Tao Yuanmei, Zhang Hang, Jin Meijiang, Xu Hanmei, Zou Shoukang, Deng Fang, Huang Lijuan, Zhang Hong, Wang Xiaolan, Tang Xiaowei, Dong Zaiquan, Wang Yanping, Yin Li
Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
The Fourth People's Hospital of Chengdu, Chengdu, Sichuan, China.
Front Psychiatry. 2023 Feb 23;14:1065417. doi: 10.3389/fpsyt.2023.1065417. eCollection 2023.
We explored the DNA methylation and messenger RNA (mRNA) co-expression network and hub genes in first-episode, drug-naive adolescents with major depressive disorder (MDD). To preliminarily explore whether adolescent MDD has unique mechanisms compared with adult MDD.
We compared DNA methylation and mRNA profiles of peripheral blood mononuclear cells from four first-episode and drug-naive adolescents with MDD and five healthy adolescent controls (HCs). We performed differential expression analysis, constructed co-expression network, and screened the hub genes. And enrichment analysis was performed based on Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). We also downloaded DNA methylation and mRNA datasets of adults with MDD (GSE113725/GSE38206) from the GEO database, and performed differential expression and enrichment analysis.
Our clinical data showed that 3034 methylation sites and 4190 mRNAs were differentially expressed in first-episode, drug-naive adolescents MDD patients compared with HCs. 19 hub genes were screened out according to the high degree value in the co-expression network. The results from the GEO database showed that compared with adult HCs, there were 290 methylation sites and 127 mRNAs were differentially expressed in adult MDD patients.
Compared with adolescent HCs and adult MDD patients, the DNA methylation and mRNA expression patterns of first-episode, drug-naive adolescent MDD patients were different. The co-expression network of DNA methylation and mRNA and the screened hub genes may play an important role in the pathogenesis of MDD in first-episode, drug-naive adolescents. Compared with adult MDD, adolescent MDD is more enriched in metabolism in terms of function and pathways.
我们探究了首发、未用药的青少年重度抑郁症（MDD）患者的DNA甲基化和信使核糖核酸（mRNA）共表达网络及枢纽基因。初步探讨青少年MDD与成人MDD相比是否具有独特机制。
我们比较了4例首发、未用药的青少年MDD患者和5例健康青少年对照（HCs）外周血单个核细胞的DNA甲基化和mRNA谱。进行差异表达分析，构建共表达网络，并筛选枢纽基因。基于基因本体论（GO）和京都基因与基因组百科全书（KEGG）进行富集分析。我们还从基因表达综合数据库（GEO）下载了成人MDD患者的DNA甲基化和mRNA数据集（GSE113725/GSE38206），并进行差异表达和富集分析。
我们的临床数据显示，与HCs相比，首发、未用药的青少年MDD患者中有3034个甲基化位点和4190个mRNA存在差异表达。根据共表达网络中的高度值筛选出19个枢纽基因。来自GEO数据库的结果显示，与成人HCs相比，成人MDD患者中有290个甲基化位点和127个mRNA存在差异表达。
与青少年HCs和成人MDD患者相比，首发、未用药的青少年MDD患者的DNA甲基化和mRNA表达模式不同。DNA甲基化和mRNA的共表达网络及筛选出的枢纽基因可能在首发、未用药的青少年MDD发病机制中起重要作用。与成人MDD相比，青少年MDD在功能和通路方面在代谢方面更富集。
