UC Davis has been at the forefront of research on the role of environment in risk for neurodevelopmental disorders like autism and other learning and behavioral disorders. The UC Davis MIND Institute has been home to the Center for Children’s Environmental Health (CCEH) since 2001. Funded jointly by the National Institute of Environmental Health Sciences and the US Environmental Protection Agency, the CCEH focuses its research on connections and interactions between the immune system, genetic susceptibility, and environmental exposures (for example pesticides, air pollution and others), and autism risk. The CCEH is one of fourteen Children’s Environmental Health Centers across the country. CCEH scientific papers can be viewed and downloaded here.
Environmental Epidemiology – Irva Hertz-Picciotto, MPH, PhD
In 2003, the CCEH launched Childhood Autism Risk from Genes and Environment (the CHARGE Study), a retrospective, case-control study of California children ages 2-5 years of age. The CHARGE study is currently ongoing and has enrolled approximately 2000 children and their immediate family members. With a highly multidisciplinary team and approach, the CHARGE study has explored a wide range of environmental and internal factors that have the potential to influence risk and resilience in the development of autism. Some of the factors the CHARGE Study has investigated include: heavy metals; pesticides; flame retardants; traffic-related air pollutants; maternal health conditions; immune factors; and prenatal vitamins such as folic acid.
To complement the knowledge made possible by the CHARGE Study, a new study was launched in 2006. Markers of Autism Risk in Babies–Learning Early Signs (the MARBLES Study) is a prospective pregnancy cohort study which enrolls women who already have at least one child with autism and who are either pregnant or planning a pregnancy. The MARBLES Study follows the mothers during their pregnancy and follows their infants until age three. Like the CHARGE Study, MARBLES is studying the maternal and child environment and biological characteristics that together may influence a child’s risk for developing autism.
Perinatal Epigenetics – Janine LaSalle, PhD and Rebecca Schmidt, PhD
Though autism has a high rate of heritability in families, environmental factors can modify genetic risk. Epigenetics is the study of factors that determine how and when genes are turned on and off, and can help to understand processes in the maintenance of health and in the development of disease, including neurodevelopmental disorders like autism. Drs. Janine LaSalle and Rebecca Schmidt are studying the role of epigenetic influences during pregnancy and early in an infant’s life when both the nervous and immune systems are highly dynamic. In particular, they are interested in the relationship between exposure to certain environmental chemicals and effects on DNA methylation, an epigenetic signalling tool that keeps genes turned off. Additionally, they are interested in the effect on DNA methylation from prenatal supplementation with folic acid, a nutrient that has been shown to reduce risk for neural tube defects and, more recently autism.
For a short educational video on epigenetic influences on development, click here.
Immune and Environment in Autism – Judy Van de Water, PhD and Paul Ashwood, PhD
Although autism primarily affects brain function, CCEH research led by Dr. Judy Van de Water has identified widespread changes in the immune system of children with autism. The relationship between the immune and nervous systems and the pathways through which environmental exposures can interfere with these highly interdependent developmental processes is an important avenue of research into the causes and contributing factors in autism. Dr. Van de Water’s research for the CCEH is exploring mTOR pathways (which have been linked to other diseases), and exposure to the class of flame retardant chemicals called PBDEs (polybrominated diphenyl ethers). In her earlier groundbreaking research, Dr. Van de Water discovered that a subgroup of mothers who have a child with autism, have autoantibodies that target proteins in the fetal brain, potentially interfering with important developmental processes.
Gene-Environment Interactions that Influence Autism Risk – Pam Lein, PhD and Isaac Pessah, PhD
The Lein and Pessah labs are applying the biological technology of induced pluripotent stem cells (iPSCs) to develop cell culture models that will enable screening for environmental chemicals or maternal cytokines that interact with autism genes to increase individual risk for autism. The FMR1 gene is considered a risk factor in autism because mutations in the FMR1 gene cause FXTAS or Fragile X Syndrome and individuals with FMR1-linked disorders are much more likely to have autism than individuals without these mutations. iPSCs are being used to create neurons (nerve cells) with one form of the FMR1 gene that is normal, and neurons with the mutated form of the FMR1 gene that gives rise to neurons with structural and signaling problems that are related to autism. The iPSCs allow the research team to study how the different forms of the FMR1 gene interact with environmental factors, particularly environmental chemicals that are known to be harmful to the brain and immune system. This approach has the potential to shed light on the intricate molecular and cellular mechanisms by which gene-environment interactions can result in disruption of brain development resulting in disorders like autism.