Functional connectivity in distinct cognitive subtypes in psychosis.

Background: Cognitive dysfunction is common in psychotic disorders, and may reflect underlying pathophysiology. However, substantial cognitive heterogeneity exists both within and between diagnostic categories, creating challenges for studying the neurobiology of cognitive dysfunction in patients. The aim of this study was to identify patients with psychosis with intact versus impaired cognitive profiles, and to examine resting state functional connectivity between patient groups and compared to healthy controls to determine the extent to which patterns of connectivity are overlapping or distinct.

Methods: Participants with affective or non-affective psychosis (n=120) and healthy controls (n=31) were administered the MATRICS Consensus Cognitive Battery, clinical and community functioning assessments, and an fMRI scan to measure resting state functional connectivity (RSFC). Cognitive composite scores were used to identify groups of patients with and without cognitive dysfunction. RSFC was compared between groups of patients and healthy controls, controlling for demographic and clinical variables.

Results: Both cognitively intact and cognitively impaired patients showed decreased intrinsic connectivity compared to controls in frontoparietal control (FPN) and motor networks. Patients with cognitive impairment showed additional reductions in FPN connectivity compared to patients with intact cognition, particularly in subnetwork A.

Conclusions: We leveraged the heterogeneity in cognitive ability among patients with psychosis to disentangle the relative contributions of cognitive dysfunction and presence of an underlying psychotic illness using resting state functional connectivity. These findings suggest at least partially separable effects of presence of a psychotic disorder and neurocognitive impairment contributing to network dysconnectivity in psychosis.