Research and Mentoring on Brain and Peripheral Bioenergetics in Schizophrenia

 描述（由申请人提供）：这是一个K24职业中期研究者在以患者为导向的研究奖的申请。我是一名精神病学家，在精神病方面具有临床专长，并具有神经生物学背景。我一直在进行非侵入性神经影像学研究，探索精神分裂症和双相情感障碍的细胞异常。我已经建立了一个年轻的研究人员小组，从事以病人为导向的研究，我是姆克林医院精神疾病科的主任。然而，我需要保护的时间来加强我的指导活动，并开发新的专业领域，以满足我的长期职业目标，即确定精神障碍的治疗目标，并培训该领域的下一代研究人员。 在这份建议书中，我概述了一个为我的研究小组招募和留住高素质的初级研究人员的指导计划。此外，我将获得线粒体功能，大脑生物能量学和外周葡萄糖代谢/糖尿病的额外培训。迄今为止，我的研究已经检查了多巴胺能和GABA能神经传递的异常。我将利用这次培训来扩展我的研究到31 P磁共振波谱，它提供了有关ATP合成和代谢的详细信息-与神经传递密切相关的过程。有多种迹象表明，脑代谢也与外周代谢有关。由于精神病患者也容易发生代谢综合征，我还将启动一系列关于肌肉代谢和胰岛素抵抗外周标志物的新研究。我预测，这些指标将与大脑指标相关，它们将为治疗精神分裂症提供潜在的新机会--这是一个巨大的未满足需求的领域。

 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.