Distinct striatum pathways connected to salience network predict symptoms improvement and resilient functioning in schizophrenia following risperidone monotherapy

Abstract Abnormal interactions between the striatum and salience network (SN) are considered as etiological and treatment-sensitive marker in schizophrenia. However, whether alterations in the intrinsic dynamics as reflected by resting-state functional connectivity (RSFC) between the striatum and salience network may predict treatment response to the widely used antipsychotic treatment strategies (risperidone, monotherapy) has not been examined systematically. To this end, treatment-naive first-episode schizophrenia patients (n = 41) underwent task-free resting-state fMRI assessment before (baseline) and after 8 weeks of risperidone monotherapy (n = 38). Intrinsic connectivity between striatal sub-regions and core salience processing nodes were examined and compared to carefully matched healthy controls (HC) to determine disorder-specific and treatment-predictive neural markers. Findings demonstrate hypo-connectivity of both ventral and dorsal striatal-SN pathways in patients at baseline. Importantly, specifically the dorsal striatal pathway at baseline could predict negative symptoms improvement in patients; while ventral striatal pathways could predict positive symptoms improvement. Together, results indicate that distinct striatal-SN pathways represent specific treatment-success markers for the effects of risperidone, suggesting that alterations in dorsal versus ventral striatal network markers may represent brain-based markers for specific symptomatologic improvements following risperidone mono-therapy.