News Release

UPMC Researcher Discovers Brain Abnormality That May Lead To Greater Understanding Of Depression

Peer-Reviewed Publication

University of Pittsburgh Medical Center

PITTSBURGH, April 23 -- Newly discovered abnormalities in an area of the brain that helps control reactions to emotional experiences may lead to a new understanding of why people develop depression and other mood disorders, says a researcher at the University of Pittsburgh Medical Center (UPMC) in today's scientific journal Nature. The study, which found depressed patients had substantial brain tissue loss, may provide an important starting point for further research into some of the most common mental illnesses.

Mood disorders affect nearly 20 million people in the United States. These findings not only give researchers new insights into the causes of mood disorders, but also may provide information they can use to more effectively treat them.

Using positron emission tomographic (PET) images of blood flow and glucose metabolism rates to measure brain activity, Wayne C. Drevets, M.D., associate professor of psychiatry and radiology at UPMC, and his colleagues at Washington University and the University of Iowa, found that an area in the prefrontal cortex (the forehead area of the brain) in individuals with bipolar or unipolar depression had abnormally decreased activity. Previous studies have linked this area of the brain, called the subgenual prefrontal cortex, with emotional processing. It also has extensive connections to other areas of the brain responsible for controlling the neurotransmitters dopamine, norepinephrine and serotonin, which are thought to be important in regulating mood. A total of 49 patients with mood disorders were involved in the study.

Further measurements using magnetic resonance imaging (MRI) indicated that this decreased activity was due in part to a corresponding reduction in brain tissue volume in the same area, reported the team.

"We learned that there was a significant decrease in brain tissue in depressed people. The mean reduction in gray matter was 39 percent in people with bipolar and 48 percent in people with unipolar depression," said principal investigator Dr. Drevets. "This area plays an important role in modulating emotional responses and has strong ties to the neurotransmitter systems that regulate mood," Dr. Drevets said. "It may act as a set of brakes for emotional responses, helping us maintain appropriate emotional tones. When that brain tissue does not function properly, it may be analogous to having lost the emotional brakes, such that abnormal swings in mood occur. Antidepressant medications may work by compensating for that loss."

It isn't completely clear whether the reductions in blood flow and metabolism, and the corresponding decrease in brain tissue, are caused by a problem in brain development or an effect of recurrent illness, said Dr. Drevets. "What is most important is that we now have one more piece of information we can use to help us understand how present treatments work and to guide us in developing future, more effective treatments."

Other researchers involved in the study were Joseph L. Price, Ph.D., Joseph R. Simpson Jr., Richard D. Todd, Ph.D., M.D., Theodore Reich, M.D. and Marcus E. Raichle, M.D., all of Washington University, and Michael Vannier, M.D., of the University of Iowa.

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