Disrupted asymmetry of inter- and intra-hemispheric functional connectivity in patients with drug-naive, first-episode schizophrenia and their unaffected siblings

Background Lack of normal asymmetry in the brain has been reported in patients with schizophrenia. However, it remains unclear whether disrupted asymmetry originates from inter-hemispheric functional connectivity (FC) and/or intra-hemispheric FC in this patient population. Methods Forty-four patients with drug-naive, first-episode schizophrenia, 42 unaffected siblings, and 44 healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) scan. The parameter of asymmetry (PAS) and support vector machine (SVM) were used to analyze the data. Patients were treated with olanzapine for 8 weeks. Findings Compared with healthy controls, patients showed lower PAS scores in the left middle temporal gyrus (MTG)/inferior temporal gyrus (ITG), left posterior cingulate cortex (PCC)/precuneus and left angular gyrus, and higher PAS scores in the left precentral gyrus/postcentral gyrus. Unaffected siblings also showed lower PAS scores in the left MTG/ITG and left PCC/precuneus relative to healthy controls. Further, SVM analysis showed that a combination of the PAS scores in these two clusters in patients at baseline was able to predict clinical response after 8 weeks of olanzapine treatment with 77.27% sensitivity, 72.73% specificity, and 75.00% accuracy. Interpretation The present study suggests disrupted asymmetry of inter- and intra-hemispheric FC in drug-naive, first-episode schizophrenia; in addition, a reduced asymmetry of inter-hemispheric FC in the left MTG/ITG and left PCC/precuneus may serve as an endophenotype for schizophrenia, and may have clinical utility to predict response to olanzapine treatment. Fund The National Key R&D Program of China and the National Natural Science Foundation of China.

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