A systematic review and meta-analysis of transdiagnostic impairments in white matter integrity across the psychosis continuum

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 examines fractional anisotropy and mean diffusivity using diffusion tensor imaging in PSD. Across 96 studies (N = 4,424 PSD, N = 5,004 controls for fractional anisotropy; N = 1,607 PSD, N = 1,709 controls for mean diffusivity), fractional anisotropy reductions were consistently observed in the corpus callosum, whereas mean diffusivity increases were found in cortico-spinal projections. Controlling for age and gender strengthened these findings, suggesting that 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.