Autism and environmental influences: review and commentary.
Bello SC. Developmental Pediatrics, PLLC, Latham, New York 12110, USA. Rev Environ Health. 2007 Apr-Jun;22(2):139-56.
Progress has been slow in identifying pre- and post-natal environmental exposures that might trigger the features that characterize autism. During the past thirty years, research in the field of autism has been conducted in a setting in which diagnostic criteria for this condition have changed and broadened, and differences of opinion regarding diagnostic issues and diagnostic terminology continue. The documented prevalence of all forms of autism has increased steadily during this time, suggesting one or more environmental contributors. Not established, however, is whether an increasing incidence of autism is responsible for increasing prevalence. The increase in documented prevalence could result from expanding and changing case definitions and increased reporting due to increased awareness on the part of professionals who work with children and by the public. This review provides a background for the evolving story of autism and describes the research on the relation between autism and the environment, with a particular focus on some of the more recently proposed environmental triggers. Critical analysis of this body of scientific research in a historical framework helps to explain the often controversial nature of the proposed relations between autism and environmental factors, as well as to rationalize some of the pitfalls in research design and in the often questionable interpretation of data so obtained.
Autism and the environment: challenges and opportunities for research.
Altevogt BM, Hanson SL, Leshner AI. Institute of Medicine, Forum on Neuroscience and Nervous System Disorders, 500 Fifth St, NW, Washington, DC 20001, USA. baltevogt@nas.edu Pediatrics. 2008 Jun;121(6):1225-9.
Autism spectrum disorder is a complex developmental disorder that dramatically affects the lives of patients and their families and the broader community. The causes of autism are unknown; however, evidence increasingly suggests that a complex interplay among environmental stressors, genetic mutations, and other biological factors likely plays a significant role in the development and/or progression of autism spectrum disorder. On April 18 and 19, 2007, the Institute of Medicine’s Forum on Neuroscience and Nervous System Disorders hosted a workshop to provide a venue to bring together scientists; major sponsors of autism-related research; and members of the autism patient, family, and advocacy community to discuss the most promising and urgent scientific questions and opportunities. Broad participation by the autism community enriched the meeting significantly by contributing a valuable and personal perspective that is often missing from scientific meetings. It also began a much improved public-private partnership in which all stakeholders are represented. On the basis of the presentations and the discussions that followed, an array of important scientific opportunities were identified in 5 general categories: (1) opportunities to advance clinical research; (2) opportunities to enhance epidemiologic studies; (3) opportunities to improve the understanding of autism’s pathology and etiology; (4) tools and infrastructure needs; and (5) opportunities for public-private partnerships. This workshop demonstrated that full public engagement can greatly enhance activities such as this workshop and its outcomes. Furthermore, we expect that this listing of scientific challenges, needs, and opportunities will help to frame a more comprehensive research agenda.
The CHARGE study: an epidemiologic investigation of genetic and environmental factors contributing to autism.
Hertz-Picciotto I, Croen LA, Hansen R, Jones CR, van de Water J, Pessah IN. 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. ihp@ucdavis.edu Environ Health Perspect. 2006 Jul;114(7):1119-25.
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.
Identifying environmental contributions to autism: provocative clues and false leads.
Lawler CP, Croen LA, Grether JK, Van de Water J. Division of Extramural Research and Training, National Institute of Environmental Health Sciences, PO Box 1123, MD EC-23, Research Triangle Park, NC 27709, USA. lawler@niehs.nih.gov Ment Retard Dev Disabil Res Rev. 2004;10(4):292-302.
The potential role of environmental factors in autism spectrum disorders (ASD) is an area of emerging interest within the public and scientific communities. The high degree of heritability of ASD suggests that environmental influences are likely to operate through their interaction with genetic susceptibility during vulnerable periods of development. Evaluation of the plausibility of specific neurotoxicants as etiological agents in ASD should be guided by toxicological principles, including dose-effect dependency and pharmacokinetic parameters. Clinical and epidemiological investigations require the use of sufficiently powered study designs with appropriate control groups and unbiased case ascertainment and exposure assessment. Although much of the existing data that have been used to implicate environmental agents in ASD are limited by methodological shortcomings, a number of efforts are underway that will allow more rigorous evaluation of the role of environmental exposures in the etiology and/or phenotypic expression of the disorder. Surveillance systems are now in place that will provide reliable prevalence estimates going forward in time. Anticipated discoveries in genetics, brain pathology, and the molecular/cellular basis of functional impairment in ASD are likely to provide new opportunities to explore environmental aspects of this disorder.