Retinal Layer, Microvascular and Electroretinographic Determinants of Early Course Schizophrenia

早期精神分裂症的视网膜层、微血管和视网膜电图决定因素

基本信息

批准号：
10589934
负责人：
Paulo L Lizano
金额：
$ 19.2万
依托单位：
BETH ISRAEL DEACONESS MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10589934
关键词：
Address Affect Anatomy Angiography Animals Antipsychotic Agents Area Biological Markers Blood Vessels Brain Cell physiology Cells Cellular biology Central Nervous System Cerebrum Cessation of life Chronic Chronic Disease Chronic Schizophrenia Clinical Cognition Cognitive Collaborations Consensus Data Development Diagnostic Diameter Dimensions Dropout Ear Early Intervention Electroretinography Eye Functional Imaging Functional disorder Ganglion Cell Layer Goals Health Care Costs Histologic Human Imaging Device Imaging technology Impaired cognition Infrastructure Injury Inner Plexiform Layer Israel Lateral Geniculate Body Link Magnetic Resonance Imaging Measures Medical center Medicine Meta-Analysis Methods Morphology Nerve Degeneration Nerve Fibers Neurosciences Nuclear Occipital lobe Ophthalmology Optical Coherence Tomography Outcome Pathology Patients Perfusion Phenotype Photoreceptors Physiologic Intraocular Pressure Population Process Psychiatry Psychopathology Psychoses Psychotic Disorders Research Resolution Resources Retina Retinal Ganglion Cells Retrograde Degeneration Role Schizophrenia Selection for Treatments Structural defect Structure Structure-Activity Relationship Symptoms Synapses Technology Testing Thalamic structure Thick Thinness Time Tissues Training Training Programs Trans-Synaptic Degeneration Universities Visual Visual Cortex Visual Pathways Visual System Visual impairment Work biological research biomarker validation brain magnetic resonance imaging brain volume cerebral atrophy clinically relevant comorbidity comparison control cost effective disabling disease disease classification experience functional disability functional loss ganglion cell gray matter imaging approach imaging study in vivo indexing injured multidisciplinary multimodality neuroimaging neuropsychiatry novel outcome prediction outer plexiform layer personalized intervention psychotic symptoms responsible research conduct retinal imaging retinal nerve fiber layer structural imaging therapy resistant tool treatment response venule vision science visual processing

项目摘要

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.

项目概要候选人请求支持为期五年的培训和研究计划，以更好地了解视网膜功能、结构和脉管系统的指标如何帮助我们理解病理生理学早期精神分裂症（ECS）的机制。在拟议的培训计划中，候选人将基于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将在贝斯以色列女执事医疗中心开展一个多学科项目他的培训内容包括：1) 视觉科学，2) ECS 的神经精神评估，以及 3) 负责人进行研究。视觉感知异常影响超过 60% 的精神分裂症患者，已可靠地证实这些改变与更差的核心临床结果相关。先前的研究表明，精神分裂症的相干断层扫描（coherence tomography）和功能性（视网膜电图）变化。没有试图理解视网膜结构与功能的关系、视网膜到中枢的过程神经系统病理学以及视网膜表型在 ECS 中的作用此外，这些变化是否先于这些变化。并导致皮质变化，反之亦然，或者两者是否由于一般原因同时发生此前尚未在精神分裂症中探索过神经退行性过程。该候选人的研究计划旨在：1）提出在成本中捕获的 ECS 的视网膜表型使用新颖的视网膜成像工具（例如视网膜电图），以有效、实用和临床相关的方式，光学相干断层扫描和血管造影来表征维度集成和平移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，3）表明逆行性突触变性是否是一种精神分裂症发生的潜在病理生理机制。本研究建议利用基于视网膜成像的表型分析方法来解决这一假设横截面，主要通过结构和功能成像，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以为临床、认知和功能提供信息该研究将针对 ECS 对象进行为期 4 年的横断面研究。这项研究的更广泛目标是开发、评估和实施视网膜成像技术推进精神病学诊断、生物标志物和治疗的工具，重点是 ECS。通过眼睛了解精神分裂症的病理生理学可能有助于发展疾病的视网膜生物标志物可能为生物学研究提供更好的目标，为疾病的发展提供信息对精神疾病进行个性化干预，并帮助支持精神分裂症的早期干预。