Grant: Operating Grant

Bipolar disorder is a serious psychiatric illness in which subjects experience severe recurrent episodes of mania and depression, and a high rate of psychosocial disability. Lithium and valproate are the most commonly used mood stabilizing drugs in treatment of bipolar disorder, and have been found to protect brain cells from damage. We recently found that these two drugs specifically inhibit oxidative damage to brain cells. We also found that lithium and valproate regulate the essential brain antioxidant glutathione and functionally related enzyme glutathione s-transferase. Both glutathione and glutathione s-transferase play important roles against oxidative damage to cells. We will further determine if lithium and valproate regulate glutathione and glutathione s-transferase in brain regions specifically related to mood using animal models for mania and depression. The results of these studies will further clarify the mechanism of action of mood stabilizing drugs and may lead to the identification of new treatments for bipolar disorder.