Magazine article Psychology Today

Depression, Dissected

Magazine article Psychology Today

Depression, Dissected

Article excerpt

I DEPRESSION RESEARCH HAS become something of a downer. The first drug to ease the torments of those afflicted with the disorder hit the market more than half a century ago, and since then dozens more have emerged. All essentially operate on the same elements of brain biology- tne neurotransmitters serotonin, norepinephrine, and dopamine-and for many people, they work quite well. Yet none has altered the stubborn fact that one-third of patients don't get better no matter how many meds they try. With 16 million Americans estimated to have suffered a major depressive episode in the past year according to the National Institute of Mental Health, that adds up to a lot of unmitigated suffering-and a lot of psychiatrists frustrated by their inability to help.

Enter inflammation, which has been associated with depression since at least the 1990s, although the nature of the connection has been unclear and the research focus on it marginal. "It never had enough traction to grab the field's attention," says psychiatrist Andrew Miller of Emory University.

That may be changing. For five years, research on inflammation and depression has been accelerating, pulling it from the periphery into the spotlight, and the pace has increased markedly in just the past year. Although there's still no tidy illustration of how the two conditions are linked, there's a growing confidence that inflammation has a significant role in the depression equation. In a field that Miller describes as being at "a crisis point looking for new ideas and conceptual frameworks that might yield more effective treatments," emerging findings about inflammation have been received "like the Second Coming."

As a physiological process, inflammation might seem like an unlikely facet of what's commonly perceived as a disease of the mind. Inflammation evolved to defend the body against injury and infection-chemical compounds released by white blood cells usher blood to the scene, provoke swelling to immobilize injured tissue, and raise the temperature to kill invading microbes. The same chemicals induce the malaise of illness, forcing the injured or infected body to conserve energy for healing.

But the process can go very wrong, attacking the body's own tissues in autoimmune diseases such as rheumatoid arthritis, psoriasis, and ulcerative colitis. In recent years, research has connected chronic low-level inflammation with a growing list of unlikely ills, such as heart disease and diabetes, and brain disorders, including schizophrenia and Alzheimer's disease.

The evidence for a link to depression is particularly compelling. Patients with a medical illness where inflammation is prominent have long been observed to suffer high depression rates. Injecting healthy people with inflammatory messenger chemicals such as cytokines provokes depressive symptoms. And depressed individuals tend to have elevated blood levels of the proteins that signal chronic inflammation.

But beyond these intriguing correlations, basic questions remain unanswered: Is inflammation the horse or the cart, a cause or effect of depression? Or does it simply signify some more fundamental malfunction? "At the end of the day, you have to show that people get better when you block inflammation, and no definitive studies have done that," Miller says. Drug trials have been on the whole disappointing: A 2014 meta-analysis of 14 of them found some benefits in adding anti-inflammatories to antidepressants, but they were modest and uneven.

A big part of the problem, Miller says, has been a failure to appreciate that inflammation is likely only a piece of the depression story. "Hidden in the data are subgroups of patients who have increased inflammation-between a third and a half." Identifying these subgroups, he says, "is the cutting edge of where the field is right now."

In the past year, a number of studies have explored this territory, shedding light on underlying processes that might yield novel treatments. …

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