Abstract
Major depressive disorder (MDD) is a leading cause of disability worldwide. Adolescence is a crucial period for the occurrence and development of depression. There are essential distinctions between adolescent and adult depression patients, and the etiology of depressive disorder is unclear. The interactions of multiple genes in a co-expression network are likely to be involved in the physiopathology of MDD. In the present study, RNA-Seq data of mRNA were acquired from the peripheral blood of MDD in adolescents and healthy control (HC) subjects. Co-expression modules were constructed via weighted gene co-expression network analysis (WGCNA) to investigate the relationships between the underlying modules and MDD in adolescents. In the combined MDD and HC groups, the dynamic tree cutting method was utilized to assign genes to modules through hierarchical clustering. Moreover, functional enrichment analysis was conducted on those co-expression genes from interested modules. The results showed that eight modules were constructed by WGCNA. The blue module was significantly associated with MDD after multiple comparison adjustment. Several Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways associated with stress and inflammation were identified in this module, including histone methylation, apoptosis, NF-kappa β signaling pathway, and TNF signaling pathway. Five genes related to inflammation, immunity, and the nervous system were identified as hub genes: CNTNAP3, IL1RAP, MEGF9, UBE2W, and UBE2D1. All of these findings supported that MDD was associated with stress, inflammation, and immune responses, helping us to obtain a better understanding of the internal molecular mechanism and to explore biomarkers for the diagnosis or treatment of depression in adolescents.
Highlights
Major depressive disorder (MDD) is a leading cause of disability worldwide
These results indicated that our transcriptome sequencing data were of high quality and sufficient for identifying differentially expressed genes (DEGs) and building the co-expression network
weighted gene co-expression network analysis (WGCNA) was applied to construct a gene-weighted coexpression network to detect key gene modules and hub genes which were highly related to MDD in adolescents
Summary
Major depressive disorder (MDD) is a leading cause of disability worldwide. Adolescence is a crucial period for the occurrence and development of depression. Five genes related to inflammation, immunity, and the nervous system were identified as hub genes: CNTNAP3, IL1RAP, MEGF9, UBE2W, and UBE2D1 All of these findings supported that MDD was associated with stress, inflammation, and immune responses, helping us to obtain a better understanding of the internal molecular mechanism and to explore biomarkers for the diagnosis or treatment of depression in adolescents. Major depression disorder (MDD), a serious and common mental disease, is characterized by a poor mood, cognitive impairment, social withdrawal, and even suicide tendencies [1]. It is one of the major causes of disability worldwide, with profound social and economic consequences [2]. Self-reporting and clinical behavioral observation [16] do not adequately reflect the neurobiological alterations that induce the modified behavioral patterns in depressive patients [17]
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