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.

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Next post:  xiii. DSPS-sleep

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6 Comments »

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  1. You say
    “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.”

    Can you expand on that please?

    Steve

  2. I’ve read that several times, but haven’t learned it well enough to explain it, I think. The bit I remember is that DSPS people have a longer period between body temperature minimum (nadir) and wake than normal. This is more similar to morning types than evening ones. I’ll ask my co-blogger if he can explain more. He has a much better system for finding the papers he’s looking for, than I have, and he’s good at explaining. Thanks for your comments, Steve.

  3. delayed2sleep got it right. There are two rhythms involved. One is the body temperature rhythm which reflects the rhythm of the basic body clock. Body temperature cycles during the day and night and reaches a minimum in the early morning hours. The other rhythm is the sleep wake cycle — the timing of when one falls asleep and awakes.
     
    In both DSPS and evening chronotypes, both the temperature rhythm and the sleep cycle are delayed relative to morning types. In this way DSPS and eveningness are similar.
     
    But they are different in another way. In evening types the temperature rhythm is delayed *more* than the sleep cycle. So the sleep cycle may be delayed by 1 hour and the temperature minimum by 2 hours. It is the opposite in DSPS. In DSPS the sleep cycle is delayed more than the temperature cycle. So the temperature minimum may be 2 hours delayed and the sleep cycle 3 hours delayed.
     
    This difference in the sleep and temperature rhythm is what is called a difference in internal phase angle. It is often measured by the time interval between the body temperature minimum and the wake time. In DSPS this interval is abnormally long. In evening types it is unusually short.
     
    Another way of describing it is the say that the body clock of both DSPS and evening types is delayed. But evening types sleep early relative to their own body clock, while DSPS persons sleep late relative to their own body clock.
     
    This difference suggests that the cause of DSPS is more than just an exaggeration of an evening chronotype. Something else is going on related to the sleep cycle.
     
    (The same conclusion may apply in a converse fashion to ASPS and morningness, although that is not as well established. Incidentally the study of internal phase angles also shows that N24 is similar to DSPS but more extreme in its abnormal phase angles.)
     
    To complicate the subject even more, there are also suggestions that evening types may come in two subtypes, one subtype being similar to DSPS and the other different as I just described.
     
    There are several studies on the phase relationships in DSPS and eveningness.. Here are a couple:
     
    http://www.ncbi.nlm.nih.gov/pubmed/10198570
     
    http://www.ncbi.nlm.nih.gov/pubmed/15155011
     
    Thanks for the question.
     
    LivingwithN24

  4. Thanks for this insight

  5. Quote: “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.”
    .
    Is it a coincidence that the key change is from serine to glycine?
    .
    “Glycine is considered a glucogenic amino acid, which means it helps supply the body with glucose needed for energy.” see: http://www.vitaminstuff.com/amino-acid-glycine.html for more info
    .
    And glucose is regulated in the body by cortisol…

  6. And when reading the entire page about the glycine info they also mention a study where glycine was used to treat several sleep deprived conditions.
    .
    And they also mention that glycine has a positive effect on treating several types of cancer including keeping the prostate healthy. I mention this because I suspect that my entire family is suffering from DSPS running whole the way back to my grand mother. I recently talked to her about this and she also mentioned that all of her brothers (4 in total) died from prostate cancer… It seems to me that this is more than just a coincidence!


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