Posted by Alycia Halladay, PhD, Autism Speaks director for environmental research.
Researchers studying how environmental pollutants may contribute to autism are focusing on the epigenetic effects of these chemicals. They study the way chemicals affect the activity of genes. (I explain more about epigenetics here.)
Now, a new study in the journal Environmental and Molecular Mutagenesis has furthered our understanding of two chemicals common in our modern environment. They include polybrominated diphenyl ethers (PBDEs), which are flame retardants, and polychlorinated biphenyls (PCBs). The commercial use of PCBs was largely discontinued in 1976, after they were linked to cancer. Unfortunately, they had accumulated in our environment, where they persist to this day.
Geneticist Janine LaSalle, Ph.D., of the MIND Institute at the University of California-Davis, led a recent investigation into whether the brains of individuals with autism have higher levels of these chemicals than the brains of typically developed persons and how those levels may affect expression of genes. (Dr. LaSalle described her previous research on flame retardants in this blog for Autism Speaks.)
For their study, Dr. LaSalle’s team obtained postmortem brain tissue from Autism Speaks Autism Tissue Program. The tissue had been stored at the Harvard Brain and Tissue Resource Center and the NICHD Brain and Tissue Bank for Developmental Disorders.
They analyzed brain samples from three groups of individuals. One group had autism of unknown genetic cause. A second had autism and a neurodevelopmental disorder with a known genetic basis such as Down syndrome, Rett syndrome, Angelman syndrome or Prader–Willi syndrome. A third, comparison group had no known neurodevelopmental problems.
Through a collaboration with toxicologist Paul Kostyniak, Ph.D., at SUNY Buffalo, the researchers measured levels of eight PCBs and seven PBDEs in the tissue samples.
The study found increased levels of one PCB – PCB95 – in those with autism linked to a known genetic disorder. Most individuals in this group had a rare disorder called Dup15q, which is caused by a duplication of genes on chromosome 15. Some had Prader Willi Syndrome, caused by a genetic mutation on chromosome 15. Curiously, they were all born after 1980, or after PCBs were banned. This is important because it supports other findings that PCBs persist in the environment and are detected in tissues from individuals born after they should not have been directly exposed.
The brain samples of those with autism associated with no known genetic disorder did not have significantly elevated levels of PCBs. Clearly, banning such chemicals can make a big difference with many PCBs, while others persist in the environment.
Why were the levels of PCB 95 significantly elevated only in the group who had a genetic mutation on chromosome 15? It could be that this genetic mutation interfered with the way that PCBs are broken down in the body. The investigators did not directly test this.
The researchers also analyzed all of the brain tissue samples for DNA methylation, an epigenetic marker. This involves the addition of methyl groups that essentially shut down gene activity. PCBs had been shown to alter methylation in other studies. In fact, the researchers found a significant decrease in methylation in the group with the highest level of PCBs.
This suggests that gene activity was probably turned on. Potentially, this could turn on a gene that disrupts normal functioning. However, it is not clear whether the PCB or the genetic mutation affected methylation.
Last, this study demonstrated that researchers can use postmortem brain tissue to study gene-environment interactions in autism. Brain tissue has unique types of cells that can provide information that other cells in the body can’t. Also, these findings suggest that identifying genetic markers in ASD can further our understanding of the role of environmental exposures in the brain’s development.
The results of her study surprised Dr. LaSalle. She explained: “We had intended the group with known genetic disorders to be a control group because we knew the cause of their disorder. But these results have now opened my eyes to think about how persistent environmental chemicals may predispose individuals to genetic changes. We have much more work to do to fully understand the implications of these surprising results.”