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


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Noyan H., Erdağ E. , Tüzün E. , Yaylım İ. , Küçükhüseyin Ö. , Hakan M. T. , ...More

Schizophrenia Research, vol.229, pp.27-37, 2021 (Journal Indexed in SCI)

  • Publication Type: Article / Article
  • Volume: 229
  • Publication Date: 2021
  • Doi Number: 10.1016/j.schres.2021.01.014
  • Title of Journal : Schizophrenia Research
  • Page Numbers: pp.27-37

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 patientswith schizophrenia spectrumdisorders (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.