www.Psycheducation.org (home)
traduit du site remarquable du Dr Phelps

Horloges biologiques et troubles bipolaires.
(Minor update 8/2004)

Il y a ci-dessous quelques dessins et graphiques remarquables. Ils doivent vous aider à illustrer que les troubles bipolaires sont un problème "biologique". Dans ces troubles, les horloges biologiques se dérèglent et entrainent des changements physiques qui ne devraient pas survenir. J'aime ces dessins car ils rendent le problème des horloges évident. Et nous en avons besoin, car souvent l'entourage familial et professionnel  et même parfois les patients eux-mêmes ne reconnaissent pas qu'une phase de dépression ou d'irritabilité peut provenir de quelque cycle anormal biologique et non d'un manque de volonté, par exemple.

So, here is a fellow who cycles every 24 hours, literally "like clockwork". [UPDATE 8/2004:  "48-hour rapid cycling" is a recognized, though rare, bipolar variation.^Voderholzer  Since writing this in 2002, I've seen one such person in my practice.]  In the graphs below, each dot marks a day.  The first graph is a mood scale.  You can see that his mood changes every 24 hours-- one day up in mood, next day down.  On the right, you see his mood after treatment with a mood stabilizer:  

But look at how many things cycle the same way as mood.  First,  cortisol, a stress hormone (again the curve on the right is after treatment):  

and growth hormone, which has many roles in the brain: 

and two members of the epinephrine family, other basic stress hormones: 

His handwriting changed every 24 hours: 

Even his brain activity seemed to vary every 24 hours:  

The red line points at this man's right thalamus; the purple line points at his left thalamus.  On manic days, his left thalamus isn't as active as his right one -- can you see that?  Look at right versus left on each of the "manic days", especially day 5.  The difference is not dramatic, until you compare depressed days, where this pattern is not seen at all.  

What these changes in activity mean, we don't know -- but to see these brain changes match such consistent changes in hormones and mood, sure makes me wonder just what that thalamus is doing on manic days...

What's the point? 

These graphs show that in bipolar disorder, fundamental parts of a person's body -- hormones and brain activity  -- cycle according to a clock that is out of control.  Fundamental ways of relating to the world -- from handwriting to mood -- are changing in the same way.  The point is that people with bipolar disorder are not physically in control of how they feel in the same way that people without this disorder are.  Note that I didn't say people with bipolar disorder are "out of control".  It's just that their experience of their bodies is different -- so how much control over how they feel and act could be very different also.  

Biologic Clocks and Treatment

This will take a little explaining, and then we'll come around to the treatment issue.  First, here's a story from the great research team at the National Institutes of Mental Health (NIMH), reported in Bipolar Network News (a great source; here's the latest issue): 

Here is the same record, starting from the severe depressive episode marked before (***), and now continuing into treatment -- beginning at *.   Notice that almost as soon as treatment begins, his sleep becomes more organized (neat black and gray bands); his total sleep per 24 hours starts to be consistent *; and his mood curve starts to settle toward the middle *.   So, what was this treatment?  NO MEDICATIONS.  That sounds great, doesn't it?  But it wasn't easy: the NIMH research team required this man to stay in darkness 14 hours every night, from 6 pm to 8 am the next morning.  (After a few weeks they eased up: only 10 hours of "enforced darkness").   How could "darkness" treat rapid cycling? And what does this mean for your treatment?

How does darkness treat rapid cycling? 

Once again we turn to the biological clock.  Remember the evidence (from the 24-hour cycling pattern we saw) that the biologic clock, and all its hormonal changes, is involved in bipolar disorder.  The NIMH team theorized that in rapid cyclers, their clocks have lost the ability to respond to the timing of natural day and night. 

They knew that the a specific part of the hypothalamus, the suprachiasmatic nucleus (SCN), has direct nerve connections from the eyes.  It gets direct signals about how much light is out there.  The SCN has been shown to be the main location of the "biological clock" in many animals, including humans.  The NIMH team believed the SCN might get "desensitized" in some susceptible people by too much light, namely too much artificial light at night.  

They hoped that they could reverse this with its opposite -- enforced darkness at night.  They believed that the SCN could become more sensitive again, if given this treatment.  Perhaps then it would then have more influence over the body's cycling, and keep a man like this more stable?   

They set out to test this idea by taking a person with rapid cycling, on no medications, and helping him get "plenty of dark".  In fact, they made sure that's what he got!  Every night he came to their research program and went into a room with a bed, but no lights.  He didn't have to sleep, but he couldn't do anything -- there was no light to read by, no television, no phone: "enforced bed rest and darkness".  You can see how well this worked for him from the curves above.  

What does this mean for your treatment? 

I hope the implications are obvious: you might be able to get by with less medication if you avoid late evening light and activity.  Unfortunately, because there is no pharmaceutical manufacturer selling "darkness", we don't have lots of funding to support research on this treatment.  So there have not been formal tests of this approach.  Thus, I have no data to present to you to support this treatment, just this one case report.  

On the other hand, here's one treatment that has very few risks (the other is exercise, if you haven't read about that yet).  And it would be easy to move at least a little bit in the direction of less artificial light, and less late evening activity.  At worst, you'd spend some evenings lying there in the dark.  I know from my patients' reports that this is not trivial: it means lying there with your thoughts, which can be pretty rough.  However, look at this guy's curves again -- he did it, and look how fast things started changing for him (on no medications): 

I don't recommend that you try to treat yourself with darkness alone, that's not the point.  Rather, I suggest that you look at how much artificial light you're getting, particularly late at night, and try to cut back on that.  If it helps your mood stability, great; if not, you hopefully won't have suffered too much finding out whether this could work for you.  

Another researcher (Dr. David Avery at the University of Washington, who studies seasonal affective disorder, another "clock" problem), suggests that people put dimmers on all the lights they use after 9 pm.  He especially worries about the light in the bathroom -- you know, that bright one made for shaving and putting on make-up?  Imagine what that does to your suprachiasmatic nucleus, illuminating your eyes at 10:30 pm when your body is supposed to think "it's dark now, it's time to sleep now"....!

What does this mean about what causes bipolar disorder? 

The biologic clock seems clearly to be involved in bipolar disorder (I hope you agree after seeing the two important stories above).  So whatever genes are involved in bipolar disorder, one of them will almost certainly be related to the clock.   Call it a "clock gene".  

The UCSD genetics research team, led by John Kelsoe, believes that multiple genes are probably responsible.  They have identified a very likely gene that is involved in the brain's use of dopamine, a widespread neurotransmitter.  

With a dopamine gene, and a probable clock gene, we're getting closer to a working model of bipolar disorder.  It's going to be a genetic story, with some final environmental triggers (probably some kind of loss or trauma, although highly susceptible individuals may require only their own hormone surge at puberty to act as a trigger).  See the "Bipolar Genetics" section, if you haven't been there yet.   

Back to "What the latest on the cause of bipolar disorder?"

Home