Identification of gene co-expression modules and core genes related to immune disorders in major depression disorder

Abstract

Introduction: Various studies have confirmed the connection between the mental state and the immune system, that is, mental activities can regulate immune function, and immune system disorders can not only lead to bodily diseases but also changes related to mentality, behavior, personality, and aging. However, the specific regulatory mechanism and key genes are still unclear. Methods: We obtained the peripheral blood gene sequencing data from patients with major depression and normal volunteers from the GEO database and evaluated the scores of different immune cells by immune scoring algorithm. Using the immune scores as clinical data, a weighted gene co-expression network analysis (WGCNA) was carried out to study the association between the clinical characteristics and modules. Therefore, providing an oppor-tunity to lock modules and core genes which are highly related to the immune regulation of major depression. Results: Thirteen co-expression modules were clustered from 20,011 genes, the yellow module had a positive correlation with CD4+ T cell, CD8+ T cell, B cell, and NK cell immune scores, and a negative correlation with purple module. Functional annotation and signaling pathway analysis illustrated that the yellow module is mostly enriched in thymus development, T cell co-stimulation and differentiation, and B cell activation. Genes in the purple module were primarily related to inhibition of protein phosphoryla-tion, leukocyte migration, promotion of apoptosis and hypoxia and other signaling path-ways. Additionally, hub genes in the yellow and purple modules were detected, in which SKAP1 and RALB may be important regulatory genes affecting the immune status of patients with depression. Discussion: In general, our study reveals the key genes related to the decrease in CD4+ T cells, CD8+ T cells, and B cells, in the peripheral blood of patients with depression, which provides some new insights and understandings for the clinical treatment and diagnosis of major depression. Drug design targeting these targets may provide the possibility for the treatment of major depression.