Energy Metabolism Markers of Cognitive Function in Early Psychosis and Risk

项目摘要 背景：有证据表明，对精神障碍进行早期干预， 轨迹和残疾。由于认知缺陷和功能不良没有充分针对目前的 因此，迫切需要研究这些缺陷在早期精神病中的潜在机制。 和患精神病的风险此K23应用程序提出了一个职业发展计划， 严格的培训与创新的研究议程，旨在确定早期干预目标的认知 早期精神病的缺陷。候选人：我是哈佛医学院的精神病学讲师， 在姆克林的OnTrack项目中，我是一名专门照顾首发精神病患者的精神病学家 医院我毕业于马萨诸塞州总医院/姆克林精神病学住院医师， 完成了哈佛医学院的NIMH T32临床研究培训计划。我有一个临床 精神病首发和高危研究背景。这个K23奖将为我提供 在必要的支持下，成为以患者为导向的精神病研究专家， 发展独立的临床研究事业。研究：初步证据显示， 在患有首次发作精神病的个体和那些处于精神病高风险的个体中，代谢功能障碍。作为 人类的大脑是高度代谢活跃的，代谢异常可能在出现中起关键作用。 神经元功能障碍的症状这项研究将使用31 P磁共振技术。 磁共振波谱（MRS）、功能性磁共振成像（fMRI）和代谢测量来确定 生物能量和胰岛素异常对首发精神病患者认知功能影响 和他们未受影响的兄弟姐妹在一年的随访过程中。职业发展和未来计划 研究：我建议获得培训的领域：1）认知神经科学，包括功能磁共振成像; 2)大脑中的代谢信号传导;以及3）纵向数据分析的统计方法。这些目标将是 由一个非常合格的科学家团队完成正式的课程和指导， 与提案直接相关的国际公认的研究领导者。完成建议 研究和培训目标将使设计一个大规模的纵向R 01研究，旨在调节 能量代谢，以改善早期精神病的认知和功能，同时绘制偶然途径 使用多模式成像和代谢方法学。本K23提案将提供以下方面所需的培训 我作为一名独立调查员的发展重点是确定认知障碍的早期干预目标， 风险轨迹和早期精神病的缺陷。它将为一项研究计划提供基础 促进个性化临床干预的发展，以改变早期精神病的病程， 最终，预防疾病和降低风险。

PROJECT ABSTRACT Background: Evidence points to the importance of early intervention in psychotic disorders to alter illness trajectory and disability. As cognitive deficits and poor functioning are not adequately targeted with current treatment, there is an urgent need to investigate underlying mechanisms of these deficits in early psychosis and risk for psychosis. This K23 application proposes a career development program that incorporates rigorous training with an innovative research agenda aimed at identifying early intervention targets for cognitive deficits in early psychotic illness. Candidate: I am an Instructor in Psychiatry at Harvard Medical School and a psychiatrist specialized in the care of patients with first episode psychosis in the OnTrack Program at McLean Hospital. I am a graduate of the Massachusetts General Hospital/McLean Psychiatry Residency and completed the NIMH T32 Clinical Research Training Program at Harvard Medical School. I have a clinical research background in first episode psychosis and high risk for psychosis. This K23 award will provide me with the support necessary to become an expert in patient-oriented research in psychotic disorders and develop an independent clinical research career. Research: Preliminary evidence shows that energy metabolism is dysfunctional in individuals with first episode psychosis and those at high risk for psychosis. As the human brain is highly metabolically active, metabolic abnormalities may play a key role in the emergence of neuronal dysfunction in psychotic disorders. The proposed research will use 31P magnetic resonance spectroscopy (MRS), functional magnetic resonance imaging (fMRI) and metabolic measures to determine the impact of bioenergetic and insulin abnormalities on cognitive function in patients with first episode psychosis and their unaffected siblings over the course of one-year follow-up. Career development and future program of research: I am proposing to acquire training in the areas of: 1) Cognitive neuroscience, including fMRI; 2) Metabolic signaling in the brain; and 3) Statistical methods for longitudinal data analysis. These goals will be accomplished by formal coursework and mentorship by an exceptionally-qualified team of scientists who are internationally-recognized leaders in research directly relevant to the proposal. Completion of the proposed research and training aims will enable the design of a large-scale longitudinal R01 study aimed at modulating energy metabolism to improve cognition and functioning in early psychosis, while mapping casual pathways using multimodal imaging and metabolic methodology. This K23 proposal will provide the training needed for my development as an independent investigator focused on identifying early intervention targets for cognitive deficits across trajectories of risk and early psychosis. It will provide the foundation for a program of research facilitating the development of personalized clinical interventions to alter the course of early psychotic illness, and ultimately, illness prevention and risk reduction.