Fetal and postnatal metal dysregulation in autism

• Published in: Nature communications Vol. 8; no. 1; pp. 15493 - 10
• Main Authors: Arora, Manish, Reichenberg, Abraham, Willfors, Charlotte, Austin, Christine, Gennings, Chris, Berggren, Steve, Lichtenstein, Paul, Anckarsäter, Henrik, Tammimies, Kristiina, Bölte, Sven
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-06-2017; Nature Publishing Group; Nature Portfolio
• Subjects: 631/378/2649; 692/617/375; Adolescent; Attention Deficit Disorder with Hyperactivity - metabolism; Autism; Autistic Disorder - metabolism; Biomarkers; Biomarkers - metabolism; BLOOD LEAD; Case-Control Studies; CHEMICALS; Child; CHILDREN; DE-NOVO MUTATIONS; Environmental Health and Occupational Health; Female; Fetus - metabolism; Heavy metals; Humanities and Social Sciences; Humans; Hypotheses; Male; MANGANESE EXPOSURE; Medicin och hälsovetenskap; Metals - metabolism; Miljömedicin och yrkesmedicin; multidisciplinary; Neurosciences; Neurovetenskaper; Science; Science (multidisciplinary); Severity of Illness Index; SPECTRUM DISORDERS; Sweden; TEETH; Tooth - metabolism; TWIN; Twin Studies as Topic; Twins; ZINC; New York; United States > US; Sweden
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/ncomms15493

Genetic and environmental factors contribute to the etiologies of autism spectrum disorder (ASD), but evidence of specific environmental exposures and susceptibility windows is limited. Here we study monozygotic and dizygotic twins discordant for ASD to test whether fetal and postnatal metal dysregulation increases ASD risk. Using validated tooth-matrix biomarkers, we estimate pre- and post-natal exposure profiles of essential and toxic elements. Significant divergences are apparent in metal uptake between ASD cases and their control siblings, but only during discrete developmental periods. Cases have reduced uptake of essential elements manganese and zinc, and higher uptake of the neurotoxin lead. Manganese and lead are also correlated with ASD severity and autistic traits. Our study suggests that metal toxicant uptake and essential element deficiency during specific developmental windows increases ASD risk and severity, supporting the hypothesis of systemic elemental dysregulation in ASD. Independent replication in population-based studies is needed to extend these findings.
The contribution of metal exposure to the etiology of ASD is unclear. Here the authors tested whether elemental dysregulation contributes to ASD risk by analysing tooth metal biomarkers from ASD discordant twins, and found significant differences in metal uptake between ASD cases and their control twin siblings, but only during certain developmental periods.