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Association between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorder

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dc.contributor.authorRaghavan, Ramkripaen
dc.contributor.authorAnand, Neha S.en
dc.contributor.authorWang, Guoyingen
dc.contributor.authorHong, Xiumeien
dc.contributor.authorPearson, Colleenen
dc.contributor.authorZuckerman, Barryen
dc.contributor.authorXie, Hehuangen
dc.contributor.authorWang, Xiaobinen
dc.date.accessioned2022-11-01T15:08:51Zen
dc.date.available2022-11-01T15:08:51Zen
dc.date.issued2022-07-09en
dc.description.abstractAlterations in tryptophan and serotonin have been implicated in various mental disorders; but studies are limited on child neurodevelopmental disabilities such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD). This prospective cohort study examined the associations between levels of tryptophan and select metabolites (5-methoxytryptophol (5-MTX), 5-hydroxytryptophan (5-HTP), serotonin, N-acetyltrytophan) in cord plasma (collected at birth) and physician-diagnosed ASD, ADHD and other developmental disabilities (DD) in childhood. The study sample (n = 996) derived from the Boston Birth Cohort, which included 326 neurotypical children, 87 ASD, 269 ADHD, and 314 other DD children (mutually exclusive). These participants were enrolled at birth and followed-up prospectively (from October 1, 1998 to June 30, 2018) at the Boston Medical Center. Higher levels of cord 5-MTX was associated with a lower risk of ASD (aOR: 0.56, 95% CI: 0.41, 0.77) and ADHD (aOR: 0.79, 95% CI: 0.65, 0.96) per Z-score increase, after adjusting for potential confounders. Similarly, children with cord 5-MTX >= 25th percentile (vs. <25th percentile) had a reduction in ASD (aOR: 0.27, 95% CI: 0.14, 0.49) and ADHD risks (aOR: 0.45, 95% CI: 0.29, 0.70). In contrast, higher levels of cord tryptophan, 5-HTP and N-acetyltryptophan were associated with higher risk of ADHD, with aOR: 1.25, 95% CI: 1.03, 1.51; aOR: 1.32, 95% CI: 1.08, 1.61; and aOR: 1.27, 95% CI: 1.05, 1.53, respectively, but not with ASD and other DD. Cord serotonin was not associated with ASD, ADHD, and other DD. Most findings remained statistically significant in the sensitivity and subgroup analyses.en
dc.description.notesThis study is supported in part by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) under grant number R40MC27443, Autism Field-initiated Innovative Research Studies Program; and grant number UJ2MC31074, Autism Single Investigator Innovation Program. The Boston Birth Cohort (the parent study) was supported in part by the National Institutes of Health (NIH) grants (R21AI079872, R01HD086013, 2R01HD041702, R01HD098232, R01ES031272, R01ES031521). This information or content and conclusions are those of the authors and should not be construed as the official position or policy of, nor should any endorsements be inferred by HRSA, HHS, or the U.S. Government.en
dc.description.sponsorshipHealth Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) [R40MC27443, UJ2MC31074]; National Institutes of Health (NIH) [R21AI079872, R01HD086013, 2R01HD041702, R01HD098232, R01ES031272, R01ES031521]en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1038/s41398-022-01992-0en
dc.identifier.issn2158-3188en
dc.identifier.issue1en
dc.identifier.other270en
dc.identifier.pmid35810183en
dc.identifier.urihttp://hdl.handle.net/10919/112328en
dc.identifier.volume12en
dc.language.isoenen
dc.publisherSpringer Natureen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectplatelet serotonin levelsen
dc.subjectpineal-glanden
dc.subject5-methoxytryptophol rhythmsen
dc.subjectelectrical responsesen
dc.subjectseasonal-variationsen
dc.subjectmelatonin levelsen
dc.subjectyoung-adultsen
dc.subjectchildrenen
dc.subjectpregnancyen
dc.subjectcellsen
dc.titleAssociation between cord blood metabolites in tryptophan pathway and childhood risk of autism spectrum disorder and attention-deficit hyperactivity disorderen
dc.title.serialTranslational Psychiatryen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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