Category Archives: Rhythmic Human

Larks, Owls and Hummingbirds

I regularly get Google News alerts for articles that contain the word “circadian” in them. Most of them are not too exciting, but when a really good one comes along, I like to point it out to you. Today, you should go and read Larks, Owls and Hummingbirds, a guest post by Leon Kreitzman over on Olivia Judson’s blog. Highly recommended – about human circadian rhythms, chronotypes (i.e., owls and larks), etc., both from a scientific and a societal point of view.
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Related:Everything You Always Wanted To Know About Sleep (But Were Too Afraid To Ask)
Books: Snooze…Or Lose! – 10 No-War Ways To Improve Your Teen’s Sleep Habits by Helene A. Emsellem, MD

Is your pilot too sleepy to land you safely?

Ask the pilot:

Ask yourself this: Whom would you prefer at the controls of your plane on a stormy night, a pilot who smoked a joint three days ago, or one who had six hours of sleep prior to a 13-hour workday in which he’s performed half a dozen takeoffs and landings? The first pilot has indulged in a career-ending toke; the second is in full compliance with the rules. I have to assume that the FAA realizes the foolery of such enforcement policies, but it nonetheless chooses to put its resources into drug testing and other politically expedient issues. Meanwhile it procrastinates, performing study after study and poring over data from NASA circadian rhythm experiments in an attempt to answer one of the world’s most perplexing questions: Is exhaustion a detriment to job performance?

The Scientist special topic: Sleep

Nice four articles:
The Gears of the Sleep Clock By Allan Pack:

When people have trouble sleeping–such as, in extreme cases, shift workers–those problems are not always rooted in disturbances in circadian rhythm, argues the University of Pennsylvania’s ALLAN PACK. Instead, his studies of sleep have shown that the master clock is only one player in the molecular control of sleep.

Sleep adjusts fly synapses by Bob Grant:

New findings support a controversial hypothesis about the biological role of sleep: Snoozing may be a way for the brain to clear clutter accumulated after a hard day of synapse forming and strengthening. Two Science studies published today suggest that the brains of sleeping Drosophila undergo an overall depression in synaptic strength and number, eliminating some minor neuronal connections while merely weakening stronger ones.

Disappearing Before Dawn By Kelly Rae Chi:

Gene expression studies are lending support to a new, somewhat counterintuitive hypothesis for why every animal sleeps. KELLY RAE CHI visits the University of Wisconsin-Madison, where scientists are gathering evidence suggesting that we need sleep to prune back synapses, which tend to increase in strength throughout the day.

Why sleep?:

Sleep takes up around a third of our lives, and is an object of fascination during the other two thirds. “I dreamt that…” is surely among the top 10 conversation topics of all time. Given this, it is surprising how little attention is paid to the anthropology of sleep. Intriguing (but too little) work has been done on sleep practices in nonindustrialized societies, 1 and there has been some engaging speculation about sleep patterns; 2 it all points to our Western conventions as being a behavioral outlier.

How to catch a fly sleeping:

John Zimmerman at the Center for Sleep and Respiratory Neurobiology explains a new technique for determining when a fly is sleeping or awake – a prerequisite for fly-based sleep research:

Human circadian rhythms and sleep

BBC 4 had a fascinating half-hour show yesterday, interviewing Till Roenneberg and Helen Emsellem on all sorts of fascinating new findings in the field of human chronobiology. Well worth a listen. But hurry up as the podcast is available only for another six days! (what do they do afterwards? why such a limited time? archives should be freely available forever).

A good review of human circadian rhythms and disorders

Circadian rhythms: Of owls, larks and alarm clocks in Nature News (download PDF while the article is still freely available), written by Melissa Lee Phillips is an excellent overview of the current state of knowledge about human circadian rhythms, underlying genetics, and circadian disorders.
I get several Google Alerts every day for media articles about clocks and most of them are too ‘meh’ for me to bother linking here, but this one is good and worth your time. J’approve.
Related….

Daylight Saving Time

Yup, it’s tonight.
If you were around here a few months ago, the day after the Fall Back day, you probably read this post.
Disregarding the debate over rhetoric of science, that is probably my best, most detailed explanation for what happens to our bodies on those too strange days of the year – Spring Forward and Fall Back day.
Spring Forward is much more dangerous, so be very careful in the mornings next week, especially on Monday. Take it easy, get up slowly, be a little late for work if you can afford it. Life and health are more important than a few minutes of work and being punctual on a day like that.
And that post also contains a bunch of links at the bottom to other posts on the topic.

How rumors spread….

NYTimes:

Eliminating daylight time would thus accord with President-elect Barack Obama’s stated goals of conserving resources, saving money, promoting energy security and reducing climate change.

Eugene Sandhu:

In order to conserve energy, President-elect Barak Obama should eliminate daylight saving time.

Boing Boing:

President-elect Obama wants to get rid of daylight saving time in the United States to conserve energy.

The game of broken telephones? Or lack of reading comprehension, or just wishful thinking? I though we were the Reality-Based Community.
More….

Add yet another factor to the circadian hypothesis of morning heart-attacks

Related to this discussion, there is a new interesting study out – Daily rhythms in blood vessels may explain morning peak in heart attacks:

It’s not just the stress of going to work. Daily rhythms in the activity of cells that line blood vessels may help explain why heart attacks and strokes occur most often in early morning hours, researchers from Emory University School of Medicine have found. Endothelial cells serve as the interface between the blood and the arteries, controlling arterial tone and helping to prevent clots that lead to strokes and heart attacks, says Ibhar Al Mheid, MD, a postdoctoral cardiology researcher at Emory.

Spring Forward, Fall Back – should you watch out tomorrow morning?

If you live in (most places in) the United States as well as many other countries, you have reset your clocks back by one hour last night (or last week). How will that affect you and other people?
One possibility is that you are less likely to suffer a heart attack tomorrow morning than on any other Monday of the year. Why? Let me try to explain in as simple way as possible (hoping that oversimplification will not lead to intolerable degrees of inaccuracy).
Almost all biochemical, physiological and behavioral parameters in almost all (at least multicellular) organisms display diurnal (daily) rhythms and most of those are directly driven by the circadian clock (or, more properly, by the circadian system). Here is an old and famous chart displaying some of the peaks (acrophases) of various physiological functions in the human:
human%20acrophases.JPEG
It may be a little fuzzy, but you can see that most of the peaks associated with the cardiovascular function are located in the afternoon. The acrophases you see late at night are for things like “duration of systole” and “duration of diastole” which means that the Heart Rate is slow during the night. Likewise, blood pressure is low during the night while we are asleep.
Around dawn, heart rate and blood pressure gradually rise. This is a direct result of the circadian clock driving the gradual rise in plasma epinephrine and cortisol. All four of those parameters (HR, BP, Epinephrine and Cortisol) rise roughly simultaneously at dawn and reach a mini-peak in the morning, at the time when we spontaneously wake up:
heartrate%20and%20epinephrine%20circadian.JPG
This rise prepares the body for awakening. After waking up, the heart parameters level off somewhat and then very slowly rise throughout the day until reaching their peak in the late afternoon.
Since the four curves tend to be similar and simultaneus in most cases in healthy humans, let’s make it easier and clearer to observe changes by focusing only on the Cortisol curve in the morning, with the understanding that the heart will respond to this with the simultaneous rise in heart rate and blood pressure. . This is how it looks on a day when we allow ourselves to wake up spontaneously:
circadiancortisol%20-%20spontaneous.JPG
But many of us do not have the luxury of waking up spontaneously every day. We use alarm clocks instead. If we set the alarm clock every day to exactly the same time (even on weekends), our circadian system will, in most cases (more likely in urban than rural areas, though), entrain to the daily Zeitgeber – the ring of the alarm-clock – with a particular phase-relationship. This usually means that the rise in cardiovascular parameters will start before the alarm, but will not quite yet reach the peak as in spontaneous awakening:
circadiancortisol%20-%20alarmclock.JPG
The problem is, many of us do not set the alarm clocks during the weekend. We let ourselves awake spontaneously on Saturday and Sunday, which allows our circadian clock to start drifting – slowly phase-delaying (because for most of us the freerunning period is somewhat longer than 24 hours). Thus, on Monday, when the alarm clock rings, the gradual rise of cortisol, heart rate and blood pressure will not yet be as far along as the previous week. The ring of the alarm clock will start the process of resetting of the circadian clock – but that is the long-term effect (may take a couple of days to complete, or longer.).
The short term effect is more dramatic – the ring of the alarm clock is an environmental stressor. As a result, epinephrine and cortisol (the two stress hormones) will immediately and dramatically shoot up, resulting in an instantenuous sharp rise in blood pressure and heart rate. And this sharp rise in cardiovascular parameters, if the heart is already damaged, can lead to a heart attack. This explains two facts: 1) that heart attacks happen more often on Mondays than other days of the week, and 2) that heart attacks happen more often in the morning, at the time of waking up, than at other times of day:
circadian%20rhythm%20of%20cardiovascular%20events.JPG
Now let’s see what happens tomorrow, the day after the time-change. Over the weekend, while you were sleeping in, your circadian system drifted a little, phase delaying by about 20 minutes on average (keep in mind that this is an average – there is a vast variation in the numerical value of the human freerunning circadian period). Thus, your cardiovascular parameters start rising about 20 minutes later tomorrow morning than last week. But, your alarm clock will ring an entire hour later than last week – giving you an average of a 40-minute advantage. Your heart will be better prepared for the stress of hearing the ringing than on any other Monday during the year:
circadiancortisol%20-%20Fall.JPG
Now let’s fast-forward another six month to the Spring Forward weekend some time in March or April of next year. Your circadian system delays about 20 minutes during the weekend. On top of that, your alarm clock will ring an hour earlier on that Monday than the week before. Thus, your cardiovascular system is even further behind (80 minutes) than usual. The effect of the stress of the alarm will be thus greater – the rise in BP and HR will be even faster and larger than usual. Thus, if your heart is already damaged in some way, your chances of suffering an infarct are greater on that Monday than on any other day of the year:
circadiancortisol%20-%20Spring.JPG
This is what circadian theory sugests – the greater number of heart attacks on Mondays than other days of the week (lowest during the weekend), the greatest number of heart attacks on the Monday following the Spring Forward time-change compared to other Mondays, and the lowest incidence of heart attacks on the Monday following the Fall Back time-change compared to other Mondays.
A couple of days ago, a short paper appeared that tested that theoretical prediction and found it exactly correct (Imre Janszky and Rickard Ljung, October 30, 2008, Shifts to and from Daylight Saving Time and Incidence of Myocardial Infarction, The New England Journal of Medicine, Volume 359:1966-1968, Number 18.). The authors looked at a large dataset of heart attacks in Sweden over a large period of time and saw that (if you look at the numbers) the greatest number of heart attacks happens on Mondays compared to other days of the week (and yes, the numbers are lowest during the weekend), the greatest number of heart attacks occur on the Monday following the Spring Forward time-change compared to Mondays two weeks before and after, and the lowest incidence of heart attacks happens on the Monday following the Fall Back time-change compared to Mondays two weeks before and after:
infarcts%20by%20day%20after%20time%20change.JPG
Thus, the predictions from the circadian theory were completely and clearly correct. But I was jarred by the conclusions that the authors drew from the data. They write:

The most plausible explanation for our findings is the adverse effect of sleep deprivation on cardiovascular health. According to experimental studies, this adverse effect includes the predominance of sympathetic activity and an increase in proinflammatory cytokine levels.3,4 Our data suggest that vulnerable people might benefit from avoiding sudden changes in their biologic rhythms.
It has been postulated that people in Western societies are chronically sleep deprived, since the average sleep duration decreased from 9.0 to 7.5 hours during the 20th century.4 Therefore, it is important to examine whether we can achieve beneficial effects with prolonged sleep. The finding that the possibility of additional sleep seems to be protective on the first workday after the autumn shift is intriguing. Monday is the day of the week associated with the highest risk of acute myocardial infarction, with the mental stress of starting a new workweek and the increase in activity suggested as an explanation.5 Our results raise the possibility that there is another, sleep-related component in the excess incidence of acute myocardial infarction on Monday. Sleep-diary studies suggest that bedtimes and wake-up times are usually later on weekend days than on weekdays; the earlier wake-up times on the first workday of the week and the consequent minor sleep deprivation can be hypothesized to have an adverse cardiovascular effect in some people. This effect would be less pronounced with the transition out of daylight saving time, since it allows for additional sleep. Studies are warranted to examine the possibility that a more stable weekly pattern of waking up in the morning and going to sleep at night or a somewhat later wake-up time on Monday might prevent some acute myocardial infarctions.

And in the quotes in the press release they say the same thing, so it is not a coincidence:

“It’s always been thought that it’s mainly due to an increase in stress ahead of the new working week,” says Dr Janszky. “But perhaps it’s also got something to do with the sleep disruption caused by the change in diurnal rhythm at the weekend.”

Dr.Isis has already noted this and drew the correct conclusion. She then goes on to say something that is right on the mark:

And, of course, my first thought is, what about all the other times we are sleep deprived by, you know, one hour. Is waking up in the middle of the night to feed Baby Isis potentially going to cause Dr. Isis to meet her maker early? In that case Baby Isis can freakin’ starve. But, this is the New England Journal of Medicine and Dr. Isis appreciates the innate need that authors who publish here have to include some clinical applicability in their work.

The authors responded to Dr.Isis in the comments on her blog and said, among else:

We wonder whether you have ever tried to publish a research letter somewhere. The number of citations (maximum 5!) and the number of words are strictly limited. Of course we are familiar with studies on circadian rhythms and cardiovascular physiology. There was simply no space to talk more about biological rhythms than we actually did.

But what they wrote betrays that even if they are familiar with the circadian literature, they do not really understand it. Nobody with any circadian background ever speculates about people’s conscious expectations of a stressful week as a cause of heart attacks on Monday mornings. Let me try to explain why I disagree with them on two points they raise (one of which I disagree with more strongly than the other).
1) Sleep Deprivation. It is important to clearly distinguish between the acute and the chronic sleep deprivation. Sleepiness at any given time of day is determined by two processes: a homeostatic drive that depends on the amount of sleep one had over a previous time period, and a circadian gating of sleepiness, i.e., at which time of day is one most likely to fall asleep. Sleep deprivation affects only the homeostatic drive and has nothing to do with circadian timing.
Humans, like most other animals, are tremendously flexible and resilient concerning acute sleep deprivation. Most of us had done all-nighters studying for exams, or partying all night with non ill effects – you just sleep off the sleep debt the next day or the next weekend and you are fine. Dr.Isis is not going to die because her baby wakes her up several times during the night. This is all part of a normal human ecology, and human physiology had adapted to such day-to-day variations in opportunities for sleep.
The Chronic sleep deprivation is a different animal altogether. This means that you are getting less sleep than you need day after day, week after week, month after month, year after year, with rarely or never sleeping off your sleep debt (“catching up on sleep”). As a result, your cognitive functions suffer. If you are a student, you will have difficulties understanding and retaining the material. If you are a part of the “creative class”, you will be less creative. If you are a scientist, you may be less able to clearly think through all your experiments, your data, and your conclusions. No matter what job you do, you will make more errors. You may suffer microsleep episodes while driving and die in a car wreck. Your immune system will be compromised so you will constantly have sniffles and colds, and may be more susceptible to other diseases.
And yes, a long term chronic sleep deprivation may eventually damage your heart to the extent that you are more susceptible to a heart attack. This means that you are more likely to suffer a heart attack, but has no influence on the timing of the heart attack – it is the misalignment between the natural circadian rhythms of your body and the social rhythms imposed via a very harsh stressor – the alarm clock – that determines the timing. Being sleep deprived over many years means you are more likely to have a heart attack, but cannot determine when. Losing just one hour of sleep will certainly have no effect at all.
Thus, the data presented in the paper have nothing to say about sleep deprivation.
2) Cytokines. These are small molecules involved in intercellular signaling in the immune system. Like everything else, they are synthesized in a diurnal manner. But they act slowly. Maybe they play some small part in the gradual damage of the heart in certain conditions (prolonged inflammation, for instance), thus they may, perhaps, have a role in increasing risk of a heart attack. But they play no role in timing of it. Thus they cannot be a causal factor in the data presented in the paper which are ONLY about timing, not the underlying causes. The data say nothing as to who will suffer a heart attack and why, only when you will suffer one if you do.
If I was commissioned to write a comprehensive review of sleep deprivation, I may have to force myself to wade through the frustratingly complicated and ambiguous literature on cytokines in order to write a short paragraphs under a subheading somewhere on the 27th page of the review.
If I had a severe word-limit and needed to present the data they showed in this paper, I would not waste the space by mentioning the word “cytokine” at all (frankly, that would not even cross my mind to do) as it is way down the list of potential causes of heart attack in general and has nothing to do with the timing of heart attacks at all, thus irrelevant to this paper.
So, it is nice they did the study. It confirms and puts clear numbers on what “everybody already knew for decades” in the circadian community. But their interpretation of the data was incorrect. This was a purely chronobiological study, yet they chose to present it as a part of their own pet project instead and tried mightily to make some kind of a connection to their favourite molecules, the cytokines, although nothing warranted that connection. Nails: meet hammer.
The fake-insulted, haughty and inappropriate way/tone they responded to Dr.Isis is something that is important to me professionally, as is there misunderstanding of both the role and the tone of science blogs, so I will revisit that issue in a separate post later. I promise. It is important.
But back to Daylight Saving Time. First, let me ask you (again) to see Larry’s post from last year, where you will find a lot of useful information and links about it. What is important to keep in mind is that DST itself is not the problem – it is the time-changes twice a year that are really troubling.
Another important thing to keep in mind is that DST was instituted in the past at the time when the world looked very different. At the time when a tiny sliver of the population is still involved in (quite automated and mechanized) agriculture, when electricity is used much more for other things than illumination (not to mention that even the simple incandescent light bulbs today are much more energy efficient than they used to be in the past, not to mention all the newfangled super-efficient light-bulbs available today), when many more people are working second and third shifts than before, when many more people work according to their own schedules – the whole idea of DST makes no sense any more.
Even if initially DST saved the economy some energy (and that is questionable), it certainly does not do so any more. And the social cost of traffic accidents and heart attacks is now much greater than any energy savings that theoretically we may save.
Furthermore, it now seems that circadian clocks are harder to shift than we thought in the past. Even that one-hour change may take some weeks to adjust to, as it is not just a singular clock but a system – the main pacemaker in the SCN may shift in a couple of days, but the entire system will be un-synchronized for some time as it may take several weeks for the peripheral clocks in the liver and intestine to catch up – leading to greater potential for other disorders, e.g., stomach ulcers.
The social clues (including the alarm clocks) may not be as good entraining agents as we thought before either, especially in rural areas where the natural lighting still has a profound effect.
Finally, the two time-change days of the year hit especially hard people with Bipolar Disorder and with Seasonal Affective Disorder – not such a small minority put together, and certainly not worth whatever positives one may find in the concept of DST. We should pick one time and stick with it. It is the shifts that cost the society much more than any potential benefits of DST.
Related reading:
Daylight Saving Time
Daylight Savings Time worse than previously thought
Time
Sun Time is the Real Time
Seasonal Affective Disorder – The Basics
Lesson of the Day: Circadian Clocks are HARD to shift!
Lithium, Circadian Clocks and Bipolar Disorder
Everything You Always Wanted To Know About Sleep (But Were Too Afraid To Ask)

‘Normal’ body temperature? Not really.

Once a year, I go back to my alma mater and do a guest lecture about biological clocks in an Anatomy & Physiology class. Knowing how many pre-meds are among the 200 students in the room, I try to start with some examples of rhythms in human physiology (and disease), and the first one is body temperature, busting the myth that 98.6F (37C) is the “normal” temperature:
thermometer.gif
Now Orac links to an excellent post that explains it all – the entire history of the idea that 37C is normal and what the real difference, means and fluctuations there are. Read the whole thing.
thermometer2.gif

What I try to do when I travel abroad across several time zones

How do I try to beat jet-lag:
– book an overnight flight that lands at the destination in the morning, if possible. This really helps.
– start gradually shifting my daily schedule of meals, activities, sleep, a few days in advance.
– once I pass security and have about an hour before take-off, I take clonapen (not sleeping pills and no, not melatonin, though some people swear about it – it makes me depressed because of my extreme owl-eness and SAD). This (as I am a little anxious of flying) helps me fall asleep very quickly, sometimes before we are airborn, sometimes right after they serve the dinner.
– then I sleep the entire flight and wake up just before landing.
– once I arrive, I make sure to do three things throughout the morning (or even the whole day): be outside in order to get exposed to light, eat breakfast and lunch at local time, exercise. It is usually easy to combine the three: sightseeing around the city, stopping at a street vendor for food, traipsing around all day.
– in the evening, have dinner at local time, with little or no alcohol (could not avoid that last time in London, but I was OK), go to bed with a book and try to sleep. It usually works for me.
– what I find is that most of my physical functions adjust to new time in a day or two (no real jet-lag, i.e., nausea, headaches, lack of appetite), but my time-perception takes longer (i.e., my ability to estimate the time of day without looking at the clock).
On the way back, it is harder to do all of the above, so I usually do get jet-lagged once I arrive home from Europe. Still have to make myself more disciplined about it (also, the London-Raleigh flight is daytime, which makes it hard to use the flight itself as a resetting mechanism).

Time Perception news

Carl Zimmer: How Your Brain Can Control Time:

For 40 years, psychologists thought that humans and animals kept time with a biological version of a stopwatch. Somewhere in the brain, a regular series of pulses was being generated. When the brain needed to time some event, a gate opened and the pulses moved into some kind of counting device.
One reason this clock model was so compelling: Psychologists could use it to explain how our perception of time changes. Think about how your feeling of time slows down as you see a car crash on the road ahead, how it speeds up when you’re wheeling around a dance floor in love. Psychologists argued that these experiences tweaked the pulse generator, speeding up the flow of pulses or slowing it down.
But the fact is that the biology of the brain just doesn’t work like the clocks we’re familiar with. Neurons can do a good job of producing a steady series of pulses. They don’t have what it takes to count pulses accurately for seconds or minutes or more. The mistakes we make in telling time also raise doubts about the clock models. If our brains really did work that way, we ought to do a better job of estimating long periods of time than short ones. Any individual pulse from the hypothetical clock would be a little bit slow or fast. Over a short time, the brain would accumulate just a few pulses, and so the error could be significant. The many pulses that pile up over long stretches of time should cancel their errors out. Unfortunately, that’s not the case. As we estimate longer stretches of time, the range of errors gets bigger as well.

Chris Chatham: Impulsivity Due to Distortions in Time: Hyperbolic Discounting and Logarithmic Time Perception:

New research from Wharton and the Carlson School shows that a methodologically-appealing measure of impulsivity – hyperbolic discounting rate – may actually reflect a systematic “skew” in the way people perceive time.
Previous work has shown that people tend to decreasingly discount the usefulness or appeal of a reward with increasing delays; that is, a reward provided now is more appealing than a reward provided 1 week or 1 month from now, but that change in appeal is nonlinear (hyperbolic) across time. In other words, people prefer to behave impatiently now, but prefer to act more and more patiently in the future – suggesting that this “hyperbolic discounting rate” might be related to impulsivity.

Vaughan: The future is nonlinear:

These are quite different concepts – for example, we know logically that waiting four weeks is exactly four times as long as waiting a week, but it might not feel exactly four times as bad.

When Clocks Go Bad

Today in PLoS Genetics: a nice review of some interest to my readers: When Clocks Go Bad: Neurobehavioural Consequences of Disrupted Circadian Timing by Alun R. Barnard and Patrick M. Nolan:

Progress in unravelling the cellular and molecular basis of mammalian circadian regulation over the past decade has provided us with new avenues through which we can explore central nervous system disease. Deteriorations in measurable circadian output parameters, such as sleep/wake deficits and dysregulation of circulating hormone levels, are common features of most central nervous system disorders. At the core of the mammalian circadian system is a complex of molecular oscillations within the hypothalamic suprachiasmatic nucleus. These oscillations are modifiable by afferent signals from the environment, and integrated signals are subsequently conveyed to remote central neural circuits where specific output rhythms are regulated. Mutations in circadian genes in mice can disturb both molecular oscillations and measurable output rhythms. Moreover, systematic analysis of these mutants indicates that they can express an array of abnormal behavioural phenotypes that are intermediate signatures of central nervous system disorders. Furthermore, the response of these mutants to psychoactive drugs suggests that clock genes can modify a number of the brain’s critical neurotransmitter systems. This evidence has led to promising investigations into clock gene polymorphisms in psychiatric disease. Preliminary indications favour the systematic investigation of the contribution of circadian genes to central nervous system disease.

‘Ecology’ of human light exposure and circadian disruption

In the Journal of Circadian Rhythms:
A new approach to understanding the impact of circadian disruption on human health (pdf):

Background
Light and dark patterns are the major synchronizer of circadian rhythms to the 24-hour solar day. Disruption of circadian rhythms has been associated with a variety of maladies. Ecological studies of human exposures to light are virtually nonexistent, however, making it difficult to determine if, in fact, light-induced circadian disruption directly affects human health.
Methods
A newly developed field measurement device recorded circadian light exposures and activity from day-shift and rotating-shift nurses. Circadian disruption was quantified for these two groups using phasor analyses of the circular cross-correlations between light exposure and activity. Circadian disruption also was determined for rats subjected to a consistent 12-hour light/12-hour dark pattern (12L:12D) and ones subjected to a “jet-lagged” schedule.
Results
Day-shift nurses and rats exposed to the consistent light-dark pattern exhibited pronounced similarities in their circular cross-correlation functions and 24-hour phasor representations except for an approximate 12-hour phase difference between species. The phase difference reflects the diurnal versus nocturnal behavior of humans versus rodents. Phase differences within species likely reflect chronotype differences among individuals. Rotating-shift nurses and rats subjected to the “jet-lagged” schedule exhibited significant reductions in phasor magnitudes compared to the day-shift nurses and the 12L:12D rats. The reduction in the 24-hour phasor magnitude indicates a loss of circadian entrainment compared to the nurses and the rats with a consistent light-dark exposure.
Conclusions
This paper provides a quantitative foundation for systematically studying the impact of light-induced circadian disruption in humans and in animal models. Ecological light and activity data are needed to develop the essential insights into circadian entrainment/disruption actually experienced by modern people. These data can now be obtained and analyzed to reveal the interrelationship between actual light exposures and markers of circadian rhythm such as rest-activity patterns, core body temperature, and melatonin synthesis. Moreover, it should now be possible to bridge ecological studies of circadian disruption in humans to parametric studies of the relationships between circadian disruption and health outcomes using animal models.

Yes, Seasonal Affective Disorder is real

No matter how cutesy the acronim SAD is. Joseph reports on a study that links SAD to serotonin. But serotonin itself may not be necessary to understand how SAD works, though an intimate link between serotonin and melatonin (the former is the biochemical precursor of the latter) suggests that serotonin should be looked at in this context.
Also, if you suffer from SAD you should be very careful preparing for your long-distance travel: getting jet-lagged may trigger a bout of a few days of depression regardless of the time of year.

The Amplitude Problem

From the Archives

Blogging on Peer-Reviewed Research

If you are one of the few of my readers who actually slogged through my Clock Tutorials, especially the difficult series on Entrainment and Phase Response Curves, you got to appreciate the usefulness of the oscillator theory from physics in its application to the study of biological clocks. Use of physics models in the study of biological rhythms, pioneered by Colin Pittendrigh, is an immensely useful tool in the understanding of the process of entrainment to environmental cycles.
Yet, as I warned several times, a Clock is a metaphor and, as such, has to be treated with thought and caution. Is the physics model always applicable? Is it sometimes deceptive? How much does it oversimplify the behavior out in the natural environment?

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Development of the human sleep patterns

Development of the human sleep patternsWhat it really means when we are talking about babies “sleeping through the night” (from September 22, 2005)

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When Should Schools Start in the morning?

When Should Schools Start in the morning?The fourth part of a four-part series on the topic, this one from April 02, 2006….

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More on sleep in adolescents

More on sleep in adolescentsThis is the third part of the series on the topic, from April 01, 2006…

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Sleep Schedules in Adolescents

Blogging on Peer-Reviewed Research
Blogging on Peer-Reviewed Research

Sleep Schedules in AdolescentsEarlier this year, during the National Sleep Awareness Week, I wrote a series of posts about the changes in sleep schedules in adolescents. Over the next 3-4 hours, I will repost them all, starting with this one from March 26, 2006. Also check my more recent posts on the subject here and here…

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Adolescent Sleep Schedule

From the ArchivesThis kind of ignorant bleating makes me froth at the mouth every time – I guess it is because this is my own blogging “turf”.
One of the recurring themes of my blog is the disdain I have for people who equate sleep with laziness out of their Puritan core of understanding of the world, their “work ethic” which is a smokescreen for power-play, their vicious disrespect for everyone who is not like them, and the nasty feeling of superiority they have towards the teenagers just because they are older, bigger, stronger and more powerful than the kids. Not to forget the idiotic notions that kids need to be “hardened”, or that, just because they managed to survive some hardships when they were teens, all the future generations have to be sentenced to the same types of hardships, just to make it even. This is bullying behavior, and disregarding and/or twisting science in the search for personal triumphalism irks me to no end.

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Books: “Snooze…Or Lose! – 10 “No-War” Ways To Improve Your Teen’s Sleep Habits” by Helene A. Emsellem, MD

Snooze%20or%20Lose.jpgMy regular readers are probably aware that the topic of adolescent sleep and the issue of starting times of schools are some of my favourite subjects for a variety of reasons: I am a chronobiologist, I am an extreme “owl” (hence the name of this blog), I am a parent of developing extreme “owls”, I have a particular distaste for Puritanical equation of sleep with laziness which always raises its ugly head in discussions of adolescent sleep, and much of my own research is somewhat related to this topic (see the bottom of this post for Related Posts).
So, I was particularly pleased when Jessica of the excellent Bee Policy blog informed me of the recent publication of a book devoted entirely to this topic. Snooze…or Lose! by Helen Emsellem was published by National Academies and Jessica managed to get me an Advanced Reading Copy to review.

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‘Insomnia: A Cultural History’

Book excerpt in today’s Wall Street Journal: Chapter 6: Wired:

It is likely that insomnia will increase with the expansion of the 24-hour economy into more and more lives, and more of each life, because wakefulness and the wired world go together. The more interconnected we are, the more we communicate, and the more we communicate, the more we rely on our interconnected powers of thinking. In addition to work, many of our leisure pursuits, while seemingly soporific, actually undermine the likelihood of restful sleep, from drinking alcohol to surfing the net to watching thrillers on late-night television. At the same time, these are often required to enable the passage between our increased workday and our decreased sleeping night to occur at all. In some cases, our leisure and workday activities may be conflated by medium — many of us use computers or mobile phones at work, and go on line or into text-mode for personal, leisure-related reasons as well. Or our sleeping times may be disrupted by shift work necessarily done while others sleep or in cognisance of the fact — as in the financial sector — that at any moment somewhere in the world the populace is working and awake, and that there is no time to lose in speculating upon its — or its capital’s — futures.

It is longish but worth your time.

Shift Work labeled as a Probable Cause of Cancer

Shift Work May Be Cancer Risk:

In an announcement to be published Saturday in the journal Lancet Oncology, the International Agency for Research on Cancer, part of the World Health Organization, will label shift work as a “probable cause” of cancer.
The designation — rooted in the theory that the disruption of circadian rhythms could be a culprit — puts shift work on a par with ultraviolet radiation or anabolic steroids as suspected carcinogens, but does not say it is a definitive cause of cancer, such as cigarette smoking.

A random schedule of shifts – working a couple of days a week at night, a couple of days during the day – is the worst.
A phase-advancing shift-rotation (a week at night, followed by a week in the afternoon, followed by a week in the morning) is just as bad.
A slower, phase-delaying rotation (a month in the morning, followed by a month in the afternoon, followed by a month at night) is a little bit better.
Staying constantly on the night shift is almost as bad, mainly as it is almost impossible to keep it consistent, i.e., completely avoiding light during the day and exposing oneself to bright light during the night even on one’s days off. Social events and weekends produce a state of permanent jet-lag nonetheless.
But as in everything biological, there is a variation in population – some people are affected much more strongly than others. Let workers self-select their schedules as they can best feel on their own how the night work is affecting their physical and mental health.

Daylight Savings Time worse than previously thought

I am sure I have ranted about the negative effects of DST here and back on Circadiana, but the latest study – The Human Circadian Clock’s Seasonal Adjustment Is Disrupted by Daylight Saving Time (pdf) (press releases: ScienceDaily, EurekAlert) by Thomas Kantermann, Myriam Juda, Martha Merrow and Till Roenneberg shows that the effects are much more long-lasting and serious than previously thought. It is not “just one hour” and “you get used to it in a couple of days”. Apparently it takes weeks for the circadian system to adjust, and in some people it never does. In this day and age of around-the-clock life, global communications, telecommuting, etc., the clock-shifting twice a year has outlived its usefulness and should go the way of the dodo. The research also shows why studies of photoperiodism is not some arcane field, but has real-world applications.

Anyone going to this?

Symposium Light, Performance and Quality of Life is on Thursday, 8 November 2007 in Eindhoven, the Netherlands:

Introduction
The ancient Greek already referred to the wholesome effects of the (sun)light on mankind. Ever since the industrialization, more and more people are devoid of bright daylight for a large part of the day. With the ongoing industrialization and the current information-society the number of persons that spent al large part of the day indoors further increases.
The light in these buildings is, also due to the modern trend of small windows and low lighting-levels, notably lower than the biological need for light of people. Also the energy crisis in the early seventies has been an influence on driving back sufficient light, as a result sometimes reducing the level of light inside buildings to nearly ” biological darkness”.
Rediscovery of light in relation to health.
The past 15 to 20 years light has returned to the full attention of the scientific community. Particularly visible light that reaches the retina of the human eye brings about a number of biological effects. The fact that light, besides a necessity to see, also regulates biological functions, has lead to research programs at different institutes and universities. The questions with which these centres occupy themselves are among others:
* Which bio-mechanisms are influenced by light that falls on the eye?
* What possibilities are there to use light for curative and preventive means?
In the end the increasing social importance of research and applications of light on health, have lead to the foundation of the “Stichting Onderzoek Licht & Gezondheid”, the Light & Health Research Foundation (SOLG).
The Light & Health Research Foundation is based at Eindhoven, University of Technology

Yes, delay the school starting times

From the Independent:

The head has identified research which says that teenagers would be more likely to take in what they are learning if they started school two hours later. He is considering changing the school timetable for sixth-formers as a result.
“We have always assumed that learning early in the morning is best, probably because it is best for young children and adults,” he writes. ” Unfortunately, it is not true for teenagers. When teenagers are woken up at our morning time, their brain tells them they should be asleep. So they use stimulants such as coffee and cigarettes to get themselves awake. But at night, when we go to sleep, their neurological clock tells them it’s not time to sleep so they drink alcohol or take drugs to get them to sleep.
“Schools and universities only make it worse, he adds. The importance of neurological patterns of time as a factor in our learning and our lives has largely been ignored. We need to fit learning to these patterns of times. ”

(Hat-tip: nbm)
Related….

Phase-Response Curves to Melatonin

NBM found an excellent online article (which I have seen before but I forgot) depicting Phase-Response Curves (PRC) to injections of melatonin in humans, rodents and lizards.
melatonin%20PRCs.gif
Note how the shape is roughly opposite to that of a PRC to light pulses, i.e., at phases at which light elicits phase-delays, melatonin produces advances and vice versa:
melatonin-light-PRC%20small.jpg
The lizard PRC was actually constructed in our lab, about ten years before I joined. The article, though, gives the wrong reference to this:
Underwood, H. and M. Harless (1985). “Entrainment of the circadian activity rhythm of a lizard to melatonin injections.” Physiology & Behavior 35(2): 267-70.
In that paper, lizards were entrained by daily melatonin injections. The PRC was reported in a different paper the following year:
H Underwood (1986) Circadian Rhythms in Lizards: Phase Response Curve for Melatonin, Journal of Pineal Research 3 (2), 187-196.
Update: an alert reader sends a better figure, taken from this freely available recent paper:
human%20PRC%20light%20and%20melatonin.jpg

Are you SAD?

Why are Orli and Joseph thinking about this in the middle of the summer? I am happy (and South enough). I am wondering if people with SAD living in the high latitudes either moved South or, being all gloomy, had a lower reproductive rate in the past, thus lowering the rates of SAD in the population.

The Amplitude Problem

Blogging on Peer-Reviewed Research

If you are one of the few of my readers who actually slogged through my Clock Tutorials, especially the difficult series on Entrainment and Phase Response Curves, you got to appreciate the usefulness of the oscillator theory from physics in its application to the study of biological clocks. Use of physics models in the study of biological rhythms, pioneered by Colin Pittendrigh, is an immensely useful tool in the understanding of the process of entrainment to environmental cycles.
Yet, as I warned several times, a Clock is a metaphor and, as such, has to be treated with thought and caution. Is the physics model always applicable? Is it sometimes deceptive? How much does it oversimplify the behavior out in the natural environment?
The few tests of the theory conducted in the field demonstrate that the models of entrainment (the PRCs) work quite well, though not always perfectly. Use of Limit Cycles (something that is, IMHO, too complex for me to try to explain on a blog) is also useful. The theory appears to work quite well in regard to period and phase, but the effects of amplitude of the oscillation are not as well tested, although a number of studies, especially regarding photoperiodism in non-mammalian vertebrates and invertebrates, suggests that the amplitude is an important parameter of a biological rhythm.
oscillation.jpg
The main problem with the amplitude is that it is not clear if the measured amplitude of the overt rhythms (e.g., activity, body temperature, melatonin release, etc.) faithfully reflects the amplitude of the underlying oscillator. It is not even certain that the amplitude of the expression of core clock genes and proteins is the equivalent of the amplitude of the idealized physical system.
In a recent paper (provisional PDF) in the Journal of Circadian Rhythms (an Open Access journal, where you can also comment on the papers, just like on PLoS ONE), Daniel Kripke, Jeffrey Elliott, Shawn Youngstedt and Katharine Rex, using that most difficult laboratory model of all – the human – tried to kill two birds with one stone: test if the physical oscillatory models apply for the amplitude of circadian clocks and test if the amplitude of the overt rhythms is a good reflection of the amplitude of the underlying biological oscillator. The medical implicaitons of their work, no matter what the results, is quite obvious as well.
It is well known that the amplitude of overt rhythms (activity, sleep-wake cycle, temperature, melatonin, cortisol, etc.) gets a little smaller with advanced age in humans. Measuring simultaneously several overt rhythms (always a good thing!) while constructing a Phase-Response Curve to light pulses in two groups – young and old people – they excpected, from theory, to see a change in the shape and size of the PRC. According to theory, an oscillator with a higher amplitude (young) would be more difficult to shift, i.e., the size of phase-shifts would be smaller than in the old cohort (for some odd reason – typo perhaps? – they state they expected the opposite, i.e., smaller shifts in the older group).
If they got positive results, i.e., if the size of phase-shifts differed between the two age groups, they would have demonstrated that a) physical model of oscillatons applies to biological clocks in respect to amplitude, and b) that the amplitude of overt rhythms faithfully reflects the amplitude of the underlying biological oscillator.
But, their results were negative, i.e., there was no difference in the size of phase-shifts between young and old cohorts (or, for that matter, between women and men), though the phase of all rhythms (except temperature and the offset of melatonin metabolites in the urine – likely due to the slower metabolism itself) was advanced and the PRCs, as expected, moved somewhat to the left to reflect this.
This unfortunate result suggests one (or both) of the two possibilities:
– Oscillator models borrowed from physics do not apply to biology in regard to amplitude, or
– Amplitude of overt rhythms does not reflect the amplitude of the underlying oscillator
As they say, more work needs to be done.

Sleep News

More stuff from SLEEP 2007, the 21st Annual Meeting of the Associated Professional Sleep Societies:
Sleep Deprivation Affects Eye-steering Coordination When Driving:

Driving a vehicle requires coordination of horizontal eye movements and steering. Recent research finds that even a single night of sleep deprivation can impact a person’s ability to coordinate eye movements with steering.

Extra Sleep Improves Athletes’ Performance:

Athletes who get an extra amount of sleep are more likely to improve their performance in a game, according to recent research.

Going To Bed Late May Affect The Health, Academic Performance Of College Students:

College students who go to bed late are more likely to have poor quality sleep, which may affect their mental health and academic performance, according to new research.

Safety And Well-being Of Medical Interns And Patients At Risk From Extended Duration Work Shifts:

Working an extended duration shift can pose a risk to not only the safety and well-being of medical interns, but also to that of their patients, according to a recent research.

Sleep-related Breathing Disorder Common Among Aggressive, Bullying Schoolchildren:

Aggressive behavior and bullying, common among schoolchildren, are likely to have multiple causes, one of which may be an undiagnosed sleep-related breathing disorder (SRBD), according to recent research.

Late Weekend Sleep Among Teens May Lead To Poor Academic Performance:

Teenagers who stay up late on school nights and make up for it by sleeping late on weekends are more likely to perform poorly in the classroom. This is because, on weekends, they are waking up at a time that is later than their internal body clock expects. The fact that their clock must get used to a new routine may affect their ability to be awake early for school at the beginning of the week when they revert back to their old routine, according to new research.

Sleep Deprivation Can Lead To Smoking, Drinking:

Sleep loss or disturbed sleep can heighten the risk for adolescents to take up smoking and drinking, two habits that may prove to be detrimental to their health, according to recent research.

Children’s Brain Responses Predict Impact Of Sleep Loss On Attention:

The brain responses of those children who don’t get enough sleep can accurately predict the impact sleep loss has on their ability to pay attention during the course of a day, according to a recent research.

Snoring Children: Poor Sleep Hygiene In Children Associated With Behavioral Problems:

A snoring child’s poor sleep hygiene habits can have a negative influence on his or her daytime behavior, according to a new study.

Chronic Sleep Restriction Negatively Affects Cardiac Activity:

Chronic sleep restriction has a negative effect on a person’s cardiac activity, which may elevate the risk of cardiovascular disease and mortality, according to a research abstract presented at SLEEP 2007, the 21st Annual Meeting of the Associated Professional Sleep Societies (APSS).

Sleep Deprivation Is Common Among Members Of The US Marine Corps:

Members of the U.S. Marine Corps (USMC) experience combined stressors, including physical exertion and the threat of enemy fire. A research abstract that presentedJune 13 at SLEEP 2007, the 21st Annual Meeting of the Associated Professional Sleep Societies, finds that sleep deprivation, which can result in fatigue, is another factor that can impair troops’ vigilance and decision-making with potentially dangerous consequences.

Catastrophic Events Can Affect A Person’s Sleep:

A significant disruption of day-to-day life can take place in those areas affected by a natural disaster. One of the more recent disasters occurred when Hurricane Katrina struck the Gulf Coast in late August 2005, causing loss of lives, extensive damage, and the evacuation of hundreds of thousands of residents. Disasters such as Hurricane Katrina are more likely to affect the quality and the quantity of a person’s sleep, according to recent research.

Previously

Rotating shifts shorten lives

This is the first study I know that directly tested this – the effects of rotating shifts on longevity – in humans, though some studies of night-shift nurses have shown large increases in breast cancers, stomach ulcers and heart diseases, and similar studies have been done in various rodents and fruitflies:
Working in shifts shortens life span: Study:

A study of 3,912-day workers and 4,623 shift workers of the Southeastern Central Railway in Nagpur showed the former lived 3.94 years longer than their counterparts on shift duties, said the study by Atanu Kumar Pati of The School of Life Sciences in Pt Ravishankar Shukla University, Raipur.
—————
Shift work affects the circadian rhythm, the 24-hour cycle in the physiological processes of humans that leads to several sleep-related and social problems.
Circadian rhythms are important in determining the sleeping and feeding patterns of all animals, including humans. Brain wave activity, hormone production, cell regeneration and other biological activities are linked to this daily cycle.
Pati and his colleague K Venu Achari analysed a database of dates of death, retirement and death of each worker and published their findings in the latest issue of “current science”.
They also studied data on deaths due to all causes of 594 railway employees, including 282 day workers and 312 shift workers, over a span of 25 years. The cause of death was not documented in the database. An analysis of the data showed that day workers tend to live 3.94 years longer than counterparts working in shifts.
All day workers performed duty between 9 am and 6 pm with an hour-long lunch break from 1 pm and included those on office job and doing miscellaneous duties, the study said.
Those coming for shift duties worked in a rotating system consisting of a day shift (8 am to 4 pm), first night (4 pm to midnight) and second night (midnight to 8 am).
They worked in each shift continuously for six days and had a single day break before resumption of the next shift. The shift workers included running staff, gangmen and those doing miscellaneous jobs.
“The longevity of each worker was computed from the dates of birth, retirement and death,” Pati said. The researchers cited a number of animal studies that documented the life-shortening effects of weekly shifting of light-dark cycles.
It has been argued that these effects could be mediated through disruption of the circadian rhythm. Lighting schedule manipulation has also been reported to produce detrimental effects on the lifespan of insects.

The Owls Of The World, Unite!

Apparently, in Denmark, the ‘larks’ (early-risers) are called ‘A-people’ while ‘owls’ (late-risers) are ‘B-people’. We all know how important language is for eliciting frames, so it must feel doubly insulting for the Danish night owls.
Today, in the age of the internets, telecommuting and fast-increasing knowledge about our rhythms and sleep, retaining the feudal/early capitalism work schedules really does not make sense.
And owls are by no means minority. Among kids and adults, they comprise about 25% of the population (another 25% are larks and the rest are in between). But among the adolescents (roughly 14-30 years old), owls are the most prevalent chronotype.
So, the Danes decided to organize, to eliminate being frowned upon and deemed “lazy“, and to change their society.
You can check out The B-Society website both in Danish and in English:

Why do we still get up at cockcrow and when the cows moo,
when only 5% of the population work within agriculture or fishing?
Why does everything have to take place in the same rhythm and pace,
resulting in a huge problem with our infrastructure?
Why has the societal framework primarily been arranged to suit
people working from 8 am to 4 pm?
Let the tyranny of A-time end. Let us create a B-society.
Let us create B-patterns in our work and in our families.
Let us have quiet mornings and active evenings.
Life is too short for traffic jams. Let us have more all-night shops!

Hat-tip: NBM, frequent commenter on this blog.

A potential animal model for Bipolar Disorder

It has been known for quite a while now that bipolar disorder is essentially a circadian clock disorder. However, there was a problem in that there was no known animal model for the bipolar disorder.
Apparently that has changed, if this report is to be believed:

“There’s evidence suggesting that circadian genes may be involved in bipolar disorder,” said Dr. Colleen McClung, assistant professor of psychiatry and the study’s senior author. “What we’ve done is taken earlier findings a step further by engineering a mutant mouse model displaying an overall profile that is strikingly similar to human mania, which will give us the opportunity to study why people develop mania or bipolar disorder and how they can be treated.”

Daylight Saving Time

This is the time when everyone is talking about the Daylight Saving Time and I always feel pressure to blog about it from a chronobiological perspective. And I always resist. As I will this year. So, here are a couple of related links instead:
Larry provides a brief history of time zones and the Dalyight Saving Time (and a cool map that goes with it).
Dave finds some data that the DST does not actually save any energy.
Among numerous newspaper articles, I thought this Boston Globe one gives the most accurate summary of what DST does to our circadian rhythms and sleep. It explains why it takes us several days to adjust to DST when our clocks are normally capable of phase-shifting one hour in one day. Why are there 10% more car accidents today than on any other day of the year? However, it does not mention that people with circadian disorders such as SAD and Bipolar Disorder suffer more due to DST (the SAD patients throughout the winter – today is the happy day of final release from the winter blues; the BP patients suffer most on the two days of the year at which the shifts happen).

PERIOD clock gene variants affect sleep need in humans

The most exciting thing about this study is that this is, as far as I am aware, the first instance in which it was shown that a circadian clock gene has any effect on sleep apart from timing of it, i.e., on some other quality or quantity of sleep (not just when to fall asleep and wake up, but also the depth of sleep and the amount of sleep need):
Performing Under Sleep Deprivation: Its In Your Genes:

People are known to differ markedly in their response to sleep deprivation, but the biological underpinnings of these differences have remained difficult to identify.
Researchers have now found that a genetic difference in a so-called clock gene, PERIOD3, makes some people particularly sensitive to the effects of sleep deprivation. The findings, reported by Antoine Viola, Derk-Jan Dijk, and colleagues at the University of Surrey’s Sleep Research Center, appear in the journal Current Biology, published by Cell Press.
There are two variants of the PERIOD3 gene found in the human population, encoding either long or short versions of the corresponding protein. Each individual will possess two copies of the gene, either of which might be the long or short form. Previous work had indicated that the different forms of the gene appear to influence characteristic morning and evening activity levels–for example, “owl” versus “lark” tendencies.
In the new work, a multidisciplinary research team consisting of biological scientists and psychologists compared how individuals possessing only the longer gene variant and those possessing only the shorter one coped with being kept awake for two days, including the intervening night. The researchers found that although some participants struggled to stay awake, others experienced no problems with the task.
The results were most pronounced during the early hours of the morning (between 4 and 8 a.m.), during which individuals with the longer variant of the gene performed very poorly on tests for attention and working memory.
The authors point out that this early-morning period corresponds to stretches of time when shift workers struggle to stay awake, during which many accidents related to sleepiness occur. But the scientists also emphasize that the new research was conducted in the laboratory, and whether forms of the PERIOD3 gene also predict individual differences in the tolerance to night-shift work remains to be demonstrated.
An additional finding was that the effects of this gene on performance may be mediated by its effects on sleep. When the volunteers were allowed to sleep normally, those possessing only the longer form of the gene spent about 50% more of their time in slow-wave sleep, the deepest form of sleep. Slow-wave sleep is a marker of sleep need, and it is known that carrying a sleep debt makes it very difficult to stay awake and perform at night.
The findings highlight a possible role for clock genes in human sleep physiology and structure, and the influence these genes might have on performance by unrested individuals.

Lesson of the Day: Circadian Clocks are HARD to shift!

This is a story about two mindsets – one scientific, one not – both concerned with the same idea but doing something very different with it. Interestingly, both arrived in my e-mail inbox on the same day, but this post had to wait until I got out of bed and started feeling a little bit better.
First, just a little bit of background:

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Seasonality of Pre-term Births

Matt found a conference paper that shows that the risk of pre-term birth is the lowest in spring, rising through summer and fall and the greatest in winter.
The paper, IMHO erroneously, focuses on the time of conception (because it is an easy marker used to calculate the supposed birth-date). Matt correctly shifts the discussion to the time of birth. After all, pre-term births are much more likely to be caused by something happening around that time than anything at the time of conception.
On the other hand, Matt, though cautiously and almost tongue-in-cheek, makes an attempt at an adaptive explanation. To do this, he had to consider not just the time of birth but also the duration of pregnancy which brings us back to the consideration of the time of fertilization.
I don’t think there is an adaptive explanation (Matt thinks so, too, but tries to come up with one anyway). Pre-term births are not healthy shorter pregnancies. They are pathological events. I don’t think that natural selection works on preserving pathological events.
Both in the primitive state, and in today’s modern society, winter is the most stressful time of year (remember that silly formula for January 20-something being the most stressful day of the year?). Spring is the best time of year: people are coming out of their Winter Blues (or even full-fledged SAD), there is an abundance of food and it is not as hot and scorched-earth yet. The timing of birth is determined by the fetus, not the mother, but the fetus will often respond to the perceived stress of the mother.
Out of the left field: Perhaps the increase of pre-term births in industrial societies (compared to developing world and/or the past times) has something to do with Christmas and its commercialization!

Greenwich time to remain Greenwich time

In light of my post earlier today about the discrepanices between ‘real time’ and ‘clock time’ (or ‘social time’), it is heartening that the Parliament in the U.K. wisely decided not to switch their clocks to the time the rest of Europe observes. If they did, they would be seriously out of whack. After all, at Zero Meridian in Greenwich (yup, I stood astride it, of course), midnight is really midnight – it is the middle of the time zone. Resetting it by one hour would put the Brits at the far Western edge of another time zone and they would always experience true midnight a long time (60-120 minutes!) after the clocks say it is midnight (the same goes for dawn, noon, dusk and any other time).
Now, if they (and us and everyone else) could only decide not to go through the twice-annual ritual of re-setting the official clocks by one hour (Spring forward, Fall back), that would save a lot of lives….

New Model for Interval Timing

While study of Time-Perception is, according to many, a sub-discipline of chronobiology, I personally know very little about it. Time perception is defined as interval timing, i.e., measuring duration of events (as opposed to counting, figuring which one of the two events happened first and which one second, or measuring time of day or year).
Still, since this blog is about all aspects of biological timing, I have to point you to a new paper in Neuron (press release) about a new computer model for human time-perception.

“If you toss a pebble into a lake,” he explained, “the ripples of water produced by the pebble’s impact act like a signature of the pebble’s entry time. The farther the ripples travel the more time has passed.
“We propose that a similar process takes place in the brain that allows it to track time,” he added. “Every time the brain processes a sensory event, such as a sound or flash of light, it triggers a cascade of reactions between brain cells and their connections. Each reaction leaves a signature that enables the brain-cell network to encode time.”

Of course, this is a little vague as far as neurophysiology goes, and we need to remember that even the most brilliant mathematical model may end up being wrong. Still, the model seems nifty and I hope they follow up with real lab work to test it.
Steve of Omni Brain has more and points to this 2005 review of the topic in Nature Review Neuroscience.

Sun Time is the Real Time

Blogging on Peer-Reviewed Research

If you really read this blog “for the articles”, especially the chronobiology articles, you are aware that the light-dark cycle is the most powerful environmental cue entraining circadian clocks. But it is not the only one. Clocks can also be entrained by a host of other (“non-photic”) cues, e.g., scheduled meals, scheduled exercise, daily dose of melatonin, etc.

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New potential sleeping pill

If you discover a brain chemical which, when missing or malfunctioning (due to a mutation in its receptor) abruptly puts people and animals to sleep when they don’t want to – a condition called narcolepsy – then you can work on creating a drug that acts in the opposite way and induces sleep when you want to.
Apparently, that is what a Swiss team just did (Nature news report here and Nature blog commentary here). The drug, still without a sexy name, is known by its “code-name” ACT-078573.
The target of the drug is the orexin system. Orexins (also known as hypocretins – the discovery was simultaneous in two laboratories several years ago and both terms are in equal use in the literature – you may remember one of the studies as it received some media coverage because it tested narcoleptic Doberman pinchers) are two closely related neuropeptides (orexin 1 and orexin 2). They are produced by cleavage of a single precursor protein. They are strongly conserved through the vertebrate evolution. They are produced in a small cluster of nerve cells, but those cells make projections widely across the brain.
The major function of orexins is to integrate circadian, sleep and metabolic information to determine if the animal should be awake or asleep. The connection to metabolism is also responsible for a secondary role of orexins in the control of appetite.
In narcoleptic people (or dogs), the levels of orexin are very low, or the orexin receptor is not functioning. In other words, the funciton of orexins is to promote wakefulness. ACT-078573 is an orexin antagonist – it blocks effects of orexin, thus promoting sleepiness.
It is too early to talk to your physician about this drug yet. This was just a first preliminary study. The drug was given only once, so we do not know possible effects of prolonged use. It was given to 42 healthy males with no history of sleep disorders, thus we do not know how it would effect women, children or people WITH sleep disorders – exactly those who would potentially benefit from this drug.
Just because a single use did not provoke other symptoms of narcolepsy – loss of muscle tone, loss of coordination and hallucinations – does not mean that long-term use of the drug would not result in such side-effects (after all, even the early narcoleptic events in affected people do not usually have such side-effects – they develop over time).
Another consideration is timing. In the study, the drug was given during the day when the orexin levels are naturally high (remember – orexin promotes wakefulness). We do not know what effect, if any, the orexin antagonist would have at night when orexin levels are naturally low. After all, as with all drugs targeting the circadian system, the effect is highly dependent on timing.
Another concern is with a possible side-effects of the drug on the appetite. Though this may be turned into a positive for the drug if it can be shown to be useful in control of appetite. Nothing sells better than sleep pills except the diet pills, after all!

The Cultural Politics of Sleep

Nicole Eugene recently defended her Masters Thesis called Potent Sleep: The Cultural Politics of Sleep (PDF) on a topic that I find fascinating:

Why is sleep, a moment that is physiologically full and mentally boundless, thought to be a moment of absence and powerlessness? Where did this devalued notion of sleep come from and how can we situate sleep studies within a continuation of a historical processes and economic infuences? In other words, how does sleep effect and exist within systems of power? To answer these questions I turn to a range of scholarship and theoretical studies to examine the complexities and dynamics at work within the cultural discourses on sleep. By creating a genealogy of sleep I am able to track the way notions of sleep have changed and evolved over time. I develop a theoretical framework to examine how the Enlightenment effected notions of sleep by strengthening a cultural disposition for logical, rational and phonomenological modes of knowledge. I find that the advent of modernity is signified by the moment in which sleep, darkness and unknowing become negative while being awake, light and knowledge become positive. To understand how sleep (and sleep studies) operates in contemporary situations I examine them within the economy of time in which clock time is conflated with money. Here I also visit the way sleep functions in relation to work in a neo-Taylorist management era. I offer an account of sleep’s connections to passivity within the patriarchal systems of thought. I determine that the cultural politics of sleep and sleep disorders point to a rift in the Western Self because of a presumed simultaneity of thinking, acting and being. I have engaged in a range of disciplines and use theory, historical studies, textual analysis , and autoethnography as methodologies to outline some of the major cultural discussions that surround sleep.

And she is not the only one in the world interested in cultural, social and political aspects of sleep. I wish someone would pay for me to go and liveblog the Workshop: New Directions in the Social and Cultural Study of Sleep to be held in Vienna on 7-9 June 2007:

This international and interdisciplinary workshop aims at exploring new directions in the study of sleep from the perspectives of the Humanities, Social and Cultural Sciences. The aim is to raise awareness of the social, cultural, political, and environmental influences on sleep behaviour and to describe in detail variations of sleep patterns in different countries and social groups as well as the meanings people attribute to their sleep and sleep-related behaviour.

Once I read the 191 pages of Nicole’s thesis (and I’ll have to find some time to do it), I will post my thoughts on it here, so stay tuned.
(Related)

This aired too early in the day for my adolescent brain…

I was too busy with the conference so I missed the NPR Morning Edition story on one of my favourite subjects: Adolescent Sleep, which was followed by two more stories on the same subject! I am glad to see this topic becoming this prominent.
Hat-tip: Mind Hacks

Sleep Number Bed?

Adjust your sleep number for the best performance! Or, what does your sleep number say about your performance?

No, light behind the knee does NOT shift the clock!

For science bloggers, a study older than a week is often too old to blog about. For scientists, last five years of literature are the most relevant (and many grad students, unfortunately, never read the older stuff). I thought that for journalists, 24-cycle was everything. Apparently not.
Northwest Explorer’s ‘Senior Life’ columnist is having a Senior Moment, I guess. In this article about Seasonal Affective Disorder, he mentions a study that is several years old and, what’s worse, has been shown to be wrong. No, the mammalian circadian clock CANNOT be reset by shining a light at the region of the leg just behind the knee.
When that study came out in Science several years ago (in 1998), there was quite a media frenzy about it. However, a few months later, while the PI (Dr.Campbell) was still publically defending the study, the co-authors and other lab members were already privately conceding that they could not replicate the data in their own lab. No need to mention that several labs have immediatelly tested the proposition, both in humans and in other mammals, and nobody could get to replicate the effect. While the study was never officially retracted, it quietly went away – there is probably not a single person in the field, Dr. Campbell included, who still believes in this. Except this columnist. And his unfortunate readers.
For more information about SAD, see here.

Sleep Deprivation – Societal Causes and Effects

Sleep Deprivation - Societal Causes and EffectsHere is the second guest-post by Heinrich (from March 20, 2005):

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I Am Dangerous

Well, not me, but people who know what I know. Heinrich aka Sir Oolius explains how the US military uses the knowledge of circadian rhythms and sleep in applications to torture. Just place the prisoners in a state of perpetual jet-lag and no temporal cues, then interrogate them at the time where their circadian rhythm of cognitive performance is at its lowest.

New York Times Gets It Right, Just To Screw Up At The End In Blind Adherence To The He Said/She Said Journalism

New York Times Gets It Right, Just To Screw Up At The End In Blind Adherence To The He Said/She Said JournalismNow behind the Wall, but plenty of excerpts available in this March 26, 2005 post…

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Fetal Alcohol Syndrome Affects The Basic Properties Of The Circadian Clock

Fetal Alcohol Syndrome Affects The Basic Properties Of The Circadian ClockHow does that work? (April 03, 2005)

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