley Online Library&pos=0&uri=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1475-097X.1996.tb00722.x)
• [The Human Endogenous Circadian System Causes Greatest Platelet Activation during the Biological Morning Independent of Behaviors](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=The Human Endogenous Circadian System Causes Greatest Platelet Activation during the Biological Morning Independent of Behaviors&pos=0&uri=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0024549)
• [Estimation of Circadian Body Temperature Rhythm Based on Heart Rate in Healthy, Ambulatory Subjects | IEEE Journals & Magazine | IEEE Xplore](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Estimation of Circadian Body Temperature Rhythm Based on Heart Rate in Healthy%2C Ambulatory Subjects %7C IEEE Journals %26 Magazine %7C IEEE Xplore&pos=0&uri=https://ieeexplore.ieee.org/abstract/document/7414381)
• [Mechanisms and Mediators of Psychological Stress-Induced Ris... : Psychosomatic Medicine](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Mechanisms and Mediators of Psychological Stress-Induced Ris... %3A Psychosomatic Medicine&pos=0&uri=https://journals.lww.com/psychosomaticmedicine/Fulltext/2001/05000/Mechanisms_and_Mediators_of_Psychological.18.aspx?casa_token=6avKhWUEnTIAAAAA:kUki3K2miyFXzwXb6rBKgXRBvSNd-0DAfzmE3mmHSZ3e24L062BWNW8b4ich7BsF00XNSlJ8nqgum6q5Z2tUQ2nS__z0r2o)
• [Dual orexin receptor antagonist induces changes in core body temperature in rats after exercise | Scientific Reports](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Dual orexin receptor antagonist induces changes in core body temperature in rats after exercise %7C Scientific Reports&pos=0&uri=https://www.nature.com/articles/s41598-019-54826-3)
• [Modafinil, d‐amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood, fatigue, cognitive performance and body temperature - PIGEAU - 1995 - Journal of Sleep Research - Wiley Online Library](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Modafinil%2C d‐amphetamine and placebo during 64 hours of sustained mental work. I. Effects on mood%2C fatigue%2C cognitive performance and body temperature - PIGEAU - 1995 - Journal of Sleep Research - Wiley Online Library&pos=0&uri=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2869.1995.tb00172.x)
• [Entrainment of the mouse circadian clock by sub-acute physical and psychological stress | Scientific Reports](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Entrainment of the mouse circadian clock by sub-acute physical and psychological stress %7C Scientific Reports&pos=0&uri=https://www.nature.com/articles/srep11417?message-)
• [Body temperature and sleep architecture in response to a mild cold stress in women - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Body temperature and sleep architecture in response to a mild cold stress in women - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/abs/pii/0031938486904592)
• [Core body temperature is normal in chronic fatigue syndrome - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Core body temperature is normal in chronic fatigue syndrome - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/abs/pii/S0006322397832143)
• [Overweight/Obesity and Concurrent Disorders, Symptoms, Behaviour, and Body Temperature | SpringerLink](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Overweight%2FObesity and Concurrent Disorders%2C Symptoms%2C Behaviour%2C and Body Temperature %7C SpringerLink&pos=0&uri=https://link.springer.com/chapter/10.1007/978-3-030-32545-9_3)
• [Metabolic dysfunction and circadian rhythm abnormalities in adolescents with sleep disturbance - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Metabolic dysfunction and circadian rhythm abnormalities in adolescents with sleep disturbance - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/pii/S1053811909002225?casa_token=PO70J94__osAAAAA:AJMrnmrs-jRI6bL6iB_etmvltzzM70tM2g8hDmSERrws_rMmeEWudFlXPw3YrFKP3RXAjjFhDNVv)
• [Circadian rhythm disruption and mental health | Translational Psychiatry](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Circadian rhythm disruption and mental health %7C Translational Psychiatry&pos=0&uri=https://www.nature.com/articles/s41398-020-0694-0)
• [Circadian Rhythm of Body Core Temperature in Neurodegenerative Diseases | SpringerLink](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Circadian Rhythm of Body Core Temperature in Neurodegenerative Diseases %7C SpringerLink&pos=0&uri=https://link.springer.com/chapter/10.1007/978-88-470-2275-1_4)
• [Treatment of Circadian Rhythm Sleep-Wake Disorders - PubMed](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Treatment of Circadian Rhythm Sleep-Wake Disorders - PubMed&pos=0&uri=https://pubmed.ncbi.nlm.nih.gov/34493186/)
• [Effects of controllable vs. uncontrollable stress on circadian temperature rhythms - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Effects of controllable vs. uncontrollable stress on circadian temperature rhythms - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/abs/pii/003193849190289Z)
• [Full article: The Circadian Rhythm of Core Temperature: Origin and some Implications for Exercise Performance](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Full article%3A The Circadian Rhythm of Core Temperature%3A Origin and some Implications for Exercise Performance&pos=0&uri=https://www.tandfonline.com/doi/full/10.1081/CBI-200053477?casa_token=mTpgcvEE1wYAAAAA%3AYpbZq4-Ic3Sfi8t__LEYKIBGkn66mS3rWgGxfhsYS-MuzbU2yuUluHcdf2eiJGW0ksieaqy758v6Tp8)
• [Continuous Exposure to a Novel Stressor Based on Water Aversion Induces Abnormal Circadian Locomotor Rhythms and Sleep-Wake Cycles in Mice](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Continuous Exposure to a Novel Stressor Based on Water Aversion Induces Abnormal Circadian Locomotor Rhythms and Sleep-Wake Cycles in Mice&pos=0&uri=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0055452)
• [2nd Edition of ISLR is now available and free from the authors! It looks 1.5x bigger than the previous edition! : datascience](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=2nd Edition of ISLR is now available and free from the authors! It looks 1.5x bigger than the previous edition! %3A datascience&pos=0&uri=https://www.reddit.com/r/datascience/comments/oyi7a1/2nd_edition_of_islr_is_now_available_and_free/)
• [Sleep science: The biggest mistake “successful” people make](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Sleep science%3A The biggest mistake “successful” people make&pos=0&uri=https://www.inverse.com/mind-body/sleep-success-science)
• [Sleep and depression: Why a one hour change could make a difference](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Sleep and depression%3A Why a one hour change could make a difference&pos=0&uri=https://www.inverse.com/mind-body/sleep-depression-study)
• [HPA Axis and Sleep - Endotext - NCBI Bookshelf](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=HPA Axis and Sleep - Endotext - NCBI Bookshelf&pos=0&uri=https://www.ncbi.nlm.nih.gov/sites/books/NBK279071/)
• [Psychophysiological Stress Indicators of Heart Rate Variabil... : Simulation in Healthcare](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Psychophysiological Stress Indicators of Heart Rate Variabil... %3A Simulation in Healthcare&pos=0&uri=https://journals.lww.com/simulationinhealthcare/FullText/2020/02000/Psychophysiological_Stress_Indicators_of_Heart.8.aspx)
• [Thieme E-Journals - Seminars in Thrombosis and Hemostasis / Full Text](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Thieme E-Journals - Seminars in Thrombosis and Hemostasis %2F Full Text&pos=0&uri=https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0037-1608906)
• [Carbon fiber based electrochemical sensor for sweat cortisol measurement | Scientific Reports](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Carbon fiber based electrochemical sensor for sweat cortisol measurement %7C Scientific Reports&pos=0&uri=https://www.nature.com/articles/s41598-018-37243-w)
• [Stress-Lysis: A DNN-Integrated Edge Device for Stress Level Detection in the IoMT | IEEE Journals & Magazine | IEEE Xplore](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Stress-Lysis%3A A DNN-Integrated Edge Device for Stress Level Detection in the IoMT %7C IEEE Journals %26 Magazine %7C IEEE Xplore&pos=0&uri=https://ieeexplore.ieee.org/abstract/document/8830476)
• [A State-Space Approach for Detecting Stress from Electrodermal Activity | IEEE Conference Publication | IEEE Xplore](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=A State-Space Approach for Detecting Stress from Electrodermal Activity %7C IEEE Conference Publication %7C IEEE Xplore&pos=0&uri=https://ieeexplore.ieee.org/abstract/document/8512928)
• [Hearables: Here come the: Technology tucked inside your ears will augment your daily life | IEEE Journals & Magazine | IEEE Xplore](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Hearables%3A Here come the%3A Technology tucked inside your ears will augment your daily life %7C IEEE Journals %26 Magazine %7C IEEE Xplore&pos=0&uri=https://ieeexplore.ieee.org/abstract/document/8701198)
• [A wearable, cotton thread/paper-based microfluidic device coupled with smartphone for sweat glucose sensing | SpringerLink](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=A wearable%2C cotton thread%2Fpaper-based microfluidic device coupled with smartphone for sweat glucose sensing %7C SpringerLink&pos=0&uri=https://link.springer.com/article/10.1007/s10570-019-02396-y)
• [Towards a bacterial treatment for armpit malodour - Callewaert - 2017 - Experimental Dermatology - Wiley Online Library](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Towards a bacterial treatment for armpit malodour - Callewaert - 2017 - Experimental Dermatology - Wiley Online Library&pos=0&uri=https://onlinelibrary.wiley.com/doi/full/10.1111/exd.13259)
• [Sweat mechanisms and dysfunctions in atopic dermatitis - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Sweat mechanisms and dysfunctions in atopic dermatitis - ScienceDirect&pos=1758.4000244140625&uri=https://www.sciencedirect.com/science/article/pii/S0923181117309787?casa_token=yoEVH_5AETQAAAAA:RkT1Ibhm4Zo5lFweUqDe_BKRG-9jW-4ZYm8qeW444Ij9vG0J1hkGRhXREwQNX3m4aQ7WyhRnK5Ou)
• [Biosensors | Free Full-Text | Identification of Suitable Biomarkers for Stress and Emotion Detection for Future Personal Affective Wearable Sensors](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Biosensors %7C Free Full-Text %7C Identification of Suitable Biomarkers for Stress and Emotion Detection for Future Personal Affective Wearable Sensors&pos=0&uri=https://www.mdpi.com/2079-6374/10/4/40)
• [Encoding fear intensity in human sweat | Philosophical Transactions of the Royal Society B: Biological Sciences](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Encoding fear intensity in human sweat %7C Philosophical Transactions of the Royal Society B%3A Biological Sciences&pos=0&uri=https://royalsocietypublishing.org/doi/full/10.1098/rstb.2019.0271)
• [Emotional Body Odors as Context: Effects on Cardiac and Subjective Responses | Chemical Senses | Oxford Academic](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Emotional Body Odors as Context%3A Effects on Cardiac and Subjective Responses %7C Chemical Senses %7C Oxford Academic&pos=0&uri=https://academic.oup.com/chemse/article/43/5/347/4956803?login=true)
• [Rogiest_68901400_2019.pdf](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Rogiest_68901400_2019.pdf&pos=0&uri=file:///C:/Users/THEMATRIXNEO/Downloads/Rogiest_68901400_2019.pdf)
• [emotional stress circadian rhythm core body temperature - Google Scholar](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=emotional stress circadian rhythm core body temperature - Google Scholar&pos=0&uri=https://scholar.google.com/scholar?start=60&q=emotional+stress+circadian+rhythm+core+body+temperature&hl=fr&as_sdt=0,5)
• [Normal body temperature of rats: the setpoint controversy - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Normal body temperature of rats%3A the setpoint controversy - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/pii/S0149763497000511?casa_token=J9JYJBF-AN4AAAAA:DBnlNPbV7O_LE8gsL5qDRA33_BPHMHcDcXNxAKWFqJxeSa2hyj-sT2QdoROpiYLg3_znxHEBUTsM)
• [Alterations in core body temperature, locomotor activity, and corticosterone following acute and repeated social defeat of male NMRI mice - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Alterations in core body temperature%2C locomotor activity%2C and corticosterone following acute and repeated social defeat of male NMRI mice - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/pii/S0031938401005418?casa_token=cHgjYLwVsoIAAAAA:uuT_taxskk0kLS6_9kljklCOwqzaKtvCG0-cid5OoEVFxMWsJwwHNnCJ7TGKROpdfKBZgZZ93srp)
• [Full article: The effect of stress on core and peripheral body temperature in humans](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Full article%3A The effect of stress on core and peripheral body temperature in humans&pos=0&uri=https://www.tandfonline.com/doi/full/10.3109/10253890.2013.807243?casa_token=cSUkqf1i2B4AAAAA%3AzRrKXZLsKMpjniwiOghaQYxqmNTqfODrjybxSnYKCgEaZbMmTG2dO5TcRafsHlqbz_YQ2uX2wz75j04)
• [Behavior and body temperature in rats following chronic foot shock or psychological stress exposure - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Behavior and body temperature in rats following chronic foot shock or psychological stress exposure - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/pii/S0031938400003395?casa_token=VLWqSlqDbP8AAAAA:GSTMo1M7h-5EMWTWmjcNv2bsyTYVqthVfRzLMGex31ZEmTnxHe_0IO42lKJ6urVTJqfD-SoUUmpm)
• [Full article: Psychogenic fever: how psychological stress affects body temperature in the clinical population](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Full article%3A Psychogenic fever%3A how psychological stress affects body temperature in the clinical population&pos=0&uri=https://www.tandfonline.com/doi/full/10.1080/23328940.2015.1056907)
• [Increased core body temperature in astronauts during long-duration space missions | Scientific Reports](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Increased core body temperature in astronauts during long-duration space missions %7C Scientific Reports&pos=0&uri=https://www.nature.com/articles/s41598-017-15560-w?source=post_page---------------------------)
• [Full article: Influence of circadian disruption on neurotransmitter levels, physiological indexes, and behaviour in rats](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Full article%3A Influence of circadian disruption on neurotransmitter levels%2C physiological indexes%2C and behaviour in rats&pos=0&uri=https://www.tandfonline.com/doi/full/10.3109/07420528.2015.1105250?casa_token=JGLV6dZvUiwAAAAA%3AbPMFDUtRhJhtum5EtSVRIyhCBpRcT3Zf6tR5qMUvhyYdnQch4FBO83F_QSRE4F47F5ZNBN0h1LzqqBI)
• [Regular exercise counteracts circadian shifts in core body temperature during long-duration bed rest | npj Microgravity](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Regular exercise counteracts circadian shifts in core body temperature during long-duration bed rest %7C npj Microgravity&pos=0&uri=https://www.nature.com/articles/s41526-020-00129-1)
• [Juvenile stress impairs body temperature regulation and augments anticipatory stress-induced hyperthermia responses in rats - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Juvenile stress impairs body temperature regulation and augments anticipatory stress-induced hyperthermia responses in rats - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/pii/S0031938411001958?casa_token=eHHb-CVZhDkAAAAA:YeB9qWLRo0MetUf4yuM_8Lmi5SnjkfOz26vZoTU8zcJbA0rwEKSu3HNoY91RU24M47qtZCG5Bzlw)
• [The circadian rhythm of body temperature - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=The circadian rhythm of body temperature - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/abs/pii/0031938492901888)
• [Impact of mental stress, the circadian system and their interaction on human cardiovascular function - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Impact of mental stress%2C the circadian system and their interaction on human cardiovascular function - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/pii/S0306453018310448?casa_token=Ime3rVhRQgMAAAAA:b5lSKBgU4j35DkT0mI1Fq1VaEBptsuZzQ1phcMcCZCKjkQPRZD0ymea5Ss8Em1LE59Rokl00et0A)
• ["Regulation of core body temperature and the immune system determines s" by Ian J. Martins](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=%22Regulation of core body temperature and the immune system determines s%22 by Ian J. Martins&pos=0&uri=https://ro.ecu.edu.au/ecuworkspost2013/4855/)
• [Effects of Chronic Social Defeat Stress on Sleep and Circadian Rhythms Are Mitigated by Kappa-Opioid Receptor Antagonism | Journal of Neuroscience](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Effects of Chronic Social Defeat Stress on Sleep and Circadian Rhythms Are Mitigated by Kappa-Opioid Receptor Antagonism %7C Journal of Neuroscience&pos=0&uri=https://www.jneurosci.org/content/37/32/7656.abstract)
• [Disturbances in Melatonin, Cortisol and Core Body Temperature Rhythms after Major Surgery | SpringerLink](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Disturbances in Melatonin%2C Cortisol and Core Body Temperature Rhythms after Major Surgery %7C SpringerLink&pos=0&uri=https://link.springer.com/article/10.1007/s00268-006-0256-5)
• [Mechanisms and Mediators of Psychological Stress-Induced Ris... : Psychosomatic Medicine](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Mechanisms and Mediators of Psychological Stress-Induced Ris... %3A Psychosomatic Medicine&pos=0&uri=https://journals.lww.com/psychosomaticmedicine/Fulltext/2001/05000/Mechanisms_and_Mediators_of_Psychological.18.aspx?casa_token=6avKhWUEnTIAAAAA:kUki3K2miyFXzwXb6rBKgXRBvSNd-0DAfzmE3mmHSZ3e24L062BWNW8b4ich7BsF00XNSlJ8nqgum6q5Z2tUQ2nS__z0r2o)
• [Entrainment of the mouse circadian clock by sub-acute physical and psychological stress | Scientific Reports](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Entrainment of the mouse circadian clock by sub-acute physical and psychological stress %7C Scientific Reports&pos=0&uri=https://www.nature.com/articles/srep11417?message-)
• [Body temperature and sleep architecture in response to a mild cold stress in women - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Body temperature and sleep architecture in response to a mild cold stress in women - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/abs/pii/0031938486904592)
• [Circadian Rhythm of Body Core Temperature in Neurodegenerative Diseases | SpringerLink](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Circadian Rhythm of Body Core Temperature in Neurodegenerative Diseases %7C SpringerLink&pos=0&uri=https://link.springer.com/chapter/10.1007/978-88-470-2275-1_4)
• [Effects of controllable vs. uncontrollable stress on circadian temperature rhythms - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Effects of controllable vs. uncontrollable stress on circadian temperature rhythms - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/abs/pii/003193849190289Z)
• [Full article: The Circadian Rhythm of Core Temperature: Origin and some Implications for Exercise Performance](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Full article%3A The Circadian Rhythm of Core Temperature%3A Origin and some Implications for Exercise Performance&pos=0&uri=https://www.tandfonline.com/doi/full/10.1081/CBI-200053477?casa_token=mTpgcvEE1wYAAAAA%3AYpbZq4-Ic3Sfi8t__LEYKIBGkn66mS3rWgGxfhsYS-MuzbU2yuUluHcdf2eiJGW0ksieaqy758v6Tp8)
• [Continuous Exposure to a Novel Stressor Based on Water Aversion Induces Abnormal Circadian Locomotor Rhythms and Sleep-Wake Cycles in Mice](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Continuous Exposure to a Novel Stressor Based on Water Aversion Induces Abnormal Circadian Locomotor Rhythms and Sleep-Wake Cycles in Mice&pos=0&uri=https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0055452)
• A systematic review and meta-analysis of cognitive and behavioral interventions to improve sleep health in adults without sleep disorders, 2018 https://doi.org/10.1016/j.smrv.2017.12.003

Chronic fatigue syndrome:

• [Dissociation of body‐temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome - Williams - 1996 - Clinical Physiology - Wiley Online Library](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Dissociation of body‐temperature and melatonin secretion circadian rhythms in patients with chronic fatigue syndrome - Williams - 1996 - Clinical Physiology - Wiley Online Library&pos=0&uri=https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1475-097X.1996.tb00722.x)
• [Core body temperature is normal in chronic fatigue syndrome - ScienceDirect](chrome-extension://nmeadenijghcffdbebhcdkpljkiakffd/suspended.html#ttl=Core body temperature is normal in chronic fatigue syndrome - ScienceDirect&pos=0&uri=https://www.sciencedirect.com/science/article/abs/pii/S0006322397832143)

Chronotherapy and CBT-i and psychotherapies for CRSWDs

• BEST CRITICAL CONFIRMATION: psychotherapy research has a lot of methodological issues and biases, very well explained here: http://drnormanhoffman.com/?p=76 (mirror: https://web.archive.org/web/20200926053857/http://drnormanhoffman.com/?p=76) (and also says that CBT-i is a scam!)
  • "A major bias that should be in favour of CBT is the reality that CBT basically trains people to report less symptoms, while emotionally based therapies encourage people to express their feelings. It has been long recognized, and shown in research, that people will want to please their therapists and comply with expectations. If a therapist gives consistent positive feedback when patient reports less negative feelings, than a patient will with time report less negative feelings. If a therapist gives positive feedback whenever a patients expresses painful feelings than the patient will continue to express painful feelings. If one then gives these patients a tool that measures these feelings, the patient who was encouraged to report less feelings should show “better” response on this tool regardless of whether or not the person is doing better in life. This is the exact situation that occurs when comparing CBT to more emotionally based therapies, yet CBT, on these tools, does not show better results. This clearly indicates that CBT is an inferior therapy." → No CBT-i study using an objective measure of sleep or circadian rhythm such as actigraphy and core body temperature, because subjective measures are more easily biased and hence more easily provide significant results.
  • Clearly in psychotherapy research there are no real double blind studies. The therapists always know if they are doing a placebo or sham therapy. Thus the therapists who may be part of the control group are not going to have much belief or enthusiasm for their treatment. They are also forced to do really bad therapy, as they are restricted from using any of the modalities that are a part of the studied therapy, and are only allowed to make simplistic comments. Thus, if CBT is being compared to a “supportive” psychotherapy, the therapist doing the control therapy is only allowed to make “supportive” comments and not help the individual with real life problems or try to put together issues the control subject brings up. Basically, control psychotherapies are carried out by therapists who aren’t allowed to use most of their skills and are designed to frustrate both the therapist and the patient.
  • Classical cbt-i cannot change the circ rhythm. The only kind that can are including overexposure to artificial or natural bright (sun)light, in other words light therapy disguised as cbt-i.
  • Also cbt-i can include chronotherapy, which is highly detrimental to people with a circadian rhythm disorder since it not only increase sleep deprivation and hence health issues but has the potential to worsen the disorder. That's the issue with CBT-i: since it is not standardized, it's a melting pot of different sorts of interventions depending on the practitioner, which may include effective treatments such as light therapy and ineffective or even worsening interventions such as chronotherapy, and it's hence impossible to determine whether CBT-i is effective or not, since it depends on the "blocks" used by a specific practitioner to define their specific CBT-i.
  • Systematic review 2021 by AASM: https://doi.org/10.5664/jcsm.8988 — they support CBT-i but objective metrics show a reduction of sleep duration and sleep efficiency, and the quality of evidence was low.
• Also video youtube by leslieexp
• Sleep-restriction therapy as in CBT-i, horrible!!! https://www.medscape.com/answers/1187829-70570/what-is-sleep-restriction-therapy-for-insomnia#:~:text=Sleep%2Drestriction therapy is based,and more regular and predictable.
  • Sleep Restriction Therapy for Insomnia is Associated with Reduced Objective Total Sleep Time, Increased Daytime Somnolence, and Objectively Impaired Vigilance: Implications for the Clinical Management of Insomnia Disorder , 2014 https://doi.org/10.5665/sleep.3386
  • Lack of standardization of CBT-i: "Findings indicate that a large proportion of papers (39%) do not report any details regarding sleep restriction therapy parameters and, for those papers that do, variability in implementation is present at every level (sleep window generation, minimum time-in-bed, sleep efficiency titration criteria, and positioning of sleep window). Only 7% of papers reported all parameters of sleep restriction treatment. Poor reporting and variability in the application of sleep restriction therapy may hinder progress in relation to evidence synthesis, specification of mechanistic components, and refinement of therapeutic procedures for patient benefit." https://doi.org/10.1016/j.smrv.2015.02.003
  • "Reported side-effects were common, with ⩾50% of patients reporting impairment in 8 out of 12 listed symptoms as a consequence of initiating treatment. The four most common side-effects were ‘fatigue/exhaustion’ (100%), ‘extreme sleepiness’ (94%), ‘reduced motivation/energy’ (89%) and ‘headache/migraine’ (72%) [Mean number of symptoms per patient = 7.2 (2.4); range 3–11]." https://doi.org/10.1016/j.sleep.2011.03.016
    • Makes the link with CBT-i, SRT is part of CBT-i
  • Sleep-restriction therapy is the new lobotomy.
  • Example in practice, because sometimes they say they use a modified sleep restriction therapy when it's just typical sleep restriction: "Participants were also instructed to maintain a consistent arising time, even after a poor night's sleep, to synchronize the endogenous circadian rhythm that regulates sleep and wakefulness." https://doi.org/10.1001/archinte.164.17.1888
  • Lack of proper control conditions: "In addition, many of the meta-analytic studies included studies with small sample sizes or inadequate control groups." https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584580/
  • https://en.wikipedia.org/w/index.php?title=Psychotherapy&oldid=993482215#General_critiques
  • "Research on adverse effects of psychotherapy has been limited for various reasons, yet they may be expected to occur in 5% to 20% of patients. Problems include deterioration of symptoms or developing new symptoms, strains in other relationships, and therapy dependence. Some techniques or therapists may carry more risks than others, and some client characteristics may make them more vulnerable." https://en.wikipedia.org/w/index.php?title=Psychotherapy&oldid=993482215#Adverse_effects
  • BEST CONFIRMATION: exactly what I said, psychotherapy assumes it works by working on memory consolidation! "It is not yet understood how psychotherapies can succeed in treating mental illnesses.[141] Different therapeutic approaches may be associated with particular theories about what needs to change in a person for a successful therapeutic outcome. In general, processes of emotional arousal and memory have long been held to play an important role. One theory combining these aspects proposes that permanent change occurs to the extent that the neuropsychological mechanism of memory reconsolidation is triggered and is able to incorporate new emotional experiences." https://en.wikipedia.org/w/index.php?title=Psychotherapy&oldid=993482215#Mechanisms_of_change
• BEST: "Some observers perceive a gap between scientific theory and its application—in particular, the application of unsupported or unsound clinical practices.[249] Critics say there has been an increase in the number of mental health training programs that do not instill scientific competence.[250]" https://en.wikipedia.org/w/index.php?title=Psychology&oldid=993054192#Contemporary_issues_in_methodology_and_practice
  • "The field of metascience has revealed significant problems with the methodology of psychological research. Psychological research suffers from high bias,[204] low reproducibility,[205] and widespread misuse of statistics.[206] These finding have led to calls for reform from within and from outside the scientific community.[207]"
  • "In 1959, statistician Theodore Sterling examined the results of psychological studies and discovered that 97% of them supported their initial hypotheses, implying a possible publication bias.[208][209][210] Similarly, Fanelli (2010)[211] found that 91.5% of psychiatry/psychology studies confirmed the effects they were looking for, and concluded that the odds of this happening (a positive result) was around five times higher than in fields such as space- or geosciences. Fanelli argues that this is because researchers in "softer" sciences have fewer constraints to their conscious and unconscious biases."
  • House of cards : psychology and psychotherapy built on myth, 1936 https://archive.org/details/houseofcardspsyc00dawerich/page/n359/mode/2up
• Replication/reproducibility crisis in psychology: https://en.wikipedia.org/wiki/Replication_crisis
• Karl Popper explicitly used psychoanalysis as an example of unfalsifiable domain, and hence pseudoscientific: https://en.wikipedia.org/w/index.php?title=Falsifiability&oldid=992351166#The_problem_of_induction
• ME: CBT even used for medically unexplained physical symptoms (MUS), so without knowing what causes the patient's ailment, they apply CBT and expect to find a positive result! That's crazy and totally unscientific and non-evidence based medicine! And even then, they only find small effect with low quality studies! https://pubmed.ncbi.nlm.nih.gov/25362239/
  • ME: Think about it: did you ever see anything that can fix all your issues in life, whether small or big? Well, CBT practitioners claim that CBT does! It's literally a miracle cure that applies to anything and everything! Without even knowing or caring to explain how it can work, they just blindly try it on lots of disorders with no idea what they are doing! That's just crazy!
  • See this review of meta-analysis, they just tried CBT on every (non-organic) disorder possible... https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3584580/
  • My criticism on reddit: https://www.reddit.com/r/DSPD/comments/ka8kfx/is_there_any_hope/gfd9mod?utm_source=share&utm_medium=web2x&context=3

• Tocheck if I have: The Cumulative Cost of Additional Wakefulness: Dose-Response Effects on Neurobehavioral Functions and Sleep Physiology From Chronic Sleep Restriction and Total Sleep Deprivation

• Effectiveness of Cognitive-Behavioral Insomnia Treatment in a Community Sample of Older Individuals: More Questions than Conclusions https://link.springer.com/article/10.1007/s10880-005-3275-8

• BEST ME TOADD: About CBT studies, prevalent issues include poor study design with low sample size and use of subjective sleep measures instead of objective ones, the uncontrolled confound due to the non standardization of CBT procedures (eg, such as by using artificial or sun light therapy as part of CBT-i), and the very restrictive exclusion criteria for any organic disorder. Although CBT studies only study non-organic insomnia and other non-organic disorders, proponents and therapists often unduly extrapolate these results by applying CBT on organic disorders such as DSPD and non-24, for which there is no evidence of efficacy. If you accept the existence of non-organic disorders, then CBT may be effective for non-organic insomnia (and still the results are mixed, nothing proven) and other non-organic disorders. However, there is absolutely no evidence that CBT can be effective for organic disorders such as circadian rhythm disorders including DSPD and non-24. In any case, CBT, and other psychotherapies, do not offer a reasonable theory to explain how or why they would work to treat any disorder, although there are some hypothesis about memory consolidation and modifying emotional processing (which remain unproven hypotheses), and which would not explain at all why they would work for sleep disorders.
• Sleep restriction is a psychology tool, part of CBT-i https://www.psychologytools.com/resource/sleep-restriction/
• Theory behind sleep restriction https://doi.org/10.3399/bjgp15X686137
  • "The sleep restriction component of CBT-I consolidates fragmented sleep by reducing the time allowed in bed (the sleep opportunity); thereby inducing mild sleep deprivation to enhance the endogenous sleep drive."
  • BEST CRITICAL: original source of sleep restriction therapy: Treatment of chronic insomnia by restriction of time in bed, 1987 https://pubmed.ncbi.nlm.nih.gov/3563247/ — again only subjective measures
  • ME: It was not even a real sleep restriction but just teaching patients to self manage their sleep with a sleep diary + not staying in bed if not sleeping. They did not restrict the sleep, they have restricted the time spent awake in bed without sleeping.
  • "The total time in bed allowed in the sleep prescription was equal to the average total sleep duration plus 50% of the total time spent awake in bed (therefore reducing the total additional ‘wake time’ by half), with a minimum time in bed of 5 hours. Actual bedtime and wake-up times were negotiable. Participants were asked to continue with a sleep diary until the next visit."
  • "Participants attended a second visit 2 weeks later. If participants were sleeping for <85% of the time they spent in bed (according to their diary), the time allowed in bed was further reduced to total sleep duration plus 30 minutes. If patients felt excessively sleepy, they were advised to spend 30 minutes more in bed each night. Wherever possible, wake-up time was kept constant, and any changes required were made to bedtime. Participants were also given a written flowchart summarising change options (available from authors on request) and asked to self-adjust their sleep every 2 weeks thereafter. Control participants also attended a second visit after 2 weeks where their general sleep progress according to sleep hygiene guidelines was discussed. Scripts were used for the delivery of instructions to both groups."
  • BEST CRITICAL: The evidence base of sleep restriction therapy for treating insomnia disorder, 2014, review https://pubmed.ncbi.nlm.nih.gov/24629826/
    • My analysis: https://www.reddit.com/r/insomnia/comments/leli86/sleep_hygiene_all_tips_in_one_place/gmhgwlv?utm_medium=android_app&utm_source=share&context=3
  • BEST CRITICAL: AASM 2021 systematic review on CBT-i https://pubmed.ncbi.nlm.nih.gov/33164741/
    • "Insomnia symptoms occur in a high percentage of the adult population, with estimates ranging from 35%–50%.6–8 Chronic insomnia disorder, defined by specific diagnostic criteria, has an estimated prevalence of 5%–15%.4,5,8 Chronic insomnia disorder is more common among women, those with lower socioeconomic status, and those with medical or psychiatric illness.6–8 The course of chronic insomnia disorder is typically measured in years or even decades, with spontaneous remission rates generally less than 50%.9 Isolated sleep-onset difficulties are less common than sleep maintenance difficulties, although a substantial proportion of people with insomnia report difficulties with both sleep onset and sleep maintenance."
    • Insomnia includes circadian rhythm disorders for the AASM: "The etiology of chronic insomnia disorder is multifactorial. Emerging research indicates that some individuals may be genetically predisposed to insomnia as a result of clock gene polymorphisms or other genetic factors."
    • NO SOURCE!!! WTF! "In addition, unhelpful behaviors can have a direct impact on the physiological systems controlling sleep. For example, variability in the timing of sleep-wake behaviors can create circadian dysregulation, and excessive time in bed can diffuse the homeostatic drive for deep sleep and can also lead to conditioned arousal."
    • Sleep diary is becoming a standard in insomnia assessment too: "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."
    • BEST: the various types of behavioral therapies, WTF with paradoxical intention and intensive sleep training, these are torture!
    • Wrist actigraphy is OK for objective assessment: "However, objective evidence of sleep disturbance is not required to establish a diagnosis of insomnia disorder. When objective information is deemed necessary, wrist actigraphy is a suggested option for clinicians to consider."
    • "Although discrepancies may exist between the magnitude of self-reported and objectively measured daytime impairments,31 daytime impairment from insomnia is what often leads patients to seek treatment. Thus, perceptions about daytime functioning are important to target with behavioral and psychological treatments. These daytime correlates of insomnia can be measured by a variety of methods, but a limited number of valid and reliable self-report instruments have been recommended for insomnia research.25 Because daytime fatigue is among the most common daytime symptoms of insomnia, various self-report questionnaires designed to assess daytime fatigue have been included in the studies included in this systematic review. Finally, the Dysfunctional Beliefs and Attitudes About Sleep (DBAS) scale32 is a sleep-specific scale that is often included in clinical insomnia trials to determine changes in unhelpful sleep-related beliefs that can serve to perpetuate insomnia."
    • All institutions recommend CBT-i !! WTF! "Assessment and treatment of chronic insomnia in adults has been addressed in numerous recent practice guidelines and clinical recommendation statements.3,30,33–36 Recent guidelines and statements that address comprehensive treatment for chronic insomnia uniformly support the use of cognitive-behavioral therapies (CBTs) as first-line treatment for the disorder.34,35,37,38 A report from the American College of Physicians34 recommended that all adult patients receive CBT for insomnia (CBT-I) as the first-line treatment method for chronic insomnia disorder. Likewise, in 2017 the Australian Sleep Association developed recommendations for a limited set of psychological and behavioral treatments for insomnia disorder, noting that CBT-I should be considered first-line treatment.39 The Australian Sleep Association also noted emerging evidence for mindfulness-based treatments for insomnia. The British Association for Psychopharmacology’s recent consensus statement also notes that CBT-I should be considered a first-line approach.38"
    • They were looking for clinical significance: "the members of the TF determined that their overall confidence that the estimated effect found in the body of evidence was representative of the true treatment effect that typical adult patients with insomnia would experience. The overall quality of the evidence was based on outcomes that the TF deemed critical for decision-making. The TF considered remission and responder rates as the most influential critical outcomes in determining the quality of evidence."
    • "Benefits vs harms: Based on any harms/adverse effects reported within the accepted literature and on the clinical experience and expertise of the TF, the TF determined whether the beneficial outcomes of using each intervention outweighed any harms."
    • "Drafts of the systematic review with supplemental materials and accompanying clinical practice guideline1 were made available for public comment for a 2-week period on the AASM website. AASM members, the general public, and other relevant stakeholders were invited to provide feedback on the drafts. The TF considered all the comments received and made decisions about whether to revise the draft based on the scope and feasibility of the comments. The public comments and revised documents were submitted to the AASM board of directors, which subsequently approved the final documents for publication."
    • For remission rate, they use PSQI, it's still a behavioral scale... "The PSQI is a measure of global sleep quality, and the ISI more specifically measures self-reported insomnia symptom severity, but both are categorical scales and provide total scores that can be evaluated across treatment and accepted scale-specific criteria for defining treatment response and remission.26–28 These categorical measures, especially insomnia remission, are increasingly recognized as being of primary importance for evaluating the benefits of treatment."
      • They also mix ISI and sleep diary metrics, but not actigraphy.
      • "Clinical cutoff of ≤ 8 indicating no insomnia, PSQI with a clinical cutoff of ≤ 5 indicating normative sleep quality. The task force considered remission and responder rates as the most influential critical outcomes."
      • BEST CONFIRMATION that only sleep diary measured outcomes should be considered critical in determining a therapy's efficacy: only sleep-diary reported outcomes are accounted for, it's great it's like what we already are doing! "The following outcomes were determined by the TF to be critical for decision-making when recommending the use of this intervention: sleep quality, sleep latency, WASO, remission rate, and responder rate; of these outcomes, remission rate and responder rate were considered the most important. The TF also determined that only diary-reported outcomes were considered critical, but data reported using other tools (PSQI, actigraphy, PSG) are also reported in this section for sleep quality, sleep latency, and WASO."
      • FLAW: remission rates are based on WASO (wake after sleep onset) or sleep latency
    • CBT-i: No clinically significant improvement in sleep efficiency, nor total sleep duration.
      • "Meta-analysis of 12 studies64–66,70,72,85,91,97,99–101,140 reporting total sleep time measured by actigraphy reported a clinical significant reduction of total sleep time of 19.15 minutes lower (95% CI: 7.00–31.29 minutes lower) favoring control at the post-treatment time for CBT-I as compared to control (Figure S70)." → when using actigraphy, we even find the opposite: that the behavioral interventions REDUCE total sleep duration (ie, increase sleep deprivation!), so they are actually detrimental!
      • "In subgroup analyses of patient populations, meta-analysis of 4 studies64,66,85,101 that used actigraphy in patients with insomnia and no comorbidities found a clinically significant 23 minutes lower (95% CI, 51.11 minutes lower–5.11 minutes higher) total sleep time for CBT-I as compared with control (Figure S71)."
      • But: "Meta-analysis of 25 studies60,61,63,64,72,73,75,77–80,85,87,89,90,94–97,99–101,106,107,119 reported a clinically significant 33% higher (95% CI, 28–39% higher) remission rate for CBT-I compared with control (Figure S25)." — but not necessarily with sleep diary or actigraphy
      • "Nine studies77,87,88,96,97,99,107,116 measured by PSG did not meet the clinical significance threshold at posttreatment for CBT-I as compared with control (Figure S73). In subgroup analyses of patient populations, meta-analysis of 3 studies87,88,107 reporting total sleep time measured by PSG among patients with insomnia and no comorbidities showed a clinically significant mean difference of 23.38 minutes higher (95% CI, 20.18 minutes lower–66.93 higher) total sleep time, favoring CBT-I over control (Figure S74). One study99 reporting total sleep time measured by PSG in patients with insomnia and comorbid psychiatric conditions reported a clinically significant 33.60 minutes higher (95% CI, 17.27 minutes lower–84.47 minutes higher) total sleep time for CBT-I at posttreatment compared with control (Table S28)."
      • LOL big bias in favor of sleep restriction: "the TF assessed that these harms are generally temporary, resolve as treatment continues, are small in magnitude, and tolerable to most patients. The TF noted that most RCTs of CBT-I did not include assessments of side effects associated with treatment, so adequate data on the direct harms associated with CBT-I are lacking. Based on the available literature and their clinical experience, the TF determined that the overall benefits of CBT-I strongly outweighed the harms for adults with chronic insomnia."
      • "The limited available data indicate that CBT-I is preferred to pharmacological treatment because it is perceived to have better long-term efficacy,150 to benefit daytime symptoms more, and to have fewer side effects."
    • BTI:
      • "Results of 1 study161 reporting beliefs and attitudes about sleep on the DBAS scale did not show any clinically significant BTI vs control differences (Table S37). The quality of the evidence for beliefs and attitudes about sleep was low because of imprecision and a risk of bias."
    • Sleep restriction:
      • low quality evidence to support its use, and several harms shown but the authors talk "about their experience"!!! LMAO!
        • "In the experience of TF members, these effects are usually transient and dissipate as treatment progresses and the time-in-bed restriction is eased as sleep improves. Hence the potential harms may occur in the early phases of treatment but decline as treatment progresses. At posttreatment, actigraphy- and PSG-measured total sleep time were shorter for sleep restriction vs control; however, these results are sometimes expected as part of sleep restriction therapy, and long-term follow-up data and TF experience suggest that there is a subsequent increase in total sleep time from the end of acute treatment to long-term follow-up timepoints. Based on their clinical experience, the members of the TF determined that the undesirable effects are minimal and that the balance of benefits vs harms strongly favors the use of sleep restriction therapy."
        • Horrible: https://www.verywellhealth.com/sleep-restriction-and-behavioral-therapy-for-insomnia-3015232 and https://www.verywellhealth.com/understanding-and-treating-waso-3015394
          • they use this ref as a source to claim that "If you do have trouble sleeping, you might convince yourself that you need to stay in bed for a longer period of time to make up for it. [...] You will cause a shift in your body’s circadian rhythm and diminish your drive to sleep." but it's not in the source! https://doi.org/10.1016/j.ncl.2012.08.011
            • It's recommending chronotherapy, but it's not saying what they think it's saying!
            • BEST (added): interesting RCT therapy for jet lag, melatonin works but only under dim light conditions, showing that light therapy is still the most powerful tool and can counteract melatonin: "One recent placebo-controlled study showed that bedtime administration of ramelteon (1 mg), a melatonin receptor agonist, reduced sleep latency in subjects traveling eastward across 5 time zones.126 However, this effect was only seen under dim-light conditions, indicating that light is still the most powerful stimulus for phase resetting of circadian rhythms." https://doi.org/10.1016/j.ncl.2012.08.011
            • Plus case study showing that even if can sleep soundly with zolpidem, if still struggles to wake up, it's likely a circadian rhythm disorder.
    • ISR:
      • "Based on their clinical experience, the members of the TF determined that the undesirable effects are minimal and that the balance of benefits vs harms favors the use of ISR." → they are practicing these, they are super biased! Of course they want their therapies to work!
    • They did not control for bright light exposure!!! + behavioral therapies content varies highly (especially CBT-i!)
      • "Variability of the intervention content and intervention delivery method across studies: Although studies generally described the components of treatment, there was not a sufficient number of studies to compare outcomes based on variations in content. For example, studies of CBT-I varied; for example, some included relaxation therapy as a component of the treatment package and some did not. In addition, the cognitive therapy strategies used across studies varied. Likewise, multiple biofeedback methods were used across studies, but there was not a sufficient number of studies to evaluate each specific biofeedback method relative to control. The TF therefore could not make specific recommendations about intervention content."
      • "The TF considered conducting a network meta-analysis to compare the various delivery methods, but because of the heterogeneity of samples included in the various studies considered, the TF decided against conducting such an analysis."
      • "Many of the single-component therapy studies were conducted more than 10 years ago, and there was not always sufficient information about the study methods or outcomes of interest."
      • "Small sample sizes in studies of some single-component therapies (stimulus control, sleep restriction therapy, biofeedback, paradoxical intention, and relaxation therapy): The quality of evidence for a number of studies was downgraded because of small sample size. As noted in number 3 above, this primarily was a concern for studies that were conducted more than 10 years ago."
      • "Dropout rates not considered: The analyses conducted did not consider treatment dropout rates and whether these rates differed between treatment and control conditions."
      • "Lack of data concerning adverse effects of treatments: In general, adverse events/effects from the treatments were not assessed or reported in the majority of studies included in this systematic review. Thus, such effects remain in question."
      • They mention that insomnia should not be considered secondary either: "the first ISR trial192 was published in 2007, the first BTI trial was published in 2011,154 and the first mindfulness trial was published in 2014.189 Because of the relatively recent development of these treatments, there are few studies on their efficacy and much of the research has been conducted by a small number of research groups. Thus, even with promising data, more studies conducted by different centers/researchers are needed to ensure replicability and generalizability. In contrast to these emerging treatments, some treatments (eg, biofeedback, relaxation therapy) emerged decades ago and thus reflect clinical conventions of those times, such as a focus on sleep-onset insomnia and conceptualization of most insomnia as a symptom of another disorder; therefore, they do not reflect current diagnostic or assessment standards."
      • "Studies are also needed to improve our understanding of the moderators and mediators of treatment response and methods to target CBT-I components based on patient presentation and insomnia characteristics."
      • "Although there is evidence of the long-term sustained benefits of CBT-I, similar data are not widely available for single-component treatments. There is limited research evaluating the long-term benefits of single-component treatments. Further, there is limited research examining any follow-up treatments after the delivery of a single-component therapy. Sleep hygiene is one of the oldest treatment approaches for insomnia in adults; however, recent evidence shows that it is no longer supported as a single-component therapy. Given that sleep hygiene is commonly delivered as single-component therapy in current practice, often without systematic follow-up, studies to develop and evaluate dissemination strategies for educating patients and providers about more effective approaches are needed."
      • "The TF noted that most randomized clinical trials do not include assessments of adverse effects associated with these psychological/behavioral therapies, so adequate data on the direct harms associated with them are lacking."
      • "The limited available evidence does suggest that patients’ acceptance of behavioral and psychological therapies is greater than their acceptance of pharmacological therapies150,193,194; however, not all patients will be interested in these approaches. Among the available psychological treatments themselves, it seems that patients may initially believe sleep restriction therapy to be undesirable; however, those who improve with this treatment rate it positively." → LOL of course if it works for them they will be happy! What about those for whom it didn't? And what is the rate of inefficacy? And drop-out (which can include patients that didn't see improvements but were rejected by the clinic as drop-outs)?
    • BEST ME: this AASM 2021 systematic review on behavioral therapies for insomnia show how biased this field is and how archaic the current treatments for insomnia are. They do not even take into account how sleep works, they disregard harm, and use the metrics that best suit their assumption that the therapies work.

• TOREAD: It's worth noting that a previous institutional review found cognitive behavioral therapies (CBT) to also be effective for a wide range of mental afflictions, such as anxiety related disorders. https://pubmed.ncbi.nlm.nih.gov/21348158/
  • "Nevertheless, insofar as a therapy is proposed for a given syndrome, improvement in the syndrome represents a common standard to assess the different therapies."
  • Psychanalysis is ineffective. But CBT is, especially for anxiety related disorders.
  • See also: https://fr.m.wikipedia.org/w/index.php?title=Wikip%C3%A9dia:Requ%C3%AAte_aux_administrateurs&oldid=191735188
  • and https://fr.wikipedia.org/w/index.php?title=Psychanalyse&oldid=191701702#Efficacit%C3%A9_th%C3%A9rapeutique

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