Neuroimaging of the Biological Correlates of Early Psychosis: A MR-PET Study

早期精神病生物学相关性的神经影像学：MR-PET 研究

• 批准号: 9751969
• 负责人: AMANDA ELLIS LYALL
• 金额: $ 17.77万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9751969
• 关键词: Acute; Affect; Area; Astrocytes; Biological; Biological Factors; Biometry; Blood; Brain; Cerebrum; Clinical; Clinical Data; Clinical assessments; Cognitive; Collection; Cross-Sectional Studies; Data; Data Collection; Development; Diffusion; Diffusion Magnetic Resonance Imaging; Disease; Environment; Evolution; Exhibits; Future; Glutamates; Goals; Hybrids; Image; Immune; Immune response; Immune system; Inflammation; Inflammatory; Injury; Institution; Investigation; Link; Location; Longitudinal Studies; Measures; Mediating; Mental disorders; Mentors; Mentorship; Mitochondrial Proteins; Multimodal Imaging; Nature; Neuraxis; Neurobiology; Neurocognitive; Neuroglia; Onset of illness; Outcome; Patients; Performance; Peripheral; Physiological; Pilot Projects; Population; Positron-Emission Tomography; Price; Proteins; Psychology; Psychotic Disorders; Recovery; Reporting; Research; Research Design; Research Personnel; Role; Sampling; Schizophrenia; Severities; Structure; Symptoms; System; Testing; Thick; Time; Tissues; Training; Water; base; career; cognitive performance; cohort; cytokine; experience; extracellular; first episode psychosis; first episode schizophrenia; follow-up; gray matter; immune activation; immunoregulation; interdisciplinary approach; medical schools; metabotropic glutamate receptor 5; multimodality; neuroimaging; neuroinflammation; radioligand; receptor expression; resilience; response; white matter; white matter damage

Project Summary In the resubmission of this K01 application, we propose to conduct a hybrid cross-sectional and longitudinal multi-modal neuroimaging study aimed at understanding the biological nature and time course of an acute brain response previously observed in first-episode schizophrenia patients. The acute brain response, characterized by a global increase in extracellular free water in first-episode patients, has been previously linked to neuroinflammation. Recent evidence suggests that the acute brain response may be part of a compensatory immune-related action related to recovery or resiliency. In this proposal, we suggest and investigate the hypothesis that this compensatory response may be related to the increased expression of Group I subtype metabotropic glutamate receptor 5 (mGluR5), which have been shown to serve a beneficial immunomodulatory role in the central nervous system. The central scientific goal of this K01 proposal is to utilize a comprehensive data collection paradigm to 1) understand the biological nature and trajectory of the acute brain response in early psychosis by investigating its connection to mGluR5 and 2) investigate the hypothesis that these markers of cerebral immune activation in FEP are linked to resiliency. To achieve this goal, we will leverage the state-of-the-art, simultaneous collection of structural, diffusion, and positron emission tomography (PET) images utilizing the mGluR5 radioligand [18F] FPEB. With our hybrid, cross-sectional and longitudinal study design, we will collect multi-modal imaging, blood, neurocognitive, and clinical data from a cohort of first-episode patients and healthy matched controls. We hypothesize that patients with greater acute brain responses and mGluR5 expression will exhibit less structural damage and better clinical and cognitive performance after 6 months. This will be the first study to investigate the role of mGluR5 in early psychosis and the results of this pilot study will be valuable for gaining a greater understanding of the neurobiological components underlying resiliency after illness onset. To carry out the proposed scientific aims, I identified four principal areas of training and associated mentors/advisors: 1) PET image acquisition and analysis under the mentorship of Dr. Jacob Hooker (primary mentor) and advisors Drs. Julie Price and Ciprian Catana; 2) clinical and neurocognitive assessments under the mentorship of Dr. William Stone (co-mentor) and advisor Dr. Matcheri Keshavan; 3) biostatistics with advisor Dr. Mark Vangel; 4) professional development under the mentorship of Dr. Marek Kubicki (co-mentor). This project will take place at multiple institutions within Harvard Medical School, which, combined, create an ideal environment for the execution of the scientific aims and proposed training plan. Upon completion of this K01, I will have acquired the expertise to become an independent researcher and the preliminary data for a future R01.

项目摘要 在重新提交此K 01申请时，我们建议进行混合横截面和 纵向多模态神经影像学研究，旨在了解生物学性质和时间 急性脑反应的过程中观察到的首次发作的精神分裂症患者。急性 脑反应，其特征是在首次发病患者细胞外游离水的整体增加， 以前与神经炎症有关。最近的证据表明，急性脑反应可能是 与恢复或复原力有关的补偿性免疫相关的动作。在这份提案中，我们建议， 研究这种代偿反应可能与组蛋白表达增加有关的假设。 I亚型代谢型谷氨酸受体5（mGluR 5），其已被证明是有益的。 在中枢神经系统中的免疫调节作用。K 01提案的核心科学目标是 利用全面的数据收集范例，1）了解生物学性质和轨迹， 通过研究其与mGluR 5的联系，研究早期精神病的急性脑反应; 假设FEP中的这些脑免疫激活标志物与弹性有关。为了实现这一目标， 我们将利用最先进的技术，同时收集结构、扩散和正电子发射 使用mGluR 5放射性配体[18F] FPEB的断层扫描（PET）图像。通过我们的混合，横截面和 纵向研究设计，我们将收集多模态成像、血液、神经认知和临床数据 首次发病患者和健康匹配对照组。我们假设， 更大的急性脑反应和mGluR 5表达将表现出更少的结构损伤和更好的临床和 6个月后的认知表现。这将是第一个研究mGluR 5在早期糖尿病中的作用的研究。 精神病和这项试点研究的结果将是有价值的，以获得更好的理解， 发病后恢复力的神经生物学成分。 为了实现所提出的科学目标，我确定了四个主要的培训领域和相关的 导师/顾问：1）在Jacob Hooker博士的指导下进行PET图像采集和分析（主要 导师）和顾问博士朱莉价格和Ciprian Catana; 2）临床和神经认知评估下 William Stone博士（共同导师）和顾问Matcheri Keshavan博士的指导; 3）生物统计学， 4）在Marek Kubicki博士（共同导师）的指导下进行专业发展。 该项目将在哈佛医学院的多个机构进行，这些机构联合起来， 执行科学目标和拟议培训计划的理想环境。在完成此 K 01，我将获得专业知识，成为一个独立的研究人员和初步的数据， 未来的R 01