Environmental Factors in the Etiology of Autism

University of California, Davis  

Environmental Factors in the Etiology of Autism
Isaac Pessah, Ph.D.
inpessah@ucdavis.edu
http://www.vetmed.ucdavis.edu/cceh/

Project Description

The mission of the University of California-Davis Center for Children's Environmental Health (CCEH) is to promote daily interactions among a multidisciplinary team of scientists whose main research interest is to understand the complex web of etiologic factors that contribute to autism. The shared philosophy among Center participants is that a better understanding of the immunological and neurobiological mechanisms associated with this neurodevelopmental disorder can not only lead to a better understanding of the mechanisms that influence it but can also accelerate the discovery of effective intervention strategies. The goals of the CCEH are to: (1) better understand the mechanisms by which environmental, immunologic, and molecular factors interact to influence the risk and severity of autism; (2) identify early immunologic, environmental, and genomic markers of susceptibility to autism; (3) develop mouse models of immunologic susceptibility to environmental triggers and define the impact of these triggers on the development of complex behaviors, key brain structures and neurotransmitter receptors relevant to autism; (4) translate the research findings into diagnostic tools that can be used in clinical practice to predict early autism risk; and (5) supply the community with accurate and timely information about autism risk factors. The CCEH organized three interrelated hypothesis-based Research Projects that are supported by five Facility Cores (Administrative, Community Outreach and Translation, Analytical Chemistry, Molecular Genomics, and Statistics). The projects are: Project 1, Environmental Epidemiology of Autism, builds upon the investigators' discovery of immunologic and molecular biomarkers specific to children with autism found in 2-5 year olds enrolled in the CHARGE (Childhood Autism Risks from Genetics and Environment) study. Working closely with the Community Outreach and Translation Core and Project 2, newborn bloodspots and a second set of blood samples (CHARGE-BACK study) from CHARGE children examine the stability over time of these biomarkers. CHARGE-BACK blood samples also provide peripheral immune cells to study how autism alters properties of cell activation, and susceptibility to known immunotoxicants. The investigators launched a new cohort study called Markers of Autism Risk in Babies-Learning Early Signs (MARBLES) that tracks 200 women at high risk of giving birth to an autistic child, starting from early pregnancy and following the pregnancies and the babies to the age of three years. Project 2, Immunological Susceptibilities in Autism, works closely with Project 1 to test the overall hypothesis that autistic children have fundamental defects in cellular immunity that ultimately lead to abnormalities in immune dysfunction and heightened susceptibility to environmental triggers. Project 3, Models of Neurodevelopmental Susceptibility, develops and uses mouse models to understand the relationships between immune system dysfunction and perinatal exposure to environmental toxicants in the development of neurobehavioral disorders in sociability and seizure susceptibility. Working closely with Project 2, the investigators test mouse strains with low (C57BL/6J) or high (SJL mice) susceptibility to autoimmunity to determine how perinatal exposures to methylmercury, noncoplanar PCB, or polybrominated diphenyl ether 47 (BDE 47) influence brain development, complex social behaviors, and immune system function.

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Project Highlights

Several disclosures have been filed for developing diagnostic markers of autism. One of these is based on the initial result obtained from transcriptional analysis that identified 5 dysregulated CD8+ and NK genes that distinguish autism from general population and MR/DD. A second disclosure focuses on immune markers including autoantibodies in a larger percentage of mothers of autistic children and the children themselves. These discoveries are likely to have an impact on clinical medicine through the development of early diagnostic markers. Importantly the findings are already redefining what kind of environmental triggers we should be concerned about in autism risk and how to study their potential influence.

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