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: 10002036
• 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/10002036
• 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.

项目总结