Transformations in Plasma Metabolic Profiles of Patients with Major Depression During Treatment: A Pilot Metabolomics Study

Abstract Background Major depression disorder (MDD) is a mental disease that seriously endangers human physical and mental health. The purpose of present study is to detect the differences of plasma metabolic profiles between MDD patients and healthy controls. Moreover, the hospitalization process of MDD patients was followed to explore the reversal of metabolic abnormalities in MDD patients by conventional treatment in the form of self-control.Methods Ultra-Performance Liquid Chromatography- Mass Spectrometry (UPLC-MS) was used to detect the metabolic profiles in 47 plasma samples from 12 controls and 12 MDD patients. Multivariate statistical analysis and K-means clustering were operated to search for significantly different metabolites (SDMs) between pair-comparison groups and specific metabolites (SMs) with ideal variation trend in relative content. Finally, the metabolites were integrated into Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways to preliminarily explore the potential mechanism of MDD disrupting the metabolic process.Results There were significant differences in plasma metabolic profiles between healthy controls and MDD patients. A total of 14 SDMs between untreated MDD patients and healthy controls were classified into the top ten KEGG pathways enrichment, among which the relative contents of 4 SMs, 9-HPODE, imidazoleacetic acid, thromboxane B2 (TXB2), and arachidonic acid (AA) showed a regular variation trend after MDD patients’ treatment. A new metabolite-pathway network containing 4 SMs and 8 pathways was accessed after further integration analysis. The sample size calculation showed that a verification set of 84-135 subjects (containing healthy controls and MDD paients) was desired to confirm the results of this study.Conclusion The results indicate that the transition in metabolic pathways during the occurrence and treatment process of MDD is mainly dominated by transformations in lipid metabolism and its relevant signaling pathway system. Additionally, histidine metabolism is also engaged. Subsequent large-scale validation study is acquired to evaluate whether the selected metabolites have the potential to diagnose and access the therapeutic effect of MDD, and to explore the probable mechanism of MDD in combination with other technologies.