Energy Metabolism Markers of Cognitive Function in Early Psychosis and Risk

项目摘要 背景：有证据表明对精神病患者进行早期干预以改变病情的重要性。 轨迹和残疾。由于认知缺陷和功能不良不能充分针对当前的 治疗上，迫切需要研究这些缺陷在早期精神病中的潜在机制 精神错乱的风险。这份K23应用程序提出了一项职业发展计划，其中包括 严格的培训和创新的研究议程，旨在确定认知障碍的早期干预目标 早期精神病的缺陷。应聘者：我是哈佛医学院的精神病学讲师 McLean OnTrack项目中专门护理首发精神病患者的精神病学家 医院。我毕业于马萨诸塞州综合医院/麦克莱恩精神病学住院医生， 在哈佛医学院完成了NIMH T32临床研究培训计划。我有个诊所 首发精神病和精神病高危的研究背景。这个K23奖项将为我提供 有必要的支持，成为以患者为中心的精神障碍研究的专家 发展独立的临床研究事业。研究：初步证据显示，能源 在首发精神病和精神病高危人群中，新陈代谢紊乱。AS 人脑的新陈代谢高度活跃，代谢异常可能在这种情况下的出现起到关键作用 精神病患者的神经功能障碍。拟议中的研究将使用31P磁共振 波谱(MRS)、功能磁共振成像(FMRI)和代谢指标以确定 生物能量和胰岛素异常对首发精神病患者认知功能的影响 和他们未受影响的兄弟姐妹在一年的跟踪过程中。职业发展和未来计划 研究方向：我计划接受以下领域的培训：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；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课程和指导，他们是 与该提案直接相关的研究领域的国际公认的领导者。完成拟议的 研究和培训目标将使旨在调制的大规模纵向R01研究的设计成为可能 能量代谢改善早期精神病患者的认知和功能，同时绘制随意路径图 使用多模式成像和代谢方法学。这份K23提案将提供以下所需的培训 作为一名独立调查员，我的发展重点是确定认知障碍的早期干预目标 在风险和早期精神病的轨迹上存在缺陷。它将为一项研究计划提供基础 促进个性化临床干预措施的发展，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.