Transdiagnostic Relations Between Functional Brain Network Integrity And Cognition

Background: Cognitive impairment occurs across the psychosis spectrum; however, it is unknown whether these shared manifestations of cognitive dysfunction also reflect shared neurobiological mechanisms, or whether the source of impairment differs. The current study aims to determine whether the general cognitive deficit observed across psychotic disorders is similarly associated with functional integrity of two brain networks widely implicated in supporting many cognitive domains. Methods: 201 healthy controls, 143 schizophrenia, 103 schizoaffective, and 129 bipolar disorder with psychosis patients from the Bipolar-Schizophrenia Network on Intermediate Phenotypes (B-SNIP1) consortium were included in the analyses. All participants underwent cognitive testing and a resting-state fMRI scan. Network integrity was measured through estimations of global and local efficiency of the whole brain, cingulo-opercular network (CON), frontoparietal network (FPN), and auditory network (AUD). Group differences in network measures, relationships between cognition and network measures, and mediation models were tested. Results: Schizophrenia and psychotic bipolar patients showed significantly reduced CON global efficiency compared to healthy controls (Ps < .01). All psychotic disorders had significantly reduced CON local efficiency (P s < .03), but the clinical groups did not differ from one another. CON global efficiency was significantly associated with general cognitive ability across all groups (β = .109, P = .003), and significantly mediated the relationship between psychotic disorder status and general cognition (P < .05). Conclusion: These findings provide evidence for a role of reduced CON efficiency in the general cognitive deficits observed across the psychosis spectrum. They also support the hypothesis that a shared neurobiological mechanism underlies the dimension of cognitive impairment in psychotic disorders.