At the NIEHS Autism Awareness Month seminar on April 11, speakers focused on gene-environment associations in autism and how tailored learning environments for children with autism can improve their ability to learn and communicate.
The event, moderated by Cindy Lawler, Ph.D., and Astrid Haugen, both from the NIEHS Division of Genes, Environment and Health, included presentations from fellows at the institute Heather Volk, Ph.D.from Johns Hopkins University and John Constantino, MD, from the Washington University School of Medicine. Volk and Constantino’s research overlaps in a number of ways, including the fact that both scientists use twin or family studies to explore gene-environment interactions involved in neurodevelopmental conditions such as autism spectrum disorder (ASD).
“NIEHS supports research that investigates how environmental factors such as air pollution, pesticides, or maternal nutrient levels may interact with genetic factors during development to increase or decrease risk of ASD,” Haugen said.
Heritability, Diagnosis, Intervention
Constantino initially focused on metrics of heritability uncovered from studies of twin children where both or only one of the twins is autistic.
“If a child has autism and they have an identical twin, there’s a 90 percent chance that their twin also has autism,” he said. “If you take a pair of twins who grew up in the same environment and exposures, but cut the twins’ genetic similarity in half, the odds of both being autistic drops to 20%.”
According to Constantino, 85% of autism is caused by a 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 the environmental impact on a disease from twin studies like this one [because] these environmental factors go unmeasured,” he said. “Unless we measure them and study how they interact with genetic factors, we cannot know causality.”
Constantino stressed the importance of early diagnosis and intervention. Unfortunately, he noted, there is a significant increase in inequalities in care between black and African American populations. This could be due to a variety of issues, ranging from the impact of socioeconomic stress to the increased likelihood of polluting industries being located in areas where most residents belong to minorities.
“There is a very sad correlation between genes and environment in our country,” he said. “If your skin color is black or tan, it is associated with cognitive impairment that disproportionately aggravates autism. There is evidence that this is largely due to a general lack of access to services and delays in diagnosis. This delay does not occur because families are uninsured or parents were unaffected, but because of an average 42-month delay in making a diagnosis and racial disparities in accessing intervention services after a diagnosis is made. There is no longer any excuse for that. This is an environmental variable that we have control over and we need to do something about it.”
According to Constantino, there is good news. He found that children who received just five hours of targeted intervention per week for nine weeks showed significant cognitive gains in a current pilot program that pairs early diagnosis with a definitive, autism-specific intervention.
“It would be great to prevent and treat core symptoms, but it’s very important to point out that improving adaptive function — even if the core symptoms don’t change — is very desirable,” he said. “Improvements in communication, composure, and/or response to unexpected everyday events can improve or decrease the quality of life of a person with autism and change the way they adapt to their condition and express themselves.”
environmental stress and autism
Volk also focused on heredity and autism in families, with particular attention to the potential role of air pollution. Both Volk and Constantino found that in families with one child with autism, the frequency of the condition increases with the number of children, but symptoms and severity vary significantly.
“If you look at the ASD phenotype, there’s clearly something happening here,” Volk said. She added that genetic risks are likely to be amplified by environmental stresses, but researchers are not yet sure to what extent.
Constantino and Volk agreed that a limitation of research into autism is that most genetic samples come from people of European descent, which also likely contributes to delays in diagnosis in non-white populations.
“If you want a polygenic risk score that works across all ancestors, you need to test it across all ancestors so that it reflects all of human diversity,” Constantino said. “And we haven’t done that yet.”
Environmental epidemiology suggests that, according to Volk, there are many sites where interventions can improve the quality of life and functioning levels of people with ASD. These include limiting exposure to chemicals in air pollution and pesticides, and limiting maternal exposure in utero, such as alcohol and tobacco. Maternal body mass index and gestational diabetes appear to be influential, but so does “neighborhood deprivation,” i.e.,
“Air pollution has far-reaching effects on developing brain and neurodevelopment,” Volk said. “Numerous studies deal with prenatal air pollution and ASD. Recent work finds poor performance in ASD cases when exposed to environmental pollutants.”
Volk pointed out that the temporal nature of some stresses, such as to heavy metals, makes it difficult to measure the impact on autism risk. Potential avenues for future studies include assessing the body’s exposure to microplastics, flame retardants and other endocrine disrupting chemicals.
(Kelley Christensen is a contract writer and editor for the NIEHS Office of Communications and Public Liaison.)