Monday, May 17, 2010

The circadian prison

This post was chosen as an Editor's Selection for ResearchBlogging.org
I had no idea my sleep-wake cycle was pathological until I saw a presentation a few years ago by the geneticist Thomas Bourgeron. One of his interests is clock genes in autism. In fact only by speaking with him did it dawn on me that I lack a circadian rhythm.

As it turns out, autistics are considered to have circadian clocks "gone bad." Two reviews (Bourgeron, 2007; Glickman, 2010) cover the evidence with respect to autism and circadian rhythms, most of it in the direction of comprehensive atypicalities. Glickman (2010) summarizes the problem:
Disturbed sleep-wake patterns and abnormal hormone profiles in children with autism suggest an underlying impairment of the circadian timing system.
And autistic children's bad timing, when it comes to sleeping and waking, is considered disruptive or worse, both to themselves and their sleep-deprived families. Bourgeron (2007) raises the further concern that typical sleep-wake patterns are essential for "appropriate" development, for the functioning of memory, and so on. Apparently there is nothing good about autistics' bad circadian clocks.

Autistics whose sleep-wake cycles carry on independently from environmental and social cues are said to be "freerunning." My form of freerunning is extreme. I can sleep whenever I want--a few hours here, twelve hours there, as necessary, no matter the time of day or night. I enjoy sunlight but its absence has no effect on my mood, or on my sleep. I can work through nights, no problem, and shift to days in a blink. I've never suffered through jet lag. And so on. Until I ran into Bourgeron I had no idea this was considered pathological, at least in an autistic.

The usual response to freerunning in autism is to see this as an autism-related sleep disorder. There is very preliminary evidence that freerunning autistics can be successfully treated with melatonin. Bourgeron (2007) refers to a short case study about an autistic whose free-running was remediated by melatonin treatment.

Of course nonautistics take melatonin too. They put themselves through sleep hygiene routines and they go to sleep clinics in droves. They suffer terribly from shift work and jet lag, and inadequate efforts to eradicate this suffering are everywhere, from new drugs to new iPhone apps.

There is an enormous market for products and services that can treat individuals who stray from the proper expected sleep-wake cycle. Remarkably, the goal is never to free people from their circadian prisons but to return them there and keep them there. The schedule may be changed, with effort, but the prison remains the same.

The next time I spoke with Bourgeron, I told him there should be a sort of anti-melatonin which would allow people to freerun like me, ergo avoiding the ills of jet lag, shift work, and what-all. It seems possible no one has seriously thought of this.

I suggested the anti-melatonin idea to some nonautistic colleagues. They burst into stories about destroyed careers, disrupted lives. In constrast with autistics like me, my colleagues have perfectly "good" circadian clocks--which turn out to be incompatible with their challenging lives. They suffered, for being normally chained to their normal circadian rhythms.

If there was a pill that could give them my very dysfunctional clock so they could freerun to the extreme, they would buy it in bulk. But there isn't. Instead there is the assumption that everyone has to live in a circadian prison.

Glickman (2010) speculates that some autistics' failure to chain our sleep-wake cycles to environmental cues (you can find information about entrainment, as this process is called, here) may arise from our atypical perception. My totally wild guess might be that an extreme freerunning phenotype in autism may be contributed to in part by cognitive versatility in autism, which would result in perceived environmental cues affecting sleep-wake cycles in an optional rather than mandatory way.

The renowned Bora Zivkovic, who unlike me knows all about circadian clocks, recently wrote that--unlike me--typical people have "have complex circadian systems that are easy to get out of whack" with dire consequences:
In the state of almost permanent jet-lag that many of us live in, a lot of things go wrong. We get sleeping disorders, eating disorders, obesity, compromised immunity leading to cancer, problems with reproduction, increase in psychiatric problems, the Seasonal Affective Disorder, prevalence of stomach ulcers and breast cancer in night-shift nurses, etc.
BoraZ was writing enviously about reindeer who live with drastic changes of season yet have escaped this kind of misery, possibly by having a "low-amplitude" clock. They just stroll out of their circadian prisons, whenever it's adapative. How can poor suffering human beings do this, is the question--finally. It's a very good question.


References:

Bourgeron, T. (2007). The Possible Interplay of Synaptic and Clock Genes in Autism Spectrum Disorders Cold Spring Harbor Symposia on Quantitative Biology, 72 (1), 645-654 DOI: 10.1101/sqb.2007.72.020

Glickman, G. (2010). Circadian rhythms and sleep in children with autism Neuroscience & Biobehavioral Reviews, 34 (5), 755-768 DOI: 10.1016/j.neubiorev.2009.11.017


Postscript: This post has been included in the 32nd edition of Scientia Pro Publica.

28 comments:

oscilor said...

I have a circadian rhythm disorder but unlike you I have a robust circadian clock- it just does not entrain well to 24hr days and runs at about 24.6hr days. I had my melatonin levels measured every weekend over a 6 week period and they also free-ran.

I can force myself on 24hr days by getting bright light in the morning or taking melatonin at night, but this appears to only entrain some rhythms or to entrain them at an awkward phase angle to each other or to the light-dark cycle eg on 24hr days most people have peak melatonin at about 3.30am whereas mine peaked at 7.30am, so I was waking up when my clock still thought it was night.

As circadian clocks underlie many if not all aspects of physiolgy, and clock genes are present in brain regions outwith the hypothalamic master clock, anything that disrupts them has far reaching effects.

I function better on my own cycle but that is not ideal either as I am often disrupted.

oscilor said...

Melatonin does not drive the clock. The clock (really clocks) are endogenous in that they are created inside single cells by interlocking feedback loops of clock genes. There are some humans and animals who lack melatonin but still have clocks.

However melatonin is suppressed by light, so anti-melatonin exists, and constant light does disrupt circadian organization in some animals. Bright light at night has been used to help shift workers adapt.

There are mutant mice who have no circadian rhythms and lack VPAC2 receptor. It is not involved in the core clock feedback loops but in synchronising clock cells to each other in the suprachiasmatic nucleus, the master clock.

MJ said...

You really don't present the problems caused when a person's circadian rhythms are out of whack. I have just spent the past three months getting very little sleep because of dealing with two children with autism who are unable to regulate their sleep patterns. And, unlike your rose colored view of "freerunning", they had real problems from the disruption - problems like irritability, inability to focus, and self injurious behaviors.

There is a reason that your body has circadian rhythms and flippantly suggesting that it would be better if there was a pill to short circuit them while ignoring the real problems that the disruptions can cause is harmful to children with autism.

Michelle Dawson said...

Those--and they were all adults, for clarity--to whom I mentioned this idea, and who seized on it for themselves for a range of reasons, never mentioned giving the extremely hypothetical anti-melatonin to children of any age. Nor have I, for reasons I assumed were obvious.

In a presentation, Bergeron mentioned one individual whose sleep-wake cycle works much like mine (sleep any time, no problem). This person was not autistic, but had an autistic child.

MJ said...

Then perhaps you could clarify for me what the specific difference between a child with autism and an adult with autism would be with respect to disregulation of a crucial bodily function such as the circadian rhythm.

Michelle Dawson said...

Part of MJ's first message seemed to require a reply. That was lapse of language comprehension on my part, sorry.

MJ's 2nd message makes it clear that neither it nor MJ's first has anything to do with what I've written.

By the way, after BoraZ lists some of the bad things that happen to people whose clocks work the way human clocks are supposed to, he writes:

"Why do we get all that and reindeer don't? What is the trick they evolved to stay healthy in conditions that drive us insane and sick? Can we learn their trick, adopt it for our own medical practice, and use it?"

That's for those who didn't read the whole post from BoraZ. You should, it's excellent.

MJ said...

I am assuming from your response that you don't have an answer to my question.

It is clear that you have not spent any significant amount of time dealing with the problems that this disruption causes for children. This is yet another attempt on your part to minimize or ignore the very real difficulties that children with autism have.

Here's a hint, this disruption isn't caused by "cognitive versatility", it is caused by something not working the way it should.

Instead of writing about how "normal" people have problems because of their "circadian prison", perhaps you should take the time to understand what exactly this regulatory process does and why it is harmful to a person when it breaks down. Perhaps you could spend the time talking about strategies for dealing with and mitigating this disruption instead of trying to pretend that is is a good thing. That would actually be helpful for people with autism.

Anemone said...

This is interesting. A bunch of us were talking about this a while back on Here Be Dragons. (I can't find the link.) There most of us had very long or very short circadian rhythms, rather than freerunning. Mine is super short (about 20 hours) and I actually like it a lot of the time. I like being wide awake at 3 am when it's super quiet out.

Anemone said...

found the link:
http://turnerandkowalski.wordpress.com/2010/03/20/weekend-linkfest-3/

and in the comments to http://turnerandkowalski.wordpress.com/2010/03/16/you-dont-get-it/

Gwyneth Bison said...

one drug that allow people to stay awake : modafinil : http://en.wikipedia.org/wiki/Modafinil

Michelle Dawson said...

I've taken note that MJ is sure my wild guess (based on some of Glickman's speculation) about atypical perception in autism is wrong.

This blog post was chosen as a ResearchBlogging editor's selection for this week. See this, also this.

Lili Marlene said...

I can think of many advantages to having the ability to sleep in a flexible way, but I believe there are also important disadvantages. I believe shift work has a number of important bad effects on health, and it is the out-of-cycle sleeping this is identified as the cause I believe. There was an interesting cluster of breast cancers among the staff at the ABC studio at Brisbane, and irregular sleeping has been blamed. http://www.abc.net.au/news/stories/2010/03/26/2857128.htm

I do beleive that some people are born with more flexibility in sleeping than others, based on my personal observations of family members, but I also beleive that regular humans can do a lot to modify their sleeping patterns. Fitting in with family life and work and schooling often means that sleep needs to be highly regulated (in a natural or unnatural way), but more flexibility might be useful if you are not subject to such external constraints. I also believe in the link between breast cancer and irregular sleep, based on my personal observations.

A while ago the wife of the Prime Minister of Australia told an interviewer that our leader has only needed 3 to 5 hours of sleep a night for as long as they have been married, which is a long time, which suggests that there is something biologically unusual about Kevin Rudd. I have argued that he is autistic and also noted his wife's connections to the autistic spectrum. Despite the revelations about Rudd's unusual sleeping pattern I have not noticed people labelling Rudd as pathological or suggesting that he take pills to normalise himself. Effective and powerful people are not biological freaks, they are exceptional, in the eyes of others.

Phil Schwarz said...

@Michelle: And here I thought (at 3:05 am local time) that circadians were those bugs that dig themselves into the ground, go dormant for a large prime number of years, and then emerge to make a racket for a couple of weeks before mating and keeling over...

When do you experience a desire for sleep? Is it completely arbitrary? Or perhaps tied to levels of various forms of exertion (physical, cognitive, sensory, communicative, etc.) in a preceding stretch of time?

FWIW, I seem to experience a not-very-regular but eventual desire for sleep (after almost always > 24 hours by at least a few hours), if I don't attempt to sleep before then. When I can't let go of something I'm thinking about or anxious about, I can't get to sleep at will -- but otherwise I do seem to be able to do so.

@Anemone: ditto, re. quiet and uncrowdedness-of-social-landscape in the wee hours.

@LiliMarlene: point well taken about eccentricity in effective and powerful people :-P.

Anonymous said...

I'm autistic and my circadian clock is intact. Maybe that's related to the mildness of my autism. It's the quality of my sleep that is a problem. When I was 14, I started waking briefly before dawn. I had my last good night's sleep without medication over 20 years ago. It is now rare for me to sleep through the night, even with the medication I take to help my sleep and treat the symptoms of ADHD.

As for jet lag, when I was a child I didn't get it, even when I crossed 8 time zones. Now, I adjust at a rate of about 2 hours/day.

Michelle Dawson said...

To my knowledge, the health of humans who have very low-amplitude clocks has not been studied.

On the other hand, humans who have typical "healthy" clocks are, in circumstances common in many human lives, susceptible to numerous health problems such as those listed by BoraZ (see original post).

I get tired like anyone else, and need probably about a low-average amount of sleep, but can sleep whenever I want, including to suit the demands on my time.

Lili Marlene said...

I spoke too soon regarding Kevin Rudd!

Sara said...

Pretty interesting about the clocks that regulate sleep.

I probably have Asperger Syndrome, though mostly self-diagnosed and from some people's non-professional opinions. Some professionals said I couldn't possibly have AS, cause I don't have flapping or other such behaviors and I can function more or less normally (except socially, where I'm no good).

I can sleep at almost any time, provided I actually am somewhat sleepy. I take naps almost daily at various times (could be 2 pm or 8 pm) that vary in lenght (30 min to 2 hours), sleep sometimes at 11 pm, sometimes 3 am, depending on my mood more than anything.

One thing of note: I'm easily awakened once my sleepiness is passed some point (like slept 5-6 hours during a night) if I have to wake (work or anything with specific time). Unless I'm drunk dead, you can't "surprise me" (do stuff on me without my knowing or remembering) and I won't oversleep unless I choose to.

I've been depressed in my early twenties and could sleep 15-20 hours a day, in periods of 7-10 hours in a row (with about 2-3 hours awake in between).

It seems my system can compensate food energy with sleep energy-saving to some extent (you still can't live off of sleep, but it diminishes your energy consumption).

Also, bit off-topic, I heard Asperger to be somewhat common in transsexual people, especially trans men, but also trans women (rarely researched in the latter).

The ability to think outside the box without shame about being different (and not caring about difference in self) and the non-dismissal of ideas that go against common sense (ie the notion of having the wrong body for the brain) is probably for something in this.

I had to "learn" common sense. Not common to me.

Lili Marlene said...

Ruddy won't be getting too much sleep tonight!

Heather Babes said...

I want to thank you for posting this. The sources you site are the very ones I've been looking for, for years.

I'm on the spectrum and have two boys on the spectrum. Both myself and my oldest have trouble with wake/sleep cycles and doing it at "normal" times. My youngest does not seem to have this problem. It's interesting to me.

Cris said...

It would be unsurprising were a lot of transmen (aka FTM transsexuals) on the autistic spectrum, as both are likely linked to high levels of prenatal testosterone in the mother's womb! (I am both, BTW).

My whole household has a circadian rhythm disorder! My Aspie housemate just needs 5 hours sleep; his wife who is bipolar needs more like 16. I get what I can for the moment, but noise and light both really disrupt my ability to sleep.

daelm said...

@MJ

"Perhaps you could spend the time talking about strategies for dealing with and mitigating this disruption instead of trying to pretend that is is a good thing. That would actually be helpful for people with autism."

Ummm...what would be good for people with autism is for them to understand their own neurology, as far as is possible and be able to capitalize and mitigate using that understanding. It's an elementary trusim that having a better self-understanding is a positive good.

What you seem to be seeking is something that would be good for people who have to deal with people with autism, while not having autism themselves. This is evident from your complaint about the extent of the disruption your children's autism imposes on you. Their rhythm not being aligned with yours is not a problem for them - it's a problem for you. The situational problems that they will experience as a result of non-aligned rhythms aren't related to their health - they're situationally arisen and relate to the mismatch between their routines and others' routines.

When you say "they had real problems from the disruption - problems like irritability, inability to focus, and self injurious behaviors", I'd put money on it that they had those kind of problems because you expected them to function on their own timeline and on yours. That would cause anyone to have problems.

Michelle's point is encapsulated in your (seemingly antagonistic) question about "dis-regulation of a crucial bodily function such as the circadian rhythm". Variance in circadian regulation is just that - variance. It's only dis-regulation in respect of a preferential frame of reference. While this does not minimize the extent to which people with autism will struggle in a world organised along lines that don't suit us, it does shift the focus away from describing us as a 'problem'.

MJ said...

@daelm -

Ah yes, you hit the nail on the head. My interest in helping my children deal with their sleep disruptions comes only from my concern for my own sleep schedule. If only I were to take your advice and let them manage their own schedules then all would be right with the world.

Not.

Seriously, you think that having a massively disrupted sleep schedule and, by implication, circadian rhythms is just a normal "variation"?

I suggest that you pick up your money from your ill-conceived bet about the source of their problems and invest it becoming educated about the topic. Here is some light reading to get you started.

Lewy, Alfred J, Bryan J Lefler, Jonathan S Emens, and Vance K Bauer. 2006. “The circadian basis of winter depression.” Proceedings of the National Academy of Sciences of the United States of America 103:7414-9.

Gooley, Joshua J. 2008. “Treatment of circadian rhythm sleep disorders with light.” Annals of the Academy of Medicine, Singapore 37:669-76.

Leu, Roberta M et al. 2010. “Relation of Melatonin to Sleep Architecture in Children with Autism.” Journal of autism and developmental disorders.

Wright, Barry et al. 2010. “Melatonin Versus Placebo in Children with Autism Spectrum Conditions and Severe Sleep Problems Not Amenable to Behaviour Management Strategies: A Randomised Controlled Crossover Trial.” Journal of autism and developmental disorders.

These just happened to be at the top of my list of research, there are many more that go into much greater detail about the problems with circadian disruption and sleep problems in children with autism.

I suggest you read them so next time you have some idea what you are talking about and don't have the audacity to suggest that my children's issues are due to a lack of accommodation of their needs.

daelm said...

@MJ

" If only I were to take your advice and let them manage their own schedules then all would be right with the world."

Nope. Not only did I not say that, it's merely an extended inference on your part that assumes views on mine, in much the same way as you have pegged Michelle's views as version of assumptions of your own.

For the record, as far as your children go - and I have no idea what their state is - all I can offer is that their adjustment problems - like mine - will require much greater efforts than 'letting them run their own schedules'.

Nevertheless, their difficulties are compounded and made vastly more complex by occurring in a frame-of-reference/system that conflicts with whatever their own working rhythm turns out to be. (This is a version of the general statement that functioning autistic adults experience problems that arise contextually).

That's a class of facts that they will have to consistently address throughout their lives and at least as much time and effort should be spent on preparing them for a working adulthood - if that's a viable possibility for them - as should be railing against the manner in which adult autistics attempt to navigate the terrain of their disabilities.

To explore that navigation, the experience of adult autistics who have made such accommodations, who have navigated before, is a useful body of knowledge, and so, unless there is some prior experience with Michelle that conditions you towards the hostility on display here, it's difficult to understand.

In my experience, for functioning adult autistics knowledge is medication - contextual awareness of the reason for a dissonance between yourself and others helps to ameliorate your own response to it, for example, and thereby helps stave off secondary emotional difficulties, while the ongoing act of defining an adult identity without it being vested in disparagement is much more than an option - it's a working necessity.

It's that kind of framing exercise that I read Michelle as performing here, in her speculations about divergent circadian rhythms and the possible costs and benefits thereof. While I can see your visible frustration with your children's autism (or rather, I assume that something like that motivates your seeming belligerence on this comments thread), I wonder whether you can see that Michelle's approach is a natural one for a person who *has* autism themselves, especially an adult, one who has had to - to some extent - relinquish the kind of supportive environment that you (hopefully) provide for your children. An adult autistic, seeking some kind of functional independence must create their own rules, routines, systems and axioms of operation. In that exercise, the approach taken by Michelle is quite natural.

All this is moot, to some extent, depending on the severity of your children's experience - not stated here - but even in the case where even severely limited independence is ruled out entirely, the exercise of framing your children's qualities in a neutral manner could provide you with unexpected solutions to the problems they and you experience.

I 'm replying on the fly, and it's all pretty ad hoc, so if I've missed your main points, feel free to ignore what I wrote. I also see that Michelle herself is not making herself available as a target for you, and so maybe I am merely engaging a discussion that you have already refused to entertain.

If that is the case, then no hard feelings either.

Good luck with your daughters.

d

Michelle Dawson said...

What I wrote about:

1. Currently a lot of human beings (autistic, nonautistic) experience major sleep-related problems with very serious consequences.

2. Currently available attempts to alleviate these problems aren't necessarily adequate or ideal for everyone. The ongoing misery level seems to be pretty high.

3. So it's still worth thinking about ways to approach human sleep problems.

4. This is what BoraZ did in one of the best blog posts I have ever read. Please read it.

5. My own post suffers a lot in comparison, as it should, but the point is the same: how can we improve things? How can we do better than we are doing now? What can we learn from atypical individuals (e.g., healthy individuals who just may--maybe, possibly--have low-amplitude clocks)?

MJ said...

Daelm,

I took you (and Michelle) at what you wrote, not what you think you said. Your implication was that their problems were in large part because I expect them to be able to function on the same schedule as we do. You said almost exactly that when you said -

"Their rhythm not being aligned with yours is not a problem for them - it's a problem for you"

and

"I'd put money on it that they had those kind of problems because you expected them to function on their own timeline and on yours."

and that is complete nonsense.

They are not "free-running" when it comes to their sleep/wake patterns and this lack of regulation causes them very real problems. Their problems in this regard have nothing to do with frame-of-reference conflicts and everything to do with the fact that their bodies have a hard time regulating themselves.

We see it in their sensory imbalances, we see it in their immune system disregulation, we see it in their inability to maintain an appropriate balance of essential nutrients, and we see it in their inability to keep themselves on a normal sleep/wake cycle. All of these imbalances cause them very real problems.

While I would agree that it is important for a person to understand the biology of their condition so that that they can make adjustments, this nonsense about pretending that all of us "normal" people live in a "circadian prison" is just absurd. Your body works a certain way and no amount of wishful thinking or air quotes is going to turn what is a very real problem for many children with autism into a good thing.

But even more than that, this cavalier treatment of what is a very serious problem for many children and their families is harmful in that it minimizes the difficulties that this disregulation causes. Children with autism deserve better than to have their problems trivialized.

As to framing my children's qualities in a "neutral manner", well I prefer to deal with reality. I prefer to look at what is causing them trouble and, instead of just trying to rationalize it, trying to help them compensate and restore their ability to function.

For example, we have found a decent way to help put them back into the "circadian prison" with a combination of a low nightly dose of melatonin, a seasonal affective disorder light in the morning, and replacing all of the incandescent lights in our house with full-spectrum light bulbs. These simple changes have allowed them to get back onto a healthier sleep schedule, reduced their tantrums and self-injurious behaviors, and given them a better ability to focus.

Now, which do you think is better, waxing poetic about how "typicals" suffer in our circadian prison and could use an anti-melatonin or helping my children get past the disabling aspects of their disability?

Michelle Dawson said...

The ongoing sleep/circadian problems experienced by nonautistics are not trivial.

The ongoing sleep/circadian problems experienced by autistics who haven't been helped by melatonin (etc) are not trivial.

Repeating what I wrote just recently (could repeat the whole thing, but...):

"how can we improve things? How can we do better than we are doing now? What can we learn from atypical individuals (e.g., healthy individuals who just may--maybe, possibly--have low-amplitude clocks)?"

There's a sleep lab down the hall (works with autistics and nonautistics). It would not exist, if there was no need to improve things and no need to learn.

Donna McMahon said...

I am an ultrasonographer specializing in fetal ultrasound. I have been observing fetal behavior and fetal sleep wake cycles since 1981. Over the years I have repeatedly noticed a fetal condition which seems to disturb sleep and equally effects routine behavior while awake. I would like to share my information with someone who can take this a step further and measure the effects of this behavior. Occasionally this condition will resolve early in the pregnancy. When that happens, sleep and waking behavior seem to fall into a more normal pattern. If you are still blogging and still interested in this please contact me, Donna,by email: myparadym@aol.com

Alana said...

I have never needed particularly a lot of sleep. I certainly didn't sleep like my sisters... who got tired and just fell asleep in the car on the 2 hour drives home from LA, even as a toddler. I would fall asleep in my bed because that was where you would sleep. I know it was probably annoying for my mother when I stopped taking my (one, 20 minute long nap) when I was a 1.5 years old (because I could imagine that it would be nice to be able to have time to get things done around the house while you could put the child somewhere quiet/asleep for a while). I don't remember getting grumpy from staying up late much when I was young, but mostly from being hungry (because if you stay up late then you haven't eaten in a while). My parents taught me relatively early that after I was put to bed, I had to stay quiet in my room in the dark (so I wouldn't wake up my sister) but never that I actually had to sleep during that time. So I grew up never thinking it was some horrible thing but just that different people sleep different ways.
Now, I do get grumpy sometimes when I am out late, but I think that is more from overload of people. I get tired for a while after moving new places, but it has never really been the sort of thing related to jet lag when you wake up at the wrong times or whatever. (Although I call it jet lag because then people understand why I am grumpy). I tend to sleep more at the ends of travel because traveling and new places is overloading and tiring.
I also learned recently that sleep is a great defense (and escape) mechanism, because it doesn't hurt people's feelings but is a good reason to leave. And usually I will go to sleep when I go home because sleep is quiet (and also my bed is super cozy so I just like chilling in it at night anyway).
Well, that was a bit long, which I'm sorry about.