The candidate is an Assistant Professor of Clinical Psychiatry at the Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine. He is proposing a career development plan designed to acquire additional clinical skills, and research skills in platelet membrane neurochemistry and neurochemical brain imaging with in vivo magnetic resonance spectroscopy (MRS). These skills will be used to investigate in vivo the intracellular phosphatidylinositol (PI) pathway, and examine the hypothesis of a dysfunction in this pathway in bipolar disorder patients. The PI pathway may be dysfunctional in bipolar disorder, and this may be an important mechanism underlying its pathophysiology, and the mechanisms of action of lithium and other treatments for this condition. Thirty unmedicated patients meeting criteria for bipolar type I according to DSM-IV (10 manic, 10 depressed, and 10 euthymic), and 20 lithium-treated euthymic bipolar patients will be studied. As a comparison group, 20 age, sex, and educational-matched healthy controls will be recruited. Patients will provide blood samples for determination of platelet membrane phosphoinositides, which will be done with two-dimensional thin-layer chromotography followed by scanning laser densitometry. They will also undergo a 1.5 T proton MRS brain scan, which will allow the quantitation of myoinositol in a voxel placed in the anterior cingulate. The career development plan will prepare the candidate for a full-time clinical research career devoted to the investigation of possible neurobiological mechanisms implicated in causation of bipolar disorder, and the mechanisms of action for the treatment of this condition. It is designed to allow the candidate's transition into an independent career in patient-oriented research in this field. These activities may result in substantial contributions to a better understanding of the pathophysiology of bipolar disorder, and ultimately contribute to the development of new treatments for this condition.