Kynurenine pathway and autism spectrum phenotypes: an investigation among adults with autism spectrum disorder and their first-degree relatives

Increasing literature highlighted alterations of tryptophan (TRP) metabolism and kynurenine (KYN) pathway in children with autism spectrum disorder (ASD). However, no study specifically focused on adult samples. Meanwhile, several authors stressed the relevance of investigating neurobiological corre...

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Published inCNS spectrums Vol. 28; no. 3; pp. 374 - 385
Main Authors Carpita, Barbara, Nardi, Benedetta, Palego, Lionella, Cremone, Ivan M., Massimetti, Gabriele, Carmassi, Claudia, Betti, Laura, Giannaccini, Gino, Dell’Osso, Liliana
Format Journal Article
LanguageEnglish
Published New York, USA Cambridge University Press 01.06.2023
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Summary:Increasing literature highlighted alterations of tryptophan (TRP) metabolism and kynurenine (KYN) pathway in children with autism spectrum disorder (ASD). However, no study specifically focused on adult samples. Meanwhile, several authors stressed the relevance of investigating neurobiological correlates of adult forms of ASD and of those subthreshold ASD manifestations frequently found in relatives of ASD probands, known as broad autism phenotype (BAP). This work aimed to evaluate circulating levels of TRP and metabolites of KYN pathway in a sample of ASD adults, their first-degree relatives and controls (CTLs), investigating also the correlations between biochemical variables' levels and ASD symptoms. A sample of ASD adults, together with a group of first-degree relatives (BAP group) and unrelated CTLs were assessed by means of psychometric scales. Circulating levels of TRP, KYN, quinolinic acid (QA), and kynurenic acid (KYNA) were assessed in all subjects. ASD patients reported significantly higher total scores than the other groups on all psychometric scales. BAP subjects scored significantly higher than CTLs. ASD patients reported significantly lower TRP levels than BAP and CTL groups. Moreover, significantly lower levels of KYNA were reported in both ASD and BAP groups than in CTLs. Specific patterns of associations were found between autism symptoms and biochemical variables. Our findings confirm in adult samples the presence of altered TRP metabolism through KYN pathway. The intermediate alterations reported among relatives of ASD patients further stress the presence of a continuum between subthreshold and full-threshold ASD phenotypes also from a biochemical perspective.
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ISSN:1092-8529
2165-6509
DOI:10.1017/S1092852922000840