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UC Davis Center for Children’s Environmental Health
EPA Grant Number: R833292Center: UC Davis Center for Children’s Environmental Health
Center Director: Pessah, Isaac N.
Title: UC Davis Center for Children’s Environmental Health
Investigators: Pessah, Isaac N.
Institution: University of California - Davis
EPA Project Officer: Fields, Nigel
Project Period: September 1, 2007 through August 31, 2011
Project Amount: $7,500,000
RFA: Centers for Children’s Environmental Health and Disease Prevention Research (2005)
Research Category: Children's Health , Health Effects
Description:
Objective:The principal concern of the UC Davis Center for Children’s Environmental Health (CCEH) is to identify and understand environmental, immunologic, and genetic risk factors contributing to the incidence and severity of childhood autism. Autism is a heterogeneous neurodevelopmental disorder defined by core deficits in social reciprocity, communication, and restrictive/repetitive patterns of interest and behavior. Generally accepted estimates of prevalence range from 1:750 for the narrowest diagnostic criteria, to 1:166 for autism spectrum disorder (ASD). The California Department of Developmental Services records on average approximately 700-750 autism diagnoses each quarter. Although autism may be one of the most heritable complex disorders, the defective genes conferring autism risk do not segregate in a simple Mendelian manner. The prevalence of autism is approximately four times higher in males than in females. Results from over ten genome-wide autism screens indicate that potential susceptibility genes are spread across the entire genome. Estimates of the number of genes involved in autism range from 3-10 to 15 and up to 100. However no single locus alone appears to be sufficient to cause the full clinical phenotype. Evaluation of a broader autistic phenotype that included communication and social disorders increased concordance from 60% to 92% in monozygotic twins and from 0% to 10% in dizygotic pairs. These results indicate that interactions among multiple genes are likely to contribute to autism, and that epigenetic factors and exposure to environmental modifiers may contribute significantly to variable expression of autism, and autism-related traits.
The mission of the 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.
Approach:Since it is generally accepted that the earlier an intervention is begun in autistic children, the greater the chances of improvement, an intervention that can be implemented before symptoms have fully manifested should have the strongest impact in reducing severity and potentially even preventing some cases. Thus, early markers of risk are needed to identify children who are at risk. These may include behavioral, environmental, physiologic, biochemical, and genomic markers, and those based on morphological and neuroimaging parameters.
Expected Results:The goals of the CCEH in the next five years 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 our 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.
Supplemental Keywords:autism, genes, environment, mercury, PCBs, PBDEs, immune, autoimmune, neurodevelopment, developmental neurotoxicity, persistent organic pollutants, CHARGE, MARBLES,
Subprojects under this Center:
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R833292C001 PROJECT 1: Environmental Epidemiology of Autism
R833292C002 PROJECT 2: Immunological Susceptibility in Autism
R833292C003 PROJECT 3: Models of Neurosusceptibility