A Significant Factor in Autism: Methyl Mercury Induced Oxidative Stress in Genetically Susceptible Individuals
The dramatic increase in prevalence rates of Autism Spectrum Disorders (ASDs) over recent decades likely reflects the influence of multiple factors. In the current paper, it is argued ASDs can result from an interaction between genetic susceptibilities and environmental exposures. Specifically, we hypothesize that fetal or infantile exposure to methyl mercury containing pollution by individuals with biologically inhibited antioxidant functions contributes to development of autism. Correlational data reveal that ASD rates are higher in areas of greater pollution levels, and autistic individuals exhibit biological evidence of mercury toxicity. Further, oxidative stress and decreased antioxidant activities are manifested in individuals with ASDs, specifically autism. Taken together, available evidence supports a methyl mercury-induced oxidative stress model of the disorders for at least some sufferers. Consequently, legislative efforts should focus on preventing exposures to methyl mercury and other toxicants that can adversely impact neurodevelopment.
KeywordsAutism Toxic exposures Mercury Oxidative stress Genetic predisposition
- Akyol, O., Kerken, H., Uz, E., Fadillioglu, E., Unal, S., Sogut, S., et al. (2002). The indices of endogenous oxidative and antioxidative processes in plasma from schizophrenic patients: the possible role of oxidant/antioxidant imbalance. Progress in Neuropsychopharmacology & Biological Psychiatry, 26, 995–1005. doi:17544,35400010489459.0250.CrossRefGoogle Scholar
- Burbacher, T. M., Shen, D. D., Liberato, N., Grant, K. S., Cernichiari, E., & Clarkson, T. (2005). Comparison of blood and brain mercury levels in infant monkeys exposed to methylmercury or vaccines containing thimerosal. Environmental Heath Perspectives, 113, 1015–1021. doi:10.1289/ehp.7712.CrossRefGoogle Scholar
- Chez, M. G., Buchanan, C. P., Aimonovitch, M. C., Becker, M., Schaefer, K., Black, C., et al. (2002). Double-blind, placebo-controlled study of L-carnosine supplementation in children with autism spectrum disorders. Journal of Child Neurology, 17, 833–837. doi:10.1177/08830738020170111501.PubMedCrossRefGoogle Scholar
- Christen, Y. (2000). Oxidative stress and Alzheimer’s disease. American Journal of Clinical Nutrition, 71, 621S–629S. Retrieved from http://www.ajcn.org/cgi/reprint/71/2/621s.
- Herken, H., Uz, E., Ozyurt, H., Sogurt, S., Virit, O., & Akyol, O. (2001). Evidence that the activities of erythrocyte free radical scavenging enzymes and the products of lipid peroxidation are increased in different forms of schizophrenia. Molecular Psychiatry, 6, 66–73. Retrieved from http://www.nature.com/mp/journal/v6/n1/pdf/4000789a.pdf
- James, S. J., Melnyk, S., Fuchs, G., Reid, T., Jernigan, S., Pavliv, O., et al. (2009). Efficacy of methylcobalamin and folinic acid treatment on glutathione redox status in children with autism. The American Journal of Clinical Nutrition, 89, 425–430. doi:10.3945/ajcn.2008.26615.PubMedCrossRefGoogle Scholar
- Madsen, K. M., Lauritsen, M. B., Pedersen, C. B., Thorsen, P., Plesner, A., Andersen, P. H., et al. (2003). Thimerosal and the occurrence of autism: negative ecological evidence from Danish population-based data. Official Journal of the American Academy of Pediatrics, 112, 604–606. doi:10.1542/peds.112.3.604.Google Scholar
- Millodot, M. (2009). Oxidative stress. Author. In Dictionary of optometry and visual science (7th ed.). Location: Butterworth-Heinemann.Google Scholar
- Rice, C. (2006). Prevalence of autism spectrum disorders. Retrieved from Centers of Disease Control and Prevention, National Center on Birth Defects and Developmental Disabilities website: http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5810a1.htm.
- Sajdel-Sulkowska, E. M., Lipinski, B., Windom, H., Audhya, T., & McGinnis, W. (2008). Oxidative stress in autism: elevated cerebellar 3-nitrotyrosine levels. American Journal of Biochemestry and Biotechnology, 4, 73–84. Retrieved from http://www.scipub.org/fulltext/ajbb/ajbb4273-84.pdf.
- Schechter, R., & Grether, J. K. (2008). Continuing increases in autism reported to California’s developmental services system. Archives of General Psychiatry, 65, 19-24. Retrieved from http://archpsyc.ama-assn.org/cgi/reprint/65/1/19.
- Söğüt, S., Zoroglu, S. S., Ozyurt, H., Yilmaz, H. R., Ozurgurlu, F., Sivasli, E., et al. (2003). Changes in nitric oxide levels and antioxidant enzyme activities may have a role in the pathophysiological mechanisms involved in autism. Clinica Chimica Acta, 331, 111–117. doi:10.1016/S0009-8981(03)00119-0.CrossRefGoogle Scholar
- U.S. Environmental Protection Agency (2009). Toxic air pollutants: about air toxics. Retrieved November 29, 2010, from http://www.epa.gov/air/toxicair/newtoxics.html.
- Venkataraman, P., Krishnamoorthy, G., Vengatesh, G., Srinivasan, N., Aruldhas, M. M., & Arunakaran, J. (2008). Protective role of melatonin on PCB (Aroclor 1254) induced oxidative stress and changes in acetylcholine esterase and membrane bound ATPases in cerebellum, cerebral cortex and hippocampus of adult rat brain. International Journal of Developmental Neuroscience, 26, 585–591. doi:10.1016/j.ijdevneu.2008.05.002.PubMedCrossRefGoogle Scholar
- Willam, A. (2008). Autism statistics information. Retrieved December 5, 2009, from http://ezinearticles.com/?Autism-Statistics-Information&id=1665735, November 7.
- Woods, J. S., Bowers, M. A., & Davis, H. A. (1991). Urinary porphyrin profiles as biomarkers of trace metal exposure and toxicity: studies on urinary porphyrin excretion patterns in rats during prolonged exposure to methyl mercury. Journal of Toxicology and Applied Pharmachology, 110, 464–76.CrossRefGoogle Scholar
- Zoroglu, S. S., Armutcu, F., Ozen, S., Gurel, A., Sivasli, E., Ozer, Y., et al. (2004). Increased oxidative stress and altered activities of erythrocyte free radical scavenging enzymes in autism. European Archives of Psychiatry and Clinical Neuroscience, 254, 143–147. doi:10.1007/s00406-004-0456-7.PubMedGoogle Scholar