Cognitive subtypes and brain network differences in antipsychotic-naïve first-episode psychosis

Cognitive functioning within psychosis is heterogeneous, and data-driven approaches may help evaluate this heterogeneity. Brain network connectivity within first-episode psychosis (FEP) may provide an additional tool for understanding cognitive heterogeneity. FEP participants and healthy controls (HC) completed the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), and premorbid intellectual functioning was estimated using The American National Adult Reading Test (AmNART). k-means clustering of RBANS domain scores identified cognitive subgroups within FEP. Resting-state functional connectivity (FC) of the default mode (DMN), dorsal attention (DAN), executive control (ECN), and salience networks (SN) was assessed at baseline (prior to antipsychotic treatment), 6-, and 16 weeks. Voxelwise linear mixed models evaluated group-by-time interactions within each network. Two cognitive subgroups were identified within FEP (impaired and intact). All subjects had average premorbid intellectual functioning. At baseline, the cognitively impaired FEP subgroup showed reduced functional connectivity relative to healthy controls across regions within the DAN and ECN, with no significant differences observed between FEP subgroups (P_FDR < .05). Over time, the impaired subgroup exhibited fluctuating FC in the DAN and ECN, while the intact subgroup showed FC changes only in the ECN (P_FDR < .05). HCs also showed minor changes in the DAN and ECN. Distinct FEP cognitive subgroups show differential changes in FC. Notably, the impaired subgroup's shift from average premorbid intellectual functioning to impaired cognition suggests potential cognitive deterioration in a subset of psychosis participants. These results underscore the importance of considering both cognitive and neural heterogeneity in FEP.