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Depression
There’s a Clock in Your Brain That Rules Your Life
We all dance to the same tune: and a little bunch of nerve cells is why
Posted April 4, 2018
Imagine looking at a slow-motion film, taken from above your town. It records what happens over several days. You run the film: it’s easy to see waves of activity: a rush of traffic in the morning, a surge of pedestrians around midday, a second flood of traffic in the early evening. You also notice that the lights go on in the early morning (exactly when will depend on where you live and the season of your recording), and go off again in the late evening. You’re watching the rhythm of life: your life. And that of most other people. What you may not know is that this rhythm isn’t spontaneous, or regulated by habit or work, but by a tiny clock in your brain.
The clock is a collection of nerve cells, called the suprachiasmatic nucleus, an impossibly long name that always shortened (even by neuroscientists) to SCN. It’s a true clock, because it ticks away all by itself (energy provided by its blood supply – like the clockwork or battery in your watch). But it can’t tell the time, and like your watch, has to be set to enable your rhythm to match those of others and the external world. It’s connected to your eyes, and special sensors tell it when the lights come on (the sun rises) and when they go off (sunset), so it’s synchronised to daylength. If you put someone in a dimly lit (red light) cave for several weeks, then the SCN clock reverts to its natural rhythm. The fascinating result is that each of us has a slightly different rhythm: yours might be 24.6 hours, mine 23.8, and so on (it’s never too far from 24). If you were asked to keep a count of the number of days you had spent in the cave (there is no other information available to you) then you would underestimate the time, because each of your ‘days’ is now longer then it should be: I would do the opposite. But we would both revert to the same 24 hour rhythm when we returned to the normal world with its 24 hour day. This is why, despite these differences in the ticking of our SCN clock in the cave, in real life we are all (more or less) synchronised with each other.
But these differences don’t disappear altogether, even in the everyday world. You may be a ‘evening’ person (an owl): I may be morning one (a lark). That’s because your SCN clock finds it more difficult to reduce it’s natural rhythm to 24 hours from 24.6 (or whatever) whereas mine finds it easier. So your ‘peak’ of SCN rhythm may be later. Interestingly, during adolescence the SCN clock tends to delay its peak, which may be why young people have such a problem getting out of bed in the morning!
How does this tiny part of the brain work? Not like the watch on your wrist, whether it’s a clockwork or electronic one (they are quite different as well, but that’s another story). Each day, there is a rhythmic surge of a number of proteins in the SCN: these regulate the signal it gives to the rest of the brain, and indeed, to the body. The formation of these proteins is, in turn, regulated by a number of genes. The rhythm occurs because as the amount of protein increases, it does two things: signals the time of day, but also suppresses its own formation by acting on the gene that makes it. So the concentration of protein falls, but as it does so, it liberates the gene. You can see how this will result in an oscillation that will be rhythmic. Genes are not exactly all the same in all of us (mutations) which accounts for why your rhythm may differ from mine. But in both of us our behavior is driven by our SCN, itself modulated by light, and so the world moves in synchrony, and there’s a daily rush hour.
Most of us have experienced jet lag. If you fly from London to New York, your clock has to shift by about 5 hours: it takes several days do this. In the meantime you feel awful: tired (you wake too early), bad tempered, even somewhat depressed. Your body is a temporary mess. This shows you how important the SCN is: your body needs to synchronise with the environment (and with other people): during jet lag, each organ becomes temporarily out of sync with others; hence you feel so bad. Imagine if this lasted weeks or months: you’d quickly seek medical advice. There are circumstances in which rhythms do become disturbed for long periods: one of them is depression. Which brings us to consider how the SCN clock tells the rest of the body the time of day and so synchronises each part. Incidentally, because the SCN clock finds it easier to lengthen rather than shorten its onset (eg dawn), jet lag is usually worse if you fly east (to London) than west (to NYC).
The clock genes aren’t limited to the SCN. Most tissues have them, and they appear to do much the same: control the rhythms of activity in that tissue. Hence some people find drinking alcohol has lesser effects on them in the evening, because the enzymes (proteins) that break it down change rhythmically and can be higher on the evening. But these local clocks are under the control of the SCN. How does it do it? Some of the mechanisms (there are several) are still rather mysterious, but we do know about one. Which brings us to hormones.
The adrenal gland, just above your kidneys, secretes cortisol. This has a huge daily rhythm: levels are about 5-6 times as high as you wake up than when you go to bed. The SCN controls this rhythm by sending a periodic signal to the part of the brain (the hypothalamus) that controls the pituitary gland, which in turn secretes a hormone (called ACTH) that controls the adrenal. This chain of command is one way: the adrenal can’t alter the clock in the SCN. The SCN is the master clock. But cortisol does act as a signal to some of the tissues, so they regulate their activity according to the time of day.
Depression is not a single disorder: about 50 % (the figure varies according to whom you read) of those with severe depression have abnormal cortisol rhythms. Typically, levels are somewhat higher in the morning than normal, but don’t decrease as they should during the day, so the daily rhythm is flattened. We know that this will affect brain function, and that giving people cortisol-like steroids that have a similar effect can result in depressed mood. So how much is cortisol responsible for some episodes of depression, or is it a reflection of the disorder? Arguments rage on about this: but treating disordered cortisol is not part of standard therapy for depression. Maybe it should be, but only in those in which the cortisol rhythm is disturbed. We do know that exposing the brain to higher cortisol, or disturbed cortisol rhythms, may damage it, or make it more susceptible to other damaging agents, including, it seems, those responsible for Alzheimer’s disease, in which cortisol rhythms are also abnormal. This may be one reason why Alzheimer sufferers tend to wander round the house at night.
Under more normal conditions shift work will disturb rhythms, including cortisol. The SCN clock has constantly to reset itself as people move onto, and off, night shifts. There is a huge literature on the consequences of shift work for health, and methods have been developed for making transitions from one environment to another as easy and non-damaging as possible. Aircraft crews are another instance of frequent changes in time zone. No-one has really shown that this is damaging, but airlines take precautions about the number and rate of time zones to which their staff are exposed.
Remember, next time you sit in that traffic jam, that it’s just a little bunch of nerve cells in the brain that drives the rhythm of the life that you, and everyone else, lives.
