Enhanced Baseline Activity in the Left Ventromedial Putamen Predicts Individual Treatment Response in Drug-Naive, First-Episode Schizophrenia: Results from Two Independent Study Samples

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 = 0.002; r = 0.511, p = 0.003, respectively).   Interpretation: Our study suggests that left ventromedial putamen activity 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.   Funding Statement: This study was supported by grants from the National Key R&D Program of China (2016YFC1307100 and 2016YFC1306900) and the National Natural Science Foundation of China (Grant Nos. 81571310, 81771447, and 81630033). Declaration of Interests: Dr Fan reported receiving research support from the National Institute on Alcohol Abuse and Alcoholism, National Institute on Drug Abuse, the Stanley Medical Research Institute, the Baer Foundation, the Shine Foundation, the Vanguard Group, Janssen, Avanir Pharmaceuticals, Neurocrine, and Alkermes; and reported receiving honoraria for serving on an advisory board for Allergen. Other authors reported no disclosures. Ethics Approval Statement: The study was reviewed and approved by the ethics committees of the Second Xiangya Hospital of Central South University and the Second Affiliated Hospital of Guangxi Medical University. A written informed consent was obtained from each subject.