Differential trajectories of corticostriatal structural connectivity in individuals at clinical high risk for psychosis according to functional outcome

Dysconnectivity in the corticostriatal pathway, which is central to psychosis pathophysiology, is also known to be present in individuals at clinical high risk for psychosis (CHR-P). Considering that the corticostriatal pathway actively matures until adulthood and that neuroanatomical maturation is suggested to be related to functional outcomes in individuals at CHR-P, longitudinal studies on the corticostriatal structural pathway in individuals at CHR-P are warranted. To characterize the longitudinal trajectory of corticostriatal structural connectivity, diffusion-weighted images were collected from 23 individuals at CHR-P and 20 healthy controls (HCs) at baseline and at a 2-year follow-up visit. Probabilistic tractography was performed to segment the pathways between seven cortical regions and the striatum. The relative connectivity between each cortical region and associated striatal subregion was calculated. The CHR-P group was divided into subgroups according to the functional outcome of the modified Global Assessment of Functioning score at follow-up. A significant group‒time interaction between the left orbitofrontal cortex and its associated striatal subregion was found, with a negative slope in the CHR-P group and positive slope in the HC group. In the left orbitofrontal corticostriatal relative connectivity, the group‒time interaction between HCs and individuals at CHR-P with poor functional outcomes at follow-up was statistically significant, whereas that between HCs and individuals at CHR-P with good functional outcomes at follow-up was not. These findings indicate abnormal white matter maturation of the orbitofrontal corticostriatal pathway in individuals at CHR-P. Abnormal neuroanatomical maturation of the orbitofrontal corticostriatal pathway may reflect prognosis for functional outcomes in these individuals.