Using evidence found in baby teeth, researchers from the Institute for Exposomic Research at the Icahn School of Medicine at Mount Sinai report that cycles involved in zinc and copper metabolism are dysregulated in autism spectrum disorder (ASD), and can be used to predict who will later develop the disease. The researchers used the teeth to reconstruct prenatal and early-life exposures to nutrient and toxic elements in healthy and autistic children.
Results of the study were published online in Science Advances, a journal published by the American Association for the Advancement of Science.
This is the first study in the world to generate a 90 percent accurate fetal and early childhood biomarker of ASD using a longitudinal analysis of distinct metabolic pathways, and to replicate it in four independent study populations. The results of this research could produce a new diagnostic approach for ASD early in life, before the disorder appears, and could catalyze new treatments and prevention strategies.
About 1 in 68 children has been identified with ASD, according to the U.S. Centers for Disease Control and Prevention. To determine the effects of the dysregulation of zinc and copper metabolism on developing ASD, Mount Sinai researchers used biomarkers in baby teeth collected from twins living in Sweden and replicated these findings in three other populations: a group of non-twin siblings in New York, and two populations of non-related participants from Texas and the United Kingdom.
During fetal and childhood development, a new tooth layer is formed every day. As each of these ‘growth rings’ forms, an imprint of many of the chemicals circulating in the body is captured in each layer, which provides a chronological record of exposure. The research team used lasers to sample these layers and reconstruct the past exposures along incremental markings, similar to using growth rings on a tree to determine the tree’s growth history. This technique, discovered by Manish Arora PhD, BDS, MPH, at Mount Sinai, has informed research in the field of exposomics, the study of the effects of the totality of environmental exposures across the lifespan. It has provided a crucial piece missing from most exposomic analyses of environmental exposures: time. This technique allowed Dr. Arora and his team to reconstruct past exposure including that experienced before birth.
“We found significant divergences between ASD-affected children and their healthy siblings, and used these biomarkers to predict the emergence of disease,” said one of the study’s first authors, Paul Curtin, PhD, Assistant Professor in the Department of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai. “These findings suggest that the cyclical metabolism of nutrients and toxicants is critical to healthy neurodevelopment, and the emergence of autism.”
The other first authors of the study are all from the Mount Sinai Institute for Exposomic Research and the Department of Environmental Medicine and Public Health at the Icahn School of Medicine: Christine Austin, PhD, Instructor; Austen Curtin, PhD, Data Analyst; Chris Gennings, PhD, Director of the Division of Biostatistics and Research Professor; and Manish Arora, PhD, BDS, MPH, FICD, Professor and Vice Chairman of the Department.
“The results of this study are important because they identify specific pathways related to autism pathology, and could lead to an early warning system for ASD and other neurodevelopmental disorders,” said Dr. Arora. “If ASD is diagnosed at a younger age, parents can take advantage of the early introduction of therapies.”
Methods such as tooth analysis has provided the Mount Sinai Institute for Exposomic Research a wide-net approach to observe multiple exposures and patterns at a time. In future studies, the research team plans to use baby teeth to study the association of metal metabolic cycles with attention deficit-hyperactivity disorder and other disorders.
Other institutions involved in this study include the Karolinska Institute, Sweden; the Stockholm County Council, Sweden; the University of Bristol, England; Kings College London, England; University College London, England; Cardiff University, Wales; and the University of Texas.
About The Institute for Exposomic Research
The Institute for Exposomic Research at the Icahn School of Medicine at Mount Sinai is the world’s first research institute devoted to the intensive study of the exposome, or the totality of environmental influences on human health. The mission of the Institute is to understand how the complex mix of nutritional, chemical, and social environments affect health, disease, and development later in life and to translate those findings into new strategies for prevention and treatment. For more information, visit http://icahn.mssm.edu/exposomics.