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Exploring the Environmental Contributions of Autism

March 2, 2010 3 comments

This post is by guest blogger Dr. Philip Landrigan. Philip J. Landrigan, M.D., M.Sc., the Ethel Wise Professor and Chair of the Department of Preventive Medicine, is a pediatrician, epidemiologist, and internationally recognized leader in public health and preventive medicine. He has been a member of the faculty of Mount Sinai School of Medicine since 1985, the Chair of the Department of Preventive Medicine since 1990 and is also the Director of the Children’s Environmental Health Center. Dr. Landrigan has been a leader in developing the National Children’s Study, the largest study of children’s health and the environment ever launched in the United States.

The causation of autism is the subject of intense inquiry. Genetic factors are clearly important, and elegant genetic research has identified a series of anomalies – gene mutations, gene deletions, and copy number variants (CNVs) – that are persuasively linked to autism. But none accounts for more than a relatively small fraction of cases. Moreover there is substantial imbalance between the extensive and highly sophisticated information on the genetics of autism and the scarcity of investigation into potential environmental causes. This situation raises the possibility that still undiscovered environmental exposures also contribute to causation of autism perhaps acting in synergy with inherited genetic vulnerabilities.

The article I recently published in Current Opinion in Pediatrics explores the possible contribution of early environmental exposures in the causation of autism, with particular focus on the possible role of toxic chemicals. Support for the possibility of an environmental contribution to autism comes from the following two sources:

(1)   Current understanding of the exquisite vulnerability of the developing human brain to toxic exposures in the environment; and

(2)   Proof-of-concept studies that specifically link autism to environmental exposures experienced prenatally. These include thalidomide, misoprostol, valproic acid, maternal rubella infection, and most recently the organophosphate insecticide – chlorpyrifos, which is linked in prospective epidemiologic studies to Pervasive Developmental Disorder, a form of autism. The time of greatest vulnerability to these exposures appear to be the first trimester of pregnancy.

There is no credible evidence that vaccines cause autism. To address the possibility of a connection between the MMR vaccine or thimerosal and autism, a dozen highly credible studies have been undertaken in the US, the UK, Europe, and Japan.  None have found credible evidence for a connection between the MMR vaccine or thimerosal and autism. Most persuasive among these studies is an investigation in Yokohama, Japan. There, the MMR vaccination rate declined significantly between 1988 and 1992, and no MMR vaccine was administered in 1993 or thereafter. Despite declining immunizations, the cumulative incidence of ASD increased significantly each year from 1988 through 1996 and rose especially dramatically beginning in 1993. Overall incidence of autism nearly doubled in those years. 

To reveal as yet undiscovered environmental causes of autism, an interdisciplinary autism discovery strategy is proposed that combines toxicological screening, neurobiological research and prospective epidemiological study. Although the MMR vaccine and thimerosal are not credible causes of autism, the possibility remains open that there exist unrecognized environmental causes of autism. Most likely these are to be found among the High Production Volume chemicals to which pregnant women and children today are routinely exposed. The rationale for seeking environmental causes of autism is that, once discovered, these causes are potentially preventable.

A successful strategy for discovering the environmental causes of autism will need to be highly interdisciplinary. It will need to bring together researchers from toxicology, epidemiology, developmental psychology, developmental neurobiology, neuropathology, molecular genetics, genomics, proteomics, functional neuroimaging and medical informatics. Key elements will include toxicological testing of chemicals to which pregnant women are at risk of exposure, basic neurobiological research and prospective epidemiologic study.

Large-scale, prospective epidemiological studies such as the recently launched US National Children’s Study are extraordinarily powerful engines for discovery of the environmental causes of autism. The National Children’s Study is the largest study of children’s health ever undertaken in the US. It will follow 100,000 children—a statistically representative sample of all children born in the United States from conception to age 21. It is the first large-scale prospective study of children’s health to specifically measure children’s environmental exposures, prenatally as well as after birth, using a combination of maternal and infant biological markers and direct sampling of the ambient environment. It will collect samples for genetic analysis from each mother and child. The National Children’s Study will attempt to link children’s prenatal and postnatal environmental exposures with the subsequent appearance of disease and dysfunction.

Given the currently reported prevalence of autism in the US, the study can be expected to include nearly 700 children with autism. The National Children’s Study will provide an unparalleled opportunity to examine interactions between genetic and environmental factors in the genesis of autism. It will also bring together the researchers needed to succeed in understanding the causes of a complex disorder like autism. Potential for breakthrough discovery is high.

Landrigan, P (2010) What causes autism? Exploring the environmental contribution. Current Opinion in Pediatrics 22.

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