Alterations in white matter microstructure and cortical thickness in individuals at ultra-high risk of psychosis: A multimodal tractography and surface-based morphometry study.

There is increasing evidence of white matter (WM) and grey matter pathology in subjects at ultra-high risk of psychosis (UHR), although a limited number of diffusion-weighted magnetic resonance imaging (DW-MRI) and surface-based morphometry (SBM) studies have revealed anatomically inconsistent results. The present multimodal study applies tractography and SBM to analyze WM microstructure, whole-brain cortical anatomy, and potential interconnections between WM and grey matter abnormalities in UHR subjects. Thirty young male UHR patients and 30 healthy controls underwent DW-MRI and T1-weighted MRI. Fractional anisotropy; mean, radial, and axial diffusivity in 18 WM tracts; and vertex-based cortical thickness, area, and volume were analyzed. We found increased radial diffusivity in the left anterior thalamic radiation and reduced bilateral thickness across the frontal, temporal, and parietal cortices. No correlations between WM and grey matter abnormalities were identified. These results provide further evidence that WM microstructure abnormalities and cortical anatomical changes occur in the UHR state. Disruption of structural connectivity in the prefrontal-subcortical circuitry, likely caused by myelin pathology, and cortical thickness reduction affecting the networks presumably involved in processing and coordination of external and internal information streams may underlie the widespread deficits in neurocognitive and social functioning that are consistently reported in UHR subjects.