Quantitative Analyses of Schizophrenia-Associated Metabolites in Serum: Serum D-Lactate Levels Are Negatively Correlated with Gamma-Glutamylcysteine in Medicated Schizophrenia Patients

• Published in: PloS one Vol. 9; no. 7; p. e101652
• Main Authors: Fukushima, Takeshi, Iizuka, Hideaki, Yokota, Ayaka, Suzuki, Takehiro, Ohno, Chihiro, Kono, Yumiko, Nishikiori, Minami, Seki, Ayaka, Ichiba, Hideaki, Watanabe, Yoshinori, Hongo, Seiji, Utsunomiya, Mamoru, Nakatani, Masaki, Sadamoto, Kiyomi, Yoshio, Takashi
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 08.07.2014; Public Library of Science (PLoS)
• Subjects: Acids; Adolescent; Adult; Amino acids; Analytical chemistry; Antioxidants; Arachidonic acid; Behavior disorders; Biology and Life Sciences; Case-Control Studies; Comparative analysis; Computer and Information Sciences; Consent; D-Serine; Dipeptides - blood; Discriminant analysis; Fatty acids; Female; g-Glutamylcysteine; Glutathione; Glutathione - blood; Hospitals; Humans; Lactates; Lactates - blood; Lactic acid; Linoleic acid; Male; Medicine and Health Sciences; Mental disorders; Metabolism; Metabolites; Metabolome; Metabolomics - methods; Multivariate analysis; Oxidative stress; Pathogenesis; Patients; Pharmaceutical sciences; Pharmacy; Psychiatrists; Psychiatry; Psychotropic drugs; Public interest; Pyruvaldehyde; Quantitative analysis; ROC Curve; Schizophrenia; Schizophrenia - blood; Schizophrenia - metabolism; Sensitivity analysis; Serotonin; Serum levels; Threonine; Tryptophan; Tyrosine; Unsaturated fatty acids; Young Adult; γ-Glutamylcysteine; United States > US; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0101652

The serum levels of several metabolites are significantly altered in schizophrenia patients. In this study, we performed a targeted analysis of 34 candidate metabolites in schizophrenia patients (n = 25) and compared them with those in age- and gender-matched healthy subjects (n = 27). Orthogonal partial least square-discriminant analysis revealed that complete separation between controls and patients was achieved based on these metabolites. We found that the levels of γ-glutamylcysteine (γ-GluCys), linoleic acid, arachidonic acid, D-serine, 3-hydroxybutyrate, glutathione (GSH), 5-hydroxytryptamine, threonine, and tyrosine were significantly lower, while D-lactate, tryptophan, kynurenine, and glutamate levels were significantly higher in schizophrenia patients compared to controls. Using receiver operating characteristics (ROC) curve analysis, the sensitivity, specificity, and the area under curve of γ-GluCys, a precursor of GSH, and D-lactate, a terminal metabolite of methylglyoxal, were 88.00%, 81.48%, and 0.8874, and 88.00%, 77.78%, and 0.8415, respectively. In addition, serum levels of D-lactate were negatively correlated with γ-GluCys levels in patients, but not in controls. The present results suggest that oxidative stress-induced damage may be involved in the pathogenesis of schizophrenia.