Objective With a particular focus on putative cortico-striatal-thalamic-cortical (CSTC) networks current study aimed to explore robust gray matter volume (GMV) changes in non-medicated first-episode schizophrenia (FES) patients.Methods High-resolution T1-weighted images were obtained using 3.0 Tesla magnetic resonance imaging from 86 first-episode drug-naive schizophrenia patients and 86 healthy controls (CON).Severity of symptoms in patients was evaluated by using Positive and Negative Syndrome Scale (PANSS).Fourteen spherical region of interest (ROI) GMV in the CSTC loop were acquired after optimized voxel-based morphometry (VBM) analysis.GMV of Spherical ROIs and corresponding correlation coefficients were compared between FES and CON groups.The associations of GMV with PANSS subscale score and symptom dimension scores were also evaluated.Results GMV reduction was detected in bilateral hippocampus in FES group by VBM analysis.ROIs located in left inferior frontal gyrus (Brodmanns area 47) and right thalamus (medial dosal nucleus) present GMV reduction.Covariance of ROIs revealed more extensive GMV loss and disassociation between sub-regions.Conclusions Our study support that schizophrenia involves distributed rather than focal pathology and disordered connectivity.Covariation analysis could make compensation to VBM and ROI method to uncover more subtle aberrations in regional correlation.