Depression Is an Inflammatory Disease

A meta-analysis shows higher levels of two cytokines in depressed patients.

People who are chronically ill often get depressed; depressed people are prone to a variety of medical illnesses; and pro-inflammatory cytokines can alter mood and promote illness. To determine whether these proteins play a role in the overlap between depression and inflammation-associated medical disorders, researchers conducted a meta-analysis of 24 case–control studies of basal cytokine levels in a total of 438 unmedicated subjects with major depression and no comorbid illnesses and 350 medically and psychiatrically healthy controls.

Concentrations of tumor necrosis factor-alpha (TNF-) and interleukin (IL)-6 were significantly higher in depressed patients than in controls. The groups showed no significant differences in other interleukins (IL-1β, IL-4, IL-2, IL-8, or IL-10) or in interferon-gamma.

Comment: IL-6 stimulates differentiation and proliferation of immunoglobulin-secreting B-lymphocytes, and TNF- stimulates the release of other pro-inflammatory cytokines and inflammatory prostaglandins. In the brain, these substances inhibit hippocampal neurogenesis; activate the hypothalamic-pituitary-adrenal axis, thus increasing cortisol production; and indirectly increase production of agonists of the N-methyl-D-aspartate receptor, which promotes apoptosis. The central actions of these proteins reduce resiliency of the brain and contribute to the hyperactive stress response that is characteristic of depression, which is further aggravated by loss of hippocampal cells. And, the peripheral actions of these proteins can exacerbate inflammatory diseases, such as diabetes and coronary heart disease. By the same token, the effects of cytokines in the brain can induce depression in patients with these medical diseases. To the extent that inflammation is a component of depression and other systemic conditions, anti-inflammatory drugs might prove helpful (JW Psychiatry Feb 8 2006).

— Steven Dubovsky, MD

Published in Journal Watch Psychiatry March 29, 2010

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