Examining Functional Resting-State Connectivity in Psychosis and Its Subgroups in the Bipolar-Schizophrenia Network on Intermediate Phenotypes Cohort

Abstract

BackgroundWe sought to examine resting-state functional magnetic resonance imaging connectivity measures in psychotic patients to both identify cumulative differences across psychosis and subsequently probe deficits across conventional DSM-IV diagnoses and a newly identified classification using cognitive/neurophysiological data (Biotypes). MethodsWe assessed 1125 subjects, including healthy control subjects, probands (schizophrenia, schizoaffective disorder, psychotic bipolar disorder), and relatives of probands. Probands and relatives were also segregated into Biotype groups (B1–B3, B1R–B3R using a method reported previously). Empirical resting-state functional magnetic resonance imaging networks were derived using independent component analysis. Global psychosis-related abnormalities were first identified. Subsequent post hoc t tests were performed across various diagnostic categories. Follow-up linear mixed model compared significance of within-proband differences across categories. Secondary analyses assessed correlations with biological profile scores. ResultsVoxelwise tests between proband and control subjects revealed nine abnormal networks. Post hoc analysis revealed lower connectivity in most networks for all proband subgroups (DSM and Biotypes). Within-proband effect sizes of discrimination were marginally better for Biotypes over DSM. Reduced connectivity was noted in relatives of patients with schizophrenia in two networks and relatives of patients with psychotic bipolar disorder in one network. Biotype relatives showed similar deficits in one network. Connectivity deficits across four networks were significantly associated with cognitive control profile scores. ConclusionsOverall, we found psychosis-related connectivity deficits in nine large-scale networks. Deficits in these networks tracked more closely with cognitive control factors, suggesting potential implications for disease profiling and therapeutic intervention. Biotypes performed marginally better in terms of separating out psychosis subgroups compared with conventional DSM or psychiatric diagnoses.