Association of the kynurenine pathway metabolites with clinical, cognitive features and IL-1β levels in patients with schizophrenia spectrum disorder and their siblings

Abstract

Objective: There is evidence suggesting that tryptophan (TRP)-kynurenine (KYN) pathway dysregulation is involved in the pathophysiology of schizophrenia and is regulated by inflammatory cytokines. The study investigate for the first time whether this dysregulation occurs in advanced stages of the disease as a byproduct or emerges as one of the early and inherited manifestations of schizophrenia. Method: Sera of 148 patients with schizophrenia spectrum disorders (SCZ), 139 unaffected siblings (SIB) and 210 controls were investigated. Serum interleukin (IL)-1β levels were measured by ELISA, and TRP, KYN and kynurenic acid (KYNA) levels were measured by a high-performance liquid chromatography system. Also, we collected clinical data by applying Comprehensive Assessment of Symptoms and History in SCZ, and SIS-R in SIB and control groups. Results: Compared to controls, SCZ and SIB groups had lower TRP and higher KYNA levels. TRP levels showed significant differences only between SCZ and controls (p < 0.01). KYNA levels of both SCZ (p ≤ 0.001) and SIB (p < 0.05) were higher than controls. No statistical significance was found for KYN levels across groups. SCZ and SIB groups had higher serum IL-1β levels than controls (p ≤ 0.001). Conclusions: Patients with SCZ and their siblings exhibited similar clinical features and TRP metabolite levels suggesting that TRP-KYN dysregulation may be an inherited component of the disease putatively conferring increased risk to schizophrenia. Elevation of IL-1β is one of the factors promoting overconsumption of the TRP-KYN pathway leading to increased production of neuroregulatory KYNA and presumably to neurodegeneration.