Retinal Layer, Microvascular and Electroretinographic Determinants of Early Course Schizophrenia

项目摘要 候选人要求支持一个为期五年的培训和研究计划，以更好地了解 视网膜功能、结构和血管系统的指数如何告知我们对病理生理学的理解 早期精神分裂症（ECS）的发病机制。 在拟议的培训计划中，候选人将建立在他以前在细胞生物学方面的经验， 神经科学和临床精神病学在贝斯以色列女执事医疗执行多学科项目 中心他的培训包括：1）视觉科学，2）ECS的神经精神评估，以及3）负责任的 进行研究。 影响超过60%的精神分裂症患者的视觉感知异常， 与更差的核心临床结局相关。这些改变与视网膜结构（光学） 相干断层扫描）和功能（视网膜电图）的变化。先前的研究 没有试图了解视网膜结构与功能的关系，视网膜到中央的过程， 神经系统病理学和视网膜表型在ECS中的作用。此外，这些变化是否先于 并导致皮质变化，反之亦然，或者两者是否同时发生， 神经退行性过程以前没有在精神分裂症中探索过。 该候选人的研究计划旨在：1）提出在成本中捕获的ECS的视网膜表型- 有效、实用和临床相关的方式使用新的视网膜成像工具， 光学相干断层扫描和血管造影， 精神病理学和中枢神经系统病理学的预测因素; 2）了解结构-功能 视网膜参数之间的关系，以及3）表明逆行性跨突触变性是否是一种 精神分裂症的潜在病理生理机制。 这项研究提出了解决这一假设，利用视网膜成像为基础的表型方法 横截面，主要是通过结构和功能成像，以捕获视网膜细胞功能的数据， 视网膜细胞结构和视网膜微血管形态，可为临床、认知和功能提供信息 关系。本研究将在ECS受试者中进行4年的横断面研究。 这项研究的更广泛的目标是开发，评估和实施视网膜成像技术 用于推进诊断疾病分类学、生物标志物和精神病治疗的工具，重点是 ECS。通过眼睛了解精神分裂症的病理生理学可能会导致 视网膜疾病的生物标志物可能为生物学研究提供更好的目标， 个性化的精神病干预，并帮助支持精神分裂症的早期干预。

Project Summary The candidate requests support for a five-year program for training and research to better understand how indices of retinal function, structure, and vasculature can inform our understanding of pathophysiological mechanisms in early course schizophrenia (ECS). In the proposed training plan, the candidate will build upon his previous experiences in cell biology, neuroscience and clinical psychiatry to perform a multidisciplinary project at Beth Israel Deaconess Medical Center. His training includes: 1) vision science, 2) neuropsychiatric assessment of ECS, and 3) the responsible conduct of research. Visual perceptual abnormalities, which affect >60% of patients with schizophrenia, have reliably correlated with worse core clinical outcomes. These alterations are consistent with retinal structural (optical coherence tomography) and functional (electroretinography) changes in schizophrenia. Previous studies have not attempted to understand the retinal structure-to-function relationships, the course of retinal to central nervous system pathology, and the role of retinal phenotypes in ECS. Also, whether these changes precede and lead to cortical changes, or vice versa, or whether both occur at the same time due to a general neurodegenerative process has not been previously explored in schizophrenia. This candidate’s research plan seeks to: 1) propose retinal phenotypes of ECS captured in cost- effective, practical, and clinically relevant manner using novel retinal imaging tools such as electroretinography, optical coherence tomography and angiography to characterize dimensionally integrated and translational predictors of psychopathology and central nervous system pathology; 2) understand the structure-function relationships between retinal parameters, and 3) suggest whether retrograde trans-synaptic degeneration is a potential pathophysiologic mechanism occurring in schizophrenia. This study proposes to address this hypothesis by utilizing retinal imaging-based phenotyping methods cross-sectionally, primarily through structural and functional imaging, to capture data on retinal cell function, retinal cytoarchitecture and retinal microvascular morphology that can inform clinical, cognitive and functional relationships. The study will be performed cross-sectionally across 4 years in subject with ECS. The broader aim of this research is to develop, evaluate, and implement retinal imaging technology tools for advancing diagnostic nosology, biomarkers, and treatments for psychotic illnesses with a focus on ECS. An understanding of the pathophysiology of schizophrenia through the eye may allow the development of retinal biomarkers of illness that may offer better targets for biological research, inform development of personalized interventions for psychotic illnesses, and help support early interventions for schizophrenia.