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.