Research and Mentoring on Brain and Peripheral Bioenergetics in Schizophrenia

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 DESCRIPTION (provided by applicant): This is an application for a K24 Midcareer Investigator in Patient Oriented Research award. I am a psychiatrist with clinical expertise in psychotic disorders and background in neurobiology. I have been conducting noninvasive neuroimaging studies probing cellular abnormalities in schizophrenia and bipolar disorder. I have built a group of junior investigators engaged in patient oriented research and I am the Chief of the Psychotic Disorders Division at McLean Hospital. However, I have a need for protected time to enhance my mentoring activities and to develop new areas of expertise to meet my long-term career goals of identifying therapeutic targets in psychotic disorders and to train the next generation of investigators in this field. In this proposal, I outline a mentoring lan for recruiting and retaining high caliber junior investigators into my research group. In addition,I will obtain additional training in mitochondrial function, brain bioenergetics, and peripheral glucose metabolism/diabetes. My research to date has examined abnormalities in glutamatergic and GABAergic neurotransmission. I will use this training to expand my studies into 31P magnetic resonance spectroscopy which provides detailed information about ATP synthesis and metabolism - processes which are intricately linked with neurotransmission. There are multiple indications that brain metabolism is also related to peripheral metabolism. Since patients with psychotic disorders are also prone to the metabolic syndrome, I will also initiate a new series of studies on muscle metabolism and peripheral markers of insulin resistance. I predict that these measures will correlate with brain measures, and they will suggest potential new opportunities for treating schizophrenia - an area of great unmet need.