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Against Depressionby Peter Kramer (Viking).

If psychiatrist Peter Kramer's 1993 bestseller, Listening to Prozac, was provocative - it asked who we are if a mere drug can improve our personalities - his new book, Against Depression, should be a terrifying warning. A clinical professor of psychiatry in the Brown Medical School, Kramer vividly describes the bodily harm depression does to heart, blood vessels, adrenal glands, and bones - to say nothing of the cumulative and permanent damage it wreaks in the brain itself, or the mental anguish of mood disorder.

To counter still-widespread arguments that depression doesn't qualify as a disease, Kramer brings together research from such fields as neurobiology, cardiology, vascular disease, genetics, and cancer treatment. He is an extraordinarily gifted science writer, and his descriptions of the physical injuries caused by depression ought to get even the most hesitant sufferers to a shrink.

For example, brain scans and autopsies of depressed patients show significant damage in the prefrontal cortex and the hippocampus, which is associated with regulating stress hormones. Ordinarily, the hippocampus will send messages to the adrenal glands telling them to cut back on these hormones, but in people suffering from depression the hippocampus becomes overwhelmed. The excess stress hormones then destroy brain cells, causing the production of still more stress hormones. It's like a stuck switch, Kramer says. "What would otherwise be limited injuries extend, in the presence of stress hormones, into substantial brain damage. The hormones also dampen repair and regeneration functions, so that temporary injuries become permanent."

Major depression can often be inherited, and research has revealed a gene - 5-HTT - that in one form leaves humans vulnerable to neuroticism and moodiness, prompting the media to dub it the Woody Allen gene. (In another form, 5-HTT appears to protect humans from depression.) Certain personality traits and tendencies - neuroticism, perfectionism, the tendency to dwell on embarrassing events, and excessive conscientiousness - also go hand-in-hand with depression. Child abuse, the death of a family member, ill health, and financial woes all can trigger episodes of depression. And whether it is triggered by cancer medication, a stroke, bad genes, or a failed romance, depression is universally brutal on the brain.

What may be more surprising to most readers, however, is the effect depression can have on the rest of the body. Kramer notes that it may be the most reliable single risk factor for heart disease. Depression is also strongly linked to both arrhythmia and vascular stroke; in a particularly vicious cycle, strokes can trigger depression, which increases the danger of blood clotting and increases the risk of more strokes. (Fortunately, the class of antidepressants called SSRIs (selective serotonin reuptake inhibitors) helps stroke victims two ways: by relieving their depression symptoms and by thinning their blood.)

Despite all this, we are perversely attached to our sadness. And that is Kramer's real subject: From ancient Greece on, Western culture has been enamored of melancholia and its modern offspring, depression. We imagine depressives to be deep thinkers, sensitive to nuances that the shallower among us miss. We find some depressives charming in their fey self-deprecation and spaciness; we find others winsome, even seductive, in their languid passivity.

All this sensitivity, we figure, must lead to more profound understanding: take Soren Kierkegaard, Sylvia Plath, or Woody Allen. We romanticize depression's relationship to creativity, crediting van Gogh's painterly breakthroughs to his psychiatric breakdowns. While studies have linked bipolar disease (manic depression) to creativity, it's not the same for depression. We'd be better off, Kramer argues, calculating the canvases and manuscripts lost to ennui and despair.

Depression is a progressive illness: each bout renders the sufferer less resistant to the next, so that after two or three serious episodes, they come on without warning, as if out of the clear blue sky. If we had the tools in hand - a genetic implant, for instance - to head off the illness before it made its first brain-addling appearance, wouldn't we jump at the chance? What parent among us would wish on a child the brittle vulnerability of depression, the sleepless nights, the loss of appetite, the lack of joy in each day's possibilities? If we wouldn't wish it on our children, why wish it on ourselves?





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