Post Prozac Nation

Fabulous and fascinating article on anti-depressants and depression in the NYT magazine today.  Siddhartha Mukherjee nicely summarizes the evidence and controversy about whether and how SSRI’s work.  I think he goes by a little too breezily the fact that the best evidence suggests that anti-depressants actually do very little, if anything, for mild to moderate depression beyond the placebo effect (but a powerful effect it is).  That said, it’s a really interesting look at evolving theories on the neurobiology of depression.   Short version: it seems that SSRI’s in some way actually help to stimulate the growth of new brain cells in a key area of the brain.  Here’s the complicated, but succinct, explanation of what may be going on:

A remarkable and novel theory for depression emerges from these studies. Perhaps some forms of depression occur when a stimulus — genetics, environment or stress — causes the death of nerve cells in the hippocampus. In the nondepressed brain, circuits of nerve cells in the hippocampus may send signals to the subcallosal cingulate to regulate mood. The cingulate then integrates these signals and relays them to the more conscious parts of the brain, thereby allowing us to register our own moods or act on them. In the depressed brain, nerve death in the hippocampus disrupts these signals — with some turned off and others turned on — and they are ultimately registered consciously as grief and anxiety. “Depression is emotional pain without context,” Mayberg said. In a nondepressed brain, she said, “you need the hippocampus to help put a situation with an emotional component into context” — to tell our conscious brain, for instance, that the loss of love should be experienced as sorrow or the loss of a job as anxiety. But when the hippocampus malfunctions, perhaps emotional pain can be generated and amplified out of context — like Wurtzel’s computer program of negativity that keeps running without provocation. The “flaw in love” then becomes autonomous and self-fulfilling.

We “grow sorrowful,” but we rarely describe ourselves as “growing joyful.” Imprinted in our language is an instinct that suggests that happiness is a state, while grief is a process. In a scientific sense too, the chemical hypothesis of depression has moved from static to dynamic — from “state” to “process.” An antidepressant like Paxil or Prozac, these new studies suggest, is most likely not acting as a passive signal-strengthener. It does not, as previously suspected, simply increase serotonin or send more current down a brain’s mood-maintaining wire. Rather, it appears to change the wiring itself. Neurochemicals like serotonin still remain central to this new theory of depression, but they function differently: as dynamic factors that make nerves grow, perhaps forming new circuits. The painter Cézanne, confronting one of Monet’s landscapes, supposedly exclaimed: “Monet is just an eye, but, God, what an eye.” The brain, by the same logic, is still a chemical soup — but, God, what a soup.

On a quasi-related note, Mukherjee is the author of one of my favorite books I read last year.  The Emperor of All Maladies: A Biography of Cancer.

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