Energy Metabolism Markers of Cognitive Function in Early Psychosis and Risk

早期精神病和风险中认知功能的能量代谢标志物

• 批准号: 10015351
• 负责人: Virginie-Anne Chouinard
• 金额: $ 19.31万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-10 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10015351
• 关键词: Adenosine Triphosphate; Antipsychotic Agents; Area; Bioenergetics; Biological Markers; Brain; Cells; Clinical; Clinical Research; Cognition; Cognitive; Cognitive deficits; Creatine Kinase; Critical Illness; Data; Data Analyses; Development; Early Intervention; Energy Metabolism; Foundations; Functional Magnetic Resonance Imaging; Future; General Hospitals; General Population; Goals; Heritability; Hospitals; Human; Impaired cognition; Impairment; Individual; Insulin; Insulin Resistance; International; Intervention; Knowledge; Life Expectancy; Link; Longitudinal Studies; Magnetic Resonance Spectroscopy; Massachusetts; Measures; Mediator of activation protein; Memory impairment; Mentored Patient-Oriented Research Career Development Award; Mentorship; Metabolic; Metabolic Pathway; Metabolic dysfunction; Metabolism; Methodology; Multimodal Imaging; National Institute of Mental Health; Neuronal Dysfunction; Neurons; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Pathway interactions; Patient Care; Patients; Performance; Pharmaceutical Preparations; Phosphocreatine; Play; Population; Prefrontal Cortex; Prevention; Program Development; Psychiatrist; Psychiatry; Psychotic Disorders; Quality of life; Research; Research Personnel; Research Training; Residencies; Resources; Risk; Risk Reduction; Role; Schizophrenia; Scientist; Short-Term Memory; Siblings; Signal Transduction; Statistical Methods; Time; Training; Training Programs; career; career development; cognitive function; cognitive load; cognitive neuroscience; cognitive process; design; disability; experience; first episode psychosis; follow-up; functional outcomes; high risk; improved; innovation; instructor; insulin sensitivity; insulin signaling; medical schools; mitochondrial dysfunction; neuronal growth; neurotransmission; nutrition; patient oriented research; programs; reaction rate; recruit; severe psychiatric disorder

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.

项目摘要 背景：证据表明早期干预精神障碍对于改变疾病的重要性 轨迹和残疾。由于当前的认知缺陷和功能不良没有充分针对 治疗中，迫切需要研究早期精神病中这些缺陷的潜在机制 和精神病的风险。这个 K23 申请提出了一个职业发展计划，其中包括 严格的培训和创新的研究议程旨在确定认知的早期干预目标 早期精神病的缺陷。候选人：我是哈佛医学院精神病学讲师 麦克莱恩 OnTrack 项目中专门治疗首发精神病患者的精神科医生 医院。我是马萨诸塞州总医院/麦克莱恩精神病学住院医师实习的毕业生， 在哈佛医学院完成了 NIMH T32 临床研究培训计划。我有一个临床 首发精神病和精神病高风险的研究背景。这个K23奖将为我提供 获得成为以患者为中心的精神障碍研究专家所需的支持， 发展独立的临床研究生涯。研究：初步证据表明，能量 首发精神病患者和精神病高危人群的新陈代谢功能失调。作为 人类大脑代谢高度活跃，代谢异常可能在其出现中发挥关键作用 精神障碍中的神经元功能障碍。拟议的研究将使用 31P 磁共振 光谱学 (MRS)、功能磁共振成像 (fMRI) 和代谢测量来确定 生物能和胰岛素异常对首发精神病患者认知功能的影响 以及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 研究方向：我建议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 通过正式的课程作业和由非常合格的科学家团队的指导来完成 与提案直接相关的国际公认的研究领导者。完成拟议的 研究和培训目标将能够设计一项大规模纵向 R01 研究，旨在调节 能量代谢以改善早期精神病的认知和功能，同时绘制休闲路径 使用多模态成像和代谢方法。该 K23 提案将提供所需的培训 作为一名独立研究者，我的发展重点是确定认知的早期干预目标 风险和早期精神病轨迹上的缺陷。它将为研究计划提供基础 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， 最终是预防疾病和降低风险。