61. Questions and answers about Non-24

17 February 2011 at 13:56 | Posted in Circadian rhythm | 18 Comments
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About 50% of the totally blind have Non-24-hour Sleep-Wake Cycle Disorder while it is very rare among sighted people.  People with Non-24 cannot adjust to the environmental 24-hour cycle.

If Hayakawa et al. are to be believed, there have been only 96 cases of N24 in sighted people reported in studies, worldwide, ever.  The first 39 were reported in 26 separate studies dated 1970-2003.  Hayakawa’s group reported on 57 cases in a report in 2005*.  These 57 were diagnosed in Japan in 1991-2001.  So what have I learned from that paper?

Are there equally many men and women?  No, there are more than two and a half times as many men.

Is Non-24 about as common as the other Circadian Rhythm Disorders (CRDs)?  No, the other CRDs together, primarily DSPS, are six times as common.

Do people with Non-24 have anything else in common physically?  No.  Eye examinations, blood counts, serum biochemistry, electrocardiography, electroencephalography and brain MRIs show nothing special.

Socially?  89% were unmarried and 39% were unemployed.

Had they any health problems in common before the onset of free-running?  28% had psychiatric problems (obsessive-compulsive, adjustment, schizoprenia, anxiety or depression and often associated social withdrawal), not remarkably higher than the general population.  But more than a fourth had DSPS before developing Non-24.

How old were they at the onset of Non-24?  86% were ten to twenty-nine years old, none younger than ten.  Sex had no effect on the age of onset.  (None of the subjects was over 50.)

Do the hours of sleep correlate to the length of the endogenous circadian cycle?  Most of the subjects’ cycles were between 24.5 and 25.5 hours, with only one having a cycle longer than 26.5 hours.  Subjects slept between less than 7 hours to more than 12, with the majority sleeping 9-11 hours.  But there was no correlation between the period of the sleep-wake cycle and sleep length, and neither was affected by sex nor employment status.

How debilitating is the disorder?  “98% had a history of disturbed social functioning due to inability to regularly attend school or work.”

Do people with Non-24 often develop psychiatric problems after the onset of the disorder.  Yes, but depression only, not the other disorders.  “It is possible that these patients had tried to adapt themselves to their social life and failed, leading to psychological stresses that could have precipitated their depression.”

How does Non-24 in sighted people differ from that of people who are blind?  The blind generally have a shorter circadian period, and it doesn’t fluctuate over time.  In sighted people, the period tends to be longer when sleep onset is in the daytime than when a person falls asleep during nighttime.

*Tatsuro Hayakawa, Makoto Uchiyama, Yuichi Kamei et al.  Clinical Analyses of Sighted Patients with Non-24-Hour Sleep-Wake Syndrome: A Study of 57 Consecutively Diagnosed Cases.   SLEEP 2005;28(8):945-952


Next post:  62.  Psychiatric misdiagnosis of N24


xlvii. Distribution of early and late types

7 November 2009 at 02:23 | Posted in Circadian rhythm | 7 Comments
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Distribution, early and late types

The illustration above is adapted from Till Roenneberg et al., the team who invented the Munich Chronotype Questionnaire, MCTQ.  The MCTQ is a modern version of the Morningness-eveningness Questionnaire, MEQ, and it is considered to give the best estimate of morningness and eveningness chronotypes.  They have chosen to consider sleep onset at 00:30 and 01:00 as “normal” for the adult population.  Their results are 46.5% early types, 28.5% normal types and 25% late types — as shown in this table:

According to the illustration from MCTQ Percentage of population

Chronotype sleep time    % SUM
   EARLY TYPE  EXTREME> 2.0 % 20.30 – 04.30 < 0.5     46.5 %
21.00 – 05.00 < 0.5
21.30 – 05.30 < 0.5
22.00 – 06.00    2.0
MODERATE13.0 % 22.30 – 06.30    3.5
23.00 – 07.00    9.5
SLIGHT31.5 % 23.30 – 07.30  14.5  
00.00 – 08.00  17.0
NORMAL TYPE 00.30 – 08.30  16.0     28.5 %
01.00 – 09.00  12.5


SLIGHT15.0 % 01.30 – 09.30    9.0        



    25.0 %

02.00 – 10.00    6.0
MODERATE6.5 % 02.30 – 10.30    4.0
03.00 – 11.00    2.5
EXTREME> 3.5 % 03.30 – 11.30    2.0
04.00 – 12.00    1.0
04.30 – 12.30    0.5
05.00 – 13.00 < 0.5
05.30 – 13.30 < 0.5
SUM         100.0 %

But isn’t 1 AM rather late at night to be considered a “normal” bedtime?  In my opinion, normal sleepy time would be no later than 11:30 PM, midnight and perhaps 12:30 AM. 

Using my own idea of what is normal, I’ve reconstructed the table to show these results:  15% early types, 47.5% normal types and 37.5% late types, as shown here:

In my opinion, based upon their figures:

percentage of population

Chronotype sleep time    % SUM
   EARLY TYPE  EXTREME< 1.0 % 20.30 – 04.30 < 0.5     15 %
21.00 – 05.00 < 0.5
21.30 – 05.30 < 0.5
MODERATE5.5 % 22.00 – 06.00    2.0
22.30 – 06.30    3.5
SLIGHT9.5 % 23.00 – 07.00    9.5
NORMAL TYPE 23.30 – 07.30  14.5       47.5 %
00.00 – 08.00  17.0
00.30 – 08.30  16.0


SLIGHT21.5 % 01.00 – 09.00  12.5        




    37.5 %

01.30 – 09.30    9.0
MODERATE10.0 % 02.00 – 10.00    6.0
02.30 – 10.30    4.0
EXTREME6.0 % 03.00 – 11.00    2.5
03.30 – 11.30    2.0
04.00 – 12.00    1.0
04.30 – 12.30    0.5
05.00 – 13.00 < 0.5
05.30 – 13.30 < 0.5
SUM         100.0 %

So I’ve also redone the figure at the top of this page to reflect my opinion of what is early and late: 

 Distribution, early and late types

What time do you think “normal types” go to sleep at night?

See the Roenneberg 2007 review: Epidemiology of the human circadian clock.  See also the 5th comment below for an UPDATE.

Posted by Delayed2Sleep (aka “D”).


Next: Guest blogger:  Breann (again)


xii. Circadian rhythm disorders

27 November 2005 at 11:14 | Posted in Circadian rhythm | 6 Comments
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There are a great many sleep disorders. I read recently that an official list of them had been pared down to about 70. Many have to do with not getting enough sleep, or getting sleep of poor quality by several criteria. Some have obvious causes, such as chronic pain, frequent stops in breathing etc.

My interest is in the timing of sleep as my sleep seems otherwise normal. As the experts put it, I have normal “sleep architecture”. (For a good, short explanation of sleep architecture — stages and brain waves — see this page from Feinberg School of Medicine at Northwestern University in the USA.)

Nearly all of us can reset our clocks daily, adjusting the various rhythms to 24 hours. As much as I’ve read about it, I’ve not found a good enough explanation for being able to adjust to 24 hours while not being able to adjust to sleeping midnight to eight or so.

I’m not immune to the light/dark cycle. I need to get up at noon. I fly 8 hours east or west, go through jet lag like anyone else and within days I need to get up at noon in the new location. This is built in. I’m not the only one. I’d just like to understand it better.

A Japanese paper (2004) suggests these possible mechanisms:

  • reduced sensitivity of the oscillator to photic entrainment,
  • an intrinsic period beyond the range of entrainment to the 24 hour day, and
  • abnormal coupling of the sleep/wake cycle to the circadian rhythm.


The least common and most debilitating circadian disorder is the one where body temperature, melatonin secretion, sleep and other rhythms vary several times a day, in and out of phase with one another, so called Irregular Sleep/Wake Disorder. This has been reported in humans who’ve been in accidents and had physical injuries to the hypothalamus. It’s also been provoked by surgery in lab animals.

One of the most rare disorders which occurs naturally is called Non-24. Sufferers simply(?) live on a 23, 25 or 26 hour cycle, getting up one hour later each day for example, thus coming in sync with the earth’s rotation every few weeks. Their rhythms are in sync internally, just not with the light/dark cycle outside. Most, but not all, of these people are blind. 

ASPS, Advanced Sleep-Phase Syndrome, is also rare. These people fall asleep and awaken much earlier than normal. The disorder runs in families, and an American family has been studied intensively the last few years. Research on their genetic mutation was published in 2001. “Detailed sequence studies of the candidate human gene, hPer2, in the affected family members, revealed a key change in a single amino acid — from serine to glycine — at position 662 in the hPer2 protein.” The alteration “occurred in the portion of the hPer2 protein that governed binding to an enzyme called casein kinase one-epsilon (CK1e ).” In animal models, this enzyme regulates “proteins involved in controlling the length of circadian rhythms.”

Now this is beyond me, but it would appear that these disorders may be genetically programmed. Though ASPS is rare, it seems reasonable that researchers start there, since one can compare the DNA of people who are related to one other.

DSPS, Delayed Sleep-Phase Syndrome, is a bit more common. Studies indicate that somewhat more than one in a thousand adults have DSPS (Japan 0.13%, Norway 0.17%). It runs less commonly in families, but it doesn’t seem unreasonable to guess that its cause may be similar to that of ASPS.
Clearly, anyone whose health cannot tolerate frequent forced awakening earlier than 10 a.m., will have few real choices in our society. Thus, hardcore (inflexible) DSPS must be considered a disability.

Another disorder which may be related to the others is Seasonal Affective Disorder, SAD. Sufferers are normal in summer, have problems of mood, weight gain etc. when days get shorter and can often be treated successfully by bright light therapy. It seems likely that they may have a mild form of ASPS or DSPS which is “treated” by morning/evening daylight when days are long.

Diurnal preference, spoken of as “morningness”, larks, and “eveningness”, owls, is also a subject of study, the field of chronobiology. This is, reasonably enough, connected to one’s circadian rhythms. However, it does not appear that ASPS is an extreme morningness chronotype nor DSPS an extreme eveningness chronotype. The internal relationships among the various rhythms do not place these conditions on a simple continuum.


Next post:  xiii. DSPS-sleep


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