Departamento & Instituto de Psiquiatria, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Rua Dr. Ovídio Pires de Campos, 785 - LIM23 (Térreo), São Paulo, 05403-010, Brazil.
Center of Mathematics, Computation and Cognition, Federal University of ABC, São Bernardo do Campo, Brazil.
BMC Genom Data. 2021 Oct 30;22(1):45. doi: 10.1186/s12863-021-00993-0.
Obsessive-compulsive disorder (OCD) is characterized by intrusive thoughts and repetitive actions, that presents the involvement of the cortico-striatal areas. The contribution of environmental risk factors to OCD development suggests that epigenetic mechanisms may contribute to its pathophysiology. DNA methylation changes and gene expression were evaluated in post-mortem brain tissues of the cortical (anterior cingulate gyrus and orbitofrontal cortex) and ventral striatum (nucleus accumbens, caudate nucleus and putamen) areas from eight OCD patients and eight matched controls.
There were no differentially methylated CpG (cytosine-phosphate-guanine) sites (DMSs) in any brain area, nevertheless gene modules generated from CpG sites and protein-protein-interaction (PPI) showed enriched gene modules for all brain areas between OCD cases and controls. All brain areas but nucleus accumbens presented a predominantly hypomethylation pattern for the differentially methylated regions (DMRs). Although there were common transcriptional factors that targeted these DMRs, their targeted differentially expressed genes were different among all brain areas. The protein-protein interaction network based on methylation and gene expression data reported that all brain areas were enriched for G-protein signaling pathway, immune response, apoptosis and synapse biological processes but each brain area also presented enrichment of specific signaling pathways. Finally, OCD patients and controls did not present significant DNA methylation age differences.
DNA methylation changes in brain areas involved with OCD, especially those involved with genes related to synaptic plasticity and the immune system could mediate the action of genetic and environmental factors associated with OCD.
强迫症（OCD）的特征是侵入性思维和重复性动作，这表明皮质纹状体区域的参与。环境风险因素对 OCD 发展的贡献表明，表观遗传机制可能有助于其病理生理学。在 8 名 OCD 患者和 8 名匹配对照的大脑皮质（前扣带皮层和眶额皮层）和腹侧纹状体（伏隔核、尾状核和壳核）区域的死后脑组织中评估了 DNA 甲基化变化和基因表达。
在任何大脑区域都没有差异甲基化 CpG（胞嘧啶-磷酸-鸟嘌呤）位点（DMS），然而从 CpG 位点生成的基因模块和蛋白质-蛋白质相互作用（PPI）显示 OCD 病例和对照组之间所有大脑区域的基因模块都富集。除了伏隔核之外，所有大脑区域的差异甲基化区域（DMR）都呈现出主要的低甲基化模式。尽管有共同的转录因子靶向这些 DMR，但它们靶向的差异表达基因在所有大脑区域都不同。基于甲基化和基因表达数据的蛋白质-蛋白质相互作用网络报告说，所有大脑区域都富含 G 蛋白信号通路、免疫反应、凋亡和突触生物学过程，但每个大脑区域也都有特定信号通路的富集。最后，OCD 患者和对照组的 DNA 甲基化年龄差异没有显著差异。
与 OCD 相关的大脑区域的 DNA 甲基化变化，特别是与突触可塑性和免疫系统相关的基因相关的变化，可能介导与 OCD 相关的遗传和环境因素的作用。
