Depression: The Power of Mood

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Another mechanism may also be at work. It turns out that the heartbeat of a person with depression is unusually steady. That's not necessarily a good thing, says Charney, who co-chaired the DBSA conference. "Ideally, your heart rate should be variable--it means your heart can respond appropriately to the different tasks it's called upon to respond to." Yet another possible link between heart disease and depression is a chemical called C-reactive protein (CRP). The liver normally produces CRP in response to an immune-system alarm when the body is infected or injured, and CRP is associated with the inflammation that results. For reasons still unknown, though, a recent study of depressed individuals found elevated levels of CRP. And in patients whose arteries have been damaged by the buildup of cholesterol plaques, heightened inflammation may increase the chance that a bit of plaque will break off and shut down an artery.

Diabetes is another illness that doesn't go well with depression. It's well known that 10% of diabetic men and 20% of diabetic women also have depression--about twice the rate in the general population. It's natural to be depressed about having a chronic, potentially fatal illness, but that doesn't entirely explain the discrepancy. Moreover, depressed diabetics are much more likely than those without depression to suffer complications including heart disease, nerve damage and blindness. Somehow depression makes the body less responsive to insulin, the hormone that processes blood sugar--plausibly through the action of cortisol, a hormone that can interfere with insulin sensitivity and that is often elevated in depressed patients.

Cortisol may also make depressed patients more prone to osteoporosis. Studies by Dr. Philip Gold and Dr. Giovanni Cizza at the NIMH have shown that premenopausal women who are depressed have a much higher rate of bone loss than their nondepressed counterparts--and this disparity increases as women pass through menopause. Indeed, Cizza estimates that some 350,000 women get osteoporosis each year because of depression. Cortisol appears to interfere with the ability of the bones to absorb calcium and offset the natural calcium loss that comes with menopause and aging. Another class of chemicals, the pro-inflammatory cytokines, have also been implicated in osteoporosis and diabetes, but their role is less clear.

Studies have established links between the incidence of depression and several other diseases, including cancer, Parkinson's disease, epilepsy, stroke and Alzheimer's. In some cases at least, researchers have clues, if not definitive evidence, as to which molecules might be involved. In Parkinson's, the problem is the death of cells in the brain that produce the neurotransmitter dopamine. While dopamine is crucial to the control of movement, it's probably a major factor in mood as well. "Depression almost certainly has multiple causes that produce similar symptoms," observes Dr. Bruce Cohen, president of McLean Hospital in Belmont, Mass.