Wednesday, 29 August 2012

Lithium and the Bodyclock

Another interesting bit from The Disappearing Spoon:
  • Curiously, for all its potency as a drug, lithium has no normal biological role. It's not an essential mineral like iron or magnesium, or even a trace nutrient like chromium. In fact, pure lithium is a scarily reactive chemical.

    Lithium tweaks many mood-altering chemicals in the brain, and its effects are complicated. Most interesting, lithium seems to reset the the body's circadian rhythm, its inner clock. In normal people, ambient conditions, especially the sun, dictate their humours and determine when they are tuckered out for the day. They're on a twenty-four-hour cycle. Bipolar people run on cycles independent of the sun. And run and run. When they're feeling good, their brains flood them with sunshine neurostimulants, and a lack of sunshine does not turn the spigot off. Some call it "pathological enthusiasm": such people barely need sleep, and their self-confidence swells to the point that a Bostonian male in the twentieth century can believe that the Holy Spirit has chosen him as the vessel of Jesus Christ. Eventually the surges deplete the brain, and people crash. Severe manic-depressives, when the "black dogs" have them, sometimes for weeks.

    Lithium regulates the proteins that control the body's inner clock. This clock runs, oddly, on DNA, inside special neurons deep in the brain. Special proteins attach to people's DNA each morning, and after a fixed time they degrade and fall off. Sunlight resets the proteins over and over, so they hold on much longer. In fact, the proteins fall off only after darkness falls - at which point the brain should 'notice' the bare DNA and stop producing stimulants. This process goes awry in manic-depressives because the proteins, despite the lack of sunlight, remain bound fast to their DNA. Their brains don't realise they should stop revving. Lithium helps cleave the proteins from DNA so people can wind down. Notice that sunlight still trumps lithium during the day and resets the proteins; it's only when the sunlight goes away at night that lithium helps DNA shake free. Far from being sunshine in a pill, then, lithium acts as 'anti-sunlight'. Neurologically, it undoes sunlight and thereby compresses the circadian clock back to twenty-four hours - preventing both the mania bubble from forming and the Black Tuesday crash into depression.

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