Globally attention-deficit/hyperactivity disorder (ADHD) affects around 6% of children and around 5% of adults. While the exact cause of ADHD is unknown, a combination of factors including environmental and genetic are thought to play a role in this neurodevelopmental disorder. Like other psychiatric diseases, such as depression, individuals with ADHD have elevated inflammatory markers such as interleukin-6. Additionally, research has highlighted dysregulation of kynurenine pathway (KP) metabolite levels suggesting that KP activity may drive pathogenesis in ADHD. Therefore, in a recent meta-analysis study, Dr Daniele Cavaleri and colleagues looked at differences in the KP metabolite levels between ADHD patients and healthy controls.
A total of nearly 1,200 individuals were included in this meta-analysis, covering eight studies that focused on tryptophan and its metabolites. Participants with ADHD had significantly higher levels of kynurenine and lower levels of kynurenic acid (KYNA) compared with healthy controls, including individuals who were undergoing treatment. Tryptophan was significantly increased in the ADHD participants who were untreated however, this increase was not observed in individuals receiving treatment. Other KP metabolite levels investigated (3HK, AA, and 3HAA) had high variation between studies and therefore were not correlated with ADHD.
Disrupted glutamatergic transmission has also been reported in ADHD patients and there is evidence of N-methyl-D-aspartate (NMDA) receptor dysfunction. KYNA is a neuroprotective metabolite known to be an NMDA antagonist. Due to the significantly lower levels of KYNA, it is plausible that the loss of KYNA plays a role in ADHD pathogenesis. However, more research into the KP metabolite differences in ADHD needs to be investigated, especially in regard to the neurotoxic metabolite quinolinic acid (QA) given that KYNA and QA have opposite effects on the NMDA receptor.