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：
10374780
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/10374780
关键词：
Address Affect Anatomy Angiography Animals Antipsychotic Agents Area Biological Markers Brain Caliber Cell physiology Cells Cellular biology Cerebrum Cessation of life Chronic Chronic Disease Chronic Schizophrenia Clinical Cognitive Collaborations Consensus Data Development Diagnostic Dimensions Dropout Ear Early Intervention Electroretinography Eye Functional Imaging Functional disorder Ganglion Cell Layer Goals Health Histologic Human Image Imaging Device Imaging technology Impaired cognition Infrastructure Injury Inner Plexiform Layer Israel Lateral Geniculate Body Lead Link Magnetic Resonance Imaging Measures Medical center Medicine Meta-Analysis Methods Morphology Nerve Degeneration Nerve Fibers Neuraxis 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 impairment Visual system structure Work base biological research brain magnetic resonance imaging brain volume cerebral atrophy clinically relevant comorbidity 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 therapy resistant tool treatment response 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.

项目摘要候选人要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告知我们对病理生理的理解早期精神分裂症（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在贝丝以色列执事医学上执行多学科项目中心。他的培训包括：1）视觉科学，2）EC的神经精神病学评估； 3）负责进行研究。影响精神分裂症患者> 60％的视觉感知异常具有可靠性与较差的核心临床结果相关。这些改变与永久结构（光学）一致相干断层扫描）和精神分裂症的功能（电子视网膜造影）变化。先前的研究已有没有试图了解视网膜结构之间的功能关系，视网膜到中央的过程神经系统病理，以及视网膜表型在EC中的作用。另外，这些更改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尚未在精神分裂症中探讨。该候选人的研究计划旨在：1）提案以成本捕获的EC的残留表型 - 使用新型的视网膜成像工具（例如电视图），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以表征尺寸整合和翻译心理病理学和中枢神经系统病理学的预测因素； 2）了解结构功能残留参数之间的关系，3）表明逆行反式突触变性是否是一个精神分裂症中发生的潜在病理生理机制。这项研究建议通过使用基于视网膜成像的表型方法来解决这一假设横截面，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，可以告知临床，认知和功能关系。该研究将在4年的EC中进行4年的横截面进行。这项研究的更广泛的目的是开发，评估和实施剩余成像技术推进诊断性疾病，生物标志物和精神病疗法的工具，重点是 ECS。通过眼睛对精神分裂症的病理生理学的理解可能允许发展视网膜生物标志物的疾病生物标志物可能为生物学研究提供更好的靶标，为发展提供信息针对精神病的个性化干预措施，并有助于支持精神分裂症的早期干预措施。