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

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.

Metabolomic Differentials in Women With and Without Fibromyalgia

“… References used to pinpoint the pathway for each metabolite were the Human Metabolome Database (http://www.hmdb.ca/) and the Kyoto Encyclopedia of Genes and Genomes KEGG (https://www.genome.jp/kegg/). …”

“…Similarly, elevated levels of methionine sulfoxide and anthranilate have been reported. 8,30 Methionine sulfoxide is a primary oxidation product of methionine (Met) via its nucleophilic oxidation and is sometimes considered a biomarker of oxidative stress, 33 whereas anthranilate is a tryptophan metabolite that has been implicated in brain/immune communication. 34 In addition to higher levels of the metabolites described above, we found lower levels of alpha-ketoglutaric acid and metabolites associated with cellular metabolism in individuals with FM.…”

Recent advances in capillary electrophoresis‐mass spectrometry: Instrumentation, methodology and applications

“…Biomarker identification is performed in different biological fluids, blood being one of the most promising amongst them. In recent studies, metabolites and especially amino acids were identified as biomarkers in blood for amyotrophic lateral sclerosis , chronic kidney disease (CKD) , major depressive disorder , onchocercias infection , osteoporosis , Parkinson's disease , pancreatic cancer , urinary tract symptoms and metabolic syndrome in postmenopausal women by CZE‐MS. For identification and accurate quantification of biomarkers for inborn errors of metabolism from dried blood spots, DiBattista et al.…”

Oxytocin-Induced Increase in N,N-dimethylglycine and Time-Course of Changes in Oxytocin Efficacy for Autism Social Core Symptoms

“…Furthermore, because the change in metabolite levels over the 6-week oxytocin administration period could be associated with both clinical improvement and potential attenuation of oxytocin effectiveness, differences in changes in metabolite levels were also examined between the oxytocin-administered group displaying the time-course change in e cacy and the placeboadministered group. The independent t-tests were conducted for each metabolite, with absolute quantities successfully measured by CE-TOFMS measurement in at least 80% of all subjects (≧67 subjects) (34).…”