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 8weeks 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 RandD Program of China and the National Natural Science Foundation of China.