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.

中文翻译：

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精神分裂症的同位功能连接中断及其相关基因表达

研究表明，精神分裂症患者存在异常的体素镜像同伦连接（VMHC），但相关研究结果存在不一致。此外，人们对它们与大脑基因表达谱的关联知之甚少。在这项研究中，转录-神经影像关联分析使用来自 Allen Human Brain Atlas 的基因表达数据和病例对照 VMHC 发现（荟萃分析，包括总共 386 名患者和 357 名对照的 9 项研究）和复制（单独的研究）的差异。对两个数据集（包括总共 258 名患者和 287 名对照）进行组级比较，以确定与 VMHC 改变相关的基因。进行富集分析来表征已识别基因的生物学功能和特定表达，并进行 Neurosynth 解码分析来检查精神分裂症中认知相关过程和 VMHC 改变之间的相关性。在发现和复制阶段，与对照组相比，精神分裂症患者表现出一致的 VMHC 变化，这与一系列认知相关过程相关；荟萃回归分析显示，病程与小脑和中央后/中央前回的 VMHC 异常呈负相关。异常的 VMHC 模式与 1287 个基因稳定相关，这些基因富含基本生物过程，如细胞通讯调节、神经系统发育和细胞通讯。此外，这些基因在星形胶质细胞和免疫细胞中过度表达，在广泛的皮质区域和广泛的发育时间窗中富集。目前的研究结果可能有助于更全面地了解精神分裂症患者 VMHC 改变的分子机制。