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2002 Progress Report: Environmental Factors in the Etiology of Autism; Childhood Autism Risks from Genetics and the Environment (The CHARGE Study)

EPA Grant Number: R829388C004
Subproject: this is subproject number 004 , established and managed by the Center Director under grant R829388
(EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
Center: CECEHDPR - University of California at Davis Center for the Study of Environmental Factors in the Etiology of Autism
Center Director: Pessah, Isaac N.
Title: Environmental Factors in the Etiology of Autism; Childhood Autism Risks from Genetics and the Environment (The CHARGE Study)
Investigators: Hertz-Picciotto, Irva , Beckett, Laurel , Hansen, Robin
Current Investigators: Hertz-Picciotto, Irva , Croen, Lisa , Hansen, Robin
Institution: University of California - Davis
EPA Project Officer: Saint, Chris
Project Period: September 30, 2001 through September 29, 2002
Project Period Covered by this Report: September 30, 2001 through September 29, 2002
RFA: Centers for Children's Environmental Health and Disease Prevention Research (2001)
Research Category: Children's Health , Health Effects

Description:

Objective:

The causes and contributing factors for autism are poorly understood. Evidence suggests that incidence is increasing, but diagnostic changes & improvements may be playing a role. Both genetic and environmental factors appear to play a role. Autopsy studies demonstrate structural changes in the brain and clinical investigations reveal neurophysiologic differences in information processing in autistic vs. normal children. Members of our team recently demonstrated altered levels of certain neuropeptides at birth in children who later developed autism.

The proposed case-control study will be the first large-scale epidemiologic investigation of underlying causes for autism and triggers of regression. This study will capitalize on the strengths of the case-control design, which is well suited to examine a broad array of factors for rare conditions that are thought to be multifactorial. Comparisons will be made with both general population controls and mentally retarded children.

The aims are to assess the influence of exogenous exposures, the role of susceptibility factors, and the interplay between these two in the etiology of autism and its phenotypic variation. Chemicals with known or suspected neurodevelopmental toxicity, such as PCB’s, certain pesticides, and metals, will be investigated. This study will also pursue several hypotheses that have recently gained attention, including the combined measles, mumps, rubella vaccine and mercury present in vaccines given during infancy and early childhood. Additionally, biochemical susceptibility will be examined through characterization of metabolic, immunologic, and neuronal gene expression profiles and genetic polymophisms.

Progress Summary:

Start up Hiring and training of project personnel began in the fall of 2001.

IRB Approvals For the past nine months protocols have been undergoing revisions and additions. The original protocol and consent form was approved by the UC Davis IRB. These, with additional components required by UCLA, were submitted to their IRB in August 2001, revised and resubmitted in Nov. and Feb., and were finally approved in Mar 2002. Because of our use of the newborn blood spots archived by the State of California, materials were submitted in January to the State IRB, and were approved in March. Fifteen items, in all, along with their Spanish translations, have been reviewed and approved or are pending approval, including scripts, consent forms, assessment instruments, questionnaires, protocol, brochures, flyer, etc.

Regional Centers Key partners for our study are the Regional Centers (RCs) that determine eligibility and keep records on all children who qualify for Developmental Services in California. It is through these RCs that we will identify children eligible to enroll in our study as cases of autistic children, or children with mental retardation. Six RCs have signed on to participate, including: Valley Mountain RC, North Bay RC, Alta RC (northern Calif), Westside RC, Lanterman RC, East Los Angeles RC (southern Calif). In Los Angeles, this work is being carried out by Dr. Marian Sigman and Dr. Michael Bono.

Community Advisory Council The Community Advisory Council was convened in April 2002. There were 19 attendees at our first meeting, including representatives from three parent organizations (FEAT, FACES, and CAN), from the RCs for Developmental Services, and from the California Department of Developmental Services.

Assessment Protocol Development An all-day meeting was held to discuss the battery of assessment tools to be used. In addition to the instruments originally proposed, the Family History Interview was adopted as crucial to the phenotypic characterization of our cases, i.e., with regard to phenotypes of first-degree relatives. Two other draft questionnaires were presented: one on regression, i.e., loss of language and other social skills that had been acquired; the other on multiple languages used in the home.

Database Development Several internet-based systems are being developed. These will enable staff from anywhere to enter data directly into one database on a single server. This server is protected by a firewall and backups will occur daily. Information on potential participants from each Regional Center will be entered directly from the RC. Both the UCLA and UC Davis sites will track all phone contacts, appointments made, visits completed (or not), interviews, and medical records obtained. Each user will have access to only those elements they have a need to see.

Future Activities:

The protocol for control identification will be developed; the tracking and RC chart abstraction systems will be completed; and a pilot study will be conducted to test out the protocols for subject (case and control) identification, recruitment, and clinical assessment (both medical and psychometric). The pilot study will be carried out at both the UC Davis and UCLA clinic sites. Additionally, drafts of parental questionnaires on exposures will be developed. Year 2 will begin with an evaluation of the pilot study and submission of the parental interviews to the IRBs.

Journal Articles:

No journal articles submitted with this report: View all 2 publications for this subproject

Supplemental Keywords:

Autism, environmental epidemiology, neurodevelopment, neurotoxicology, , ENVIRONMENTAL MANAGEMENT, Scientific Discipline, Health, RFA, PHYSICAL ASPECTS, Susceptibility/Sensitive Population/Genetic Susceptibility, Risk Assessment, Biology, Risk Assessments, Disease & Cumulative Effects, genetic susceptability, Health Risk Assessment, Physical Processes, Chemistry, Children's Health, biomarkers, exposure assessment, xenobiotics, neurological development, autism, synergistic interactions, mechanisms, human health risk, susceptibility, halogenated aromatics, etiology, gene-environment interaction, neurotoxic, biological markers, children, neurobehavioral, pesticides, chemical exposure, exposure, biomarker, neurobehavioral effects, human exposure, neurodevelopmental, neurotoxicity

Progress and Final Reports:
Original Abstract
2003 Progress Report
2005 Progress Report


Main Center Abstract and Reports:
R829388    CECEHDPR - University of California at Davis Center for the Study of Environmental Factors in the Etiology of Autism

Subprojects under this Center: (EPA does not fund or establish subprojects; EPA awards and manages the overall grant for this center).
R829388C001 Environmental Factors in the Etiology of Autism; Analytic Biomakers (xenobiotic) Core
R829388C002 Environmental Factors in the Etiology of Autism; Cell Activation/Signaling Core
R829388C003 Environmental Factors in the Etiology of Autism; Molecular Biomakers Core
R829388C004 Environmental Factors in the Etiology of Autism; Childhood Autism Risks from Genetics and the Environment (The CHARGE Study)
R829388C005 Environmental Factors in the Etiology of Autism; Animal Models of Autism
R829388C006 Environmental Factors in the Etiology of Autism; Molecular and Cellular Mechanisms of Autism

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The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Conclusions drawn by the principal investigators have not been reviewed by the Agency.

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