67. N24 Awareness Day

24 November 2013 at 22:43 | Posted in Circadian rhythm | 8 Comments
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The online N24 community has decided to name November 24 as N24 Awareness Day.  We are encouraging bloggers and tweeters and anyone else with a platform to help spread awareness and knowledge of Non-24-Hour Sleep-Wake Disorder (N24).

The web page which links to these efforts is here (click on the N24 Day Logo):

N24 Awarenes Day Icon
This would be an appropriate time to review some events in 2013 relevant to N24.

One important advance was a paper by Kitamura et al. which measured the intrinsic circadian period in 6 patients with N24.  They compared it with two groups of individuals without a circadian disorder.  One group had an intermediate circadian preference.  The other group had an evening preference. The latter group however did not have DSPS, only a preference for being active later in the day.

Kitmura et al. found that the intrinsic period of the N24s was 24.5 hours, which was significantly longer than that of the intermediate types, but not significantly longer than that of the evening types.  The average period of the N24s was longer than that of the evening types but because of the great degree of overlap between those groups the difference was not significant.  The longest period found in an evening type subject was nearly identical to the longest period among the N24 subjects (around 24.7 hours).

These results suggest that a longer-than-average intrinsic period is a component of N24, but it is not the only causative factor.  Other factors, such as differences in phase angle between sleep and temperature rhythms, as found in several studies, may play a role.

Another paper, by An et al.  did not discuss N24 explicitly, but the results may have import for those with the condition.  They studied the effect of Vasoactive Intestinal Peptide (VIP) on shifting of circadian rhythms in mice and in cell cultures from the SCN.  They found that VIP depending on time and dose could either enhance or reduce the mutual synchronization of SCN cells.  Further, when SCN cells were less tightly synchronized together, they adapted more quickly to phase changes.  This suggests that by manipulation of VIP levels it may be possible to increase the adaptability of the SCN to phase changes.  Since N24s with a longer period need to change phase every day if they are trying to maintain a normal schedule, this approach might be of help.   It might also help people with DSPS when trying to shift to an earlier sleep phase.

–posted by LivingwithN24 (James Fadden)


Kitamura S, Hida A, Enomoto M, Watanabe M, Katayose Y, Nozaki K, Aritake S, Higuchi S, Moriguchi Y, Kamei Y, Mishima K. Intrinsic circadian period of sighted patients with circadian rhythm sleep disorder, free-running type.Biol Psychiatry. 2013 Jan 1;73(1):63-9.

An S, Harang R, Meeker K, Granados-Fuentes D, Tsai CA, Mazuski C, Kim J, Doyle FJ 3rd, Petzold LR, Herzog ED. A neuropeptide speeds circadian entrainment by reducing intercellular synchrony. Proc Natl Acad Sci U S A. 2013 Nov 12;110(46):E4355-61.


Next post:  68.  Guest post: Non-24 — Not Just a Disorder of the Blind


63. Sleep research in the USA

12 May 2011 at 19:25 | Posted in Circadian rhythm | 6 Comments
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Funding of sleep research by the National Institutes of Health (NIH) is prioritized according to the National Sleep Disorders Research Plan.  The plan resulted from 1993 legislation establishing the National Center on Sleep Disorders Research with the mandate, in part, to:

  • Conduct and support research, training, health information dissemination, and other activities with respect to a basic understanding of sleep and sleep disorders, including research on biological and circadian rhythms, chronobiology, and other sleep-related topics.

The first such plan was dated 1996.  The second and current one is from 2003:  http://www.nhlbi.nih.gov/health/prof/sleep/res_plan/sleep-rplan.pdf  

The present Sleep Disorders Research Advisory Board, chaired by Charles A. Czeisler and with Michael Twery as Executive Director, has been working for a year or so on a revision.  The 2011 research plan will provide a guide for future scientific sleep and circadian research, both basic and clinical.

While the 2003 plan is organized under such headings as Basic sleep science, Enabling technology, and Pediatrics, the 2011 plan will be organized around research goals.

The draft of April 2011 contains five goals.  They are concerned with, in short version:

  1. Sleep and circadian functions and mechanisms
  2. Factors contributing to sleep and circadian disorders and disturbances
  3. Prevention, diagnosis and treatment of sleep and circadian disorders and circadian disruption
  4. Dissemination of sleep and circadian research findings
  5. Sleep and circadian research training, to accelerate the pace of discovery

There appears to be a greatly increased emphasis on circadian disorders and research in this draft.  The word ‘sleep’ appears seldom alone; it’s always ‘sleep and circadian’.

Those of us with circadian abnormalities are perhaps most happy with goal 4.  Health care professionals, educators, policy makers and the general public are at present largely unaware of the results of research to date, and the resulting ignorance leads to misdiagnosis of most of us.  The research community knows a great deal more than the medical community does, and dissemination of that knowledge should have high priority.


Next post:  64.  Circadian Sleep Disorders Network


54. Take a Nap!

30 June 2010 at 18:27 | Posted in Circadian rhythm | Leave a comment
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Sleep researcher Sara C. Mednick has written the book Take a Nap! Change your life.  (Workman Publishing, NY, 2006)

 Yes, it  continues in the over-enthusiastic, cheer-leading tone seen in the title, and no, it doesn’t address circadian rhythm disorders.  The book is so popularized that it doesn’t even have an index.  But it’s interesting and it’s based on solid science.  It tells about sleep stages, what they are for and their circadian rhythms.

Though we spend about half our total sleep time in Stage 2 sleep, it’s been known for some time that most deep sleep appears in the first half of one’s night, and most rapid eye movement (REM) sleep appears in the last half.  Here’s a hypnogram from Wikipedia  showing a normal night’s sleep with its sleep stages:

Deep sleep (slow wave sleep) is stages 3 and 4 where Stage 3 includes 20-50% delta waves and Stage 4 includes over 50% delta waves.  The illustration clearly shows deep sleep in the early part of the night (more clearly than a more modern one might, as stages 3 and 4 often are combined into one, at least in the USA).

It would never have occurred to me, but Dr. Mednick has shown that this early night/late night division into predominantly deep sleep and predominantly REM sleep is just part of a whole circadian cycle: a morning nap will include more REM sleep while an afternoon/evening nap offers more slow wave sleep.  Sleep cycles generally contain the lowest amount of REM a couple of hours before bedtime and the greatest amount twelve hours later.  I’ve tried to illustrate this here:

And should we care which sleep stages we are getting in a nap?  In a nap of 20 minutes or less, the answer is no, as that nap includes only stages 1 and 2.  But in a longer nap, up to an hour and a half or so, we go through a whole sleep cycle and it may indeed matter which type of sleep we are wanting.

The short “Stage 2 nap” increases alertness, stamina and physical dexterity.  Drowsy drivers have a lot to gain from a 15-20-minute nap. 

The morning nap, with more REM-sleep, inspires creative insight, heightens sensory perception and consolidates newly learned material including spacial orientation.  The evening nap, with more deep sleep, provides tissue repair, improves memory and clears the mind (“prunes deadwood”).

On one point, Dr. Mednick disagrees with other experts.  She says a nap no longer than three hours ending no later than three hours before bedtime will not interfere with nocturnal sleep and may even improve it!

Take a Nap! provides detailed instructions for planning your ideal nap.  NB!  if you are not well-rested, sleep debt will demand the repaying of SWS first, whether or not that’s what you want most of.  See also Mednick’s website:  www.takeanap.info

( posted by D )


Next post: #55.  Chronotherapy: balancing benefit and risk


l(L). A Man with Too Long a Day

14 February 2010 at 01:33 | Posted in Circadian rhythm | 18 Comments
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The Physiological Society is an venerable British scientific society dating from the time of Darwin.   Articles in their journal, Proceedings of the Physiological Society, normally have rather obscure titles like “Synaptic connexions of serotonin-containing neurons in Planorbis Corneus.”  But in 1970 a paper from three scientists at  the University of Manchester appeared with a title that reads more like that of a science fiction story: “A Man with Too Long a Day”.   The man who was the subject of the paper claimed that he was unable to live on a 24-hour day.  Instead his sleep wake cycle followed a 26-hour pattern.  While humans in isolation experiments sometimes followed non-24 hour schedules, this was the first report of someone who followed such a pattern in normal life, and, more importantly to him, he was unable to live on 24 hours however hard he tried.  The scientists were able to confirm the reality of his complaint by a clever experiment.

He was then confined in an isolation unit, without a timepiece, and his
habits were recorded by a remote signalling device; he there followed an
activity cycle of 26 hr. After 5 days a clock, which he knew could be
adjusted to gain or lose several hours a day, was started, and he was asked
to try to conform his habits to the time recorded on the clock; unknown
to the subject, this clock was running at a normal rate, though its absolute
time was in error since it was started at the time which he believed it to be.
He was still unable to conform his habits to a 24 hr cycle, just as when
living in nychthemeral surroundings.

This was the first report of what is now known as Non-24 Hour Sleep Wake Cycle Disorder, more concisely N24.  The authors did not report any attempt to treat his condition.

Eight years later, doctors at the Albert Einstein College of Medicine reported another case of what they called “hypernychthemeral syndrome” after the Greek hyper (over) + nychthemeron (24-hour period of night and day).  Long-term temperature monitoring recorded his rhythms for several months.   In 1980 a third case was reported, this time of a man “John” and his partner “Mary”.  John had N24 while Mary’s sleep had previously been  normal but at times followed Johns N24 schedule.  Charts of their sleep show a kind of circadian dance as their rhythms would coincide for a while and then diverge.

None of these early cases were successfully treated.  In 1983 the Clinical Psychobiology Branch at the US National Institutes of Health reported the first successful treatment of N24, by using vitamin B-12.  Subsequent cases have reported N24s who respond to B-12 although many do not.  (It makes me much worse!)

The next known case, in 1985, responded to clonazepam but the subject reported he felt worse on the drug despite his normalized schedule and chose to stop the drug and resume an N24 schedule.  This was a pattern often found in later N24 cases — sometimes the cure is worse than the disease.

Three reports in the late 80s studied the effects of light, with differing results.   Light successfully treated one person.  Another N24 was initially able to entrain with light, but a later Internet report seems to say she (by the way the first woman with true N24) had to stop it due to migraines.  But a Japanese study found that an N24 person was resistant to the normal phase shifting effects of light, suggesting that some N24s develop the condition due to insensitivity to light.

A few more reports appeared in the early 1990s.  The NIH published a detailed study of a second patient, showing endocrine abnormalities, some of which were corrected by light treatment while others were not.  And researchers in Japan published a growing number of case reports and pioneering studies.

What’s striking about these early cases of N24 is how few of them there were: eight years between the first and second cases!  N24 appeared to be a very rare disorder, and it’s probable no N24 ever met anyone else with N24.

Then came the Internet.

As with many conditions, the Internet has broken the isolation of N24s.  It’s still a rare condition by any measure, but not as rare as once thought.  On Internet sites and mailing lists such as the NiteOwl list for DSPS and N24, more and more N24 people are popping up to say “I’m here” and the talk about the difficulties of living with and/or trying to treat their condition.  And that’s why I’m here on this blog, to talk about N24, what N24 folks say, what the science says.   This post has been about the past of N24, but we are here to make a better future for those whose sleep follows a “different drummer”.  Great thanks to delayed2sleep for inviting me on this blog.  Let’s see what we can do!


I classified “A Man with Too Long a Day” as the first medical report of a person with N24, and that is accurate and how it is generally cited in the medical literature.   However a few years ago I was reading Sylvia Nasar’s biography of John Nash, A Beautiful Mind. She devotes a chapter to Nash’s friend, the brilliant mathematician and game theorist Lloyd Shapley.  Shapley and Nash met at Princeton in 1950 when both were graduate students.  In describing Shapley, Nasar says this:

Shapley’s greatest eccentricity at the time was his claim that he was on a
twenty-five-hour sleep cycle. He worked and slept at extremely odd hours, often
transposing night and day. “Every once in a while he’d disappear from sight.”
another student recalled. “That’s what he said. We accepted anything.”

It’s not clear if Shapley’s schedule was voluntary or involuntary.  The latter would make him the first known N24.

Posted by LivingwithN24 (James Fadden).


Next post:  51. Melatonin: Less Is (Sometimes) More


xlii. Researchers mentioned here

13 June 2009 at 18:05 | Posted in Circadian rhythm | 6 Comments
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Several researchers have been mentioned / cited here, and there’ll surely be more.  They are listed below. 

Bjorvatn, Bjørn (in post vii.), is a sleep researcher at the University in Bergen, Norway, and a co-founder of Bergen Sleep Center.

Czeisler, Charles A. (in post xliii.) has been researching circadian rhythms for several decades.

Dagan, Yaron  (in post xxxviii.) in Israel, often publishing together with Judith Abadi, stated in 2001: “Certain sleep-wake schedule disorders (SWSDs) cannot be successfully managed clinically (…).  …we propose new medical terminology for such cases–SWSD disability. SWSD disability is an untreatable pathology of the circadian time structure…  It is imperative that physicians recognize the medical condition of SWSD disability in their patients and bring it to the notice of the public institutions responsible for vocational and social rehabilitation.”  In almost all of his papers, he emphasizes that people with circadian rhythm disorders often are misdiagnosed because physicians don’t know (enough) about such disorders.  Here is a case study (abstract) about a 14-year-old boy whose other diagnoses fell as soon as his sleep disorder was diagnosed.  It should perhaps be obvious that I appreciate Dagan’s work and his opinion. 

DeCoursey, Patricia (in post xix.), is the grand old, grand old of the field of chronobiology.  In 1960 she invented the Phase Response Curve when the “daily” activity rhythms of her flying squirrels, kept in constant darkness, responded to pulses of light exposure. The response varied according to the time of day — that is, the animals’ subjective “day” — when light was administered. When DeCoursey plotted all her data relating the quantity and direction (advance or delay) of phase-shift on a single curve, she created the PRC. It has since been a standard tool in the study of biological rhythms.

Dijk and Lockley (in post v.).  Derk-Jan Dijk and Steven W. Lockley often publish together.  Dijk, who studies the regulation of sleep and circadian rhythms in humans, is director of the Surrey Sleep Research Centre in the UK.  Lockley, Assistant Professor of Medicine, Harvard Medical School, and Associate Neuroscientist in Sleep Medicine, Brigham and Women’s Hospital in the USA, is particularly interested in the effects of light on the circadian pacemaker in humans.

Horne and Östberg (in post xxxviii.) published their Morningness-Eveningness Questionnaire (MEQ) in 1976.   It is based on O. Öquist’s 1970 thesis at the Department of Psychology, University of Göteborg, Sweden: ”Kartläggning av individuella dygnsrytmer”, “Charting Individual Circadian Rhythms”.  This marks the beginning of modern research into chronotypes.  Olov Östberg modified Öquist’s questionnaire and, together with J. A. (Jim) Horne, he published the MEQ (pmid 1027738, abstract ) which still is used and referred to in virtually all research on this topic. 

Roenneberg, Till (in post xxxvii. and in post xlvii.), professor at the University of Munich, is one of the best-known chronobiologists in Europe, having received international prizes for both his research and his teaching.  He has built up the Centre for Chronobiology at the Munich Medical School with its database on the sleep of over 50 000 Europeans.  In 2008 in India he collaborated with and directed a project in Mangalore chronotyping the south Indian population, with data covering nearly 75 000 participants.  Roenneberg’s work ranges from the cellular/molecular mechanisms of the circadian clock to the consequences of shift work and, as mentioned, huge surveys.

Thorpy, Michael J. (post xxxii.), board certified in sleep medicine, is a sleep researcher and a professor of clinical neurology at the Albert Einstein College of Medicine in New York.  He has held high office in the National Sleep Foundation and in the Sleep Section of the American Academy of Neurology.  Thorpy was for many years editor of The International Classification of Sleep Disorders: Diagnostic and Coding Manual (ICSD) and has been publishing books and articles since the 1980s.

Uchiyama, Makoto (in posts xxxviii. and xxvii.), professor at the Nihon University School of Medicine in Tokyo and managing editor of Sleep and Biological Rhythms, the official English language journal of the Japanese Society of Sleep Research (JSSR), is a prolific co-author of studies on sleep, particularly on DSPS and Non-24, often in cooperation with Masako Okawa, chair of the Asian Sleep Research Society. (ASRS).  This research field is very active in Japan, where study subjects often are people with these disorders.  In the west, in contrast, studies are more often done on healthy, normal people with results extrapolated to effects in people with the disorders.  The Japanese researchers have shown, for example, that the interval between the lowest core body temperature and spontaneous awakening is much longer in people with Non-24 and DSPS than the “about two hours” which is considered normal.

Zivkovic, Bora, aka “Coturnix (in posts xxxvii.xxxiii.xviii. and  xv.), should have had his PhD by now but the ideal job came along and his dissertation isn’t getting done.  He tells about that and about chronobiology and about lots more at ScienceBlogs


Next:  xliii. Blindfolding the blind


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