Sick and Down: To Fight off an Infection or Illness, the Body Shifts into a Slow-Down Mode That Mirrors Some Symptoms of Depression. in Fact, Scientists Now Think the Immune Response Itself May Even Cause the Mood Disorder

Article excerpt

When one of psychiatrist Andrew Miller's patients asked about receiving the best drug available for treating hepatitis C, Miller said: "No way." The patient--in his early 20s and accompanied by his morn to the appointment--had no job, few friends and a history of depression. While Miller knows that hepatitis C patients often benefit from the new generation of immune-boosting treatments, he's keenly aware that those same immune therapies have a strong tendency to bring people down-and, in people predisposed to depression, dangerously down.

Certain immune proteins in the body appear to mess with the minds of otherwise healthy, but depressed people as well. Those who suffer from major depression have higher levels of cytokines, immune proteins the body makes to fend off infections and to patrol the body for disease, and which laboratories mimic. Excess cytokines have also been found lurking in the postmortem brains of suicide victims. "It raises the issue, how much of how we feel--how much of who we are as people--is dictated in terms of our immune system?" says Miller, a researcher at Emory University in Atlanta.

Though the connection between the body's immune response and depression has only gained firm support in the last five years, it's already catalyzing a revolution in antidepressant drug development. In hindsight, an emotional reaction to surging immune molecules does not seem so surprising. Cytokines are among the first immune proteins to respond to infection. Some direct swelling and fevers. Others order the body to rest, and so the sick take to the bed and decline party invitations, showers and even homemade dinners. The powerful molecules influence wants and needs by altering levels of substances like serotonin in the brain. Essentially, cytokines command the body to conserve energy when it's sick. "A little depressed behavior is a survival mechanism in that sense," Miller says. But when inflammation is artificially or erroneously triggered, prolonged sickness behavior may morph into depression and do more harm than good.

Figuring out the biology behind depression should help doctors combat the disorder, which strikes an estimated 14.8 million American adults each year, according to the National Institute of Mental Health. More than one in six individuals will experience major depression in their lifetime. And when depression coincides with chronic diseases like multiple sclerosis, cancer or diabetes, patients' conditions are less likely to improve.

Psychiatrists and pharmaceutical companies have noted the downpour of evidence linking inflammation to depression. Miller says he and his colleagues have considered creating a new diagnostic category: Major Depressive Disorder with Increased Inflammation. To combat this depression, he says, researchers must find a way to alter the body's immune response. It is a risky strategy but one that offers hope to the nearly 30 percent of all depressed patients who don't respond to the antidepressants currently on the market.

Jekyll-and-Hyde changes

Cytokines emerged as the primary suspects for what's since become known as inflammation-induced depression after Miller and others noticed that cancer patients became inexplicably upset during treatment with synthetic type 1 interferons, cytokines that block viral replication in infected cells. One of these, interferon-alpha, is among the most effective drugs for patients battling cancer and the hepatitis C virus. Yet the treatment has become notorious for causing major depression and other behavioral changes in more than half of these patients, depending on the dose of the immune booster.

Miller describes a "Jekyll-and-Hyde-type change" in one of his patients after interferon therapy. Eight weeks into it, the patient dumped his girlfriend, began dressing in black and grew a goatee. And there was another woman, Miller recalls, who took a drastic downward turn. "One of my most positive patients had been battling cancer for years, yet four weeks into the cytokine therapy she was distraught," he says. …