A narrative literature review of white matter microstructure in individuals at clinical high risk for psychosis

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Abstract Schizophrenia is a severe psychiatric disorder characterized by widespread white matter (WM) alterations, manifesting as neurodevelopmental deficits and dysconnectivity abnormalities. Over the past two decades, studies have focused on the clinical high-risk (CHR) stage of psychosis and have yielded fruitful information on WM abnormalities that exist prior to the full onset of psychosis, shedding light on biological mechanisms underlying psychosis development. This review presents a summary of current findings on cross-sectional and longitudinal WM alterations in individuals with CHR and their links to clinical symptoms and neurocognitive dysfunction. Next, we review the utilization of WM characterization in predicting clinical outcomes. Taken together, the literature suggests the clinical significance of WM characteristics and their great potential in predicting the conversion to psychosis, despite some methodological and conceptual challenges that remain to be addressed in future studies. Future CHR research would greatly benefit from utilizing WM to guide pharmacological and non-pharmacological targeted treatments, optimize clinical prediction models, and enable more accurate clinical care.