SAN JUAN, P.R. — Growing evidence points to an association between inflammation and depression, according to a presentation at the annual meeting of the American College of Psychiatrists.
For example, depressed patients have elevated inflammatory markers—such as interleukin-6 and C-reactive protein. In fact, the levels of proinflammatory cytokines correlate with the severity of depressive symptoms in studies. In addition, administration of cytokine antagonists can effectively reverse depressive symptoms in patients, Dr. Andrew H. Miller said.
“We really stand at a point that is very exciting in terms of novel therapies and translation of research,” Dr. Miller said. “The notion quite simply is that stress or depression affects the HPA [hypothalamic-pituitary-adrenal] axis, [affects] the endocrine system, alters the immune system, and leaves patients open to diseases.”
Physicians from many specialties already recognize that inflammation plays a key role in cardiovascular disease, diabetes, metabolic syndrome, and cancer, said Dr. Miller, professor in the department of psychiatry and behavioral sciences at Emory University, Atlanta. “We did not want to be left out in terms of psychiatry,” said Dr. Miller, who also is director of the psychiatric oncology program at the Winship Cancer Institute at Emory.
There are multiple possible mechanisms whereby inflammation could cause depression. Inflammatory cytokines released peripherally might reach the brain through active transport, passage through leaky regions in the blood-brain barrier, or transmission through afferent nerve fibers (vagus nerve), Dr. Miller said. There is a cytokine network in the central nervous system, and glia and microglia are the richest source of cytokines in the brain. Neurons also produce and express cytokines.
“We've learned these cytokines have access to the brain and … ultimately can change behavior,” Dr. Miller said. Inflammatory cytokines cause anhedonia, fatigue, cognitive dysfunction, and other flu-like symptoms in sick patients. In addition, researchers induced behavioral changes that resemble major depression in human and animal studies with administration of proinflammatory cytokines.
Some therapeutic cytokines cause depression. A total of 60% of patients treated with IFN-α reported depressed mood in one study (Neuropsychopharmacology 2002;26:643–52). Dr. Miller and his associates found a 45% incidence of major depression in malignant melanoma patients treated with IFN-α (N. Engl. J. Med. 2001;344:961–6).