Depressed Patients Experience Excessive Inflammation During Stressful Situations

Results of the study, led by Andrew Miller, MD, and Christine Heim, PhD, of Emory's Department of Psychiatry and Behavioral Sciences, are published in the Sept. 1 issue of the American Journal of Psychiatry.

"Several examples of increased resting inflammation in depressed patients already exist in the literature, but this is the first time anyone has shown evidence to suggest that the inflammatory response to stress may be greater in depressed people," says Dr. Miller.

The study included 28 medically healthy male participants, half of whom were diagnosed with major depression and half of whom were not depressed. The participants were exposed to two moderately stressful situations during a 20-minute time period. Blood was collected every 15 minutes starting immediately before and then up to an hour and a half after the test to check for key indicators of inflammation. The researchers measured levels of a pro-inflammatory cytokine (a regulatory protein secreted by the immune system) called interleukin-6, and the activity of a pro-inflammatory signaling molecule in white blood cells called nuclear factor-kB.

While at rest (before the stress challenge), the depressed patients had increased inflammation relative to the control group. Both the depressed and the healthy groups showed an inflammatory response to the stress challenge, but people who were currently depressed exhibited the greatest increases of interleukin-6 and nuclear factor-kB.

"While inflammation is essential for us to fight bacterial and viral infections, too much inflammation can cause harm," says Dr. Miller. "There's always some collateral damage when the immune system gets fired up, and we now believe that too much inflammation, either at rest or during stress, may predispose people to become depressed or stay depressed." In addition, medical research over the last decade has shown that runaway inflammation may play a role in a number of disorders, including heart disease, cancer, and diabetes, all of which have been associated with depression.

People in the study who suffered from depression also had higher rates of early life stressful experiences. "We have found that this kind of personal life history may make people more likely to develop major depression and is actually common in depressed patients," says Dr. Heim.

It was part of a larger project at the Emory Conte Center for the Neuroscience of Mental Disorders led by Charles B. Nemeroff, MD, PhD, Reunette W. Harris Professor and Chair of Emory's Department of Psychiatry and Behavioral Sciences. The Conte Center is dedicated to understanding the contribution of early life abuse and neglect to the neurobiology of adulthood psychiatric disorders. Ongoing studies by Dr. Miller's team of researchers will attempt to determine how early life experiences contribute to excessive inflammatory stress responses.

"According to the Depression and Bipolar Support Alliance, major depression is the leading cause of disability worldwide and costs the U.S. economy $70 billion annually in medical expenditures, lost productivity, and other expenses," says Thaddeus Pace, PhD, lead author on the paper. "This study is leading us toward finding out what actually causes depression and to identifying what aspects of immune system function are abnormal in depressed people. The goal is to find potential targets within the molecular machinery of the immune system so we can better treat major depression and minimize its consequences on health."

The study was funded by the National Institute of Mental Health (NIMH) and the National Alliance for Research on Schizophrenia and Depression (NARSAD).

Other contributors to the study include Oyetunde Alagbe, MD, Tanja C. Mletzko, MS, and Dominique Musselman, MD, MS.