The role of aripiprazole in modulating putamen and thalamus functional connectivity in early psychosis patients.

Abstract

Background: Early psychosis is marked by cortico-striatal and thalamocortical dysconnectivity, yet how aripiprazole modulates these circuits remains unclear.

Methods: We examined putamen and thalamus functional connectivity (FC) in 30 early psychosis patients (ultra-high-risk, first-episode psychosis, schizophreniform disorder, or first-episode schizophrenia) and 30 matched healthy controls. At baseline, patients were naïve to dopamine receptor-targeting medication or minimally exposed (<12 weeks). All patients received flexible-dose aripiprazole, and symptoms were assessed using the Positive and Negative Syndrome Scale at baseline, days 14 and 28. Baseline resting-state functional MRI was acquired for patients and controls, and follow-up scans for patients after 41.6 ± 13.9 days of treatment.

Results: Compared with controls, patients showed hypoconnectivity within/between bilateral putamen, between putamen and thalamus, and between thalamus and salience network (SN) nodes. In contrast, hyperconnectivity was observed between the putamen and both sensorimotor (SM) and default mode network (DMN) nodes, as well as between the thalamus and SM nodes. After treatment with aripiprazole, FC increased within/between bilateral putamen, between putamen and SN nodes, and between thalamus and SN nodes, and decreased between thalamus and SM nodes and between putamen and SM nodes. At the uncorrected level (p < 0.05), increases in FC between the right ventral rostral putamen and bilateral putamen correlated with improvement in positive symptoms.

Conclusion: Findings suggest aripiprazole partially normalizes aberrant striatal-thalamic coupling early in psychosis, and putaminal FC changes may relate to clinical response. Aripiprazole may achieve therapeutic benefits by restoring integration within striatal hubs and their crosstalk with large-scale networks implicated in psychotic symptom expression.