Resting-state functional connectivity correlates of antipsychotic treatment in unmedicated schizophrenia

Background: Antipsychotics may modulate the resting state functional connectivity(rsFC) to improve clinical symptoms in schizophrenia(Sz). Existing literature has potential confounders like past medication effects and evaluating preselected regions/networks. We aimed to evaluate connectivity pattern changes with antipsychotics in unmedicated Sz using Multivariate pattern analysis(MVPA), a data-driven technique for whole-brain connectome analysis.

Methods: Forty-seven unmedicated patients with Sz(DSM-IV-TR) underwent clinical evaluation and neuroimaging at baseline and after 3-months of antipsychotic treatment. Resting-state functional MRI was analysed using group-MVPA to derive 5-components. The brain region with significant connectivity pattern changes with antipsychotics was identified, and post-hoc seed-to-voxel analysis was performed to identify connectivity changes and their association with symptom changes.

Results: Connectome-MVPA analysis revealed the connectivity pattern of a cluster localised to left anterior cingulate and paracingulate gyri (ACC/PCG) (peak coordinates:x = -04,y = +30,z = +26;k = 12;cluster-p_FWE=0.002) to differ significantly after antipsychotics. Specifically, its connections with clusters of precuneus/posterior cingulate cortex(PCC) and left inferior temporal gyrus(ITG) correlated with improvement in positive and negative symptoms scores, respectively.

Conclusion: ACC/PCG, a hub of the default mode network, seems to mediate the antipsychotic effects in unmedicated Sz. Evaluating causality models with data from randomised controlled design using the MVPA approach would further enhance our understanding of therapeutic connectomics in Sz.