The NIEHS Autism Awareness month seminar was held April 11. Speakers focused on gene-environment relationships in autism and how to tailor learning environments for children with autism.
Hosted by Cindy Lawler Ph.D., Astrid HaugenThe event featured presentations from institute grantees, both from the NIEHS Genes, Environment, and Health Branch. Heather Volk, Ph.D.Johns Hopkins University. John Constantino, M.D.Washington University School of Medicine. Research by Volk & Constantino intersects in many ways. Both scientists use twin or familial studies to study gene-environment interactions involved with neurodevelopmental conditions, such as autism spectrum disorder (ASD).
Lawler, left is the NIEHS’s lead representative for extramural autism research. Haugen, right, coordinates activities and provides oversight for the institute’s Autism and Environment program. (Photos by Steve McCaw / NIEHS“NIEHS supports research that investigates how environmental factors like air pollution, pesticides, or maternal nutrient levels may interact with genetic factors during development to increase or decrease risk of ASD,” said Haugen.
Heritability, diagnosis and intervention
Constantino’s first focus was on metrics of heritability that were discovered from studies involving twins where one or both of the twins is autistic.
“If a child has autism and they have an identical twin, there’s a 90% chance their twin has autism as well,” he said. “If you take a pair of twins reared in the same environment and the same exposures but cut the genetic similarity of the twins in half, the likelihood of both being autistic plummets to 20%.”
Constantino noted that autism is common across all socioeconomic strata of the U.S.According to Constantino, 85% of autism is caused by population-attributable inherited risk, but the role that gene-environment interactions play in influencing the likelihood of a child having autism is not yet known.
“We often underestimate what the environmental influence is for a condition through twin studies like this [because] those environmental factors remain unmeasured,” he said. “Unless we measure them and study interaction with genetic factors, we can’t know causation.”
Constantino stressed that early diagnosis and intervention are crucial. He noted that there has been a significant rise in care disparities between Black and African American communities. It could be due in part to socioeconomic stress or the increased likelihood that polluting industry are located in areas where there are fewer minorities.
“There’s a very sad gene-environment correlation in our country,” he said. “If the color of your skin is black or brown, that is associated with cognitive impairments that disproportionately compound autism. This is largely due to a lack of access to services and a delay in diagnosis. That delay occurs not because the families are not insured or parents weren’t concerned, but because of an average 42-month delay in establishing a diagnosis, and race-based disparities in access to intervention services after a diagnosis is made. There’s no excuse for this anymore. This is an environmental variable we have control over, and we must do something about it.”
Constantino says there is good news. Constantino pointed out that children who received five hours of targeted intervention per week for nine consecutive weeks showed significant cognitive gains. This is a pilot program that pairs early diagnosis with autism-specific intervention.
“It would be great to prevent and treat core symptoms, but it’s very important to make this point that improvement in adaptive functioning — even if core symptoms don’t change — is very worth pursuing,” he said. “Improvements in communication, composure, and/or response to unexpected day-to-day life events can make or break quality of life of an individual with autism and can change the manner in which they adapt to their condition and express themselves.”
Autism and environmental exposure
Volk also discussed autism in families and heritability, with a particular focus upon the potential role that air pollution could play. Both Volk and Constantino noted that in families with an autistic child, the condition’s incidence increases with the number of children, but symptoms and severity vary significantly.
“ASD occurrence varies wildly throughout the world,” Volk said. “Due to the issue of competing risks, such as bigger challenges to survival, ASD often isn’t diagnosed.” (Photo courtesy of Heather Volk)“Clearly, something is happening broadly here when looking at the ASD phenotype,” Volk said. She stated that genetic risk is likely to be increased by environmental exposures, although researchers aren’t sure to what extent.
Constantino and Volk both agreed that one limitation to the study on autism is that most genetic samples are from people of European ancestry. This likely contributes to delays in diagnosing non-Whites.
“If you want a polygenic risk score that works in all ancestral backgrounds, you have to test it in all ancestral backgrounds so that it represents all human diversity,” Constantino said. “And we haven’t done that yet.”
Volk states that environmental epidemiology suggests that interventions can improve quality and function in ASD patients. These include limiting exposures and pesticides and limiting maternal exposures. Maternal body mass index and gestational diabetes appear to be influential, but so too is “neighborhood deprivation,” meaning a lack of green space and proximity to industrial facilities where there may be greater exposure to fine particulate matter emissions.
“Air pollution has broad effects on the developing brain and neurodevelopment,” said Volk. “Numerous studies look at prenatal air pollution exposure and ASD. More recent papers note poor performance among ASD cases when there is exposure to environmental pollutants.”
Volk noted that some exposures to heavy metals can have a temporal effect, making it difficult to determine the impact on autism risk. Future studies could examine the body burden of microplastics and flame retardants as well as other endocrine-disrupting chemicals.
(Kelley Christensen, a contract writer and editor at the NIEHS Office of Communications and Public Liaison, is this author.
