A new study published online June 8 in the Nature publication, Molecular Psychiatry, 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 Mady Hornig, MD, associate professor of epidemiology and director of translational research programs at the Greene Lab, 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 10 th 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 lead author Dr. Mady Hornig. "The promise of enhanced access to thimerosal-free flu vaccines for the upcoming 2004-05 season is an encouraging step toward the establishment of rational vaccination policies, particularly for pregnant women and children," she added, referring to a report in the May 28 issue of Morbidity and Mortality Weekly Report, a publication of the Centers for Disease Control and Prevention.
"Animal models such as this one play an important role in research because they allow scientists to control for genetic contributions and other risk factors, in order to isolate specific exposures that may cause disease," stated W. Ian Lipkin, MD, a study author and director of the Greene Lab. He added, “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."
This study was supported by The M.I.N.D. Institute of University of California/Davis, Coalition for Safe Minds, The Ellison Medical Foundation, and a grant from NICHD.
The only accredited school of public health in New York City, and among the first in the nation, Columbia University's Mailman School of Public Health provides instruction and research opportunities to more than 850 graduate students in pursuit of masters and doctoral degrees. Its students and nearly 250 multi-disciplinary faculty engage in research and service in the city, nation, and around the world, concentrating on biostatistics, environmental health sciences, epidemiology, health policy and management, population and family health, and sociomedical sciences.