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Chapter 3: The Central Role of the Biological Clock
(Written 9/2007; updated 10/2007) 

Summary:
The first two parts of this story are summaries of material explained in detail elsewhere on my website (links below). The last two sections here, about night shift work, and sleep apnea, arise very directly from an understanding of the biological clock story.

Link to Chapter 4


Update: sleep deprivation activates emotional brain centers

Only a month after the essay below was written, a major new result arrived which is very consistent with everything therein.  Indeed, it strongly reinforces the importance of this whole story. Here is that stunning result.

When people do not sleep, activity increases in a brain center which is responsible for fear and emotional interpretation of events -- the amygdala. In some ways, this is not news: doesn't everyone know that when you don't sleep, you get grouchy, and more agitated?

But imagine if a person who is already prone to overactivity in their amygdala goes without sleep. This sleep loss will have more impact on them, one might expect, than on the average person. As you saw in the previous chapter on brain differences, evidence is increasing that people with bipolar disorder have overactivity in regions of their brain associated with emotional processing. 

In chapter 2, you saw pictures depicting this "limbic" hyperactivity, focusing on the hippocampus. In the picture below, we see hyperactivity in the amygdala, which sits right next door to the hippocampus and is very tightly functionally linked to it.



Participants in the study (by Matthew Walker and colleagues at UC Berkeley) were shown pictures with negative emotional overtones.  In the top panel, you see a slight increase in activity in the amygdala amongst study subjects who were allowed their normal sleep pattern prior to this brain scan.  In the bottom panel, however, you see a much greater level of activity in the amygdala on both sides of the brain; these subjects, who did not have bipolar disorder ("normal" graduate students), were deprived of sleep all night before this scan, which came about 36 hours after their last sleep.

What's the point?  In these images we see direct evidence that sleep deprivation increases activity in brain centers you do not want to have running your emotional show.as you'll see on the rest of this page, sleep is a crucial ingredient in health for people with bipolar disorder (and probably for everyone else).

The Biological Clock and Bipolar Disorder

Bipolar disorder is a disruption of the biological clock.  Well, that's almost true: clock disruption is an important part of the story in the majority of people with bipolar disorder.  Once in a while I see a patient whose sleep is completely normal but who is still having bipolar symptoms.  This is very unusual but not impossible.  That tells us the biological clock story is not common to every version of bipolar disorder. However, for most people with this illness, sleep abnormalities are a central part of the problem: when sleep gets worse, symptoms get worse; and when it gets better, symptoms often get better.

Obviously, this means your sleep is important -- which means you need to be careful about getting it!  This is one of the most important messages which emerges from understanding the biological clock story.  The good news is that by being careful with sleep -- and darkness too, as you'll see -- you can potentially improve your symptom control without relying entirely on medications.  You will also see that at least in one particular individual, nearly complete symptom control was possible without medications are all, just by very strategic use of darkness and sleep.  Unfortunately, it is not easy to have a normal life while using that treatment approach, so this is not for everyone. 

Wow, have I got your attention now?  You'll find details about that particular patien tin the essay about dark therapy, and how to apply this whole story to your version of bipolar disorder in the essay entitled Light and Darkness and Bipolar Disorder: Treatment Implications. The latter is my attempt to tell the whole story as implied by the title.  In it you will find details on how dark therapy may be possible using a simple $7 device while leaving your lights on.

How does the biological clock work?
Here's the short answer -- a link to the long version iscoming up.  In brief:  in a particular region of the brain called the hypothalamus (here is a Brain Tour) contains a collection of neurons which function as a clock.  These neurons "know" when it is morning, and start many of the biologic rhythms your body depends on during the day.  Likewise, they know when it is nighttime:  they then turn off daytime rhythms, and turn on nighttime functions including the secretion of melatonin which is associated with sleep.  Therefore your inclination to sleep is very directly controlled by the biological clock.  Likewise, your daytime wakefulness also depends on the clock.

The individual molecules associated with this biological clock function have been worked out in remarkable detail.  Originally this was done using the biological clock in a fruit fly has the model, but the mechanism in humans turns out to be remarkably similar. A recent study showed that by manipulating one of the genes responsible for a protein in this clock process, a behavioral change very much like maniac could be produced in a mouse.  It even got better when they gave the mouse lithium, causing a return to normal mouse function. Here is a picture of the normal mouse.  Can you imagine what a manic mouse looks like?  Hint: it does not crouch in the corner!


Whoops, wrong picture, that's the manic mouse.  Here is normal mouse behavior: 

Here is the full essay about how the biological clock works.

Sleep and light and darkness and the biological clock

Well, at this point you've seen links to this story enough times that by now I hope you've gone off to read it!  The "bottom line": sleep is not the only thing that matters.  Just as we use light as a therapy for depression, it may be possible to use darkness as mood stabilizer treatment for bipolar disorder.  In fact, the whole story makes you wonder whether our use of electric light, particularly televisions and computers, might be part of why bipolar disorder seems to be such a problem in our society right now.  But the good news is that we can use this understanding as part of treatment, at least as a reminder about the importance of regular sleep -- and perhaps by making sure that we get enough darkness, as well as enough light (and all at the proper time, in order to preserve our natural biological clock function).

Here again, one last time, is the remarkable story about Light and Darkness In Bipolar Disorder.  (Sorry if I'm leading you around in circles here)

Should I get off night shift?

Clearly sleep deprivation can be a trigger for manic episodes.  This can occur from travel across time zones, or shift work, for example.  I routinely write letters for my patients who work a "graveyard" shift indicating that they need at least a "swing" shift and preferably a day shift to keep from making their bipolar disorder worse by sleep deprivation.  (At least our local Corvallis, OR employers have been excellent about going along with this recommendation.  That probably would not be the case everywhere; although a case could be made that shift changes would be "reasonable accommodation" as required by the Americans with Disabilities Act.  I have not had to invoke that legal issue; for more on the Act, try these legal resources: Bazelon, basics of the ADABoston University's How to's (use their navigation bar)).

Can sleep apnea cause or look like bipolar disorder?

Sleep apnea refers to a form of snoring which leads to closure of the breathing tube, the airway to the lungs. people wake up because they are not getting any air.  Sometimes this is marked by a pattern of snoring, a "crescendo" from mild snoring to very loud and effortful -- almost gasping -- snoring followed by a momentary waking. These brief moments of waking are usually not remembered. They are sometimes accompanied by a repositioning motion in bed. Then the pattern begins again.

If you snore or if you are overweight, then you probably need to understand sleep apnea, so you can make sure you do not have it.  Here is a sleep disorders resource center you can use to learn more about apnea and other problems.  I have had several patients who report substantial improvement in the control of their symptoms after their sleep apnea (described in the above link) was treated, so this definitely warrants more attention than it is now getting.  Thanks to Dr. Robert Clark for providing the link (he does have some proprietary interest, but the basics on the site are clear and straightforward and you will probably find them useful).  

One of my colleagues, Dr. Tam Kelly, thinks that every patient who comes in with bipolar symptoms should have a test for sleep apnea.  He uses a paper and pencil test for this that he's about to give me [Under construction, August 8, 2008]. 

For now, it is not routine to get a sleep study looking for sleep apnea in every patient with bipolar symptoms.  If you have good insurance, where plenty of money, and your partner says you snore, you should consider such a test.  If you have no partner to tell you, but you have severe daytime sleepiness and fatigue, you should also consider it. 

 

Link to Chapter 4