Genetic contribution of synapse-associated protein 97 to cerebellar functional connectivity changes in first-episode schizophrenia

Abstract

Our previous study data suggested that the synapse-associated protein 97 (SAP97) rs3915512 polymorphism is significantly related to clinical performance in schizophrenia. The cerebellum exhibits abundant expression of SAP97, which is involved with negative symptoms, cognition and emotion in schizophrenia. As functional dysconnectivity with the cortical-subcortical-cerebellar circuitry has been widely shown in patients with schizophrenia, cortical-subcortical-cerebellar dysconnectivity can therefore be considered a possible intermediate phenotype that connects risk genes with schizophrenia. In this study, resting-state functional magnetic resonance imaging (fMRI) was applied to evaluate whether the SAP97 rs3915512 polymorphism changes cortical/subcortical-cerebellar resting-state functional connectivity (RSFC) in 104 Han Chinese subjects (52 first-episode schizophrenia (FES) patients and 52 matched healthy controls (HCs)). To examine RSFC between cortical/subcortical regions and the cerebellum, a ROI (region of interest)-wise functional connectivity analysis was conducted. The association between abnormal cortical/subcortical-cerebellar connectivity and clinical manifestation was further assessed in FES patients with different genotypes. The interactive effect of disease and genotype on RSFC was found between the frontal gyrus (rectus) and cerebellum. A positive correlation was suggested between RSFC in the cerebellum and the hostility scores in FES patients with the A allele, and no correlation was found in FES patients with the TT genotype. The current findings identified that SAP97 may be involved in the process of mental symptoms in FES patients via cerebellar connectivity depending on the rs3915512 polymorphism genotype.