A related question; what has a better defined clinical phenomenology, sleep disorders or bipolar? Can something like EEG be used to diagnose bipolar? My impression is that the differential diagnoses for sleep disorders are cleaner (more empirically supported) than for bipolar, but depression and chronic fatigue are far more frequently diagnosed. (Would this be limited to bipolar; I could easily see this extending to clinical depression and its cousins.) So the question seems very important...sleep deprivation is pretty much the status quo for many people nowadays, and medical doctors seem to be pretty convinced they know when to prescribe happy pills.

A previous study has posed a question as to whether circadian rhythm abnormalities are associated with Bipolar disorder.

Link: http://www.ncbi.nlm.nih.gov/pubmed/24856561

From what I could tell from this study (albeit it's small) is that there are abnormalities throughout the sleep cycle for bipolar patients.

See: Mark Lukach (2017)  My Lovely Wife: a Memoir of Madness and Hope 

His wife had an attack of psychosis (unspecified).   After the second attack (post-partum psychosis), bipolar disorder was diagnosed.   All three attacks were clearly precipitated by sleep loss, eg.

"Last time it was only four nights of no sleeping before you were in the hospital" p 237

"When do you know that you've gone psychotic?  Its never been clear to me, it just gets kind of worse with each day that you're not sleeping" p 238

"She hasn't slept well the last few days.  I don't think she slept at all last night.  Three years ago something similar happened and she went psychotic." p 177

Sleep or lack of sleep is definitely a factor.  Also following a predictable schedule is a deterrent.  This is common sense though.

"Sleep or lack of sleep is definitely a factor.  Also following a predictable schedule is a deterrent.  This is common sense though."

I am trying to make the point that lack of sleep is a specific and not just a general stressor.  For example, I do not recall anyone saying it triggers schizophrenia.

"H Jean, Self Determination Assistant for the Disabled (2010-present)

Answered Jun 29

I have bipolar II disorder. My manic episodes aren't as noticeable as someone with bipolar I. And normally my friends and family are the only ones who notice. I tend to get by on very little sleep, I talk fast and get paranoid that people are angry with me and I tend to obsess over things and spend money I don't really have as well as become easily agitated. My anxiety attacks are more frequent and easily triggered as well. Sleep is also extremely important, not enough sleep can cause a major bout of depression for me and if I go days without sleep I usually end up being hospitalized. My Manic episodes aren't as severe as with bipolar I. However my depressive episodes are much more severe and more frequent. My depression was so bad when I was 19 I underwent an impatient stay for electro convulsive (shock) therapy. "

Quora   Accessed July 9 2017

I think no. The sleep disorders are involved in bipolar (tripolar) disorders, but rare etiologically,

"I am trying to make the point that lack of sleep is a specific and not just a general stressor.  For example, I do not recall anyone saying it triggers schizophrenia."

I do believe that bipolar disorder can be considered a sleep disorder and that lack of sleep can trigger psychosis, but that is one of a number of factors (stressors) that are in a constellation leading to psychosis. For example you can't tease out whether psychosis in a person was caused by an inability to sleep, leading to rumination or paranoia and triggering psychosis or whether lack of sleep caused by dour rumination. or paranoia may lead to psychosis. The circumstances seem to gather as a constellation to me, like storm clouds gathering.

That is more the depressive side of it, then of course there is mania.  Don't mania and lack of sleep exacerbate each other? Or is lack of sleep the only way to achieve mania.  One example that mania is not necessarily triggered by lack of sleep is the triggering of mania in manic depressive patients by a relatively high dose regime of the antidepressant fluoxetine.

You see lack of sleep is more general when leading to psychosis through more than one avenue.

"you can't tease out whether psychosis in a person was caused by an inability to sleep, leading to rumination or paranoia and triggering psychosis or whether lack of sleep caused by dour rumination. or paranoia may lead to psychosis." 

 I have been putting up what I think are reliable reports from bipolar patients and their relatives where the temporal progression is quite clear -- sleep loss is the first symptom. Post-childbirth there is sleep loss in the normal population, so this is the parsimonious trigger in puerperal psychosis.  

"One example that mania is not necessarily triggered by lack of sleep is the triggering of mania in manic depressive patients by a relatively high dose regime of the antidepressant fluoxetine."

"Why does Fluoxetine cause insignificant insomnia? - iCliniq

https://www.icliniq.com › ... › Medical Forum › Psychiatry › FluoxetineCached

Hello,Welcome to icliniq.com.Fluoxetine is known to cause significant insomnia in many patients as it is an activating drug.Even if it is taken early morning, it can."

Then you are saying that insomnia or lack of sleep is the cause of psychosis in bipolar patients, and rumination, paranoia triggered by poor home life or genetics are merely coincidental artifacts, not causative agents that lead to psychosis?  It all boils down to insomnia?  That is the specific cause of psychosis in bipolar patients?  I guess that makes sense that it is the final brick in the wall, but it is not the only factor.  The stimulus and specific cause is earlier in the sequence and leads to insomnia.  I believe that a constellation of factors is necessary to lead to psychosis.  As I agreed this is a sleep disorder, but not all persons experiencing insomnia become psychotic.

"Then you are saying that insomnia or lack of sleep is the cause of psychosis in bipolar patients, and rumination, paranoia triggered by poor home life or genetics are merely coincidental artifacts, not causative agents that lead to psychosis?"

   I am pointing out that many persons independently, too many to be coincidental, think the insomnia is the prime mover.  It is only likely to end up in manic-depression if there is also a latent instability of body rhythms and physiology.   I think the psychological changes are epiphenomena.

   One prediction that now occurs to me but which I have not checked is that flying and jet lag should also trigger bipolar psychosis in susceptible individuals. 

" It is only likely to end up in manic-depression if there is also a latent instability of body rhythms and physiology. "

Cheers, instability is at the molecular level and how the organism resonates determines whether insomnia is a crucial factor (in precipitating psychosis). And so in other words, to possess that latent instability the subject must have a specific set of characteristics leading to insomnia that triggers psychosis.

"One prediction that now occurs to me but which I have not checked is that flying and jet lag should also trigger bipolar psychosis in susceptible individuals"

                          I have now done a quick check:

"Aust N Z J Psychiatry. 2016 Mar;50(3):220-7. doi: 10.1177/0004867415598844. Epub 2015 Aug 12.

Effect of transmeridian travel and jetlag on mood disorders: evidence and implications.

Inder ML1, Crowe MT2, Porter R2.

Author information

Erratum in

Corrigendum. [Aust N Z J Psychiatry. 2016]

Abstract

OBJECTIVES:

Given the sensitivity of individuals with mood disorders to circadian disruption, transmeridian travel would likely be a high-risk endeavour leading to onset or relapses in mood. A systematic review was undertaken to identify the evidence of the impact of transmeridian travel on people with mood disorders.

METHODS:

Databases search included the following: CINAHL, MEDLINE, PsycINFO and manual searching using the keywords jetlag, transmeridian travel, circadian rhythm disruption, mood disorder, bipolar, major depression, seasonal affective disorder, depression, mania and hypomania.

RESULTS:

Only three studies were identified that related to transmeridian travel and jetlag in people with mood disorders. There is some suggestion that transmeridian travel does appear to precipitate mood episodes with an increased rate of episodes of depression with westward compared with an increased rate of manic/hypomanic episodes with eastward travel. Individuals with a previous history of mood disorder appear to be more vulnerable if adherence to medication is compromised."

More evidence that sleep deprivation is not just a general stressor, but is specific to bipolar disorder:

"Can sleep deprivation cause schizophrenia and psychosis?

 ...Request From Quora

Requesting From Quora...

Hathor Gaia, personal experience

Answered Dec 16, 2016

Sleep deprivation is one of the leading causes of psychosis. You need a certain amount of REM sleep to be mentally stable…if you don’t sleep for a long time, like 36+ hours then your subconscious can start leaking in and it can become quite difficult to distinguish between “waking dream” state and consensus reality.

This doesn’t cause schizo and generally resolves itself with adequate sleep.

Psychosis can point to schizo for diagnosis purposes, but only if everything else is ruled out like drugs, sleep deprivation, injury/trauma, malnourishment, fever, or some other medical issue.

You can’t automatically assume that because someone has had a psychotic break that they are also schizophrenic.

You can’t “catch” schizo by staying up too long, but psychosis is no joke. If you are having sleep-deprivation related psychosis due to something like insomnia rather than a decision to “pull an all-nighter” you should seek medical treatment. Otherwise, take a day off and catch up on your sleep and the psychosis should subside...

 John Taylor, Outcome? Train go boom.

Answered Dec 16, 2016

 It can cause psychosis, I know from personal experience. I’ve been on the verge of falling asleep or just really tired. For example, at exams last year, I was very, very tired. To the point that on the math exam, I was hearing discussions between voices, and I was writing down my responses to them as answers. That could be just from being on the verge of sleeping, or not. I’m not entirely sure.

As for causing schizophrenia, I doubt it. Schizophrenia, as far as I know, is thought to be caused by a problem with neurotransmitters. If just sleep deprivation could do this, I don’t think we would survive much more."

"Only three studies were identified that related to transmeridian travel and jetlag in people with mood disorders. There is some suggestion that transmeridian travel does appear to precipitate mood episodes with an increased rate of episodes of depression with westward compared with an increased rate of manic/hypomanic episodes with eastward travel. Individuals with a previous history of mood disorder appear to be more vulnerable if adherence to medication is compromised."

Interesting

"Interesting"

   If true, then it should have been already noted by some of the famous bipolar celebrities.  Carrie Fisher had a fatal attack on a plane, and had complained previously of jet lag, but I do not know at this stage if she had connected relapses with jet lag.   

Anthony, 

I just read that bipolar disorder has a connection to sensitivity to sleep patterns or Circadian rhythms in connection to the Clock gene..  I believe that to be true empirically.  All of the persons that I know that are bipolar or have those tendencies have major sleep disturbances.

"Ann Med. 2002;34(5):394-400.

Human clock genes.

Piggins HD1.

Author information

Abstract

Rhythmic variations in physiological and behavioural processes are mediated by both endogenous and exogenous factors. Endogenous factors include self-sustaining biological pacemakers or clocks which in the absence of strong external influences self-sustain periodic rhythms in such diverse physiological and psychological processes as core body temperature, food intake, cognitive performance and mood. Clocks with endogenous periods near or at 24 h (called circadian clocks from the Latin, circa dies, meaning about one day) have been documented from prokaryotes to single cell eukaryotes to multi-cellular, complex animals such as flies, rodents and humans. Over the past few years, a revolution in the understanding of the molecular basis of these clocks has led to the identification of a number of core clock genes and their proteins, and the development of elegant feedback models to explain the molecular gears of circadian clocks. At least eight human orthologs of mouse core clock genes have been identified, and polymorphisms in two of these, hClock and hPer2, have been implicated in human sleep disorders. Remarkably, knowledge of these core clock genes and the development of sophisticated reporter systems to monitor clock gene promoter activity have led to the astonishing observation that our body is actually composed of millions of cellular clocks and oscillators whose co-ordinated activity gives rise to pronounced daily, monthly, and seasonal rhythms in physiology and behaviour. An idea that is gaining favour is that our physical and mental well-being is probably determined by the appropriate phasing of these millions of cellular clocks with recurring, meaningful events in the environment"

I thought this abstract from NCBI might be of interest to you.  it is easy to see wth all of the potential clocks needed to be in sink how a single disturbance in one allele might lead to a sleep disorder affecting a mood disorder.

"disturbance in one allele might lead to a sleep disorder"

  My point is that I do not think it is simply a genetic chain reaction, but requires an environmental trigger.  It is very important to distinguish the two possibilities, since steps can be taken to avoid sleep disruption.  The causal chain can be teased out by looking at circumstances where sleep disruption is an independent imposed event, not part of the bipolar disorder, as here below in shift work:

  #8 Innerzone

Grand Magnate...

 Re: Night Shifts...now my life is falling apart.

 RB! My last job often involved that shift and it really can be rough with [bipolar].   It might be that for some, a full-on shift in one's schedule helps ameliorate it, but that can be hard to do, depending on circumstances. In my situation, it wasn't feasible, as I also worked days and occasionally swing shift. Days worked and shift worked were random. That's undoubtedly the worst situation(!) One problem with that shift (in my case) was that instead of being tired come morning, I was wired. In a bad way. Also, sometimes visual perceptions went wonky. Rather freaky driving home sometimes.   There were some hallucinations, even after sleep, both visual and motion. Those things can happen to "normals" too, but I'd have to guess we're more prone to it. I never knew where one left off and the other began. 

If you are able to switch to days (or even swing shift), I'd really recommend it. Personally, I didn't find pills helpful. I very rarely have trouble staying awake for ridiculous spans of time, but on the rare sleepyhead occasion, caffeine pills were horrid. Talk about feeling shite. At the other end, trying to "un-wire" (mind you, "wired" did not require assistance) took too much chemical intervention, and even then was only successful for a few hours at best, and certainly nothing even approaching a decent amount of sleep. Then stuck in mental limbo-land. Oh. And med adjustment had no effect as it was not a med issue, but a circadian one."

"disturbance in one allele MIGHT lead to a sleep disorder"

Might is the key word here

  "My point is that I do not think it is simply a genetic chain reaction, but requires an environmental trigger."

Is bipolar disease a sleep regulation disorder?. Available from: https://www.researchgate.net/post/Is_bipolar_disease_a_sleep_regulation_disorder?view=596b4596f7b67e95dd48d0ab [accessed Jul 16, 2017].

Of course it does. Nurture/Nature.  It is both environmental and genetic.  The odds are that when you have the genetic predisposition and that happens to predispose one to a sleep disorder then eventually the subject will encounter an environmental trigger that will set off the genetic predisposition.  But the trigger is not the determining factor since there is a more or less specific age when this phenomenon occurs.  The trigger just happens to be hanging around waiting for the right opportunity to affect the subject and his/her predisposition for this very specific sleep disturbance.

Age onset of psychotic versus non-psychotic bipolar illness in men and in women

This work was presented as a poster at the APA Meeting, May 15, 2000, Chicago, IL

. Author links open the author workspace.AysegulYildiza. Numbers and letters correspond to the affiliation list. Click to expose these in author workspaceb. Numbers and letters correspond to the affiliation list. Click to expose these in author

the author workspace.Gary S.Sachs

Abstract

Objective: To investigate the relationship between psychotic symptoms and age at onset of bipolar illness. Method: The charts of bipolar patients treated at the Massachusetts General Hospital Bipolar Clinic were reviewed for age of first affective episode, demographics and history of psychotic symptoms. Results: Data was obtained for 328 bipolar patients (56.7% females) of whom 42% had psychotic symptoms sometime through the course of their illness. Overall, there was no significant difference in age of onset between the psychotic and non-psychotic groups. Additional analysis carried out separately by gender found significant difference for males but not for females. Age at onset for psychotic males was significantly lower than non-psychotic males. Psychosis was less common in males than females. The mean age of onset for psychotic males was significantly lower than psychotic females. Conclusion: This result implies that developmental physiology underlying psychosis in bipolar illness MAY differ for men and women. The different proportions of males and females in the study samples MAY account for conflicting results reported in the literature for age of onset of psychotic bipolar illness.

Because there is no significant difference in age of onset between the psychotic and non-psychotic group, because when additional analysis carried out by gender a significant difference in both incidence of psychosis was less common in males than in females, and the age of onset for psychotic males was at a significantly lower than psychotic females and lastly because common triggers are nearly always constant in an environment and so should be a non-factor since they are ubiquitous this suggest the main predisposing impetus would be genetic.  If the whole chain reaction was solely due to a trigger in the environment then a more random age of onset would be seen in the subjects but "Overall, there was no significant difference in age of onset between the psychotic and non-psychotic groups."

Age of onset of mental disorders: A review of recent literature

Ronald C. Kessler, PhD, G. Paul Amminger, MD, Sergio Aguilar‐Gaxiola, MD, PhD, Jordi Alonso, MD, Sing Lee, MD, and  T. Bedirhan Ustun, MD

Abstract

Purpose of the review

To review recent epidemiological research on age‐of‐onset (AOO) of mental disorders, focusing on the WHO World Mental Health (WMH) surveys

Recent findings

Median and inter‐quartile range (IQR; 25th–75th percentiles) of AOO is much earlier for phobias (7–14, IQR: 4–20) and impulse‐control disorders (7–15, IQR: 4–35) than other anxiety disorders (25–53, IQR: 15–75), mood disorders (25–45, IQR: 17–65), and substance disorders (18–29, IQR: 16–43). Although less data exist for non‐affective psychosis, available evidence suggests that median AOO is in the range late teens through early 20s. Roughly half of all lifetime mental disorders in most studies start by the mid‐teens and three‐fourths by the mid‐20s. Later onsets are mostly secondary conditions. Severe disorders are typically preceded by less severe disorders that seldom are brought to clinical attention.

Bipolar disorder is triggered at a fairly predictable age range (25 to 45) in life.  Since environmental factors constantly surround us and most persons with insomnia do not succumb to psychosis it is necessary to have BOTH a genetic predisposition to psychotic bipolar disorder and a triggering event that is specific to pushing the sleep disorder lurking within towards a psychotic break.  By the way.  It is not likely just one trigger, one time.  It is a series of potentially more than one trigger in which the straw breaks the camel's back.

"Sleep disorder or deprivation has often been noted in bipolar disorder, but rather than regarding it as a symptom of the disease, could it not simply be a universal trigger for it?"

I am not sure that "sleep disorder" is simply a universal trigger for bipolar disorder.  I have cited the "Clock gene" and I believe that the genetics suggest that the sleep disorder is a direct result of faulty genes driving the aberrant action seen in Circadian rhythms run amok.  The faulty Clock genes disrupt this cycle known as Circadian rhythm causing sleep deprivation which after a series of environmental insults (triggers) end in a psychotic break. Apparently the insults take about 25 to 45 years to precipitate a break, either that or the genes code for a specific age when psychosis occurs.  Again one is never sure whether nurture or nature prevails.

Is bipolar disease a sleep regulation disorder?. Available from: https://www.researchgate.net/post/Is_bipolar_disease_a_sleep_regulation_disorder?view=596b16f6f7b67e73c86f4cbd [accessed Jul 16, 2017].

"Again one is never sure whether nurture or nature prevails."

   As I have already mentioned, there are circumstances where one can be reasonably certain that sleep disruption is externally imposed not internally generated, eg jet lag, shift work, childbirth, etc.   It should be possible to do a systematic survey or even a randomised control trial of sleep as a trigger (for mania?). 

     John Read does not believe there is an illness called schizophrenia.  "This second Edition of Models of Madness challenges the simplistic, pessimistic and often damaging theories and treatments of the 'medical model' of madness".  One medical factor he has ignored is sleep disruption, despite recounting this highly revealing personal observation in the Preface to the First Edition (2004):

"After four days in Stavanger I plummeted from an enormous high (partly jet-lag, partly short Norwegian nights, but mostly the excitement of finding so many kindred spirits in such a short time) to an exhausted low in my one-night Oslo hotel, missing my new friends already.  (I remember thinking I was too old to get bi-polar disorder).  Anyway, the next morning I found the solution to my low affect."

Anthony,

Do you believe there is an illness called schizophrenia?  If so are schizophrenics psychosis triggered by lack of sleep or dysfunctional sleep patterns?

"Do you believe there is an illness called schizophrenia?  If so are schizophrenics psychosis triggered by lack of sleep or dysfunctional sleep patterns?"

   I put the previous quote up because it is an interesting and relevant personal observation, all the more valuable from a leading light in the anti-psychiatry movement, someone who does not believe schizophrenia is a medical illness.  Curiously, his textbook says nothing about bipolar disorder, which from his quote above he seems to accept is a medical condition.    There is enough similarity between the two types of psychosis such that either they both are medical illnesses, or neither are.   That said, one of the differences as shown up by the entries here is that only bipolar seems to be triggered by sleep dysregulation.

   I think schizophrenia is a real medical disease, though not a primary brain disorder.

   More evidence supporting the link between childbirth, manic-depression and sleep loss: 

"Mania coming on soon after confinement is more dangerous, as regards the life of the patient, than melancholia which comes on while suckling.   Constant want of sleep, and increasing exhaustion...are of unfavourable omen, even if the mind be apparently improved;   while good nights...are held out as favourable prospects, even though the mind continue disordered.   With regard to its duration, mania is less apt to be permanent than melancholia...

   With regard to the causes of puerperal insanity, in a large proportion of instances it arises in patients in whose families derangement has already appeared, and the individuals themselves have been persons of nervous temperament."  

R Gooch  Disorders of the mind in lying-in women.   Lond Med Gaz 1829;4:48-56

   Whilst sleep disorder may be a result of mania, it may also be a primary rather than secondary symptom:

"What are the telltale signs of bipolar disorder?

 Rachel Schwister Wife and momma of 2, boss lady..

Updated yesterday 

   Well, I will speak from experience because I get to live with it.

A sure sign someone is bipolar is they will shift moods with a quickness and for no apparent reason...

Next thing is you will notice behavior patterns. When one is manic, watch out! I can be a handful lol. I have lots of energy, don't sleep, I talk a lot and rapidly, and I make no sense...

There's also psychosis. Not all get to endure this hellish part of bipolar. Thankfully I've only been through it a few times. It was from not sleeping and being paranoid all during a manic or mixed episode... I may have been well and seen it…But I doubt it. Paranoia, another part of the fun. Not."

Quora Aug 11 2017

As a person who survived the episode of bipolar affective disorder, I can say the following: I Have never had sleep disorder before the mental disorder happened. But mental illness had led to sleep disturbance (sleep 4-5 hours a day for 10 days). 

That is, I think that sleep disorder cannot be the cause of bipolar affective disorder, this is its consequence. However character of sleep can have a significant impact on the course of the disease. That is, if after a mental disorder has happened you 

can achieve a normalization of sleep, this will greatly ease the symptoms right down absolute healing. I take good care of my sleep, that is, I strive to sleep 8 hours a night and wake up naturally (without an alarm clock). And this is one of the reasons why I have been able to maintain my peace of mind for 9 years despite of the severity of symptoms experienced by me. I understand that a sleep of bad quality can cause a relapse.

"I understand that a sleep of bad quality can cause a relapse."

   That is the main point I have been making.  It is not clear what triggers there are in the absence of sleep disorder, though it is quite possible that there do not need to be any triggers at all. 

I've actually come to believe that bipolar/schizoaffective disorders are developmental problems, specifically a processing problem.  Everything appears to be moving fast under certain conditions and so the body and mind attempt to compensate by speeding up, and not sleeping because of the hype, to function under those circumstances.  This compensation cannot be maintained (manic state).  The consequence of that compensation is the shorting out of the nervous system that can potentially lead to psychosis and or eventually a depressed state because of the energy drain.  The oscillation is observed as mood swings, the compensation period being manic, the aftermath leading to depression and psychosis and agitation being intermediate.

And by processing problem I mean that the afflicted persons are unable to filter out incoming information like the normal population is able to do by discarding what seems to be irrelevant. This is appropriate prior to teenage years in order to make sense of the world, however as a person ages the information stored becomes unmanageable in the bipolar individual because of the sheer volume, and so the person must process during down time unlike the majority of the population. Because this the processing capacity cannot meet the relatively larger amount of information presented to the brain (an imbalance between the processing capacity and the informational input), the person struggles to keep up with the unfiltered information until unable to cope with processing, then the disease is expressed.

"I've actually come to believe that bipolar/schizoaffective disorders are developmental problems,"

   For over a century some experts have recognized that schizophrenia is a developmental disorder, in other words, that abnormalities are present in infancy and lead to increased deviation from normality during childhood.   Modern research, especially cohort studies, has delineated some of these problems.

   I do not think the same can be said for bipolar disorders.   Is there any evidence for meaningful physiological anomalies in pre-illness childhood? 

"Everything appears to be moving fast under certain conditions and so the body and mind attempt to compensate by speeding up, and not sleeping because of the hype, to function under those circumstances.  This compensation cannot be maintained (manic state)."   

    This is an interesting or even insightful idea.   However, as just explained, I think it may only apply to bipolar adults.

"  For over a century some experts have recognized that schizophrenia is a developmental disorder, in other words, that abnormalities are present in infancy and lead to increased deviation from normality during childhood.   Modern research, especially cohort studies, has delineated some of these problems.

Is bipolar disease a sleep regulation disorder?. Available from: https://www.researchgate.net/post/Is_bipolar_disease_a_sleep_regulation_disorder?view=5995c5ba217e2096d918d764 [accessed Aug 18, 2017]."

" I do not think the same can be said for bipolar disorders.   Is there any evidence for meaningful physiological anomalies in pre-illness childhood?" 

I haven't looked into that and don't have time at this time.

Schizoaffective disorder is not schizophrenia, just as it is not bipolar disorder.  It does however have elements in common with both.  I believe that these conditions, schizophrenia, schizoaffective disorder, and bipolar disorder overlap in signs and symptoms.  They appear to exist on a continuum and I believe that they may have genetic abnormalities in some of the same genes.  That is my thought.  Others may have that as a theory, probably so, however I don't have time this morning to look into it.  I am going to witness the total solar eclipse that is crossing the USA on Monday. 

I am of the belief that the sleep disorder is a direct consequence of the inability to process information when the system ultimately becomes overwhelmed by the sheer volume of sensory, intellectual, emotional, ( you get the idea) input. The person is acutely aware of the ambiguity surrounding this information, can see both sides, but has difficulty resolving the ambiguity and has to live with it until enough information is gathered to resolve the question. It is a gradual process.  If it is a sleep disorder that consequently overwhelmingly floods the systems ability to process the information coming in or it is a developmental problem that is a processing issue that leads to sleep difficulties is a "which comes first the chicken or the egg".  I vote for the second scenario.

Is bipolar disease a sleep regulation disorder?. Available from: https://www.researchgate.net/post/Is_bipolar_disease_a_sleep_regulation_disorder?view=5995c5ba217e2096d918d764 [accessed Aug 18, 2017].

http://www.mayoclinic.org/diseases-conditions/schizoaffective-disorder/home/ovc-20258872

There are some relevant observations here on sleep in bipolar disease (Puerperal Mania) by F H Ramsbotham in Lond Med Gaz 1835;16:99:

"It is not confined to any kind of constitution or rank in life;  but those of acute feelings and excitable temperaments are by far more frequently its victims...

There are two distinct and well-marked forms of puerperal insanity;  the one attended with great excitement and furious delirium, the other characterized by the features of low melancholy...

The more rapid the pulse, the more perfect the want of sleep, the greater the accompanying fever...

These symptoms will sometimes shew themselves rather suddenly, on the patient's wakening from a disturbed and unrefreshing sleep...

As the disease gains ground there is great want of sleep, scarcely the least rest being obtained for many successive days and nights...

The state of melancholia is characterized by great dejection...Her nights are sleepless, and she gets no rest in the day...

A large proportion occurred in patients in whose families disordered minds had already appeared... "

"How can bipolar disorder affect your judgment?

Sam Staskiewicz    Schizoaffective w/ substance abuse problem...

Answered Sep 8  [Quora]

Everything is extreme.  I can only explain how much everything is extreme to people who have been manic or have done meth, cocaine etc   Extreme optimism, extreme love, extreme horniness, extreme anger, everything seems urgent, the present matters beyond profoundly - that is the source of the bad judgment along with sleep deprivation."

"Everything is extreme"

Everything is extreme in that the individual's perceptions are extreme and so the person overreacts to any input thus triggering an extreme reaction.

"the person overreacts to any input"

    Sleep deprivation can alter the peripheral sense organs.  Hence, the person may be reacting normally to abnormal input.   Any serious cortical malfunction is very unlikely in bipolar patients given their normal IQs.

"Any serious cortical malfunction is very unlikely in bipolar patients given their normal IQs"

I don't understand this assertion.  The brain is so complex.  Why would having a normal IQ preclude having a serious cortical malfunction.  Bipolar patients experience hypersensitivity long before they experience any form of sleep disturbance along with over-reactions to innocuous input perceived as a threat in childhood.  I believe that the hypersensitivity is innate and the basic reason that overreaction to the environment occurs due to overstimulation.  I believe this assault on the nervous system leads to the sleep disturbance.

"Why would having a normal IQ preclude having a serious cortical malfunction."

   This is based on reviewing IQ data in children.   Those with proven or generalised cortical maldevelopment have reduce IQs (usually g or non-verbal IQ).   I do not know of any disorder in children or adults where there is generalised cellular or biochemical abnormality but IQs remain normal.  If there is a generalised attentional disorder causing serious problems with living, it is serious enough to affect at least some of the many Wechsler subtests, for example.

Coming from someone who scored very highly in an IQ test in the 1960's as a child, I believe that IQ tests are hogwash.  There are all sorts of intelligence parameters within our species and only a very narrow set is defined by accepted intelligence testing.  I can imagine serious cortical functioning with being very gifted.  Maybe conventional IQ testing doesn't demonstrate that, but I think that is the reality.  Some forms of intelligence are simply not generally valued.

"only a very narrow set is defined by accepted intelligence testing."

  The most important and relevant factor, g, is the general intellectual ability underlying performance on a very wide range of cognitive tasks.   Whatever the test battery used, the extracted g is identical.

   In my opinion, and of others I believe, the findings on IQ have been the most secure and important in the history of psychology.  See this excellent summary

https://en.wikipedia.org/wiki/Intelligence_quotient

I believe that every human being has something wonderful to offer that is relevant and awe inspiring.  IQ's are only a narrow view of what is valued in society.  All humans and animals have their own unique intelligence and that cannot be quantitated because it is different for each individual and not currently valued by society to the extent that tests do not exist for the many talents that are displayed by individuals.  Some of these individuals may have "cortical damage" but it does not inhibit them from expressing exceptional talents or hinder them from possessing traits that are not detectable because of the lack of sophistication for defining them.  Who can say what goes on in the mind of someone who is not able to express themselves in a conventional way.  I used to work in a nursing home as a teenager. There was a woman who could not express herself verbally, however it was obvious from her reactions to circumstances that she had an opinion and although she appeared to most to be just a "warm body" her mind was active and lively with intelligent thought.  I can imagine being trapped in a body that lacks the means to communicate in a way that most people could appreciate while having brilliant thoughts that could not be expressed. There are example of this.  Some persons now can express thoughts otherwise lost by tapping out these ideas on computers that simulate a voice.  I have had numerous concussions.  I believe that I have cortical damage.  It hasn't made me any less intelligent but it has impaired my speed to develop thoughts and has caused me to lose focus or become distracted making it difficult to express my ideas as quickly as most. People may perceive me as "slow" because of my response time.  Their perception of my intellect is masked because of my inability to express ideas in a way that they can understand and most will not have the patience to adjust to my disability.

"I have had numerous concussions.  I believe that I have cortical damage.  It hasn't made me any less intelligent but it has impaired my speed to develop thoughts and has caused me to lose focus or become distracted making it difficult to express my ideas as quickly as most."

    For numerous different reasons, I do not believe concussion has anything to do with the brain.  All the symptoms of concussion and the post-concussion syndrome are consistent with subtle damage to the inner ear.  If concussion were due to cortical damage, it would tend to be accompanied by neurological signs, whereas it has otological accompaniments (dizziness, sensitivity to noise, etc, etc).

"All the symptoms of concussion and the post-concussion syndrome are consistent with subtle damage to the inner ear."

Not all of my symptoms are consistent with subtle damage to the inner ear.  The ones that you mentioned were very shortly lived.  The longer term ones like inability to make connections with words and memories, missing letters and words when reading, transposing letters in reading, short distracted attention span and slower thinking process seem to be more in line with synaptic damage than with inner ear damage.  In short, my brains were scrambled after my last major concussion when T boned by a truck traveling at about 25 to 30 MPH...

"The ones that you mentioned were very shortly lived."

    If you are saying you had such symptoms, I rest my case.

    Labyrinthine concussion, aka Meniere Spectrum Disorder or endolymphatic hydrops, can certainly lead to persistent and disturbing psychological symptoms, including problems with fatigue, concentration, depersonalisation, and memory, best summed up by the phrase Brain Fog.   I am not sure about the reading problems, but still think they were more likely due to disordered vestibular control of eye movements than to a stroke or brain lesion.

Why can't the various symptoms be explained by labyrinthine concussion, as well as brain damage.  I don't see how labyrinthine concussion can account for my loss in continuity for storage of new short term memories, even after 4.5 years.

"Why can't the various symptoms be explained by labyrinthine concussion, as well as brain damage"

  Occam's razor.

"I don't see how labyrinthine concussion can account for my loss in continuity for storage of new short term memories"

Meniere’s Disease and The Battle of Brain Fog – Part 1

Posted by Glenn  [on mindovermenieres.com]

"When battling Meniere’s disease, with all its hardships and difficulties, I find that sometimes it’s the lesser symptoms that are the most frustrating. Even if you happen to have gained some semblance of control over the vertigo, learned to ignore the tinnitus, and live an overall healthy lifestyle, brain fog can quickly derail any momentum you may have working for you. It can bring your productivity to a grinding halt and can rob you of precious hope.

Brain fog is an insidious phenomenon. It will not handicap you like vertigo will, but can impair your quality of life considerably. So what is brain fog? Loosely defined, brain fog is a form of fluctuating cognitive impairment that affects concentration, executive function, decision making, memory, and word recall. For sufferers of Meniere’s disease and other vestibular disorders, brain fog is a seemingly ever-present clouding of consciousness and an unfortunate reality."

Quora

Are bipolar hallucinations random, or are they triggered by things like stress?

Answers:  Request From Quora...

Thomas Engelthaler, PhD in Psychology, passionate about positive lifestyle

Answered Sep 28

I am not an expert on bipolar disorders, so take my answer with a grain of salt...

For example, I’d not be surprised if people with bipolar disorder have a lower stress threshold at which hallucinations are likely to happen. On a scale from 1–10, a person with bipolar disorder might experience hallucinations at a stress level of 8, whereas a person not diagnosed with bipolar disorder may need a level of 9. Same with lack of sleep - not sleeping for a night might be OK for some, but could be very difficult if you are mentally imbalanced to begin with.…

Kadijah Michelle Kastriba...

Answered Sep 28

I can only speak for myself.

When I hallucinate, it's usually because I'm not doing something I should be doing to take care of myself.

9 times out of 10 that means I'm following good sleep hygiene.

Drinking and drug use can cause hallucinations too, but after dealing with that enough times, I've learned to stay away from the mind altering stuff.

Stress just wears me out and makes me cranky... 

Kathleen O'loughlin, Have worked through severe mental health issues inc bipolar and depression

Answered Sep 28

No, and I’ve talked to doctor about this. On a manic high you see, you can’t sleep or can barely sleep. Anyone goes without REM long enough they will hallucinate. I’ve only had hallucinations at this time, when my body is way way suffering from lack of sleep. Usually what I call ‘fringe hallucinations’. Walls moving, music that isn’t there, hanging plants swinging in differently pattern. In S. Calif it could be an earthquake but..."

Thank you for your explanation.

"Thank you for your explanation."

    I assume you are referring to Glenn's explanation.  I find by looking around the patient forums on the Internet, I find out more about the psychological sequelae of Meniere's disease and related conditions (and other diseases as well) than from 150 years of the medical literature.

Yes, Glenn's.  Sometimes different conditions have similar symptoms.  I am not sure that my condition is related to Meniere's disease.  I still think it might be damage to the ability to connect to  my memories and I think that it could be reparable if I work at it.  I have used a technique to overwrite disturbing experiences and replace them with new more positive experiences.  During great stress the old memories still override the newer ones so I try to minimize stress in my life as much as possible.  I believe that there are ways to repair some brain damage if a person can use targeted techniques to focus on the repair.  I am having some success with my short term memory being more reliable using a targeted approach.  I guess this is really not the forum to express these ideas, but since we have digressed I just want to make the point that sometimes different conditions have similar symptoms.

There are two logical fallacies in the first sentence below. Contrary to a common view nowadays, accidents or bad events usually have more than one cause. Secondly, it does not follow that something as serious as psychosis must have an external trigger, there may be an undetected internal trigger or there may even have been a random genetic event. Nevertheless, a plausible link between sleep deprivation and bipolar disorder is indicated here (The Times Nov 11 2017 p 21):

"Work overload and improper management by his superiors are the only possible cause of Mr Ross's mental breakdown and his development of bipolar disorder at this stage in his life [age 50]...

His psychiatrist said: 'He was permitted to take on superhuman amounts of work and over this time he was increasingly working in a completely all-consuming way to get the tasks done at work'. He slept less than five hours a night and his symptoms included 'fairly clear-cut increases in energy, enthusiasm, confidence and reduced need for sleep, which constitutes a hypomanic episode."

"Contrary to a common view nowadays, accidents or bad events usually have more than one cause."

You've got this wrong about being a fallacy. Look at symptoms of disease. Many ailments have very similar signs and symptoms, but have more than one cause.

"it does not follow that something as serious as psychosis must have an external trigger, there may be an undetected internal trigger or there may even have been a random genetic event."

I agree. In fact I think that it is always an internal trigger. Circumstances are continuously present to allow an internal trigger to explode. It is like a set point. The internal trigger is constantly bombarded until the episode is ignited. Stress from sleep deprivation definitely encourages the set point to be met.

"Yes, I was drinking too fucking much, but my mania was precipitated by insomnia... (p 101)

Manic as all hell but clinging to lucidity, I knew I needed sleep...(p 180)

I was following the rules: making sure I slept enough, taking meds every morning, and smoking zero pot...(p 251)

I told her about my medication regimen and how, if I don't get enough sleep, I freak out that I'm going to have to go to hospital again...(p 259)

I was not doing well. For weeks my arthritis had been making it difficult to sleep. I'd spent substantial portions of the prior three fall/winters in mental institutions, and aching joints, which flare up as soon as the first New York cold snap hits, had become an unwelcome reminder that madness season was upon us... (p 263)

What little sleep I was getting came in weird intervals and at odd hours. I was desperate for every minute. Our whole schedule was dependent on when and for how long I could fall asleep. Add it all up, and it was enough to put mania in the starting blocks... (p 264)

I'd done my best...to work on my medication and sleep regimen, but it didn't help that New York City did not give a shit about my bipolar disorder. The cold was indifferent to the arthritis it inflicted; 6 a.m. garbage trucks didn't care that I had been awake at 5:30 a.m...the fellas on the block still needed their...music at the volume to which they were accustomed...( p 264)

I was jazzed the next morning anyway. A little dizzy, sure...(p 265)

I suddenly felt a head rush that entered through my right ear and shook my brain around in my skull...( p 266)

The solution to mania is so simple yet so hard to come by. Just sleep...(p 272)"

Zack McDermott Gorilla and the bird. 2017

Comment

Maybe it is as simple as the last line states!

See my other RG contributions for a postulated link between inner ear irritation, specifically Meniere Spectrum Disorder, and psychosis. If so, it is only likely to be found in detailed insightful accounts like this.

"RUBY Wax was at the Tabernacle in Notting Hill for a Q&A about her new book, How to Be Human. Endorsing the benefits of meditating to help you sleep, Wax rubbished claims that less sleep makes you more productive. “Sleep deprivation is the cause of mental illness. People used to say that Margaret Thatcher slept two hours a night. Well, duh, look how that turned out.” " Evening Standard Jan 30 2018

Ruby Wax is bipolar and has written books on mental illness.

Lack of sleep is one external trigger for an internal setpoint

"Lack of sleep is one external trigger for an internal setpoint"

Can you expand on this?

Is there any neurological basis to this? Probably some circuits that get disturbed during sleep deprivation trigger the disturbance in other higher order functions.

"YESTERDAY

What Mania Feels Like

Anna Lente Contributor • 288 followers Follow MeBipolar Disorder177K followers Follow Topic Be first22

Mania doesn’t always mean

Rapid-fire actions,

Inflating grandiosity,

And fast-forward choices to regret.

Sometimes mania means

Wandering off alone,

Answering “yes” to everyone,

And listening to impulse

Instead of reason.

Sometimes it means taking a train

Without figuring out the destination

First.

Sometimes it means blind faith

In con artists.

Sometimes it means craving the divine.

Sometimes it means climbing a mountain

Late at night,

Hoping to touch the face of God.

Sometimes it means hearing God speaking back,

Breathlessly retelling the story to my friends

And having my friends give me that telltale look,

That I’ve “lost my mind” again.

Sometimes mania means dissociations,

Delusions,

And the predictable crash afterwards.

Sometimes mania means my head throbbing

As I realize it’s psychosis, not divinity.

Sometimes mania means crying alone in my room,

As I feel like I am falling apart.

Mania always climbs to a feverish peak.

Then the next morning I wake up in deep depression.

I take a deep breath

And gather my strength.

Mania is done.

Time to endure the depression again.

We want to hear your story. Become a Mighty contributor here."

Note

The transition from mania to depression doesn't always happen during sleep.

What evidence do you have that lack of sleep is the sole trigger?

" What evidence do you have that lack of sleep is the sole trigger?"

I put up this RG question because I did not know the answer. Since then I have been surprised to find how important sleep disruption seems to be. I think Anna Lente's observation is very important, as something crucial is happening during sleep, at least in her. If nothing else, it highlights a physiological trigger.

"The transition from mania to depression doesn't always happen during sleep."

Is there actually any published research looking at the timing of this, investigating sudden switches?

I'm not sure. This is from personal experience. People whom I know.

"[Mariah] Carey said that she was currently in “a really good place”, and hoped that talking about her experiences would help change perceptions of the disorder. “I’m hopeful we can get to a place where the stigma is lifted from people going through anything alone. It can be incredibly isolating. It does not have to define you and I refuse to allow it to define me or control me.”

Initially, Carey believed she was experiencing a severe sleep disorder. “But it wasn’t normal insomnia and I wasn’t lying awake counting sheep. I was working and working and working … I was irritable and in constant fear of letting people down. It turns out that I was experiencing a form of mania. Eventually I would just hit a wall. I guess my depressive episodes were characterised by having very low energy. I would feel so lonely and sad – even guilty that I wasn’t doing what I needed to be doing for my career.”

People reports that Carey is in therapy and taking medication for bipolar II disorder, which is characterised by episodes of hypomania and major depression and symptoms including insomnia, irritability and hyperactivity."

The Guardian April 11 2018

More evidence of the close link between sleep disorder and mania. The strong seasonal component suggests that sleep disturbance is primary.

"Here are some tips for staying well in the spring with bipolar disorder:

1. Make sure to get plenty of sleep, regardless if your body wants it or not.

Kimberlee...• 6 hours ago

Spring is a "double" whammy for me. It's one of my worst triggers... I have mania that's all over the place. I talk more, and it's even more random than normal, I sleep less... and there are bouts of unimaginable sadness, depression and crying...

Liz... • 8 hours ago

I, too, am on DEFCON 4 Alert Status in the Spring. If I am going to have a bad bout with mania, then this is the time it’s going to happen. Like you said, you know it’s coming. Currently, I am doing the same preventative steps to try to keep hold on the reigns, but sleeping at night is more like a war zone than peaceful slumbers. I will give it one more week before I call in my guard dog (my psychiatrist) to administer some savvy sleep concoction to knock me out for the next 6-8 weeks...

Andrea ... • 8 hours ago

I am in this right now. It happens every time, like getting a cold when the weather changes. I can't sleep. I'm going ninety to nothing, I am still taking my meds so there is a light. Thank you, I felt like the only one"

themighty.com May 2018

"Disrupted sleep-wake cycle linked to mental health problems – new study

May 16, 2018 1.07am BST [The Conversation]

Daniel Smith Professor of Psychiatry, University of Glasgow

Laura Lyall Research Associate, University of Glasgow

If you have ever stepped off a long-haul flight or worked night shifts, you probably noticed changes in your mood, concentration and general well-being. These changes are the result of disturbances to your natural sleep-wake cycle, your “circadian rhythm”. And disruptions to this cycle can have worse consequences than just feeling a bit moody or distracted. Our latest research shows that it is associated with an increased risk of depression and bipolar disorder."

10 'Red Flags' That Let People Know Mania Is Coming

Matt Sloan...[themighty.com Jul 12 2018]

When you live with a mental illness, it can be helpful (and even essential) to notice warning signs that let you know your mood is about to shift, for better or worse. While this is generally good advice for anyone, it is particularly true for people with bipolar disorder and any other mental illness that includes shifts into episodes of mania...

3. Needing less sleep but still having energy.

“Not being able to sleep and still feeling very rested and energetic in the morning. Once my body starts needing less sleep, I know it’s coming.” — Lieryn B.

Having a few hours sleep but being full of energy, very buzzed and feeling like I need to do everything at a fast pace. At the time, I don’t realize it’s because I’m leading to a hypomanic episode. I only realize it when it’s passed or if someone else points a symptom out.” — Courtney B.

“I start not sleeping or I get very little sleep. Full-blown mania is when I go 24 hours or more without any sleep. Usually, I average two to four hours in the days leading up to zero hours of sleep. It makes me really agitated and on edge.” — Moon N."

From Emily's Voices by Emily Knoll (2017):

""I was diagnosed a few years ago as bipolar, but recently I've been hearing voices," I blurted out...

"I've just been fired from an au pair job that I hated," I said. The woman kept picking on me, because I kept making mistakes with the cooking. I stopped sleeping at night, and that was when I began hearing the voices..."

The pills made me feel slightly deadened and numb, but at least I could sleep at night. After getting a couple of nights of good sleep I stopped taking the pills, as I felt more positive and the voices had faded away altogether."

I don't think sleep disorders can be a trigger for the development of a BD. In fact, according to my clinical experience, this is possibly a consequence of the pathology that can occur even early when symptoms are not yet evident and this could possibly mislead. People with bipolar disorder experience unusually intense periods of emotions, changes in sleep levels and unusual levels of activity and behavior. A single manic episode is sufficient to diagnose bipolar disorder and it is common that during this manic phase patients often hear "voices" that are congruent with their mood state.

I accept that sleep disorder might just be an early symptom of the bipolar syndrome. However, if one accepts that bipolar disorder is a dysfunction of higher brain systems, then why on earth should it start by preventing sleep? A primary role for sleep disorder with subsequent disruption of the body's physiology and biochemistry in someone with a genetic predisposition is a far simpler and more plausible explanation. It also explains the episodic nature of mania, for example

However, rather than seeking an academic argument over this, I have resorted to those with more experience, the patients themselves, and have quoted examples where they have implicated their sleep disruption. I have also given examples where there were independent causes of sleep disruption -- childbirth, shift-work, jet lag, stress.

"[Neurologist Alice] Flaherty knows personally what it is like to have a sudden and uncontrollable urge to do something creative. Following the death of her premature twins, she suffered from postpartum mania. 'I couldn't sleep. All I wanted to do was talk"...

Once again she suddenly had the uncontrollable urge to write, mixed with periods of depression."

Unthinkable by Helen Thomson (2018)

Prolonged sleep deprivation is really a very stressful situation for the CNS. In fact, just to give an example, sometimes to diagnose some forms of epilepsy it is necessary to perform the EEG examination after sleep deprivation because under normal conditions the tracing would come out physiological. Because of almost all psychiatric pathologies have a multifactorial etiology in which Genetics and Familiarity play a fundamental role and moreover that such a kind of predisposition to illness can be modified by stressful events, protective factors and precipitating events, we can say that sleep deprivation could be safely considered a precipitating or stressful event.

This whole study, or at least this summary of it, is based on the assumption that sleep disorder is secondary to higher psychiatric problems. I think the sleep problems are primary , so why is this possibility not even considered, let alone argued against?

"Neural Link Between Depression and Bad Sleep Identified

NEUROSCIENCE NEWS JULY 25, 2018...

Summary: Researchers have identified a neural link between depression and sleep problems. The study reports brain regions associated with short term memory, self and negative emotions are strongly connected in those with depression, and this may lead to bad sleep quality.

Source: University of Warwick.

The neural link between depression and sleep problems has been identified for the first time in a new study by researchers at the University of Warwick (UK) and Fudan University (China).

Professor Jianfeng Feng and Professor Edmund Rolls from Warwick’s Department of Computer Science, with Dr. Wei Cheng from Fudan University, found functional connectivity between the areas of the brain associated with short-term memory, self, and negative emotions – causing sufferers to dwell on bad thoughts and leading to a poor quality of sleep.

This research could lead to better sleep quality for people with depression, and opens up the possibility of new targeted treatments...

“The understanding that we develop here is consistent with areas of the brain involved in short-term memory (the dorsolateral prefrontal cortex), the self (precuneus), and negative emotion (the lateral orbitofrontal cortex) being highly connected in depression, and that this results in increased ruminating thoughts which are at least part of the mechanism that impairs sleep quality.”...

Professor Jianfeng Feng comments that these findings could have important public health implications, as both sleep problems and depression affect a large number of people...

Professor Jianfeng Feng further commented: “The relation between depression and sleep has been observed more than one hundred years, and now we have identified the neural mechanisms of how they are connected for the first time. These findings provide a neural basis for understanding how depression relates to poor sleep quality, and this in turn has implications for treatment of depression and improvement of sleep quality because of the brain areas identified.”

Depression and sleep problems often go hand-in-hand. About 75% of depressed patients report significant levels of sleep disturbance, such as difficulty of falling asleep and short duration of sleep (insomnia). People with insomnia also have a higher risk of developing depression and anxiety than those who sleep normally.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Source: Luke Walton – University of Warwick Publisher: Organized by NeuroscienceNews.com. Image Source: NeuroscienceNews.com image is in the public domain. Original Research: Open access research for “Functional Connectivities in the Brain That Mediate the Association Between Depressive Problems and Sleep Quality” by Wei Cheng, PhD; Edmund T. Rolls, DPhil, DSc; Hongtao Ruan, MSc; Jianfeng Feng, PhD in JAMA Psychiatry. Published July 25 2018."

I have found in patients with severe mental disorders, particularly psychosis, schizoaffective and bipolar, that if they take melatonin at night there is a definite improvement in cognitive processing, processing speed and emotional processing. It is idiosyncratic though, as no clinical trials have been done per se, however it indicates that neural repair etc that occurs during sleep plays an important role in functioning.

Very interesting Cheryl what you say. Can I ask you at what dosage the melatonin gave this improvement? I ask you that because I heard in certain cases that a very high dosage of melatonin was administered to obtain some kind of improvement (e.g. in Parkinson Disease )

Hi francesco the dosage was 50mg, but I even saw improvements at 25mg. I started with incremental dosages to reach the higher doses and saw improvements in a 2-3 month period

Thank you Cheryl, this information was really helpful to me

A pleasure Francesco!

From The Years of Silence are Passed. My father's life with Bipolar Disorder

by S P Hinshaw (2002):

"He began to have trouble, however, sleeping through the night...

Despite...a huge genetic liability ...psychological factors (in particular, loss events or those stressors that disrupt daily sleep-wake cycles) are important for the onset and timing of episodes and even their recovery periods...

Most tellingly, I began to have trouble sleeping on a number of nights, both from academic pressures and from vaguer worries about what my father's disclosures really meant. What was my risk for psychosis...?

Malkoff-Schwatrz et al. have provocatively argued that key triggers for bipolar disorder are those types of stressful events that tend to disrupt daily routines or sleep-wake cycles, given the complex interplay between circadian rhythms and light/dark cycles, on the one hand, and risk for bipolar episodes, on the other. In other words, disrupted sleep is seen as a potential trigger for the onset of episodes in persons with the genetic vulnerability, as the rhythms involved in sleep are closely tied to those that may trigger mood disturbance."

"Malkoff-Schwatrz et al. have provocatively argued that key triggers for bipolar disorder are those types of stressful events that tend to disrupt daily routines or sleep-wake cycles, given the complex interplay between circadian rhythms and light/dark cycles, on the one hand, and risk for bipolar episodes, on the other. In other words, disrupted sleep is seen as a potential trigger for the onset of episodes in persons with the genetic vulnerability, as the rhythms involved in sleep are closely tied to those that may trigger mood disturbance."

I have found at the insistence of my husband that if I strive to follow a routine, then more stability is gained. Something that I have noticed in talking to bipolar patients is that they have one or more of the endocrine functions are affected in this disease.

"Melatonin is a hormone produced in the pineal gland of the brain that is responsible for regulating sleep cycles."

"The pineal gland is a small, pea-shaped gland in the brain. Its function isn't fully understood. Researchers do know that it produces and regulates some hormones, including melatonin. Melatonin is best known for the role it plays in regulating sleep patterns. Sleep patterns are also called circadian rhythms."

"Thyroid disease. An overactive thyroid gland (hyperthyroidism) can cause sleep problems. The disorder overstimulates the nervous system, making it hard to fall asleep, and it may cause night sweats, leading to nighttime arousals. Feeling cold and sleepy is a hallmark of an underactive thyroid (hypothyroidism)."

"Thyroid hormones are involved in many bodily processes. In hypothyroidism you can have both daytime and nighttime symptoms including fatigue during the day and poor sleep at night. Hypothyroidism increases risk for some sleep disorders."

"Insomnia and PMS: The estrogen connection. According to a 2007 National Sleep Foundation poll, 33% of women say their sleep is disturbed during their menstual cycles. ...Then just a few days before the start of your next period, estrogen and progesterone levels drop. And this is when many women have trouble sleeping"

"Despite the fact that it can cause lower energy levels, low testosterone can also cause insomnia and other changes in your sleep patterns."

"Insomnia hormone imbalance or sleeplessness is both a cause and effect. Basically, hormone imbalance resulting from perimenopause, menopause, adrenal fatigue or any of its other symptoms, may cause sleeplessness which in turn worsens the hormone imbalance."

And the extreme expression of hormones followed by lack of expression from fatigue could create a pattern similar to the mood swings seen in bipolar disorder.

Adrenal glands help the body recover from stress and respond to emergencies. We already know that persons with bipolar, schizoaffective disorders have trouble coping when they are under perceived stress.

"Do adrenal glands affect sleep? Sleep Disruptions. Stress and adrenal function affect sleep, particularly the circadian pattern of cortisol secretion by the adrenal glands. When the adrenals fatigue, adrenal hormone levels may become low leading to another possible source of nighttime sleep disruption---low blood sugar."

" Sleep disruptions. Stress and adrenal function affect sleep particularly the circadian pattern of cortisol secretion by the adrenal glands...Frequent or constant stress can chronically elevate these hormone levels, resulting in a hyper vigilant state incompatible with restful sleep."

I have trouble with overactive adrenal glands that oscillate between overproduction and fatigue. I think that is the cause of my illness and paralysis.

I am overcoming this tendency little by little so that I don't fall into the following trap quite as often but my tendency to overproduce adrenaline and then

Fight-flight freeze:

"Under such unnerving circumstances, “freezing up” or “numbing out”—in a word, dissociating from the here and now—is about the only and (in various instances), best thing you can do. Being physically, mentally, and emotionally immobilized by your consternation permits you not to feel the harrowing enormity of what’s happening to you, which in your hyperaroused state might threaten your very sanity. In such instances some of the chemicals (i.e., endorphins) you thereby secrete function as an analgesic, so the pain of any injury (to your body or psyche) is experienced with far less intensity."

"what was adaptive as a child—that is, dissociating from an event vastly beyond your capacity to handle—can become so frustratingly maladaptive as an adult. Paradoxically, at its extreme, a reaction of dissociation could be not at all life-preserving but, in fact, life-threatening. For when you’re stymied by inappropriate, exaggerated fear, you’re in no position to act sensibly to whatever might be menacing you."

"What happens to the body during the fight or flight response? The fight or flight response refers to a specific biochemical reaction that both animals and humans experience during intense (or perceived) stress or fear. The sympathetic nervous system releases hormones that cause changes to occur throughout the body. How is the amygdala affected by stress?: Studies on mice show that stress related hormones alter physical structures in the brain in ways that could affect memory, learning and MOOD. ...Another part of the brain that seems to be affected by stress is the amygdala...The part of the brain that regulates fear and emotions."

"Medical comorbidity in bipolar disorder: relationship between illnesses of the endocrine/metabolic system and treatment outcome

David E Kemp, Keming Gao, Philip Chan, Stephen J Ganocy, Robert L Findling, and Joseph R Calabrese"

"The primary objective of this report was to evaluate the multifaceted relationship between medical comorbidity, indicators of mood disorder severity, and response to treatment with lithium and valproate. We hypothesized that illnesses of the endocrine/metabolic system would be associated with greater psychiatric symptom burden and would negatively influence acute treatment response. Our hypothesis was based on clinical experiences with bipolar patients and published literature relating obesity to an increased risk for bipolar disorder, attempted suicide, and earlier relapses. Given that prior studies of medical comorbidity in bipolar populations have generally excluded (2, 16) or focused entirely on patients with substance use disorders (SUDs) (17), a secondary objective was to compare the burden of medical comorbidity among two cohorts with rapid-cycling bipolar disorder differing only in a recent history of an alcohol or drug use disorder."

In conclusion, in this large group of individuals with bipolar disorder taking lithium and valproate, several aspects of medical burden were positively correlated with increased severity of depressive symptoms and negatively correlated with measures of illness improvement. Additionally, a diagnosis of substance dependence significantly predicted a high burden of underlying medical problems. Clinicians should be mindful of the potential moderating effect of comorbid medical illnesses on treatment outcomes, particularly those disorders affecting the endocrine/metabolic system. Future clinical trials should analyze outcomes separately for obese and medically burdened patients in order to provide insight into the factors that may contribute to pharmacological nonresponse.

I have a feeling that rather than bipolar disorder being a sleep disorder that it is an endocrine imbalance of some sort.

"I have a feeling that rather than bipolar disorder being a sleep disorder that it is an endocrine imbalance of some sort."

Comments

Ok Anthony. You have some very good questions and a valid idea, but our approaches are not mutually exclusive. Oftentimes more than one cause can be attributed to the same outcome. Which came first the chicken or the egg? And then of course you have to throw in the environment. If sleep disorder is the driving force for bipolar disorder, schizoaffective disorder, anxiety, schizophrenia, and other illnesses how do you explain that particular force setting off so many different diseases and not a specific disease, unless losing sleep function stresses the body to trigger a predisposition for a particular mental illness.

I was wondering whether you've ever worked in medical research setting and what your background knowledge is other than the reading that you do? Do you have a medical background that allows you to understand physiology and illness? I have worked with simple organisms, bacteria (E. coli, Streptomyces species), that have one chromosome. My background is bacterial genetics and molecular biology with a veterinary nursing background. Humans are logarithmically more complex than bacteria. They have 23 pairs of chromosomes for a total of 46. Based on my journey, personal experience, knowledge, and research experience either theories are possible.

1. Occam's razor doesn't always apply in biological systems, and though it is obvious to me that you are a thinking type (Jungian types) and you will never accept this possibility I have to throw that out there. An endocrine imbalance is just a plausible as the beginning of the process of developing bipolar, schizoaffective disorders as what you are postulating, and either could lead to the same conclusion.

2. The progression that a relative experienced was first hyper-vigilance (I believe that can be attributed to home environment growing up that induced overactive adrenal glands. Whenever the patient was faced with being with a person she could feel the adrenaline surge followed by fight, flight, freeze), as a teen self imposed sleep interruptions, hypothyroidism late twenties, then a few years later a psychotic break, then extremely notable sleep disturbances as time went on. Another relative experienced hypothyroidism as a teen, then eventually developed a series of psychotic breaks in the twenties, after having children the sleep disturbances became pronounced, developed severe pathology of the pituitary gland and now has severe sleep disturbances and sleep apnea. I must admit, I have no idea when the sleep disturbances started because I didn't ask. I simply know that at this point they are severe.

3. I'm not sure that we would necessarily know whether bipolar disorder was an endocrine disorder by now. I don't think that physicians necessarily communicate with research counterparts all that well. They don't even have time to communicate with their patients other doctors and so inadvertently incompatible drugs are prescriptioncribed by two different doctors. I think that an endocrine homeostatic imbalance could be a stressor that could lead to bipolar illness. I also believe that a sleep disorder could be a stressor that could lead to bipolar illness. I also believe that the stress of having a bad home life, being a scapegoat for bullies, having some sort of traumatic experience could all lead to bipolar illness if the person was genetically predisposed. "According to one study, the often-debilitating sleep disorder insomnia can be genetic and for some, insomnia may be hereditary. Scientists say some people's genes increase their stress-reactivity. And that increased stress response increases the likelihood of poor sleep and developing insomnia." There is a population of people having sleep disorders that are not mentally ill. About 18% of people in the population are not considered mentally ill. Between 50% and 80% of mentally ill people have sleep disorders.

By going through this exercise and finding this last piece of information about "Scientist say some people's genes increase their stress-reactivity. And that increased stress response increases the likelihood of poor sleep and developing insomnia." I'm not sure that we would necessarily know whether bipolar disorder was an endocrine disorder by now. I don't think that physicians necessarily communicate with research counterparts all that well. They don't even have time to communicate with their patients other doctors and so inadvertently incompatible drugs are prescriptioncribed by two different doctors. I think that an endocrine homeostatic imbalance could be a stressor that could lead to bipolar illness. I also believe that a sleep disorder could be a stressor that could lead to bipolar illness. I also believe that the stress of having a bad home life, being a scapegoat for bullies, having some sort of traumatic experience could all lead to bipolar illness if the person was genetically predisposed. "According to one study, the often-debilitating sleep disorder insomnia can be genetic and for some, insomnia may be hereditary. Scientists say some people's genes increase their stress-reactivity. And that increased stress response increases the likelihood of poor sleep and developing insomnia." There is a population of people having sleep disorders that are not mentally ill. About 18% of people in the population are not considered mentally ill.

By going through this exercise and finding this last piece of information about "Scientist say some people's genes increase their stress-reactivity. And that increased stress response increases the likelihood of poor sleep and developing insomnia." I would say that bipolar disorder is probably triggered by stressors rather than saying it is a sleep disorder. It is a chicken-egg question though because once you have a mental illness there is an all consuming quality that leads to avoiding sleep.I would say that bipolar disorder is probably triggered by stressors and predisposition to the disease rather than saying it is a sleep disorder. It is a chicken-egg question though because once you have a mental illness there is an all consuming quality that leads to avoid sleeping that seems to worsen over time.

National Comorbidity Survey Replication data indicate that bipolar disorder is characterized by high lifetime rates of co-occurring anxiety and substance use disorders (SUDs) (Merikangas et al., 2007). Increasing evidence suggests that medical illnesses also frequently co-occur in bipolar disorder (Beyer et al., 2005; Kilbourne et al., 2004; Krishnan, 2005; McIntyre et al., 2006) and may contribute to an increase in premature mortality from natural causes of death (Osby et al., 2001). Although an increased prevalence of medical comorbidity affects nearly every organ system, the high rate of cardiometabolic conditions such as diabetes, cardiovascular disease, and dyslipidemia is particularly alarming (Angst et al., 2002; Kilbourne et al., 2007).

"Medical and Substance Use Comorbidity in Bipolar Disorder

David E. Kemp, MD, Keming Gao, MD, PhD, Stephen J. Ganocy, PhD, Emily Caldes, BA, Kathryn Feldman, BS, Philip K. Chan, MS, Carla Conroy, BA, Sarah Bilali, MA, Robert L. Findling, MD, and Joseph R. Calabrese, MD"

"National Comorbidity Survey Replication data indicate that bipolar disorder is characterized by high lifetime rates of co-occurring anxiety and substance use disorders (SUDs) (Merikangas et al., 2007). Increasing evidence suggests that medical illnesses also frequently co-occur in bipolar disorder (Beyer et al., 2005; Kilbourne et al., 2004; Krishnan, 2005; McIntyre et al., 2006) and may contribute to an increase in premature mortality from natural causes of death (Osby et al., 2001). Although an increased prevalence of medical comorbidity affects nearly every organ system, the high rate of cardiometabolic conditions such as diabetes, cardiovascular disease, and dyslipidemia is particularly alarming (Angst et al., 2002; Kilbourne et al., 2007)."

Hyperlipidemia (dyslipidemea) can also be related to a hormonal disease such as diabetes, hypothyroidism (low levels of thyroid hormone), polycystic ovary syndrome (PCOS), metabolic syndrome, and Cushing syndrome.

Endocrine disorders include hypothyroidism, congenital adrenal hyperplasia, diseases of the parathyroid gland, diabetes mellitus, diseases of the adrenal glands (including Cushing's syndrome and Addison's disease), and ovarian dysfunction (including polycystic ovary syndrome), among others.

“Is bipolar disorder an endocrine condition?” Glucose abnormalities in bipolar disorder

C. Garcia-Rizo,1,2 B. Kirkpatrick,3 E. Fernandez-Egea,2,4,5 C. Oliveira,1,2 A. Meseguer,1,2 I. Grande,2,6J. Undurraga,2,6 E. Vieta,2,7,6 and M. Bernardo1,2,7

"...Now, preliminary data concerning 7 drug-naïve DSMIV- TR bipolar I patients who underwent an oral glucose tolerance test suggest that bipolar disorder may be highly associated with abnormal glucose metabolism irrespective of pharmacotherapy. The patients were evaluated at the time of their first clinical contact for psychotic symptoms at a general academic hospital. The patients were initially classified as first episode of non-affective psychosis, but their diagnosis was changed over a year time for an affective diagnosis, namely bipolar disorder type I. All subjects gave informed consent for participation in the study, which was conducted under the supervision of the authors’ respective hospital ethics committees, and came from a larger study of metabolic abnormalities and glucose dysregulation in neuropsychiatric disorders (4). The results after an overnight fast showed a high incidence of glucose metabolism abnormalities, including impaired fasting glucose in two of seven patients and impaired glucose tolerance in six of seven patients. Abnormal glucose metabolism, measured as an increased two-hour glucose load, reflects that bipolar I disorder is associated with an elevated risk of death from cardiovascular pathologies and all causes, independently of other known risk factors.

Our data and the actual state of knowledge suggest that glucose abnormalities are linked to the diagnosis of bipolar disorder before the effects of medications and other confounders had taken place. Indeed, glucose abnormalities are the basis for the reportedly high number of medical comorbidities found in patients with bipolar disorder. The concept of ‘Allostatic Load’ has received considerable attention as a theoretic explanation of its medical burden. Allostasis is a term that describes a multisystemic view of the physiologic toll that is required for adaptation to different situations; these processes are adaptative to internal or external circumstances and so maintain the homeostasis of the organism. However, when extra loads appear pointy or over time (the adaptative mechanisms are repeatedly activated), the allostatic response becomes excessive or inefficient and the organism develops an allostatic load (overload) that can direct to abnormal responses through insulin dysfunction such as T2DM, hypertension, or arteriosclerosis (5).

The pathophysiology that underlies the association of bipolar disorder and T2DM or glucose abnormalities is far from being understood, but several explanations have been developed over time. These include possible common pathophysiological processes, genetic and epigenetic links, and environmental factors.

Dysregulation in the hypothalamic–pituitary–adrenal axis is a highly consistent finding that would explain through cortisol disturbances the abnormalities in glucose homeostasis, increased body fat deposition and atherosclerosis, although in our sample, cortisol value was in the normal range, and in another naïve bipolar I study, it was lower compared with matched controls. Dysfunction in the purinergic system has been associated with both bipolar naïve patients (6) and T2DM, as purines play a crucial role in energy homeostasis and neuroregulation. Indeed, Kraepelin already described in 1921 an association between uric acid and manic-depressive illness. Evidence implicates also mitochondrial dysfunction, impaired phospholipid metabolism and fatty acid-related signal transduction, and dysregulation of glycogen synthase kinase-3, in the common pathophysiological processes that underlie bipolar disorder and T2DM (2). Common genetic abnormalities and shared susceptibility loci have been described between T2DM and bipolar disorder; however, genetic-wide association studies have not yielded conclusive results.

However, we would like to highlight the physiology of early environmental processes (7) and its epigenetic programming in the development of metabolic disturbances. Bipolar disorder, from a gene-environment model, is associated not only with familial risk but also with a certain number of early environmental factors. Birth and gestational-related problems appear to be risk factors for both bipolar disorder and diabetes, low birth weight being the most notable example, suggesting neurobiological adaptative changes that might underlie both pathologies. Obstetric, prenatal disturbances, and early growth patterns predict an increased risk of developing T2DM (8) and other cardiovascular pathologies over time, through epigenetic pathways, a finding that could also partially explain part of the increased risk of morbidity and mortality found in patients affected with bipolar disorder.

Understanding the onset of a severe mental illness not only as psychiatric but also as a medical condition would imply a metabolic control independent of the type of treatment. Hence, all physicians should be aware of the need of implementing primary preventive strategies in an effort to reduce the overall medical burden and mortality of bipolar patients."

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Acknowledgments

Funding

The work leading to these results have been supported in part by Grant RO1 DK069265 from the National Institute of Diabetes and Digestive and Kidney Diseases (Dr. Kirkpatrick), NARSAD (Dr. Fernandez-Egea) and by the Instituto de Salud Carlos III, FEDER, Centro de Investigación Biomédica en Red de Salud Mental, CIBERSAM, Government of Catalonia, Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement (2009SGR1295) and by Esther Koplowitz Center-Barcelona (Dr. Bernardo).

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References

1. Osby U, Brandt L, Correia N, Ekbom A, Sparen P. Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry. 2001;58:844–850.  [PubMed]

2. Calkin CV, Gardner DM, Ransom T, Alda M. The relationship between bipolar disorder and type 2 diabetes: more than just co-morbid disorders. Ann Med. 2013;45:171–181.  [PubMed]

3. McIntyre RS, Mancini DA, Pearce MM, et al. Mood and psychotic disorders and type 2 diabetes: a metabolic triad. Can J Diabetes. 2005;29:122–132.

4. Fernandez-Egea E, Bernardo M, Donner T, et al. Metabolic profile of antipsychotic-naive individuals with non-affective psychosis. Br J Psychiatry. 2009;194:434–438. [PMC free article]  [PubMed]

5. Grande I, Magalhaes PV, Kunz M, Vieta E, Kapczinski F. Mediators of allostasis and systemic toxicity in bipolar disorder. Physiol Behav. 2012;106:46–50.  [PubMed]

6. Salvadore G, Viale CI, Luckenbaugh DA, et al. Increased uric acid levels in drug-naive subjects with bipolar disorder during a first manic episode. Prog Neuropsychopharmacol Biol Psychiatry. 2013;34:819–821. [PMC free article]  [PubMed]

7. Vaag AA, Grunnet LG, Arora GP, Brons C. The thrifty phenotype hypothesis revisited. Diabetologia. 2012;55:2085–2088. [PMC free article]  [PubMed]

8. Hales CN, Barker DJ. The thrifty phenotype hypothesis. Br Med Bull. 2001;60:5–20.  [PubMed]

So it appears that at least some endocrine disease have been shown to be associated with bipolar disorder.

Here are some extracts from a preliminary version of the Kemp et al study just mentioned in the previous response:

"Results

Every patient enrolled into this study had at least 1 medical illness (most commonly respiratory, 72%) and on average had 4.9 different medical conditions. Over half of patients (52%) exhibited illnesses across four or more different organ systems, 24% had uncontrollable medical illnesses, and the mean overall total CIRS score was 5.56. The average body mass index (BMI) was 28.1 with 38% being overweight and 29% being obese. High medical burden was observed in 64%...

TABLE 2

Prevalence of Affected Organ Systems Among Outpatients with Rapid-Cycling Bipolar I or II Disorder and Co-Occurring Substance Use Disorders.

Number of subjects Percentage (%)

Respiratory79 71.82

Musculoskeletal/Integument61 55.5

Neurologic41 37.3

Endocrine/Metabolic/Breast40 36.4

Genitourinary29 26.4

Head & Neck27 24.6

Vascular24 21.8

Lower GI23 20.9

Hepatic17 15.5

Upper GI17 15.5

Cardiac10 9.1

Renal7 6.7

...

Overlapping Pathophysiology between Bipolar Disorder, Substance Use, and General Medical Conditions

General medical conditions (eg. obesity) and SUDs appear subserved by related behavioral aberrations and pathophysiological abnormalities. Individuals with depression and substance dependence often neglect their general health, resulting in disrupted eating habits, nutrient absorption, and metabolism (McIntyre et al., 2007). Obesity is associated with the production of pro-inflammatory cytokines that may induce sickness behaviors resembling depression (Dantzer, 2004). Another common pathophysiological mechanism linking bipolar disorder and medical comorbidity includes allostatic load, which represents the cumulative physiological adaptations to environmental stressors (Kapczinski et al., 2008). Lastly, it is known that chronic corticosteroid elevation leads to insulin resistance and increased body fat, potentially accounting for the high rates of obesity and metabolic syndrome among individuals with bipolar disorder (Fagiolini et al., 2005). Hyperreactivity of the HPA-axis and autonomic nervous system may explain the association between bipolar disorder, abuse history, and increased medical comorbidity in this report (Akiskal, 1983; Daban et al., 2005; Merola et al., 1994).

Strengths and Limitations "

Comment

I draw the following conclusions:

I concede that the study Kemp et al study was flawed in that the subjects in the study were taking medications, so were already compromised.

The second study mentioned, C. Garcia-Rizo et al looked at 7 drug naive persons with DSM-IV TR bipolar I patients. When a person discovers that he or she has bipolar illness, the classic case is around 30 years old. These persons were not taking medication so presumably they were fairly healthy, other than the bout of psychosis.

"The results after an overnight fast showed a high incidence of glucose metabolism abnormalities, including impaired fasting glucose in two of seven patients and impaired glucose tolerance in six of seven patients." The first relative that I mentioned having bipolar illness also had abnormalities (hypoglycemia) with a fasting glucose tolerance test in her teens. She was an athlete and very healthy at that time in her life. Continued attention to healthy exercise, eating and attempts to sleep (even under ideal medication circumstances) have allowed good health. Still has extreme problems being around groups at times, occasional paranoia, and sometimes depressed, manic or overwhelmed and confused thinking. Most of the time the bipolar symptoms are well managed. Hypothyroidism is well regulated. I think that there is something to be said about the comorbidity of the impaired glucose tolerance and the incidence of diabetes. There is diabetes on both sides of the relative's families, another sibling experiences bouts of hypoglycemia even with regular meals and snacks, and both parents are mentally ill. Three of their five children are bipolar. One more has had potentially had psychosis that was not monitored (hearing voices and staying is a basement apartment until the problem passed). I wouldn't dismiss the endocrine disorder as being a minor factor.

I still think that any kind of significant stressor including sleep disturbances could plausibly trigger this illness and if you can tease out the many threads that are necessarily interdependent for homeostasis (and thus keep an organism protected from imbalance of any system) by using extremely good experimental design you will have solved a monumental problem. The best researchers keep an open mind, considering the promising possibilities until they are shown to be a red herring. At best it will take a good chunk of time, and you will need a good team and you will be dependent on other people's research. I am not convinced that any one factor determines the revelation of this illness, in fact I postulate that when less significant stressors occur at a younger age that the outcome for bipolar or schizoaffective disorder might be Asperger's syndrome or possibly ADHD. It would be interesting to know if those two outcomes are seen in more mentally stable generations in families bearing bipolar disorder. Of course I could be wrong. I follow my intuition and she is a fickle thing.

“Is bipolar disorder an endocrine condition?” Glucose abnormalities in bipolar disorder

C. Garcia-Rizo,1,2 B. Kirkpatrick,3 E. Fernandez-Egea,2,4,5 C. Oliveira,1,2 A. Meseguer,1,2 I. Grande,2,6J. Undurraga,2,6 E. Vieta,2,7,6 and M. Bernardo1,2,7

"Evidence implicates also mitochondrial dysfunction"

Medication‐induced mitochondrial damage and disease

John Neustadt Steve R. Pieczenik

Abstract

Since the first mitochondrial dysfunction was described in the 1960s, the medicine has advanced in its understanding the role mitochondria play in health and disease. Damage to mitochondria is now understood to play a role in the pathogenesis of a wide range of seemingly unrelated disorders such as schizophrenia, bipolar disease, dementia, Alzheimer's disease, epilepsy, migraine headaches, strokes, neuropathic pain, Parkinson's disease, ataxia, transient ischemic attack, cardiomyopathy, coronary artery disease, chronic fatigue syndrome, fibromyalgia, retinitis pigmentosa, diabetes, hepatitis C, and primary biliary cirrhosis. Medications have now emerged as a major cause of mitochondrial damage, which may explain many adverse effects. All classes of psychotropic drugs have been documented to damage mitochondria, as have stain medications, analgesics such as acetaminophen, and many others. While targeted nutrient therapies using antioxidants or their prescursors (e. g., N‐acetylcysteine) hold promise for improving mitochondrial function, there are large gaps in our knowledge. The most rational approach is to understand the mechanisms underlying mitochondrial damage for specific medications and attempt to counteract their deleterious effects with nutritional therapies. This article reviews our basic understanding of how mitochondria function and how medications damage mitochondria to create their occasionally fatal adverse effect If you suffer from bipolar disorder, it couldn't hurt to take coQ10

"CoQ10 levels have also been found to be lower in people with certain conditions, such as heart disease."

Medication‐induced mitochondrial damage and disease

J Neustadt, SR Pieczenik - Molecular nutrition & food research, 2008 - Wiley Online Library… Muscari, A., Mitochondrial dysfunction as an initiating event in atherogenesis: A plausible hypothesis. Cardiology 2005, 103, 137–141 … MR, Mitochondria in health and disease: Perspectives on a new mitochondrial biology. Mol. Aspects Med. 2004, 25, 365–451 …

The process of atherogenesis--cellular and molecular interaction: from experimental animal models to humans.

Ross R1, Agius L.

Author information

Abstract

Atherogenesis is a disorder of the artery wall that involves: adhesion of monocytes and lymphocytes to the endothelial cell surface; migration of monocytes into the sub-endothelial space and differentiation into macrophages; ingestion of low density lipoproteins and modified or oxidised low density lipoproteins by macrophages by several pathways, including a scavenger pathway, leading to accumulation of cholesterol esters and formation of "foam cells". These foam cells together with T lymphocytes form the fatty streak. Vascular smooth muscle cells migrate from the media into the intima and proliferate with the formation of atherosclerotic plaques. These processes which involve cell adhesion, migration, differentiation, proliferation and cell interaction with the extracellular matrix are regulated by a complex network/cascade of cytokines and growth regulatory peptides. Thus, atherosclerosis may be the result of a specialised chronic inflammatory fibroproliferative process which has become excessive and in its excess this protective response has become the disease state.

"The most complete deprivation or interference with sleep occurs in certain psychotic patients, particularly in manic-depressives."

Schizophrenia by M Sakel (1959)

"The most complete deprivation or interference with sleep occurs in certain psychotic patients, particularly in manic-depressives."

No doubt. I don't think that we will ever know the true cause/effect... Biological systems have evolved so that components are interdependent on each other. If one component waivers another steps in to compensate. Biological systems are a balancing act for homeostasis. Bipolar, schizoaffective, anxiety disorders, and obsessive-compulsive disorders are a constant torment on the mind and a constant shifting to compensate for imbalance. Having one of these disorders is a constant struggle to balance a high velocity moving target. The best I can say is that sleep interference is associated with mental illnesses. Sleep interference is a common theme. Some would say that bipolar disorder is a sleep disorder, and some would say that sleep interference is a by-product of the disease. Are all of the afflictions that I mentioned the same illness that the person has coped for using a different strategy? Maybe. Psychiatrists sometimes have a difficult time diagnosing these diseases correctly and maybe that is part of it. Just the mere fact that mental illnesses are of the mind and there is a nagging feeling associated with the ones that I have mentioned, that something is not quite right, would suggest that sleep disturbance could be an issue in that when it is time to go to sleep and the mind is unoccupied it shifts to preoccupation. Some (disorders) may be genetic and some may be environmental. It seems pretty clear to me from my understanding that manic/depressive illness is both a genetic predisposition coupled with some major trauma at as a child or even a teen, but I think a teen is stretching it. Many people that I've encountered don't seem to even be aware that a trauma occurred as a child even when describing their life. They think that the situation that they survived is a normal one. Many people go through childhood experiencing trauma after trauma and come through it escaping mental illness. Maybe these people don't have the genetic predisposition, or maybe their parents have evolved better coping skills which they have passed on to their children. I guess denial is a pretty strong protective mechanism we grapple with. I think that the reason that this disease is expressed when it is, is because the denial of the trauma can no longer be contained.

A sleep disorder seems to have been the first sign of illness, and the prime reason for the breakdown in mother-daughter relationship:

"What It Was Like Growing Up With Bipolar Disorder and an Emotionally Abusive Mother

📷 Samantha Wilson,The Mighty Wed, 15 Aug 10:50 BST ...

Getting diagnosed with bipolar disorder so young, I had no idea what I was in for. Being only a kid and having a doctor trying to explain to me what bipolar disorder is, and telling me and my mother that I show the signs and symptoms of having this mental illness… honestly, back then, I didn’t really pay much attention to what was being said because I didn’t even understand or know what a mental illness really was.

One thing I did know was that the days and nights were getting harder and harder to handle. I would wake up so late for school; that made my mother extremely angry because she would have to come straight home from work to drive me to school. Most of the mornings I woke up late, it wasn’t “my choice.” When I would tell my mother this, she would say, “Don’t give me that shit; be ready when I get home and don’t make a habit of this.” A habit it was not, but it happened quite frequently and I would feel terrible about it. That made the mornings even harder due to the sadness or anger or anxiety I woke up with. All I wanted was my bed and the darkness, especially when I would have the pleasure of having a migraine on top of all the other ailments...

Sadly, to this day — now being almost 26 years old — I still can’t communicate with my mother about my illness without her mentioning how she had to deal with it or deal with me. She always made it known I was a terrible child and I was mean, but I was a child who was still developing and, with that, I was diagnosed with bipolar disorder. No child will fully understand it, especially when many adults don’t understand it.

The other day, when I was trying to talk to her about my life and my goals for my future, I got to enjoy the hurtful and almost emotionally abusive lines of, “I dealt with this for years, Samantha,” and I finally had enough. I told her, “No, you didn’t have to deal with it; I did. I was the one who cried for hours on end until I got so tired I fell asleep. I was the one who felt so bad I wanted to die and began self-harming; I was the one who had nobody to talk to, who would just listen or at least acknowledge that yes, I may have an illness but that doesn’t define who I am.”

"My background is bacterial genetics and molecular biology with a veterinary nursing background. Humans are logarithmically more complex than bacteria".

Who would have guessed that the genetic code would have been digital, very simple, and exactly the same in bacteria and man? There is still room for Occam, and simple explanations. If wrong, they can be speedily refuted.

"Who would have guessed that the genetic code would have been digital, very simple, and exactly the same in bacteria and man?"

Not sure where you got your information. Not true. It is estimated that there are a little over 10 times as many protein coding genes in the human genome than an average bacterial genome And much of non-coding regions functions are not understood. Mother Nature is not one to waste though.

"Who would have guessed that the genetic code would have been digital, very simple, and exactly the same in bacteria and man?

Not sure where you got your information. Not true."

"Genetic code

From Wikipedia, the free encyclopedia

Each codon consists of three nucleotides, usually corresponding to a single amino acid. The nucleotides are abbreviated with the letters A, U, G and C. This is mRNA, which uses U (uracil). DNA uses T (thymine) instead. This mRNA molecule will instruct a ribosome to synthesize a protein according to this code.

The genetic code is the set of rules used by living cells to translate information encoded within genetic material (DNA or mRNA sequences) into proteins. Translation is accomplished by the ribosome, which links amino acids in an order specified by messenger RNA (mRNA), using transfer RNA (tRNA) molecules to carry amino acids and to read the mRNA three nucleotides at a time. The genetic code is highly similar among all organisms and can be expressed in a simple table with 64 entries." (emphasis added)

"Who would have guessed that the genetic code would have been digital, very simple, and exactly the same in bacteria and man?"

You brought up the subject of genetic code. I had been talking about coding regions and the number of proteins any one organism specifically makes. Humans are logarithmically more complex in their genetics than bacteria. Just try studying them.

"The genetic code is highly similar among all organisms..." not "...exactly the same"

No the genetic code is not universal in all organisms

"The universal genetic code is a common language for almost all organisms to translate nucleotide sequences of deoxyribonucleic acid (DNA) and ribonucleic acid (RNA) to amino acid sequences of proteins. However, the genetic code is still evolved. Nonuniversal genetic codes are found in some organisms and organelles. Aminoacyl‐transfer RNA (tRNA) synthetases and RNA modifications play a critical role in reassignment of the genetic code."

www.els.net/WileyCDA/ElsArticle/refId-a0000810.html

"The "not-so-universal" genetic code, its origin and its evolution

"Until relatively recently, the [genetic] code was thought to be invariable, frozen, in all organisms, because of the way in which any change would produce widespread alteration in the amino acid sequences of proteins. The universality of the genetic code was first challenged in 1979, when mammalian mitochondria were found to use a code that deviated somewhat from the universal."

So, what does "universal" mean in the above quote? It means that the above sequence gets translated into the same amino acids in every organism, from bacteria to humans. Is this true? Not always.

Take a stop codon, for example. A stop codon is a triplet of RNA nucleotides that end the translation. Think of it as a flag that says, "The protein code ends here." If the genetic code were a universal one, a stop codon would always be a stop codon, in all organisms. The first exception to this was discovered in 1985, when the stop codon UGA was found to be actually coding an amino acid in the bacteria Mycoplasma capricolum. More exceptions to the "universal" conception (other triplets that coded different amino acids instead of always the same one) were later found in other organisms and in mitochondrial DNA as well. A more realistic theory is that, being DNA dynamical, when codons "disappear" the old codons can undergo reassignments and take on a new meaning.

The "universal" view has prevailed for many years on the basis that present time proteins are so evolved that changes would most likely be lethal. The first deviations from universality were found in the late 'seventies in mitochondrial DNA. It was argued that mtDNA is considerably smaller than nuclear DNA and hence it had a better tolerance to changes.

In [1], Ohama et al. list various code changes reported in the nuclear DNA in the past three decades, and then discuss the origin of the genetic code:

"The theories to explain the early evolution of the genetic code are numerous, all of which include speculations that the coding system arose with one or a limited number of amino acids, and that others were added until a total of 20 was reached. Most of these theories are aesthetically pleasing but cannot be verified."

They assume that the most ancient genetic code had to have a minimum number of codons made of all 20 amino acids and a minimum number of corresponding tRNAs -- transfer RNA molecules that act as mediators between the mRNA and the amino acids. This first genetic code had to have very little tolerance for change. However, with the time, the development of synonymous codons (different triplets code the same amino acid), allowed for flexibility and therefore resulted in an advantageous addition.

Finally, they conclude:

"It should be stressed however that there are no organisms which use the genetic code system for more than, or less than, 20 amino acids. What were frozen are 20 amino acids (magic 20!) and not the genetic code that assigns them. Thus the genetic code is still in the state of evolution."

I'm including below a second reference [2] that goes a bit more in depth on how these codon reassignments happen, for those of you who might be interested. In this case, the authors looked at the evolution of the genetic code in yeast."

[1] Ohama T, Inagaki Y, Bessho Y, & Osawa S (2008). Evolving genetic code. Proceedings of the Japan Academy. Series B, Physical and biological sciences, 84 (2), 58-74 PMID: 18941287

[2] Miranda, I., Silva, R., & Santos, M. (2006). Evolution of the genetic code in yeasts Yeast, 23 (3), 203-213 DOI: 10.1002/yea.1350

chimerasthebooks.blogspot.com

"Distribution of the code changes

In 1979, it was reported that vertebrate mitochondria use AUA for Met and UGA for Trp, instead of Ile and stop, respectively, in the “universal code”.1) Indeed, as noted in Introduction, there are known considerable numbers of deviant mitochondrial codes in multicellular animals (see Yokobori et al.9) for a review) as well as in unicellular eukaryotes.10) To account for these changes, it was proposed that the mitochondrial genomes are much smaller (10 or so genes) than the nuclear genomes, and mitochondria can probably tolerate changes in the code that would be unacceptable to a larger and more complex system. However, the tolerance explanation for the mitochondrial code changes is no longer tenable, because, as mentioned above, it was discovered that the nuclear genome of Mycoplasma capricolum uses UGA as a Trp codon and in certain ciliated protozoans, UAA and UAG (= UAR) code for Gln. It is now known that 8 species of Mollicutes (eubacteria), including 7 species of Mycoplasma and one species Spiroplasma, use UGA as a Trp codon. CUG (Leu) is read as Ser in six species of Candida (yeasts), UAR (stop) is used for the codons of Gln in several species of ciliated protozoans (Tetrahymena, Paramecium, Stylonicia, Oxytricus) and UGA (stop) for Cys in a ciliate Euplotes. Two species of unicellular green alga (Acetabularia) also use UAR as Gln codons. For the references for the nuclear code changes until 1995, see Osawa.4) More code changes have since been reported as follows: UGA as Trp in ciliates, Colpoda inflata and Blepharisma americanum11); UAA as Glu in three peritrich species, Vorticella microstoma, Optisthoneca henneguyi and O. matiensis12); UAR as Gln in a subgroup of diplomonads (e.g., Hexamita inflata),13) and in the oxymonad Streblomatrix strix.14) Since ciliates, the ulvophycean green algae, diplomonads, and oxymonads are distantly related to each other, the use of UAR as Gln codons occurred independently in different phylogenetic lineages. Such a widespread occurrence of the deviant codes in nuclear as well as mitochondrial genomes clearly indicates that the genetic code is neither universal nor frozen. It is most likely that the deviant codes (including those in mitochondria) originated from what was used in a single progenote population for the present-day organisms."

Ohama T, Inagaki Y, Bessho Y, & Osawa S (2008). Evolving genetic code. Proceedings of the Japan Academy. Series B, Physical and biological sciences, 84 (2), 58-74 PMID: 18941287

"Disrupted Circadian Rhythm May Have Genetic Link To Mood Disorders

by Bruce B. Vanderburg August 16, 2018...

A potential genetic link between circadian disruption and mood disorders has been identified by scientists at the University of Glasgow.

Circadian rhythms are regular 24-hour variations in behaviour and activity that control many aspects of our lives, from hormone levels to sleeping and eating habits.

The new findings, from the largest ever genome wide association study of circadian rest-activity cycles in humans, follow research published earlier this year in The Lancet Psychiatry which found that disrupted circadian rhythms were associated with increased risk of mood disorders, including major depression and bipolar disorder.

Neurofascin

Circadian rhythms occur in plants, animals and throughout biology. They are fundamental for maintaining health in humans, particularly mental health and wellbeing. The findings of this new study identified two areas of the human genome that may contain genetic variants that increase risk of disruption to rest-activity cycles.

The researchers found that one of these areas contained the gene Neurofascin, which binds to the protein product of a well-known candidate gene for bipolar disorder (Ankyrin G), suggesting a direct biological link between circadian disruption and severe mood disorder. Genetic loading for circadian disruption was also significantly associated with mood instability.

For the study, the researchers used genetic information and activity data from 71,500 participants in the UK Biobank cohort to obtain an objective measure of daily rest-activity rhythms, called relative amplitude.

This measure was used in comparing gene variants carried by individuals with and without low relative amplitude to identify potential genetic associations with several mood disorder features, including mood instability, neuroticism, depression and bipolar disorder.

Complex Genetic Architecture

Finding genes for low relative amplitude suggests that disrupted rest-activity cycles have a biological basis, and are not simply the result of random or environmental circumstances. It also implies that the link between disrupted rest-activity cycles and mood disorders may originate in the action of such genes.

“These new findings extend our understanding of the complex genetic architecture of rest-activity cycles and how these might relate to mood instability, neuroticism, depression and bipolar disorder. Ultimately, our goal is to use this genetic information to develop and efficiently target or stratify new and improved treatment options,”

said Daniel Smith, Professor of Psychiatry and senior author."

Comment

Those with bipolar genes might well be expected to have disrupted sleep. So why the additional genes for sleep disruption if these were not a primary cause?

More evidence that sleep disorder is a primary trigger:

"15 'Small,' but Significant, Lifestyle Changes That Help People With Bipolar Disorder

Sarah Schuster...

4. Getting Enough Sleep

“Getting enough sleep. I can’t stress the importance of this enough!” — Emily L.

“Sleep. Getting on a decent sleep schedule has made a huge difference in my life.” — Karoline D...

6. Keeping a Routine

“Keeping a strict routine has saved me. The days I do not follow my routine I slowly become more unstable.” — Sarah G.

7. Cutting Back on Caffeine

“I cut caffeine out of my diet and added two to three cups of herbal tea per day, which has been life-changing!” — Anna A.

“Cutting out caffeine. Sleep or lack there of is my primary trigger for becoming more elevated.” — Maddison D...

11. Adjusting Your Work Schedule to Meet Your Needs

“Moving from shift work to working 9 to 5 made an unexpectedly huge difference to my mental health. It really helped me to normalize my sleep patterns.” — Saria G.

“Work from home. I do the same thing I used to do at the office, but from home. That gives me the chance to be in my own environment. I have my dogs (ESAs) with me, and have been able to reduce stress and anxiety. No commute, no waking up early, no co-workers or bosses watching my every move. Just me in my own space.” — Danmaris D...

Sarah Schuster is the mental health editor at The Mighty. She thinks every day should be a mental health day. Follow her on Twitter @saraheliztweets."

A tragic case where sleep disruption was a major primary feature:

"I went on a walk and returned to find my husband dead’

After her husband’s suicide, Kate Harding was overwhelmed by guilt and shame

Kate Harding

Sat 24 Feb 2018 06.00 GMT Last modified on Sat 24 Feb 2018

📷 Kate Harding: ‘Widowhood sucks.’ Photograph: Francesca Jones for the Guardian

I have been a widow for 11 weeks. It seems surreal to be writing that sentence and yet it is true. I was there; I know. Richard killed himself at home while I was walking the dog with my daughter, while my son was lying metres away in his bedroom. As a consultant anaesthetist and intensivist (a specialist in the care of critically ill patients), Richard knew exactly what to do. He was 47...

Richard had been living with depression and was three days away from his first appointment with a psychiatrist for a medication review. His illness was triggered last year by a complaint about him to the General Medical Council (the first he had received), just as we packed the last of our possessions into a shipping container bound for New Zealand and signed away our house. Although the complaint was thrown out in due course, as we expected it to be, it took five months. The strain this put him under was immense.

He was unable to work abroad until the GMC could issue him a “certificate of good standing”, so we had to claw back the jobs from which we had resigned and tell our children they were returning to the schools they thought they had left. Finally, the all-clear was given and the paperwork completed. We boarded our flight to Auckland, vowing never to work in the NHS again.

But once we had made the move to Northland, the stress of the previous few months caught up with Richard and he entered a period of depression. He had had an episode in his early 20s, which had lasted for months, but there had been no recurrence.

He did well on antidepressants and made a positive impression on his new colleagues. He threw himself into his new coastal life and regained his energy and verve. In rapid succession, he acquired a boat, fishing rods, a fishing kayak, three types of roof rack and an unspeakably tight-fitting open-water swimming wetsuit, accessorised with a dapper hood. He was, for a time, a happy man.

Then, in July last year, his depression recurred. This time, the medication didn’t work; in fact, it may have made things worse. Insomnia was a central feature, worsened by the frequency of his night-time call-outs, although he enjoyed his job and continued to perform well at work."

Very strange case. I have any doubt about the diagnosis of Depression, I'd rather think about a Schizoaffective disorder