From The Quarterly, Spring 2015

When people with bipolar disorder experience depressive episodes, the reward circuits in their brains show impairments similar to those that affect people diagnosed with major depressive disorder (MDD), scientists reported March 13th in the journal Neuropsychopharmacology. When these circuits are weakened, people's ability to experience pleasure diminishes.

Most clinical studies exploring how depression affects the brain have focused on people with MDD. Because patients with the two disorders may respond differently to antidepressant medications, it’s important to understand the neurobiology of both groups in order to develop effective treatments.

In patients with bipolar disorder and major depressive disorder, connections between different reward processing regions of the brain were weaker than they were in people without depression. This weakening was greater in patients with more severe depression in both groups.

The scientists did find differences between the two groups of depressed patients. Winning money activated a reward center––the ventral striatum––more strongly in patients with bipolar disorder than it did in those with major depressive disorder. And the strength of certain circuit connections was stronger in patients with bipolar disorder than it was in patients with major depressive disorder. These differences might reflect the two groups' different risks for manic episodes, during which reward responses appear to be heightened rather than dampened, the scientists say.

Why is it so important to distinguish among brain responses to reward? First, symptoms of depression–– which may be more linked to reward-system dysfunction such as loss of pleasure––tend to be less responsive to standard treatments. “Attenuated reward system response may therefore evolve to be a useful biomarker in drug discovery and clinical trials for mood disorders,” Dr. Satterthwaite says. Second, because many people with bipolar disorder first seek clinical help during depressive episodes, identifying differences between bipolar disorder and major depressive disorder could help ensure patients are accurately diagnosed from the start and receive treatment specifically designed to relieve their symptoms.

*Additional Foundation-funded team members: Claudia F. Baldassano, M.D., 2003 Young Investigator (YI) Yvette I. Sheline, M.D., 1998 YI, 2002 and 2005 Independent Investigator; Scientific Council (SC) Member Ruben C. Gur, Ph.D., 2007 Distinguished Investigator (DI) Raquel E. Gur, M.D., 1999 DI Ellen Leibenluft, M.D., SC Member