Changes in serum levels of kynurenine metabolites in paediatric patients affected by ADHD

Abstract

This study aims at determining serum levels of tryptophan and other metabolites of the kynurenine pathway in children with attention deficit hyperactivity disorder (ADHD) compared to healthy controls. Such metabolites interact with glutamate receptors in the central nervous system, potentially modulating mechanisms that are pivotal in ADHD and thus potentially representing peripheral biomarkers of the disorder. We measured serum levels of tryptophan and some metabolites of the kynurenine pathway in 102 children with ADHD and 62 healthy controls by liquid chromatography-tandem mass spectrometry (LC-MS/MS). As compared to healthy controls, children with ADHD showed a reduction in serum levels of anthranilic acid (-60%), kynurenic acid (-11.2%), and xanthurenic acid (-12.5%). In contrast, serum levels of tryptophan (+11.0%) and kynurenine (+48.6%) were significantly enhanced, and levels of quinolinic acid were unchanged in children with ADHD. In a logistic regression model, the presence of ADHD was predicted by low anthranilic acid and high tryptophan levels. These findings support the involvement of the kynurenine pathway in the pathophysiology of ADHD and suggest that anthranilic acid and tryptophan levels should be investigated as potential peripheral biomarker for ADHD.

Altered kynurenine pathway metabolites in a mouse model of human attention-deficit hyperactivity/autism spectrum disorders: A potential new biological diagnostic marker

“…In addition, shorter pregnancy durations and lower birth weights are linked to symptom severities and increased 3-HK and IFN-γ levels in children with ADHD 32 . Moreover, ADHD children with or without comorbidities show significantly reduced AA and KYNA serum levels and increased TRP and KYN levels 67 . In contrast, ADHD is associated with lower concentrations of TRP, KYNA, and 3-HAA in the serum in adults 68 , and mean serum levels of TRP and KYNA and KYNA/KYN ratio are significantly lower in patients with ASD 69 .…”

The Potential Influence of the Microbiome on the Development and Progression of ADHD

“…A Norwegian study using 133 adult ADHD patients and 133 without found that the ADHD group had lower levels of tryptophan and neuroprotective KA and XA [86]. These data were confirmed by another study testing ADHD children, which exhibited lower KA and XA levels [93]. These researchers, however, recorded higher levels of tryptophan in ADHD subjects [93].…”

Human Gut-Microbiota Interaction in Neurodegenerative Disorders and Current Engineered Tools for Its Modeling

“…In fact, many other human studies found in the literature addressing the role of gut microbiota in brain disorders are about the spectrum of behavior disorders, such as Attention-deficit/hyperactivity disorder (Jiang et al, 2018 ); stress-related disorders (Ghavami et al, 2018 ); and major depressive disorder (Lin et al, 2017 ; Chen et al, 2018 ). The approaches used to investigate possible connections between gut and brain include (i) gut microbial manipulation with antibiotics (Schmidt et al, 2018 ); (ii) pre/probiotics administration (Tillisch et al, 2013 ; Chambers et al, 2015 ); (iii) fecal microbiota transplantation (Jalanka et al, 2018 ); (iv) post-mortem examination of the brain (Zhan et al, 2016 ); (v) metabolomics/metagenomics analysis of biological samples (e.g., feces, mucosal biopsy) (Evangelisti et al, 2017 ; Labus et al, 2017 ).…”