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 involvedin the pathophysiology of schizophrenia and is regulated by inflammatory cytokines. The study investigatefor the first time whether this dysregulation occurs in advanced stages of the disease as a byproduct oremerges as one of the early and inherited manifestations of schizophrenia.Method: Sera of 148 patientswith schizophrenia spectrumdisorders (SCZ), 139 unaffected siblings (SIB) and 210controls were investigated. Serum interleukin (IL)-1β levels were measured by ELISA, and TRP, KYN andkynurenic acid (KYNA) levels were measured by a high-performance liquid chromatography system. Also, wecollected clinical data by applying Comprehensive Assessment of Symptoms and History in SCZ, and SIS-R inSIB and control groups.Results: Compared to controls, SCZ and SIB groups had lower TRP and higher KYNA levels. TRP levels showed significantdifferences 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. SCZand 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 levelssuggesting that TRP-KYN dysregulation may be an inherited component of the disease putatively conferring increasedrisk to schizophrenia. Elevation of IL-1β is one of the factors promoting overconsumption of the TRP-KYNpathway leading to increased production of neuroregulatory KYNA and presumably to neurodegeneration.