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Xiaoxin Zhao,1 Shuyi Zhu,1 Yang Cao,2 Peipei Cheng,1 Yuxiong Lin,1 Zhixin Sun,1 Wenqing Jiang,1 Yasong Du1 1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Suzhou Guangji Hospital, Suzhou, People’s Republic of ChinaCorrespondence: Yasong Du, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, No. 600 Wanping Nan Road, Shanghai, 200030, People’s Republic of China, Tel +86 18816935313, Email yasongdu2020@126.comBackground: Previous studies have indicated abnormal gray matter volume (GMV) in individuals with autism spectrum disorder (ASD); however, there is little consistency across the findings within these studies, partly due to small sample size and great heterogeneity among participants between studies. Additionally, few studies have explored the correlation between clinical symptoms and GMV abnormalities in individuals with ASD. Here, the current study examined GMV alterations in whole brain and their correlations with clinical symptoms in a relatively large and homogeneous sample of participants with ASD matched typically developing (TD) controls.Methods: Forty-eight adolescents with high-functioning ASD and 29 group-matched TD controls underwent structural magnetic resonance images. Voxel-based morphometry was applied to investigate regional GMV alterations. The participants with ASD were examined for the severity of clinical symptoms with Autism Behavior Checklist (ABC). The relationship between GMV abnormalities and clinical symptoms was explored in ASD group using voxel-wise correlation analysis within brain regions that showed significant GMV alterations in individuals with ASD compared with TD controls.Results: We found increased GMV in multiple brain regions, including the inferior frontal gyrus, medial frontal gyrus, superior frontal gyrus, superior temporal gyrus, occipital pole, anterior cingulate, cerebellum anterior lobe, cerebellum posterior lob