Wang Min, Xiang Hailin, Wei Jinxue, Dou Yikai, Yan Yushun, Du Yue, Fan Huanhuan, Zhao Liansheng, Ni Rongjun, Yang Xiao, Ma Xiaohong
Mental Health Center, Institute of Psychiatry, West China Hospital, Sichuan University, No.28 South Dianxin Street, Wuhou District, Chengdu, 610041, Sichuan, China.
Sci Rep. 2025 Jan 7;15(1):1067. doi: 10.1038/s41598-025-85431-2.
The risk of suicide in patients with major depressive disorder (MDD) poses a major concern, with studies suggesting that genetics may be a contributing factor. Although there are many transcriptomic studies on postmortem brain tissue related to suicidal behavior, the blood transcriptional mechanisms of suicidal ideation (SI) remain unknown. This study utilized a weighted gene coexpression network analysis (WGCNA) approach to investigate the associations between gene coexpression modules and SI in individuals with MDD using peripheral blood RNA-seq data from 75 MDD patients with SI (MDD_SI), 82 MDD patients without SI (MDD_nSI), and 149 healthy controls (HC). An ANCOVA was conducted to assess differences in gene coexpression modules among groups, with age and sex included as covariates. The gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) databases were used to annotate module functions. Results indicated that the magenta module (associated with RNA splicing processes) differentiated MDD_SI from MDD_nSI (p = 0.021), while the green module (related to immune and inflammatory responses) distinguished MDD_SI from HC (p = 0.004). Additionally, three modules showed differences between MDD_nSI and HC: magenta (p = 0.009), brown (related to innate immunity and mitochondrial metabolism; p = 0.001), and turquoise (associated with energy metabolism and neurodegeneration; p = 0.005). Our findings highlight that gene expression regulation, immune response, and inflammation may be linked to SI in patients with MDD, while pathways associated with innate immunity, energy metabolism, mitochondrial function, and neurodegeneration appear to be more broadly related to MDD.
重度抑郁症(MDD)患者的自杀风险是一个主要关注点,研究表明遗传因素可能是一个促成因素。尽管有许多关于与自杀行为相关的死后脑组织的转录组学研究,但自杀意念(SI)的血液转录机制仍不清楚。本研究利用加权基因共表达网络分析(WGCNA)方法,使用来自75名有自杀意念的MDD患者(MDD_SI)、82名无自杀意念的MDD患者(MDD_nSI)和149名健康对照(HC)的外周血RNA测序数据,研究MDD个体中基因共表达模块与SI之间的关联。进行协方差分析以评估组间基因共表达模块的差异,将年龄和性别作为协变量纳入。基因本体论(GO)和京都基因与基因组百科全书(KEGG)数据库用于注释模块功能。结果表明,品红色模块(与RNA剪接过程相关)将MDD_SI与MDD_nSI区分开来(p = 0.021),而绿色模块(与免疫和炎症反应相关)将MDD_SI与HC区分开来(p = 0.004)。此外,三个模块在MDD_nSI和HC之间存在差异:品红色(p = 0.009)、棕色(与先天免疫和线粒体代谢相关;p = 0.001)和蓝绿色(与能量代谢和神经退行性变相关;p = 0.005)。我们的研究结果强调,基因表达调控、免疫反应和炎症可能与MDD患者的SI有关,而与先天免疫、能量代谢、线粒体功能和神经退行性变相关的通路似乎与MDD更广泛相关。
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