The year brought advances in understanding whether and how chemical pollutants affect brain development in ways that may predispose to autism
Most scientists agree that autism involves early changes in brain development. Decades of research have clearly implicated genes that regulate how brain cells and networks develop and interconnect. This year brought increased evidence that chemical pollutants may similarly affect brain development in ways that increase autism risk.
“Environmental studies have been historically underfunded,” said Alycia Halladay, Ph.D., Autism Speaks senior director of environmental and clinical sciences. “This year we saw a greater emphasis on studies that examine the link between chemical pollutants and autism. Taken together, they show that exposure can affect the developing brain in ways that may lead to autism.”
The July issue of the journal Environmental Health Perspectives featured five articles exploring how exposure to certain pollutants may contribute to the development of autism spectrum disorder (ASD).
In “Tipping the Balance of Autism Risk,” scientists with the University of California’s MIND Institute reviewed past research on pesticide exposure, brain development and ASD. They concluded that evidence strongly suggests that certain pesticides can increase the risk for autism. They noted, however, that too little is known about how the timing or dose of exposure influences risk – or the biological mechanisms involved.
Three of the issue’s research reports helped address these questions. Two focused on polychlorinated biphenols (PCBs). This class of toxic industrial chemicals became widespread in the environment before the U.S. Congress banned their use in 1979. One of the studies used tissue cultures and the other laboratory rats to show how exposure to PCBs can disrupt the development of crucial connections between brain cells. Both studies involved exposure to PCBs at levels still commonly found in the environment.
Another research team examined a possible link between autism and smoking during pregnancy. Based on a large review of birth certificate records, their study included information on more than 3,000 children diagnosed with autism. They found no overall association between smoking during pregnancy and autism. However, they detected a small increased risk for Asperger syndrome. The researchers called for larger and more focused studies to confirm or rule out this possible association. (More on this special issue of Environmental Health Perspectives here.)
Following up on the suspected link between PCBs and autism, another MIND Institute research team compared levels of PCBs in the postmortem brain tissue of individuals with autism with those in brain tissue unaffected by autism. They found elevated levels of one PCB – PCB-95 – in the brains of those with a form of autism linked to mutations on chromosome 15. Only those with these mutations showed the increased PCB, for reasons that remain unclear. However, the researchers suggested that the mutation might affect the body’s ability to clear PCBs from the body.
The investigators also analyzed the brain tissue for DNA methylation, an epigenetic marker associated with reduced gene activity. They found significant decreases in methylation in the brains with the highest PCBs. This suggested that gene activity may have been abnormally “switched on” in ways that disrupt normal brain functioning. Appearing in the August issue of the journal Environmental and Molecular Mutagenesis, the study was made possible by postmortem donations to Autism Speaks Autism Tissue Program.
In yet another landmark environmental study this year, researchers reported some of the first direct evidence of an association between air pollution and autism. A team led by Heather Volk, Ph.D., of the University of Southern California’s Keck School of Medicine, associated exposure to high levels of air pollution during pregnancy and the first year of life with a three-fold increase in autism risk. Their report appeared in a November issue of the Archives of General Psychiatry.
Dr. Volk's team looked at air pollution records associated with the geographic location of more than 500 children and their mothers. The families were part of the California-based Childhood Autism Risks from Genetics and the Environment (CHARGE) study. Roughly half of the children had autism.
"This work has broad public health implications," Dr. Volk said. "We've known for a long time that air pollution is bad for our lungs, especially for children. We're now beginning to understand how air pollution may affect the brain." Dr. Volk and her colleagues are currently pursuing a study supported by Autism Speaks that explores how genetic predisposition to autism may increase vulnerability to certain pollutants. (More on Dr. Volk’s research here.)
Shelton JF, Hertz-Picciotto I, Pessah. Tipping the Balance of Autism Risk: Potential Mechanisms Linking Pesticides and Autism. Environ Health Perspect. 2012; 120(7): 944–951.
Wayman GA, Yang D, Bose DD, et al. PCB-95 Promotes Dendritic Growth via Ryanodine Receptor–Dependent Mechanisms. Environ Health Perspect. 2012; 120(7): 997–1002.
Wayman GA, Bose DD, Yang D, et al. PCB-95 Modulates the Calcium-Dependent Signaling Pathway Responsible for Activity-Dependent Dendritic Growth. Environ Health Perspect. 2012; 120(7): 1003–1009.
Kalkbrenner AE, Braun JM, Durkin MS, et al. Maternal Smoking during Pregnancy and the Prevalence of Autism Spectrum Disorders, Using Data from the Autism and Developmental Disabilities Monitoring Network. Environ Health Perspect. 2012; 120(7): 1042–1048.
Landrigan PJ, Lambertini L, Birnbaum LS. A Research Strategy to Discover the Environmental Causes of Autism and Neurodevelopmental Disabilities. Environ Health Perspect. 2012; 120(7): a258–a260.
Mitchell MM, Woods R, Chi LH, et al. Levels of select PCB and PBDE congeners in human postmortem brain reveal possible environmental involvement in 15q11-q13 duplication autism spectrum disorder. Environ Mol Mutagen. 2012; 53(8): 589-98.
Volk HE, Lurmann F, Penfold B, Hertz-Picciotto I, McConnell R. Traffic-Related Air Pollution, Particulate Matter, and Autism. Arch Gen Psychiatry. Published online Nov 2012.