The CHARGE Study: An Epidemiologic Investigation of Genetic and Environmental Factors Contributing to Autism

Division of Epidemiology, Department of Public Health Sciences, School of Medicine, and Medical Investigations of Neurodevelopmental Disorders (MIND) Institute, University of California-Davis, Davis, California, USA.
Environmental Health Perspectives (Impact Factor: 7.98). 08/2006; 114(7):1119-25. DOI: 10.1289/ehp.8483
Source: PubMed

ABSTRACT Causes and contributing factors for autism are poorly understood. Evidence suggests that prevalence is rising, but the extent to which diagnostic changes and improvements in ascertainment contribute to this increase is unclear. Both genetic and environmental factors are likely to contribute etiologically. Evidence from twin, family, and genetic studies supports a role for an inherited predisposition to the development of autism. Nonetheless, clinical, neuroanatomic, neurophysiologic, and epidemiologic studies suggest that gene penetrance and expression may be influenced, in some cases strongly, by the prenatal and early postnatal environmental milieu. Sporadic studies link autism to xenobiotic chemicals and/or viruses, but few methodologically rigorous investigations have been undertaken. In light of major gaps in understanding of autism, a large case-control investigation of underlying environmental and genetic causes for autism and triggers of regression has been launched. The CHARGE (Childhood Autism Risks from Genetics and Environment) study will address a wide spectrum of chemical and biologic exposures, susceptibility factors, and their interactions. Phenotypic variation among children with autism will be explored, as will similarities and differences with developmental delay. The CHARGE study infrastructure includes detailed developmental assessments, medical information, questionnaire data, and biologic specimens. The CHARGE study is linked to University of California-Davis Center for Children's Environmental Health laboratories in immunology, xenobiotic measurement, cell signaling, genomics, and proteomics. The goals, study design, and data collection protocols are described, as well as preliminary demographic data on study participants and on diagnoses of those recruited through the California Department of Developmental Services Regional Center System.

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Available from: Isaac Pessah, Sep 28, 2015
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    • "Exposure to maternal infections during critical periods of development, such as prenatal and perinatal periods, has also gained attention in the search for the etiology of autism [16] [17]. The increased incidence of autism in certain regions has suggested that there is a link between geography and the genetic predisposition to autism [18] [19] [20]. Bisphenol A (4,4 -dihydroxy-2,2-diphenylpropane; BPA) is one of the environmental toxins that has recently received increased attention. "
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    ABSTRACT: Developmental disorders such as autism and attention deficit hyperactivity disorder (ADHD) appear to have a complex etiology implicating both genetic and environmental factors. Bisphenol A (BPA), a widely used chemical in the plastic containers and in the linings of food and beverage cans, has been suggested to play a possible causative role in some developmental disorders. Here, we report behavioral modifications in Drosophila melanogaster following early exposure to BPA, which may suggest BPA as an environmental risk factor for the behavioral impairments that are the basis of diagnosis of autism and ADHD. In an open field assay with perinatally BPA-exposed and vehicle-treated control Drosophila, different parameters of locomotion (distance travelled, walking speed, spatial movement, mobility, turn angle, angular velocity and meander) were analyzed using the ethovision software. We also examined the repetitive and social interaction behaviors in these flies. In an open field assay, we identified disturbances in the locomotion patterns of BPA-exposed Drosophila that may relate to the decision-making and the motivational state of the animal. An increase in repetitive behavior was observed as an increase in the grooming behavior of Drosophila following BPA exposure. Furthermore, we also observed abnormal social interaction by the BPA-exposed flies in a social setting. These results demonstrate the effect of the environmentally prevalent risk agent BPA on the behavior of Drosophila, and suggest the practicability and the ease of using Drosophila as a model in the studies of neurobehavioral developmental disorders. Copyright © 2015. Published by Elsevier B.V.
    Behavioural Brain Research 02/2015; 284. DOI:10.1016/j.bbr.2015.02.001 · 3.03 Impact Factor
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    • "IgG was purified from blood plasma from two mothers of children with autistic disorder (MAU) and from three mothers of children with typical development (MTD). The MAU samples were collected from a group of mothers previously identified to possess IgG antibody reactivity recognizing the 37 kDa and 73 kDa fetal brain proteins, whereas no MTD samples possess fetal brain IgG reactivity 3 years after the birth of the child, immediately following verified diagnosis [22]. IgG samples were purified from plasma under sterile conditions using protein A/G columns and dialyzed against sterile saline. "
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    ABSTRACT: Multiple studies have implicated a role of maternal autoantibodies reactive against fetal brain proteins specific to autism in the etiology of autism spectrum disorders (ASD). In the current study, we examined the impact of brain-reactive maternal autoantibodies of mothers of children with autism (MAU) on offspring behavior in mice compared to offspring exposed to non-reactive IgG of mothers of typically developing children (MTD). Embryonic offspring were exposed to a single intraventricular injection of MAU or MTD IgG on embryonic day 14. Offspring were allowed to mature to adulthood and were subsequently tested for sociability and stereotypic behaviors using a 3-chambered social approach task, marble burying task, and assessment of spontaneous grooming behaviors in response to a novel environment. Results indicate that MAU offspring display autistic-like stereotypic behavior in both marble burying and spontaneous grooming behaviors. Additionally, small alterations in social approach behavior were also observed in MAU offspring compared to MTD offspring. This report demonstrates for the first time the effects of a single, low dose intraventricular exposure of IgG derived from individual MAU samples on offspring behavior.
    Behavioural brain research 06/2014; 266:46-51. DOI:10.1016/j.bbr.2014.02.045 · 3.03 Impact Factor
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    • "General population controls were recruited from state birth records, with frequency matching to the age and Regional Center distribution and the projected sex distribution of the ASD cases. Further details of the CHARGE Study have been described elsewhere [25]. "
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    ABSTRACT: The environmental contribution to autism spectrum disorders (ASD) is largely unknown, but household pesticides are receiving increased attention. We examined associations between ASD and maternally-reported use of imidacloprid, a common flea and tick treatment for pets. Bayesian logistic models were used to estimate the association between ASD and imidacloprid and to correct for potential differential exposure misclassification due to recall in a case control study of ASD. Our analytic dataset included complete information for 262 typically developing controls and 407 children with ASD. Compared with exposure among controls, the odds of prenatal imidacloprid exposure among children with ASD were slightly higher, with an odds ratio (OR) of 1.3 (95% Credible Interval [CrI] 0.78, 2.2). A susceptibility window analysis yielded higher ORs for exposures during pregnancy than for early life exposures, whereas limiting to frequent users of imidacloprid, the OR increased to 2.0 (95% CI 1.0, 3.9). Within plausible estimates of sensitivity and specificity, the association could result from exposure misclassification alone. The association between imidacloprid exposure and ASD warrants further investigation, and this work highlights the need for validation studies regarding prenatal exposures in ASD.
    Environmental Health 01/2014; 13(1):3. DOI:10.1186/1476-069X-13-3 · 3.37 Impact Factor
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