Journal Article

Homotopic functional connectivity disruptions in schizophrenia and their associated gene expression

Chen, Yayuan, Zhuo, Chuanjun, Lei, Minghuan, Wang, He, Zhang, Yijing, Zhao, Qiyu, Liu, Huaigui, Liu, Nana, Zhang, Yujie, Sun, Zuhao, Xue, Hui, Wang, Chunyang, Liu, Feng, Ji, Yuan, Zhao, Yao, Cai, Mengjing

2024

Overview

•The first study to identify genes associated with voxel-mirrored homotopic connectivity (VMHC) alterations in patients with schizophrenia using the transcription-neuroimaging association analysis approach.•This study determined the biological functions of the identified genes, as well as the cell types, brain regions and developmental stages in which they were enriched.•We also found cognitive processes related to VMHC alterations in schizophrenia.•The findings offer novel insights into the genetic mechanisms of schizophrenia-related VMHC alterations. 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.

• Publisher: Elsevier Inc,Elsevier Limited,Elsevier
• Subject: Allen human brain atlas / Astrocytes / Brain / Brain Mapping / Brain research / Cell interactions / Cerebellum / Cognitive ability / Datasets / Gene Expression / Gene loci / Genomes / Humans / Magnetic Resonance Imaging / Medical imaging / Mental disorders / Meta-analysis / Molecular modelling / Nervous system / Neural networks / Neuroimaging / Precentral gyrus / Replication / Resting-state fMRI / Schizophrenia / Schizophrenia - diagnostic imaging / Schizophrenia - genetics / Transcription-neuroimaging association analysis / Voxel-mirrored homotopic connectivity