Association of core brain networks with antipsychotic therapeutic effects in first-episode schizophrenia

Elucidating neurobiological mechanisms underlying the heterogeneity of antipsychotic treatment will be of great value for precision medicine in schizophrenia, yet there has been limited progress. We combined static and dynamic functional connectivity (FC) analysis to examine the abnormal communications among core brain networks [default-mode network (DMN), central executive network (CEN), salience network (SN), primary network (PN), and subcortical network (SCN) in clinical subtypes of schizophrenia (responders and nonresponders to antipsychotic monotherapy). Resting-state functional magnetic resonance imaging data were collected from 79 first-episode schizophrenia and 90 healthy controls. All patients received antipsychotic monotherapy for up to 12 weeks and underwent a second scan. We found that significantly reduced static FC in CEN-DMN/SN and SN-SCN were observed in nonresponders after treatment, whereas almost no difference was observed in responders. The nonresponders showed significantly higher dynamic FC in PN-DMN/SN than responders at baseline. Further, the baseline FC in core brain networks were treated as moderators involved in symptom relief and distinguished response subtypes with high classification accuracy. Collectively, the current work highlights the potential of communications among five core brain networks in searching biomarkers of antipsychotic monotherapy response and neuroanatomical subtypes, advancing the understanding of antipsychotic treatment mechanisms in schizophrenia.