BACKGROUND: Antipsychotic medications are the common treatment for schizophrenia. However, reliable biomarkers that can predict individual treatment response are still lacking. The present study aimed to examine whether baseline putamen activity can predict individual treatment response in schizophrenia. METHODS: Two independent samples of patients with drug-naive, first-episode schizophrenia (32 patients in sample 1 and 44 in sample 2) and matched healthy controls underwent resting-state functional magnetic resonance imaging (fMRI) at baseline. Patients were treated with olanzapine for 8 weeks; symptom severity was assessed using the Positive and Negative Syndrome Scale (PANSS) at baseline and week 8. Fractional amplitude of low frequency fluctuation (fALFF) and pattern classification techniques were used to analyze the data. FINDINGS: Univariate analysis shows an elevated pre-treatment fALFF in the left ventromedial putamen in both patient samples compared to healthy controls (p's < 0.001). The support vector regression (SVR) analysis suggests a positive relationship between baseline pre-treatment fALFF in the left ventromedial putamen and improvement in positive symptom at week 8 in each patient group using a cross-validated method (r=0.452, p=.002; r=0.511, p=.003, respectively). INTERPRETATION: Our study suggests that elevated pre-treatment mean fALFF in the left ventromedial putamen may predict individual therapeutic response to olanzapine treatment in drug-naive, first-episode patients with schizophrenia. Future studies are needed to confirm whether this finding is generalizable to patients with schizophrenia treated with other antipsychotic medications. FUND: The National Key RandD Program of China and the National Natural Science Foundation of China.

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.