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PLoS One. 2014 Jul 8;9(7):e101652. doi: 10.1371/journal.pone.0101652. eCollection 2014.

Quantitative analyses of schizophrenia-associated metabolites in serum: serum D-lactate levels are negatively correlated with gamma-glutamylcysteine in medicated schizophrenia patients.

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Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
Nanko Clinic of Psychiatry, Himorogi group, Medical Corporation JISENKAI, Shirakawa-shi, Fukushima, Japan.
Public Interest Incorporated Foundation, Sumiyoshi-kaiseikai Sumiyoshi hospital, Koufu-shi, Yamanashi, Japan.
Department of Clinical Pharmacy, Yokohama College of Pharmacy, Yokohama-shi, Kanagawa, Japan.
Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.


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.

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