Higher-Order Intrinsic Brain Network Trajectories After Antipsychotic Treatment in Medication-Naïve Patients With First-Episode Psychosis

Background Intrinsic brain network connectivity is already altered in first-episode psychosis (FEP), but the longitudinal trajectories of network connectivity especially in response to antipsychotic treatment remain poorly understood. The goal of this study was to investigate how antipsychotic medications affect higher-order intrinsic brain network connectivity in FEP. Methods Data from 87 antipsychotic medication-naïve FEP subjects and 87 healthy controls (HC) were used. Medication-naïve patients received antipsychotic treatment for sixteen weeks. Resting state functional connectivity (FC) of the default mode (DMN), salience (SN), dorsal attention (DAN), and executive control network (ECN) was assessed prior to treatment, six, and sixteen weeks after treatment. We evaluated baseline and FC changes using linear mixed models to test group by time interactions within each network. Associations between FC changes after sixteen weeks and response to treatment were also evaluated. Results Prior to treatment significant group differences in all networks were found. However, significant trajectory changes in FC were only found in DMN and ECN. Changes in FC in these networks were associated with treatment response. Several sensitivity analyses showed a consistent normalization of ECN FC in response to antipsychotic treatment. Conclusions Here, we found that alterations in intrinsic brain network FC not only were alleviated with antipsychotic treatment, the extent of this normalization was also associated with the degree of reduction in symptom severity. Together, our data suggests modulation of intrinsic brain network connectivity (mainly fronto-parietal connectivity) as a mechanism underlying antipsychotic treatment response in FEP.