title: Quantitative analyses of schizophrenia-associated metabolites in serum: serum D-lactate levels are negatively correlated with gamma-glutamylcysteine in medicated schizophrenia patients.
abstract: 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.
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Iizuka
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Yokota
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
authors.forename: Takehiro
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
authors.forename: Chihiro
authors.initials: C
authors.lastname: Ohno
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Kono
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
authors.forename: Minami
authors.initials: M
authors.lastname: Nishikiori
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
authors.forename: Ayaka
authors.initials: A
authors.lastname: Seki
authors.affiliation: Department of Analytical Chemistry, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Ichiba
authors.affiliation: Nanko Clinic of Psychiatry, Himorogi group, Medical Corporation JISENKAI, Shirakawa-shi, Fukushima, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Nanko Clinic of Psychiatry, Himorogi group, Medical Corporation JISENKAI, Shirakawa-shi, Fukushima, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Hongo
authors.affiliation: Public Interest Incorporated Foundation, Sumiyoshi-kaiseikai Sumiyoshi hospital, Koufu-shi, Yamanashi, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Utsunomiya
authors.affiliation: Public Interest Incorporated Foundation, Sumiyoshi-kaiseikai Sumiyoshi hospital, Koufu-shi, Yamanashi, Japan.
authors.forename: Masaki
authors.initials: M
authors.lastname: Nakatani
authors.affiliation: Department of Clinical Pharmacy, Yokohama College of Pharmacy, Yokohama-shi, Kanagawa, Japan.
authors.forename: Kiyomi
authors.initials: K
authors.lastname: Sadamoto
authors.affiliation: Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Toho University, Funabashi-shi, Chiba, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshio
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D004151:Dipeptides / Q000097:blood; D005260:Female; D005978:Glutathione / Q000097:blood; D006801:Humans; D007773:Lactates / Q000097:blood; D008297:Male; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D012372:ROC Curve; D012559:Schizophrenia / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004151:Dipeptides; D007773:Lactates; D005978:Glutathione; C017341:gamma-glutamylcysteine