Cerebellar-Cortical Connectivity and Prediction of Antipsychotic Treatment Response in First-Episode Psychosis

Abstract Background The cerebellum has traditionally been associated with motor functions, but recent evidence highlights its critical role in cognitive and emotional regulation, contributing to the neuropathology of schizophrenia. Our previous data-driven research demonstrated that cerebellar-cortical functional connectivity can predict antipsychotic treatment outcomes in first-episode psychosis (FEP). The present study aimed to investigate specific cerebellar functional systems involved in treatment prediction. Study Design This study included 127 patients with FEP who underwent 12 weeks of antipsychotic monotherapy (either risperidone or aripiprazole). Baseline resting-state functional MRI data were collected from two 3T scanners, and functional connectivity between 10 predefined cerebellar functional systems and the whole brain was analyzed. Psychotic symptom changes were measured using the Brief Psychiatric Rating Scale-Anchored version (BPRS-A). Connectivity patterns were examined in relation to treatment outcomes. Study Results Higher baseline connectivity between the cerebellar auditory system and cortical regions, including the visual cortex, dorsolateral prefrontal cortex, and the hippocampus, predicted worse treatment outcome. In contrast, stronger connectivity between cerebellar cognitive systems (default mode and frontoparietal networks) and the anterior cingulate cortex (ACC) and medial prefrontal cortex was associated with better treatment outcome. These findings were consistently present in data acquired from both scanners and both drugs. Conclusions Our results identify specific cerebellar-cortical circuitries as prognostic biomarkers for predicting psychosis treatment outcomes, and suggest that cerebellar auditory and cognitive systems may be potential targets for future interventions aimed at improving treatment efficacy in FEP.