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.

Concentrations of l-tryptophan (l-Trp) and its metabolite, l-kynurenine (l-KYN), in sera of 19 normal subjects (age: 23.6 ± 3.5 y, male: 8, female: 11) were determined by high-performance liquid chromatography with mass-spectrometric detection, following their derivatization with (R)-(−)-4-(N, N-dimethylaminosulfonyl)-7-(3-isothiocyanatopyrrolidin-1-yl)-2,1,3-benzoxadiazole (DBD-PyNCS). A significant positive correlation between l-Trp and l-KYN concentrations was observed (r = 0.532, P < 0.05). Serum l-Trp concentration in male subjects (95.65 ± 4.27 μM) was significantly higher than that in female subjects (79.20 ± 3.34 μM; P < 0.05), while no significant differences in l-KYN concentration or the l-KYN:l-Trp ratio were observed between male and female subjects.

No abstract

The concentrations of l-tryptophan (Trp) and the metabolite l-kynurenine (KYN) can be used to evaluate the in-vivo activity of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO). As such, a novel method involving derivatization of l-Trp and l-KYN with (R)-4-(3-isothiocyanatopyrrolidin-1-yl)-7-(N,N-dimethylaminosulfonyl)-2,1,3-benzoxadiazole (DBD-PyNCS) and separation by high-performance liquid chromatography (HPLC) with tandem mass spectrometric (MS/MS) detection on a triazole-bonded column (Cosmosil HILIC®) was developed to determine their concentrations. The optimized mobile phase, CH3 CN/10 mm ammonium formate in H2 O (pH 5.0) (90:10, v/v) eluted isocratically, resulted in satisfactory separation and MS/MS detection of the analytes. The detection limits of l-Trp and l-KYN were approximately 50 and 4.0 pm, respectively. The column temperature affected the retention behaviour of the Trp and KYN derivatives, with increased column temperatures leading to increased capacity factors; positive enthalpy changes were revealed by van't Hoff plot analyses. Using the proposed LC-MS/MS method, l-Trp and l-KYN were successfully determined in 10 μL human serum using 1-methyl-l-Trp as an internal standard. The precision and recovery of l-Trp were in the ranges 2.85-9.29 and 95.8-113%, respectively, while those of l-KYN were 2.51-16.0 and 80.8-98.2%, respectively. The proposed LC-MS/MS method will be useful for evaluating the in vivo activity of IDO or TDO. Copyright © 2016 John Wiley & Sons, Ltd.

No abstract