Retinal Layer, Microvascular and Electroretinographic Determinants of Early Course Schizophrenia

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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.