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Kynurenine Pathway in Autism Spectrum Disorders in Children

Journal article
Authors V. Bryn
R. Verkerk
Ola H. Skjeldal
O. D. Saugstad
H. Ormstad
Published in Neuropsychobiology
Volume 76
Issue 2
Pages 82-88
ISSN 0302-282X
Publication year 2018
Published at Gillberg Neuropsychiatry Centre
Pages 82-88
Language en
Links dx.doi.org/10.1159/000488157
Keywords Autism spectrum disorders, Kynurenine pathway, Kynurenic acid, Tryptophan, major depressive disorder, amino-acid receptors, quinolinic acid, tryptophan catabolites, brain tryptophan, metabolism, inflammation, disease, plasma, serum, Neurosciences & Neurology, Psychiatry, Psychology, one tw, 1993, pharmacological reviews, v45, p309, one tw, 1981, european journal of pharmacology, v72, p411
Subject categories Neurobiology

Abstract

Background: There is increasing evidence that altered immune responses play a role in the pathogenesis of autism spectrum disorders (ASD), together with dysfunction of the serotonergic and glutamatergic systems. Since the kynurenine (KYN) pathway that degrades tryptophan (TRP) is activated in various neuroinflammatory states, we aimed to determine whether this pathway is activated in ASD. Methods: Sixty-five pediatric ASD patients (including 52 boys) were enrolled from an epidemiological survey covering 2 counties in Norway; 30 (46.5%) of these patients were diagnosed with childhood autism, 16 (24.6%) with Asperger syndrome, 12 (18.5%) with atypical autism, 1 (1.5%) with Rett syndrome, and 6 (9.2%) with other ASD. The serum levels of the following markers were measured in the children with ASD and compared to those in 30 healthy children: TRP, KYN, kynurenic acid (KA), 3-hydroxykynurenine, and quinolinic acid. Results: The mean serum level of KA was significantly lower in the ASD group than in the healthy controls (28.97 vs. 34.44 nM, p = 0.040), while the KYN/KA ratio was significantly higher in the ASD group (61.12 vs. 50.39, p = 0.006). The same relative values were found when comparing the childhood autism subgroup with the controls. Also, the mean serum level of TRP was significantly lower in children with a subdiagnosis of childhood autism than in those with Asperger syndrome (67.26 vs. 77.79 mu m, p = 0.020). Conclusion: Our study indicates that there is an increased neurotoxic potential and also a possible lower KYN aminotransferase activity in ASD. (C) 2018 S. Karger AG, Basel

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