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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Case-Control Studies
  • Dipeptides / blood
  • Female
  • Glutathione / blood
  • Humans
  • Lactates / blood
  • Male
  • Metabolome*
  • Metabolomics* / methods
  • ROC Curve
  • Schizophrenia / blood
  • Schizophrenia / metabolism*
  • Young Adult

Substances

  • Dipeptides
  • Lactates
  • Glutathione
  • gamma-glutamylcysteine

Grants and funding

This research was financially supported by the Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C) Grant Numbers 23617027 and 25460224, and the Faculty of Pharmaceutical sciences, Toho University. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.