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

Researchers studied blood chemicals in adults with autism, their family members, and people without autism. They found that adults with autism had lower levels of certain brain chemicals (tryptophan and kynurenic acid) compared to others. Interestingly, family members of people with autism also had some of these chemical differences, but not as severe. This suggests that some biological changes related to autism may run in families and exist on a spectrum.

This 2023 study investigated tryptophan metabolism and the kynurenine pathway in adults with autism spectrum disorder (ASD), their first-degree relatives (broad autism phenotype group), and controls. The research found that adults with ASD had significantly lower tryptophan levels compared to both relatives and controls. Both ASD adults and their relatives showed significantly lower kynurenic acid levels than controls. The study also identified specific correlations between autism symptoms and biochemical markers.

These findings suggest that metabolic alterations persist into adulthood and exist on a continuum, with relatives showing intermediate biochemical changes between ASD individuals and controls.

Findings suggest tryptophan metabolism alterations persist into adulthood in ASD and may exist on a familial continuum. This could inform development of metabolic interventions for adults with ASD and screening approaches for family members. However, clinical applications require validation in larger studies.

Sample size not reported, limiting assessment of statistical power. Study design unclear from abstract. Cross-sectional design prevents determination of causality. Lack of detail about potential confounding variables or medication effects that could influence biochemical measurements.

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.