The candidate proposes new strategies to develop a research focused on improving treatment outcomes of geriatric mania and bipolar (BP) disorders. He and his colleagues will identify and test biologically meaningful predictors of response to mood stabilizer treatment. Findings are expected to improve the clinical management of geriatric mania, contribute to the understanding of treatment resistance, and open new avenues for innovative therapies for these highly disabling, yet understudied disorders. The candidate proposes to focus on the influence of neurocognitive impairments on treatment outcomes. He has obtained preliminary evidence that behavioral and neuroimaging indices of frontostriatal dysfunction are associated with poor outcomes in geriatric mania. He will use sophisticated assays of ventromedial-limbic as well as dorsolateral circuits to begin to define groups with differing functional and psychopathologic outcomes. The career enhancement plan will provide the candidate with additional background in cognitive neuroscience and in genetics that will be critical to conducting the multidisciplinary research program proposed. The training component is organized around two pilot studies and new collaborative relationships with experts in these areas. The award would also support extension of the candidate's leadership role in developing multicenter studies of geriatric mania and BP disorder; this development would enhance his own research and would provide a context for a broad range of investigation and training. The award will facilitate his contribution to new related initiatives in the Cornell IRC that pertain to this population. It will foster his mentoring of young investigators focusing on these patients. [unreadable] [unreadable]