Transdiagnostic impairments in white matter integrity across the Psychosis Continuum: a systematic review and meta-analysis of diffusion studies

Psychotic and mood disorders, including schizophrenia and bipolar disorder, are increasingly viewed as part of a psychosis spectrum disorder (PSD) continuum, sharing genetic and neurobiological features. This systematic review and meta-analysis examined fractional anisotropy (FA) and mean diffusivity (MD) using diffusion tensor imaging in PSD. Across 96 studies (N = 4,424 PSD, N = 5,004 controls for FA; N = 1,607 PSD, N = 1,709 controls for MD), FA reductions were consistently observed in the corpus callosum, while MD increases were found in cortico-spinal projections. Controlling for age and sex strengthened these findings, suggesting they contribute to PSD pathophysiology rather than reflecting disease progression. Subgroup analyses revealed overlapping but distinct patterns in schizophrenia and bipolar disorder. These findings support a transdiagnostic model of psychosis, with corpus callosum abnormalities as a potential biomarker. Future longitudinal studies are needed to clarify causality and clinical implications.