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State of the Art 9
Recent Advances in the Neurobiology of Mood Stabilizers
Prof. De-Maw Chuang
Intramural Research Program, National Institute of Mental Health, Bethesda
Lithium and valproic acid are mainstay drugs used in the treatment of bipolar disorder. At
present, neither the etiology of bipolar disorder nor the therapeutic mechanisms of mood stabilizers are
well understood. In this lecture, the potential targets for lithium and valproic acid to induce numerous
neurobiological and behavioral effects will be reviewed. Novel molecules that could contribute to
lithium responsiveness in treating bipolar patients will be discussed. Evidence based on preclinical
studies will be shown to support that lithium can potentiate the rapid antidepressant-like effects of
ketamine in a depression model of stressed animals. Preclinical results demonstrating that valproic acid
and lithium have robust neuroprotective effects and therapeutic potential for a vast number of CNS
disorders will also be presented. The roles of inhibition of histone deacetylases (HDACs) and glycogen
synthase kinase-3 (GSK-3) for valproic acid and lithium, respectively, in inducing these beneficial
effects will be discussed.
