Tags: Circadian rhythm, Core body temperature, DLMO, Entrainment, Melatonin, MEQ
I’ve earlier seen hints that there are differences in men’s and women’s sleep timing. Now a new study confirms that and has also found differences in the quantity of melatonin secretion and in the daily temperature amplitude.
The study participants were normal sleepers: 28 women and 28 men, ages 18-30, matched in pairs for age, habitual bedtime, habitual wake time and MEQ-results. Under strictly controlled conditions, so-called constant routine, their core body temperatures and melatonin levels were measured.
The women reached higher levels of melatonin in the blood.
The men had a greater amplitude in body temperature throughout the day and night.
The illustration shows the significant differences in sleep timing between women and men, on average. In each of the 28 matched pairs of participants, significant differences were found between the women and the men with regard to the intervals
- between DLMOn and bedtime,
- between wake time and DLMOff, and
- between temperature minimum and wake time.
The women were sleeping and waking at the same clock time, but at a later biological time than the men.
- MEQ = the Morningness-Eveningness Questionnaire by Östberg and Horne
- DLMOn = Dim Light Melatonin Onset
- DLMOff = Dim Light Melatonin Offset (Here, based on blood level, not offset of synthesis.)
Reference: Cain, Sean W., Christopher F. Dennison, Jamie M. Zeitzer, Aaron M. Guzik, Sat Bir S. Khalsa, Nayantara Santhi, Martin W. Schoen, Charles A. Czeisler and Jeanne F. Duffy. Sex Differences in Phase Angle of Entrainment and Melatonin Amplitude in Humans. Journal of Biological Rhythms 2010 25: 288. DOI: 10.1177/0748730410374943
Next post: Coming soon
Tags: Body clock, Circadian rhythm, Core body temperature, Melatonin
Blindfolding blind people sounds like an oxymoronic exercise. But it is clear that some people with no visual light perception, do, in fact, entrain normally. I believe it was Charles A. Czeisler who, about 1980, discovered that some blind people entrain normally to the 24-hour light/dark cycle while others do not.
These researchers, as well as others, worked on determining the circadian periods of individuals by the use of forced desynchrony, so-called constant routines. Conditions which are impossible to entrain to, allow mapping of body temperatures and melatonin levels.
The illustration above, from the 1995 paper, shows two days and nights in the lives of a sighted (above) and a blind (below) *person. They call this the “Melatonin Suppression Test”. Circadian phase is determined in the first night: the high point of the level of melatonin in the blood corresponding more-or-less to the low point of the core body temperature. The second night both subjects are submitted to 90 minutes of bright light (the white columns) at the time of their highest melatonin levels the night before. And the melatonin levels go way down in both subjects!
In a repeat of the test with the blind person blindfolded, the light had no effect. Obviously, somehow, the light signal makes it to the body clock in some blind people. More about how this works, for all of us, in the next post.
* (It seems to me to be not-too politically correct to call healthy volunteers “subjects” and healthy blind people “patients”. Czeisler et co will have to answer for that.)
Tags: Chronotype, Circadian rhythm, Core body temperature, Cortisol, DLMO, DSPS, Eveningness, Jet lag, Melatonin, MEQ, Morningness, Shift work, Sleep architecture, Sleep deprivation
“Well, I don’t like getting up before seven either,
but I have to, and I do.”
Implication: and you can, too.
But, is that true?
The article on Wikipedia about Chronotypes, morningness/eveningness, reports what researchers know so far about these normal variations, which have been studied since about 1970 and are measured by the Horne-Östberg questionnaire, the MEQ, a short version of which can be found online at Bruce Logie’s interesting site.
It can be interesting to compare normal evening types with what we know about people with Delayed Sleep-Phase Syndrome.
- like to sleep in and don’t like to go to bed early.
- are more alert in the evening than just after awakening, as opposed to morning types.
- can take a nap at 10 a.m. or noon after a night with less sleep than usual, while morning types generally don’t want a nap until 2 p.m. or later.
- experience both Dim-Light Melatonin Onset (DLMO) and the minimum of the daily cortisol rhythm later (clock time) than morning types.
So far, it sounds like people with DSPS are evening types, as the properties above apply to both groups. However, normal evening types:
- after starting a new routine requiring them, for example, to start work earlier than before, will adjust their sleep-wake schedules to the new times within a few days.
- awaken spontaneously earlier in their circadian phase than morning people; that is, the interval between the low point of the body temperature and wake time is shortest in evening types. In people with DSPS, it’s notably much longer than average.
People with DSPS do not adjust to a new schedule easily, if at all.
- Evening types have a core body temperature which is a bit lower than average, both day and night. Is this also true for people with DSPS?
- Evening types have a melatonin profile which declines much more slowly after midpoint, as compared with morning types. Is this also true for people with DSPS?
- Evening types take a long time to “get going” after awakening. In relation to the timing of spontaneous awakening, the following points contribute to this for evening types, and possibly also for people with DSPS:
- the timing of lowest body temperature,
- the timing of the cortisol minimum,
- the timing of melatonin offset, and
- the slower decline of blood levels of melatonin.
We have a disorder which, without treatment, forces us to fall asleep even later than evening types. Simply trying to enforce conventional sleep and wake times does not advance the circadian markers. It seems almost impossible to wake us much earlier than our pre-programmed wake time (as my siblings will attest). The disorder is chronic, changing little or not at all after the age of 20.
When normal chronotypes shift their schedules, all the body’s rhythms catch up and are synchronized to each other within a few days. In DSPS, the dissynchrony may continue as long as the shifted, “unnatural” schedule lasts, even for years or decades, leading to physical and psychological disorders.
It’s clear that people with DSPS who (try to) work days, have much the same set of problems that many shift workers have, whether these always work nights or are on a rotating schedule. However, shift workers’ problems receive sympathy and understanding while people with DSPS are commonly stereotyped as undisciplined and lazy. Dagan again (PDF, page 7), on adolescents, points out that “[f]requently, the patients’ parents, teachers, doctors, or psychologists believe that the patients’ biological sleep-wake problem and the accompanying dysfunction at school are motivational or psychological in nature, a belief that during the years, the patients tend to adapt themselves. This attitude toward CRSD patients, to which [they have] been subjected since early childhood or adolescence, adds psychological distress to the practical difficulties of coping with life.”
Like normal people, we do adjust (entrain) to the earth’s 24-hour rotation, but, without treatment, we don’t “learn” to wake up at a conventional, early time of day.
Tags: Chronobiotic, Circadian rhythm, Core body temperature, DLMO, DSPS, Hypnotic, Light therapy, Phase response curve, Pineal gland, Sleeping pills, Treatment
To properly treat Delayed Sleep-Phase Syndrome (DSPS), one should know the patient’s circadian rhythms. At the least, one should know
when the natural sleep onset and spontaneous wake-up times are,
when the core body temperature minimum, nadir, occurs during sleep, and
when DLMO (dim light melatonin onset) is and preferably also the midpoint of melatonin in the blood.
Treatment with melatonin “supplement”, a hormone, and bright light therapy are very dependent on knowing these things, on getting (guessing) them right.
One study I found used eight of the usual subjects: normal, healthy young men. Their rhythms were determined in detail before the start of the study. The final report included results for only seven of them. Why? With all possible expertise and equipment at hand, one factor for one of the young men was determined wrongly by half an hour, so they had to leave him out. I’m glad they admit this sort of thing in the report, but it certainly raises the question of how we ordinary, abnormal mortals are supposed to be able to find these things out.
One study mentions that the period from nadir to awakening varied in their cohort from 1 to 6.5 hours. One found about a half hour difference in the averages for men and for women.
Well, if patients haven’t messed up their systems entirely with traditional sleeping pills and long-term coping tactics, number 1 above should be possible to identify.
Number 2, nadir, is said to be approximately two hours before spontaneous awakening in normal people, longer that that in DSPS people and even longer in people with Non-24. It should occur approximately seven hours after DLMO. Bright light therapy should be used a couple of hours after nadir to advance circadian rhythms. A few hours later than that, according to the phase response curve (PRC) for light in humans, the light will have almost no effect at all. Am I one of those whose nadir is six hours before wake-up? If so, using my light box is a waste of time and effort. How to know? It is also not entirely clear that moving the timing of the sleep-phase also will move the timing of the body’s other circadian rhythms, though in theory it should.
Then we have number 3 above, the timing of endogenous (natural) and exogenous (supplemental) melatonin. We all have pineal glands which secrete this hormone at night (whenever our own “night” is). Somehow it can make us sleepy and let us fall asleep. The mechanics of that are not yet well understood.
There appear to be two schools of thought regarding the timing of supplemental melatonin. The first and most common has been mentioned before. One uses it almost as one would a sleeping pill, a hypnotic in the jargon, one-half to two hours before one wants to go to sleep. This works pretty well for me with 0.5 mg melatonin making me sleepy after about one and one-quarter hours. When I get sleepy, I must get to bed immediately as the effect wears off quickly and I can then stay up til all hours.
It’s hard to find much on the second theory, supplemental melatonin as a chronobiotic, though I see that Wikipedia now tells about the PRC for melatonin as well as the PRC for light, and I’ve seen abstracts from two small studies. One of them, here comes a link to an abstract, in 2005, was done on thirteen DSPS patients in Illinois, USA. Melatonin supplements were tried between 1.5 and 6.5 hours before DLMO (dim light melatonin onset). DLMO is generally considered to occur approximately two hours before bedtime. The study results showed that the earlier melatonin was administered, the greater was the advance in the timing of DLMO. Sleep onset was also advanced some, though to a lesser degree.
The other study at a different medical center in Illinois, also in 2005, on normal subjects both male and female, suggests that one should use melatonin much earlier than the traditional timing and “in doses small enough not to feel tired right away” to effectively advance one’s circadian rhythms. They experimented with placebo, with 0.5 mg melatonin five hours before bedtime and with 3 mg administered seven hours before bedtime. Each of the three groups was also treated with bright light in the morning. They conclude that a nearly one-hour advance, daily, in sleeping time <and> light exposure <and> administration of melatonin did not lead to misalignment of circadian rhythms during the three days of the study.
These are but two studies experimenting with the concept of the PRC for melatonin. If the theory proves to be valid, we can expect to see many more in years to come. This should be interesting to follow, and we can hope for some studies which will last longer than three days!
I still lament. When is my temperature minimum? My DLMO? Is it possible for me to advance these and all the other rhythms in alignment and keep them there, without detrimental effects on physical and mental health? The more I learn, the less clear it all becomes. Sigh.
Tags: Body clock, Core body temperature, DSPS, Japanese study, Melatonin midpoint, Non-24
Those of us who can, reset our body clocks daily. The primary cue from the environment is light. The vast majority of us need to advance our phase, that is, shorten our built-in day to match the light/dark cycle in nature. This is what normal people do so easily.
By definition, people with Delayed Sleep-Phase Syndrome (DSPS) can adjust to a 24 hour day, even though they don’t fall asleep before 2-6 a.m. or even later. People with Non-24-hour Sleep-Wake Syndrome cannot of their own accord.
M. Uchiyama et al in Japan have studied Non-24 and DSPS people, comparing both with normal controls and with each other. The following table is constructed from two of their reports, published in 2000 and 2002. No blind subjects were included in these two studies.
* Both the Non-24 and the DSPS people slept longer than the normal ones.
* Non-24 people had a short interval from sleep onset to the melatonin midpoint.
* Both Non-24 and DSPS people had a long interval from the core body temperature trough (nadir) to wake-up.
* DSPS people had a longer interval between sleep onset and nadir than Non-24 people.
We know that normal people are exposed to morning light about two hours after nadir, as that is their “hard-coded” wake-up time. Light exposure is less and less effective in resetting the body clock in the hours which follow.
Core body temperature is one marker of an individual’s circadian period.
In the table above, which shows an approximation of the intervals reported, one can see that when DSPS and Non-24 people are allowed to awaken spontaneously, their earliest light exposure occurs much more than the normal two hours after nadir.
The Japanese researchers conclude that the lack of light two hours after nadir hinders a normal adjustment of the circadian pacemaker. They also postulate that a delayed sleep onset relative to one’s own pacemaker allows for an accelerated light-induced phase-delay. As they put it, “We postulate these alterations in phase relation to be associated with phase changes of the circadian pacemaker via different illumination timings.”
Non-24 patients have a significantly more faulty phase angle between sleep onset and the circadian pacemaker than DSPS patients have.
Uchiyama M, Okawa M, Shibui K, Kim K, Tagaya H, Kudo Y, Kamei Y, Hayakawa T, Urata J, Takahashi K. Altered phase relation between sleep timing and core body temperature rhythm in delayed sleep phase syndrome and non-24-hour sleep-wake syndrome in humans. Neurosci Lett. 2000 Nov 17;294(2):101-4.
Shibui K, Uchiyama M, Okawa M. Melatonin rhythms in delayed sleep phase syndrome. J Biol Rhythms. 1999 Feb;14(1):72-6.
Okawa M, Uchiyama M. Circadian rhythm sleep disorders: characteristics and entrainment pathology in delayed sleep phase and non-24-h sleep-wake syndrome. Sleep Med Rev. 2007 Dec;11(6):485-96. Epub 2007 Oct 25.