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.