Altered KYN/TRP, Gln/Glu, and Met/methionine sulfoxide ratios in the blood plasma of medication-free patients with major depressive disorder

Hidehiro Umehara,Kiyoshi Nakahara,Shusuke Numata,Yutaka Hatakeyama,Tetsuro Ohmori,Takeshi Nikawa,Yukiko Tomioka,Makoto Kinoshita,Shin-Ya Watanabe

doi:10.1038/s41598-017-05121-6

Abstract

Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) is a comprehensive, quantitative, and high throughput tool used to analyze metabolite profiles. In the present study, we used CE-TOFMS to profile metabolites found in the blood plasma of 33 medication-free patients with major depressive disorder (MDD) and 33 non-psychiatric control subjects. We then investigated changes which occurred in the metabolite levels during an 8-week treatment period. The medication-free MDD patients and control subjects showed significant differences in their mean levels of 33 metabolites, including kynurenine (KYN), glutamate (Glu), glutamine (Gln), methionine sulfoxide, and methionine (Met). In particular, the ratios of KYN to tryptophan (TRP), Gln to Glu, and Met to methionine sulfoxide were all significantly different between the two groups. Among the 33 metabolites with altered levels in MDD patients, the levels of KYN and Gln, as well as the ratio of Gln to Glu, were significantly normalized after treatment. Our findings suggest that imbalances in specific metabolite levels may be involved in the pathogenesis of MDD, and provide insight into the mechanisms by which antidepressant agents work in MDD patients.

Highlights

Major depressive disorder (MDD) is a common neuropsychiatric disorder with a lifetime prevalence of 16.2%1
Depressive symptoms as evaluated by the HDSR were significantly improved after 8 weeks treatment with an antidepressant
Decreased levels of kynurenine (KYN) and 5-Methoxyindoleacetic acid (5-MIAA), which are associated with tryptophan (TRP) metabolism, Compound name Cystine Glutamate (Glu) Glutamine (Gln) Asparate (Asp) Inosine monophosphate (IMP) O-Acetylcarnitine Methionine sulfoxide 3-Phosphoglyceric acid Isocitric acid Asparagine (Asn) Uridine Phosphorylcholine Glyceric acid Hypoxanthine 5-Oxoproline Methionine (Met) Uric acid 2-Hydroxybutyric acid cis-Aconitic acid Creatinine Hippuric acid Kynurenine S-Methylcysteine Thiaproline 1-Methyladenosine 5-Methoxyindoleacetic acid (5-MIAA) Glycerophosphocholine Glucose 6-phosphate 2-Aminoisobutyric acid N-Methylnorsalsolinol Ethanolamine Threonic acid Isethionic acid

Summary

Introduction

Major depressive disorder (MDD) is a common neuropsychiatric disorder with a lifetime prevalence of 16.2%1. Capillary electrophoresis-time-of-flight mass spectrometry (CE-TOFMS) is a comprehensive, quantitative, and high throughput tool used to analyze metabolic profiles[5,6,7]. CE-TOFMS has been used to identify abnormalities of blood metabolites in patients with major depression (MDD), bipolar disorder, schizophrenia, and autism spectrum disorder[8,9,10]. The study which investigated MDD was conducted in a very small cohort of 9 MDD patients and 19 control subjects[9]. We used CE-TOFMS to comprehensively profile metabolites found in the blood plasma of 33 medication-free patients with MDD and 33 non-psychiatric control subjects. We followed the patients for 8 weeks to identify any changes which occurred in their metabolite levels

Methods

Results

Conclusion