Homotopic functional connectivity disruptions in schizophrenia and their associated gene expression
Mengjing Cai,
Yuan Ji,
Qiyu Zhao,
Hui Xue,
Zuhao Sun,
He Wang,
Yijing Zhang,
Yayuan Chen,
Yao Zhao,
Yujie Zhang,
Minghuan Lei,
Chunyang Wang,
Chuanjun Zhuo,
Nana Liu,
Huaigui Liu,
Feng Liu
Affiliations
Mengjing Cai
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
Yuan Ji
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
Qiyu Zhao
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
Hui Xue
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
Zuhao Sun
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
He Wang
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
Yijing Zhang
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
Yayuan Chen
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
Yao Zhao
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
Yujie Zhang
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
Minghuan Lei
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China
Chunyang Wang
Department of Scientific Research, Tianjin Medical University General Hospital, Tianjin 300052, China
Chuanjun Zhuo
Laboratory of Psychiatric-Neuroimaging-Genetic and Co-morbidity (PGNP_Lab), Tianjin Anding Hospital, Nankai University Affiliated Tianjin Anding Hospital, Tianjin Mental Health Center of Tianjin Medical University, Tianjin, 300222, China
Nana Liu
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China; Corresponding authors at: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China.
Huaigui Liu
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China; Corresponding authors at: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China.
Feng Liu
Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, Tianjin 300052, China; Corresponding authors at: Department of Radiology and Tianjin Key Laboratory of Functional Imaging, Tianjin Medical University General Hospital, No. 154, Anshan Road, Heping District, Tianjin 300052, China.
It has been revealed that abnormal voxel-mirrored homotopic connectivity (VMHC) is present in patients with schizophrenia, yet there are inconsistencies in the relevant findings. Moreover, little is known about their association with brain gene expression profiles. In this study, transcription-neuroimaging association analyses using gene expression data from Allen Human Brain Atlas and case-control VMHC differences from both the discovery (meta-analysis, including 9 studies with a total of 386 patients and 357 controls) and replication (separate group-level comparisons within two datasets, including a total of 258 patients and 287 controls) phases were performed to identify genes associated with VMHC alterations. Enrichment analyses were conducted to characterize the biological functions and specific expression of identified genes, and Neurosynth decoding analysis was performed to examine the correlation between cognitive-related processes and VMHC alterations in schizophrenia. In the discovery and replication phases, patients with schizophrenia exhibited consistent VMHC changes compared to controls, which were correlated with a series of cognitive-related processes; meta-regression analysis revealed that illness duration was negatively correlated with VMHC abnormalities in the cerebellum and postcentral/precentral gyrus. The abnormal VMHC patterns were stably correlated with 1287 genes enriched for fundamental biological processes like regulation of cell communication, nervous system development, and cell communication. In addition, these genes were overexpressed in astrocytes and immune cells, enriched in extensive cortical regions and wide developmental time windows. The present findings may contribute to a more comprehensive understanding of the molecular mechanisms underlying VMHC alterations in patients with schizophrenia.
