Dissociable Default Mode Network Connectivity Patterns Underlie Distinct Symptoms in Psychosis Risk

The Clinical High Risk (CHR) stage of psychosis is characterized by subthreshold symptoms of schizophrenia including negative symptoms, dysphoric mood, and functional deterioration. Hyperconnectivity of the default-mode network (DMN) has been observed in early schizophrenia, but the extent to which hyperconnectivity is present in CHR, and the extent to which such hyperconnectivity may underlie transdiagnostic symptoms, is not clear. As part of the Shanghai At-Risk for Psychosis (SHARP) program, resting-state fMRI data were collected from 251 young adults (158 CHR and 93 controls, M = 18.72, SD = 4.68, 129 male). We examined functional connectivity of the DMN by performing a whole-brain seed-to-voxel analysis with the MPFC as the seed. Symptom severity across a number of dimensions, including negative symptoms, positive symptoms, and affective symptoms were assessed. Compared to controls, CHRs exhibited significantly greater functional connectivity (p < 0.001 uncorrected) between the MPFC and 1) other DMN nodes including the posterior cingulate cortex (PCC), and 2) auditory cortices (superior and middle temporal gyri, STG/MTG). Furthermore, these two patterns of hyperconnectivity were differentially associated with distinct symptom clusters. Within CHR, MPFC-PCC connectivity was significantly correlated with anxiety (r= 0.23, p=0.006), while MPFC-STG/MTG connectivity was significantly correlated with negative symptom severity (r=0.26, p=0.001). Secondary analyses using item-level symptom scores confirmed a similar dissociation. These results demonstrate that two dissociable patterns of DMN hyperconnectivity found in the CHR stage may underlie distinct dimensions of symptomatology.