Deficit of glutamatergic transmission and aberrant function of kynurenine pathway, with disturbed synthesis of glutamate receptors antagonist, kynurenic acid (KYNA) and neurotoxic metabolite of kynurenine, 3-hydroxykynurenine (3-OH-KYN) have been implicated in the pathogenesis of schizophrenia.

Demonstrated by others higher level of KYNA in the brain may cause relative deficiency of glutamate-mediate transmission with resulting behavioural and cognitive changes.

Search for predictors of satisfactory response to antipsychotic treatment based on the analysis of KYNA and 3-OH-KYN serum levels.

Fifty-three patients with chronic schizophrenia and 46 healthy individuals were enrolled in the study. Quantitative analyses of KYNA and 3-OH-KYN were performed using high-pressure liquid chromatography (HPLC) and electrochemical detection, respectively. Clinical assessments (PANSS, SANS, SAPS) and blood analyses were conducted at 3 time-points: during the active phase of disease, after 4 weeks of modified pharmacotherapy, and after reaching remission.

In schizophrenia group, lower levels of KYNA (P = 0.002) and non-altered levels of 3-OH-KYN (p = 0.195), as compared to control, were detected during active phase of disease. Despite clinical improvement, no significant changes in the level of studied metabolites were observed later on. The initial level of 3-OH-KYN correlated negatively (r = –0.368; Spearman's rank) with clinical improvement (negative symptoms) (P < 0.05).

1. The peripheral dysregulation of kynurenine pathway metabolites in chronic schizophrenia manifests as relative increase in the ratio between neurotoxic 3-OH-KYN and neuroprotective KYNA. 2. The higher serum level of 3-OH-KYN during relapse of schizophrenia seems to predict poor response to antipsychotic treatment.

The authors have not supplied their declaration of competing interest.