Research and Mentoring on Brain and Peripheral Bioenergetics in Schizophrenia

 描述(由申请者提供)：这是一份K24职业中期调查员患者导向研究奖的申请书。我是一名精神病学家，具有精神病方面的临床专业知识和神经生物学背景。我一直在进行非侵入性神经成像研究，探索精神分裂症和双相情感障碍的细胞异常。我已经建立了一支从事以患者为导向的研究的初级调查小组，我是麦克莱恩医院精神障碍科的主任。然而，我需要有保护的时间来加强我的指导活动，并发展新的专业知识领域，以实现我的长期职业目标，即确定精神障碍的治疗目标，并培训这一领域的下一代调查人员。在这项建议中，我概述了一个指导区域网络，用于招募和留住高素质的初级调查人员加入我的研究小组。此外，我还将接受线粒体功能、脑生物能量学和外周葡萄糖代谢/糖尿病方面的额外培训。到目前为止，我的研究检查了谷氨酸和GABA能神经传递的异常。我将利用这次培训将我的研究扩展到31P磁共振波谱，它提供了关于ATP合成和新陈代谢的详细信息--这些过程与神经传递有着错综复杂的联系。有多种迹象表明，大脑新陈代谢也与外周新陈代谢有关。由于精神病患者也容易患代谢综合征，我还将启动一系列关于肌肉代谢和胰岛素抵抗外周标记物的研究。我预测，这些措施将与大脑测量相关，它们将为治疗精神分裂症提供潜在的新机会--这是一个巨大的未得到满足的需求领域。

 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.