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This study employed a multi-omics approach to investigate the molecular and functional underpinnings of schizophrenia by integrating blood transcriptomic profiles, neuroimaging-derived brain phenotypes, and clinical symptomatology. RNA sequencing of blood samples from 43 patients with schizophrenia and 60 healthy controls identified 994 differentially expressed genes (DEGs), the vast majority of which were downregulated (n = 921, |FC| > 1.5, P < 0.05), with enrichment in pathways related to neuronal development and inflammation. Concurrent neuroimaging analyses revealed altered functional activation in key brain regions, including the prefrontal and anterior cingulate cortices. A Partial Least Squares correlation analysis demonstrated significant cross-modal relationships among gene expression, neuroimaging patterns, and clinical presentation. Furthermore, we identified six genes—GRK2, KLF3, TAOK2, ARFGAP45, AP1M1, and GPAT2—that were shared across gene sets associated with both brain function and clinical symptoms, suggesting a common transcriptional basis for these features of schizophrenia. Collectively, these findings provide novel insights into the integrated molecular and functional changes in schizophrenia, highlighting the value of a comprehensive multi-omics strategy to decipher its pathophysiology and potentially inform improved diagnostic and therapeutic strategies.
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; Zhu, Li 6 ; Ma, Guo-Lin 7
; Cui, Long-Biao 8
; Zhang, Yue-Lang 1 1 Department of Radiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China (ROR: https://ror.org/03aq7kf18) (GRID: grid.452672.0) (ISNI: 0000 0004 1757 5804)
2 Schizophrenia Imaging Lab, Xijing 986 Hospital, Fourth Military Medical University, Xi’an, China (ROR: https://ror.org/00ms48f15) (GRID: grid.233520.5) (ISNI: 0000 0004 1761 4404); Shaanxi Provincial Key Laboratory of Clinic Genetics, Fourth Military Medical University, Xi’an, China (ROR: https://ror.org/00ms48f15) (GRID: grid.233520.5) (ISNI: 0000 0004 1761 4404)
3 Department of Psychiatry, Xijing Hospital, Fourth Military Medical University, Xi’an, China (ROR: https://ror.org/00ms48f15) (GRID: grid.233520.5) (ISNI: 0000 0004 1761 4404)
4 Department of Psychiatry, Xi’an Gaoxin Hospital, Xi’an, China
5 Centre for Cognitive and Brain Sciences, University of Macau, Macau SAR, China (ROR: https://ror.org/01r4q9n85) (GRID: grid.437123.0) (ISNI: 0000 0004 1794 8068); Faculty of Health Sciences, University of Macau, Macau SAR, China (ROR: https://ror.org/01r4q9n85) (GRID: grid.437123.0) (ISNI: 0000 0004 1794 8068)
6 Department of Radiology, General Hospital of Ningxia Medical University, Yinchuan, China (ROR: https://ror.org/02h8a1848) (GRID: grid.412194.b) (ISNI: 0000 0004 1761 9803)
7 Department of Radiology, China-Japan Friendship Hospital, Beijing, China (ROR: https://ror.org/037cjxp13) (GRID: grid.415954.8) (ISNI: 0000 0004 1771 3349)
8 Department of Radiology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, China (ROR: https://ror.org/03aq7kf18) (GRID: grid.452672.0) (ISNI: 0000 0004 1757 5804); Schizophrenia Imaging Lab, Xijing 986 Hospital, Fourth Military Medical University, Xi’an, China (ROR: https://ror.org/00ms48f15) (GRID: grid.233520.5) (ISNI: 0000 0004 1761 4404); Shaanxi Provincial Key Laboratory of Clinic Genetics, Fourth Military Medical University, Xi’an, China (ROR: https://ror.org/00ms48f15) (GRID: grid.233520.5) (ISNI: 0000 0004 1761 4404)