A quarterly publication of the Autism Research Institute
Summer, 2022 | Number 3, Volume 36
Alterations in the tryptophan pathway may play a role in autism spectrum disorders (ASD) and attention-deficit/hyperactivity disorder (ADHD), according to a new study.
Tryptophan, which is an essential amino acid, is a building block of multiple neurotransmitters. “Some of these,” Ramkripa Raghavan and colleagues note, “are well known such as serotonin, 5-hydroxytryptophan (5-HTP), and melatonin and have been implicated in a number of conditions including depression, mood disorders, ASD, and ADHD.” However, they say, “very few studies to date have assessed other less known tryptophan metabolites, especially in the context of neurodevelopmental conditions.”
To explore this issue, Raghavan and colleagues analyzed the associations between cord-blood levels of tryptophan as well as several metabolites—5-methoxytryptophol (5-MTX), 5-hydroxytryptophan (5-HTP), serotonin, and N-acetyltryptophan—and diagnoses of ASD, ADHD, and other developmental disabilities in childhood. Their study included 996 cord blood samples collected at birth from 326 neurotypical children, 87 children with ASD, 269 children with ADHD, and 314 children with other developmental disabilities (DD). Participants were enrolled in the study at birth and followed up from October 1, 1998 to June 30, 2018.
The researchers report that higher levels of cord blood 5-MTX were significantly associated with lower odds of a diagnosis of ASD or ADHD after adjusting for potential confounders. “Our study supports the hypothesis that 5-MTX may possess neuroprotective abilities with higher levels in cord blood associated with a lower risk of both ASD and ADHD,” they say. “This further suggests a shared etiology between ASD and ADHD.”
The researchers also found that higher levels of tryptophan, 5-HTP, and N-acetyltryptophan were associated with higher odds of ADHD, but not higher odds of ASD or DD. Cord serotonin was not associated with ASD, ADHD, or DD.
Raghavan and colleagues caution that their findings are preliminary, and that additional research is needed to explore temporal relationships between 5-MTX levels and the development of ASD or ADHD symptoms. They add, “Future studies can also explore the combination of metabolites [in] ASD and ADHD, since some research suggests this may lead to good discrimination between individuals with vs. without ADHD.”
“Association between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorder,” Ramkripa Raghavan, Neha S. Anand, Guoying Wang, Xiumei Hong, Colleen Pearson, Barry Zuckerman, Hehuang Xie, and Xiaobin Wang, Translational Psychiatry, July 9, 2022 (free online). Address: Xiaobin Wang, Center on Early Life Origins of Disease, Department of Population, Family and Reproductive Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, [email protected].
