Abstract
Depression is one of the most prevalent and serious mental disorders with a worldwide significant health burden. Metabolic abnormalities and disorders in patients with depression have attracted great research attention. Thirty-six metabolic biomarkers of clinical plasma metabolomics were detected by platform technologies, including gas chromatography–mass spectrometry (GC–MS), liquid chromatography–mass spectrometry (LC–MS) and proton nuclear magnetic resonance (1H-NMR), combined with multivariate data analysis techniques in previous work. The principal objective of this study was to provide valuable information for the pathogenesis of depression by comprehensive analysis of 36 metabolic biomarkers in the plasma of depressed patients. The relationship between biomarkers and enzymes were collected from the HMDB database. Then the metabolic biomarkers-enzymes interactions (MEI) network was performed and analyzed to identify hub metabolic biomarkers and enzymes. In addition, the docking score-weighted multiple pharmacology index (DSWMP) was used to assess the important pathways of hub metabolic biomarkers involved. Finally, validated these pathways by published literature. The results show that stearic acid, phytosphingosine, glycine, glutamine and phospholipids were important metabolic biomarkers. Hydrolase, transferase and acyltransferase involve the largest number of metabolic biomarkers. Nine metabolite targets (TP53, IL1B, TNF, PTEN, HLA-DRB1, MTOR, HRAS, INS and PIK3CA) of potential drug proteins for treating depression are widely involved in the nervous system, immune system and endocrine system. Seven important pathways, such as PI3K-Akt signaling pathway and mTOR signaling pathway, are closely related to the pathology mechanisms of depression. The application of important biomarkers and pathways in clinical practice may help to improve the diagnosis of depression and the evaluation of antidepressant effect, which provides important clues for the study of metabolic characteristics of depression.
Highlights
Depression is one of the most prevalent and serious mental disorders
Thirty-six metabolic biomarkers of clinical plasma metabolomics were detected by platform technologies, including gas chromatography–mass spectrometry (GC–MS), liquid chromatography–mass spectrometry (LC–MS) and proton nuclear magnetic resonance (1H-NMR), combined with multivariate data analysis techniques in previous our work [13, 14]
The relationship between biomarkers and enzymes were collected from the Human Metabolome Database (HMDB) database and the metabolic biomarkers–enzymes interactions (MEI) network was performed and analyzed to identify hub metabolic biomarkers and enzymes
Summary
The number of patients with depression has increased dramatically. In the world’s population, the lifetime prevalence of depressed patients is about 17% with a significant burden of disease [1]. Previous research reports have found that in the United States, more than 19 million adults suffer from depression in the USA and spend more than 30 billion annually, directly or indirectly [2]. Increased studies have reported the serotonin and norepinephrine dysfunction in the central nervous system of patients with depression [5]. Studies have reported that hypothalamic pituitary adrenal (HPA) axis is one of the largest neuroendocrine findings of depression [6]. Abnormal changes of inflammatory cytokines and endogenous metabolites are involved in the molecular mechanism of pathology of depression [7, 8]. The occurrence and development of depression is a complicated process, the etiology and pathogenesis mechanism of depression represent challenging issues in scientific and medical research
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