Retinal biomarkers in schizophrenia spectrum disorders: evidence and implications for the neurodevelopmental and neurodegenerative models

Retinal morphological and functional alterations, such as changes in the thickness and volume of the retinal neural layers, architecture of the microvasculature, and functioning of neurons, have been observed in schizophrenia and have been interpreted in terms of neurodegenerative aspects of the disorder. However, little consideration has been given to the issue of whether, and the extent to which, these retinal differences may reflect neurodevelopmental features of schizophrenia. There are also no current conceptualizations that integrate retinal alteration findings in schizophrenia across different stages of illness, thereby helping to integrate neurodevelopmental and neurodegenerative perspectives on pathophysiology. Therefore, the present review aims to organize evidence of retinal abnormalities in schizophrenia in terms of findings from clinical high-risk for psychosis (CHR), genetic risk, first-episode psychosis (FEP), and chronic schizophrenia samples, and to consider factors such as age and duration of illness. Our goal is to move toward a lifespan model that integrates and transcends prior neurodevelopmental and neurodegenerative viewpoints. Toward this end, we also review studies of retinal alterations among those with prenatal/perinatal insults, neurodevelopmental disorders, and neurological soft signs, as such data can inform what has been observed in schizophrenia. We also mention, where appropriate, relevant findings from neurodegenerative disorders. A better understanding of the trajectories of central nervous system differences throughout the lifespan in people with schizophrenia, as observed in the retina (often called "a window to the brain"), can aid in understanding brain dysfunction in the disorder, assist with characterizing heterogeneity in clinical course, and inform more targeted prevention, monitoring, and intervention efforts.