Looking For Clues in Reward Circuits of Bipolar and Depressed Patients

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.

A team* of scientists at the University of Pennsylvania and the National Institute of Mental Health, led by 2010 NARSAD Young Investigator grantee Theodore Satterthwaite, M.D., andDaniel H. Wolf, M.D., Ph.D., a 2005 Young Investigator Grantee, used functional magnetic resonance imaging (fMRI) to compare how the brain’s reward circuits work in depressed patients with the two disorders. Their analysis included 23 people with bipolar depression, 22 with major depressive disorder, and 32 healthy controls.
The researchers first examined reward circuits while study participants played a card game in which they earned money by correctly guessing whether cards were red or black. Money was lost for incorrect guesses. In healthy participants, winning money activated the reward-processing parts of their brains more strongly than losing money. These responses were less robust for depressed patients. The more severe a patient’s depression, regardless of their clinical diagnosis, the less their reward system responded. The team also examined reward circuits in their resting state, when study participants were not performing any activity expected to activate those parts of the brain.

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.

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