Co-expression network of mRNA and DNA methylation in first-episode and drug-naive adolescents with major depressive disorder

Yuanmei Tao; Hang Zhang; Meijiang Jin; Hanmei Xu; Shoukang Zou; Fang Deng; Lijuan Huang; Hong Zhang; Xiaolan Wang; Xiaowei Tang; Zaiquan Dong; Yanping Wang; Li Yin

doi:10.3389/fpsyt.2023.1065417

Co-expression network of mRNA and DNA methylation in first-episode and drug-naive adolescents with major depressive disorder

Front Psychiatry. 2023 Feb 23:14:1065417. doi: 10.3389/fpsyt.2023.1065417. eCollection 2023.

Authors

Yuanmei Tao¹, Hang Zhang¹, Meijiang Jin¹, Hanmei Xu¹, Shoukang Zou^{1

2}, Fang Deng^{1

2}, Lijuan Huang¹, Hong Zhang¹, Xiaolan Wang¹, Xiaowei Tang¹, Zaiquan Dong¹, Yanping Wang¹, Li Yin^{1

3

4}

Affiliations

¹ Department of Psychiatry, West China Hospital of Sichuan University, Chengdu, Sichuan, China.
² The Fourth People's Hospital of Chengdu, Chengdu, Sichuan, China.
³ Institute for Systematic Genetics, Frontiers Science Center for Disease-Related Molecular Network, Chengdu, Sichuan, China.
⁴ Sichuan Clinical Medical Research Center for Mental Disorder, Chengdu, Sichuan, China.

Abstract

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: DNA methylation; adolescent; co-expression network; mRNA; major depressive disorder.

Grants and funding

This work was supported by the National Natural Science Foundation of China (81801357), Science & Technology Department of Sichuan Province (22ZDYF1544), Health Commission of Sichuan Province Program (21PJ020), Key R&D Projects of the Science and Technology Department of Sichuan Province (2020JDKP0013 and 2020YFS0259), and Key R&D Projects of the Science and Technology Department of Chengdu (2019-YF05-00284-SN). These funding agencies were not involved in any of the research processes.