ScienceDaily (June 9, 2004) — A new study indicates that postnatal exposure to thimerosal, a mercury preservative commonly used in a number of childhood vaccines, can lead to the development of autism-like damage in autoimmune disease susceptible mice. This animal model, the first to show that the administration of low-dose ethylmercury can lead to behavioral and neurological changes in the developing brain, reinforces previous studies showing that a genetic predisposition affects risk in combination with certain environmental triggers. The study was conducted by researchers at the Jerome L. and Dawn Greene Infectious Disease Laboratory at the Mailman School of Public Health, Columbia University.

Over the past 20 years, there has been a striking increase--at least ten-fold since 1985--in the number of children diagnosed with autism spectrum disorders. Genetic factors alone cannot account for this rise in prevalence. Researchers at the Mailman School, led by Dr. Mady Hornig, created an animal model to explore the relationship between thimerosal (ethylmercury) and autism, hypothesizing that the combination of genetic susceptibility and environmental exposure to mercury in childhood vaccines may cause neurotoxicity. Cumulative mercury burden through other sources, including in utero exposures to mercury in fish or vaccines, may also lead to damage in susceptible hosts. Timing and quantity of thimerosal dosing for the mouse model were developed using the U.S. immunization schedule for children, with doses calculated for mice based on 10th percentile weight of U.S. boys at age two, four, six, and twelve months.

The researchers found the subset of autoimmune disease susceptible mice with thimerosal exposure to express many important aspects of the behavioral and neuropathologic features of autism spectrum disorders, including:

* Abnormal response to novel environments;

* Behavioral impoverishment (limited range of behaviors and decreased exploration of environment);

* Significant abnormalities in brain architecture, affecting areas subserving emotion and cognition;

* Increased brain size.

These findings have relevance for identification of autism cases relating to environmental factors; design of treatment strategies; and development of rational immunization programs. The use of thimerosal in vaccines has been reduced over the past few years, although it is still present in some influenza vaccines. Identifying the connection between genetic susceptibility and an environmental trigger for autism--in this case thimerosal exposure--is important because it may promote discovery of effective interventions for and limit exposure in a specific population, stated the lead author Dr. Mady Hornig. Because the developing brain can be exposed to toxins that are long gone by the time symptoms appear, clues gathered in these animal models can then be evaluated through prospective human birth cohorts--providing a powerful to tool to dissect the interaction between genes and the environment over time.

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Citation source: Molecular Psychiatry 2004 Volume 9, advance on line publication doi:10.1038/sj.mp.4001529

ARTICLE: "Neurotoxic effects of postnatal thimerosal are mouse strain-dependent"

M Hornig, D Chian, W. I. Lipkin

Greene Infectious Disease Laboratory, Mailman School of Public Health, Columbia University, 722 W 168th St, New York, New York 10032

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Molecular Psychiatry is published by the Nature Publishing Group. http://www.nature.com/mp

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