Discovery and Validation of Plasma Biomarkers for Major Depressive Disorder Classification Based on Liquid Chromatography–Mass Spectrometry

Abstract

Major depressive disorder (MDD) is a debilitating mental disease with a pronounced impact on the quality of life of many people; however, it is still difficult to diagnose MDD accurately. In this study, a nontargeted metabolomics approach based on ultra-high-performance liquid chromatography equipped with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) was used to find the differential metabolites in plasma samples from patients with MDD and healthy controls. Furthermore, a validation analysis focusing on the differential metabolites was performed in another batch of samples using a targeted approach based on the dynamic multiple reactions monitoring method. Levels of acyl carnitines, ether lipids, and tryptophan pronouncedly decreased, whereas LPCs, LPEs, and PEs markedly increased in MDD subjects as compared with the healthy controls. Disturbed pathways, mainly located in acyl carnitine metabolism, lipid metabolism, and tryptophan metabolism, were clearly brought to light in MDD subjects. The binary logistic regression result showed that carnitine C10:1, PE-O 36:5, LPE 18:1 sn-2, and tryptophan can be used as a combinational biomarker to distinguish not only moderate but also severe MDD from healthy control with good sensitivity and specificity. Our findings, on one hand, provide critical insight into the pathological mechanism of MDD and, on the other hand, supply a combinational biomarker to aid the diagnosis of MDD in clinical usage.

Efficacy of ketamine in the rapid treatment of major depressive disorder: a meta-analysis of randomized, double-blind, placebo-controlled studies

“…However, there are still no objective laboratory tests to help clinicians in the diagnosis of MDD, although many studies have been done to develop these tests 4–6. Our group has conducted many studies for identifying potential biomarkers for MDD diagnosis using metabolomics,7–9 which is used to identify novel biomarkers for various disease states 10–12. Another dilemma about the prevention and treatment of MDD is that no existing antidepressants could treat MDD patients with 100% response rate.…”

The Effects of Four-Week Multivitamin Supplementation on Mood in Healthy Older Women: A Randomized Controlled Trial

“…Others have shown that three months' supplementation with a drink containing multivitamins and minerals increased levels of serum serotonin, with tryptophan levels increasing over six months [34]. Serum tryptophan levels have been demonstrated to be a useful biomarker to distinguish moderate and severe depression from healthy controls [35], indicating a relationship with mood regulation. Whether changes to levels of serotonin or tryptophan occurred in the present study, especially given the shorter time period, cannot be confirmed.…”

Direct infussion Electrospray Mass Spectrometry as a new non-invasive tool for serum metabolomics in induced-stress subjects

“…Since the complexity of the human metabolome is of a great magnitude, different complementary techniques for its study are being developed [59][60][61] . The techniques most commonly used have been those based on NMR 34,[62][63][64] .…”

“…Many authors in psychiatric or neurological disease research use metabolic-profiling associated to these diseases including LC/ MS, GC/MS and EC/MS 60,65,66 . However direct infusion mass spectrometry used in this work is completely unexplored.…”