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Effects of polygenic risk of schizophrenia on interhemispheric callosal white matter integrity and frontotemporal functional connectivity in first-episode schizophrenia

Published online by Cambridge University Press:  07 January 2022

Wenjun Su
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Aihua Yuan
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Yingying Tang
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Lihua Xu
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Yanyan Wei
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Yingchan Wang*
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Zhixing Li
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Huiru Cui
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Zhenying Qian
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Xiaochen Tang
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Yegang Hu
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Tianhong Zhang
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China
Jianfeng Feng
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China
Zhiqiang Li
Affiliated Hospital of Qingdao University & Biomedical Sciences Institute of Qingdao University, Qingdao University, Qingdao 266000, China Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Collaborative Innovation Centre for Brain Science, Shanghai Jiao Tong University, Shanghai 200240, China
Jie Zhang
Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai 200433, China
Jijun Wang*
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Science, Shanghai 200031, China Institute of Psychology and Behavioral Science, Shanghai Jiao Tong University, Shanghai 200240, China
Author for correspondence: Jijun Wang, E-mail:; Jie Zhang, E-mail:; Zhiqiang Li, E-mail:
Author for correspondence: Jijun Wang, E-mail:; Jie Zhang, E-mail:; Zhiqiang Li, E-mail:



Schizophrenia is a severely debilitating psychiatric disorder with high heritability and polygenic architecture. A higher polygenic risk score for schizophrenia (SzPRS) has been associated with smaller gray matter volume, lower activation, and decreased functional connectivity (FC). However, the effect of polygenic inheritance on the brain white matter microstructure has only been sparsely reported.


Eighty-four patients with first-episode schizophrenia (FES) patients and ninety-three healthy controls (HC) with genetics, diffusion tensor imaging (DTI), and resting-state functional magnetic resonance imaging (rs-fMRI) data were included in our study. We investigated impaired white matter integrity as measured by fractional anisotropy (FA) in the FES group, further examined the effect of SzPRS on white matter FA and FC in the regions connected by SzPRS-related white matter tracts.


Decreased FA was observed in FES in many commonly identified regions. Among these regions, we observed that in the FES group, but not the HC group, SzPRS was negatively associated with the mean FA in the genu and body of corpus callosum, right anterior corona radiata, and right superior corona radiata. Higher SzPRS was also associated with lower FCs between the left inferior frontal gyrus (IFG)–left inferior temporal gyrus (ITG), right IFG–left ITG, right IFG–left middle frontal gyrus (MFG), and right IFG–right MFG in the FES group.


Higher polygenic risks are linked with disrupted white matter integrity and FC in patients with schizophrenia. These correlations are strongly driven by the interhemispheric callosal fibers and the connections between frontotemporal regions.

Original Article
Copyright © The Author(s), 2022. Published by Cambridge University Press

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These authors contributed equally to this work.

These 3 authors share joint correspondence in the work.


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