Differences in the uptake of multiple toxic and essential elements during the second and third trimesters and early postnatal periods are associated with the risk of developing autism spectrum disorders (ASDs), according to researchers from the Senator Frank R. Lautenberg Environmental Health Sciences Laboratory and the Seaver Autism Center for Research and Treatment at Mount Sinai, who used baby teeth in their work.
The critical developmental windows for the observed discrepancies varied for each element, suggesting that systemic dysregulation of environmental pollutants and dietary elements may serve an important role in ASD. In addition to identifying specific environmental factors that influence risk, the study pinpointed developmental time periods when elemental dysregulation poses the biggest risk for autism later in life.
While the genetic components of ASDs have been intensely studied, specific environmental factors and the stages of life when such exposures may have the biggest impact on the risk of developing autism are poorly understood. Previous research has linked fetal and early childhood exposure to toxic metals and deficiencies of nutritional elements with several adverse developmental outcomes, including intellectual disability and language, attentional, and behavioral problems.
“We found significant divergences in metal uptake between ASD-affected children and their healthy siblings, but only during discrete developmental periods,” said Manish Arora, PhD, BDS, MPH, director of exposure biology at the Lautenberg Environmental Health Sciences Laboratory and vice chair and associate professor in the Department of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai.
“Specifically, the siblings with ASD had higher uptake of the neurotoxin lead and reduced uptake of the essential elements manganese and zinc during late pregnancy and the first few months after birth as evidenced through analysis of their baby teeth,” Arora said. “Furthermore, metal levels at 3 months after birth were shown to be predictive of the severity of ASD 8 to 10 years later in life.”
To determine the effects that the timing, amount, and subsequent absorption of toxins and nutrients have on ASD, the researchers used validated tooth-matrix biomarkers to analyze baby teeth collected from pairs of identical and nonidentical twins, of which at least one had an ASD diagnosis. They also analyzed teeth from pairs of normally developing twins that served as the study control group.
During fetal and childhood development, a new tooth layer is formed every week or so, leaving an “imprint” of the microchemical composition from each unique layer, which provides a chronological record of exposure. The team at the Lautenberg Laboratory used lasers to reconstruct these past exposures along incremental markings in the dentine, similar to using growth rings on a tree to determine the tree’s growth history.
“Our data shows a potential pathway for interplay between genes and the environment,” said Abraham Reichenberg, PhD, professor of psychiatry and environmental medicine and public health at the Icahn School of Medicine.
“Our findings underscore the importance of a collaborative effort between geneticists and environmental researchers for future investigations into the relationship between metal exposure and ASD to help us uncover the root causes of autism and support the development of effective interventions and therapies,” said Reichenberg.
The researchers note that more studies are needed to determine whether the discrepancies in the amount of certain metals and nutrients are due to differences in how much a fetus or child is exposed to them or because of a genetic difference in how a child takes in, processes, and breaks them down. The researchers are now recruiting twins or siblings, with and without ADS, for this work. To participate, email theseavercenter@mssm.edu.
The study, “Fetal and Postnatal Metal Dysregulation in Autism,” which also involved researchers from the Karolinska Institutet in Sweden, was published by Nature Communications.
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