Yang Hyun-Ho, Han Kyu-Man, Kim Aram, Kang Youbin, Tae Woo-Suk, Han Mi-Ryung, Ham Byung-Joo
Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon, Republic of Korea.
Department of Psychiatry, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Republic of Korea.
Psychol Med. 2024 Jul;54(10):2585-2598. doi: 10.1017/S0033291724000709. Epub 2024 May 9.
Epigenetic modifications, such as DNA methylation, contribute to the pathophysiology of major depressive disorder (MDD). This study aimed to identify novel MDD-associated epigenetic loci using DNA methylation profiles and explore the correlations between epigenetic loci and cortical thickness changes in patients with MDD.
A total of 350 patients with MDD and 161 healthy controls (HCs) were included in the epigenome-wide association studies (EWAS). We analyzed methylation, copy number alteration (CNA), and gene network profiles in the MDD group. A total of 234 patients with MDD and 135 HCs were included in neuroimaging methylation analysis. Pearson's partial correlation analysis was used to estimate the correlation between cortical thickness of brain regions and DNA methylation levels of the loci.
In total, 2018 differentially methylated probes (DMPs) and 351 differentially methylated regions (DMRs) were identified. DMP-related genes were enriched in two networks involved in the central nervous system. In neuroimaging analysis, patients with MDD showed cortical thinning in the prefrontal regions and cortical thickening in several occipital regions. Cortical thickness of the left ventrolateral prefrontal cortex (VLPFC, i.e. pars triangularis) was negatively correlated with eight DMPs associated with six genes (, , , , , and ).
Through combining DNA methylation and neuroimaging analyses, negative correlations were identified between the cortical thickness of the left VLPFC and DNA methylation levels of eight DMPs. Our findings could improve our understanding of the pathophysiology of MDD.
表观遗传修饰，如DNA甲基化，参与了重度抑郁症（MDD）的病理生理过程。本研究旨在利用DNA甲基化谱识别与MDD相关的新表观遗传位点，并探讨MDD患者表观遗传位点与皮质厚度变化之间的相关性。
共有350例MDD患者和161名健康对照（HCs）纳入全表观基因组关联研究（EWAS）。我们分析了MDD组的甲基化、拷贝数改变（CNA）和基因网络谱。共有234例MDD患者和135名HCs纳入神经影像学甲基化分析。采用Pearson偏相关分析估计脑区皮质厚度与位点DNA甲基化水平之间的相关性。
共鉴定出2018个差异甲基化探针（DMPs）和351个差异甲基化区域（DMRs）。DMP相关基因富集于两个参与中枢神经系统的网络中。在神经影像学分析中，MDD患者前额叶区域皮质变薄，几个枕叶区域皮质增厚。左侧腹外侧前额叶皮质（VLPFC，即三角部）的皮质厚度与6个基因（、、、、和）相关的8个DMP呈负相关。
通过结合DNA甲基化和神经影像学分析，发现左侧VLPFC的皮质厚度与8个DMP的DNA甲基化水平呈负相关。我们的研究结果有助于增进对MDD病理生理学的理解。
