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

<div><p>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 (<i>n</i> = 25) and compared them with those in age- and gender-matched healthy subjects (<i>n</i> = 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.</p></div

Correlations between serum levels of metabolites and CP equivalent (mg) or duration of illness (months).

<p>Correlations between serum levels of metabolites and CP equivalent (mg) or duration of illness (months).</p

Serum levels of metabolites (µmol/L) that were differentially expressed between controls and schizophrenia patients.

<p>Only <i>p</i> values below 0.05 are included in this table.</p><p>*Non-parametric Mann-Whitney <i>U</i>-test.</p>a<p>Significantly different following Bonferroni correction (<0.05/34).</p

Receiver operating characteristic (ROC) curve analyses of γ-GluCys (a), lenoleic acid (b), and D-lactate (c).

<p>Receiver operating characteristic (ROC) curve analyses of γ-GluCys (a), lenoleic acid (b), and D-lactate (c).</p

Characteristics of subjects.

<p>The comparison between 2 groups was performed using the χ² test for gender difference and smoking, and the Student’s <i>t</i>-test for age and body mass index (BMI).</p

Correlation plots of D-lactate and γ-GluCys serum levels in controls (a) and in patients with schizophrenia (b), and between GSH and γ-GluCys in controls (c) and in patients with schizophrenia (d).

<p>Correlation plots of D-lactate and γ-GluCys serum levels in controls (a) and in patients with schizophrenia (b), and between GSH and γ-GluCys in controls (c) and in patients with schizophrenia (d).</p