Connectome-Wide Network Analysis of Youth with Psychosis Spectrum Symptoms

Adults with psychotic disorders have dysconnectivity in critical brain networks including the default mode (DM) and the cingulo-opercular (CO) networks. However, it is unknown whether such deficits are present in youths with less severe symptoms. We conducted a multivariate connectome-wide association study (CWAS) examining dysconnectivity with resting state functional MRI in a population-based cohort of 188 youths ages 8–22 with psychosis-spectrum (PS) symptoms and 204 typically developing (TD) comparators. We found evidence for multi-focal dysconnectivity in PS youths, implicating the bilateral anterior cingulate, frontal pole, medial temporal lobe, opercular cortex, and right orbitofrontal cortex. Follow-up seed-based and network-level analyses demonstrated that these results were driven by hyper-connectivity among DM regions and diminished connectivity among CO regions, as well as diminished coupling between frontal regions and DM regions. Collectively, these results provide novel evidence for functional dysconnectivity in PS youths, which show marked correspondence to abnormalities reported in adults with established psychotic disorders.