Your Brain on Heavy Metals.

This week in Neurochem we talked about a very controversial and growingly prevalent topic – autism. As most people know, autism is a disorder characterized by a difficulty in verbal/nonverbal communication, social interactions, relationships, and disinterest/extreme interest in various activities. And, interestingly, the disorder is becoming more and more prevalent. According to the article, “How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis,” by Deth et al. of Northeastern University, the incidences of autism have grown from 3 in every 10,000 children in 1970 to 66 in 10,000 children in 2002. This shocking increase has many people (especially mothers) wondering…why? What are we doing differently that is causing this drastic increase? While some attribute the increase to advanced diagnosis ability and awareness, it still leaves you wondering if there are other reasons as well.
When talking about the causes of autism, it’s hard not to mention the thimerosal debate. Thimerosal is an inorganic mercury compound that has been used as a preservative in vaccines since the 1930’s. In 1999, new research on the toxicity of thimerosal was conducted by the FDA, and, although research didn’t suggest anything to cause alarm, it was still decided to phase out thimerosal as a precautionary measure due to its structural relatedness to methylmercury.3 In 2000, parents of autistic children started forming groups based on the belief that vaccines had caused their children’s disorders. Although much research has disproved the thimerosal/autism link, the debate still lives on today.3
While thimerosal, a heavy metal derivative, seems not to cause autism, there is reason to believe that heavy metals could still be a culprit of the disorder. According to this week’s article, a redox/methylation hypothesis of autism is still a valid argument and explanation. This is based on the tendency of heavy metals to inhibit an important protein of sulfur metabolism, methionine synthase.
Homocysteine is an amino acid derivative of cysteine. In sulfur metabolism, HCY can be converted to three other molecules – S-Adenosyl-L-homocysteine (SAH), methionine (MET), or cystathionine, a glutathione precursor. In times of oxidative stress due to heavy metal exposure, most of this HCY is shunted to cystathionine production due to glutathione’s role as a powerful antioxidant. Essentially, methionine synthase is shut down to deal with more pressing issues – the oxidative stress. This leads to all sorts of effects for the cell.
One effect is SAH accumulation, since the reaction between HCY and SAH is reversible and no HCY is being utilized by methionine synthase. This inhibits two types of methylation reactions in the cell – DNA methylation and phospholipid methylation. DNA methylation is very important in turning certain genes on and off, so this can have astounding effects on the cell. Phospholipid methylation is related to dopamine release and neural synchronization which is responsible for attention and focus-related thinking skills. Genetic factors are very important in predisposing an individual in autism, however, they don’t totally cause autism, supporting this heavy metal hypothesis. Many genetic mutations and polymorphisms in autism appear in molecules related to this redox/methylation hypothesis.
Although the exact mechanisms of autism have yet to be elucidated, the redox/methylation hypothesis seems quite likely considering the joint environmental/genetic factors. Since it seems quite likely that the environmental part of autism could be causing the dramatic increase in cases seen in recent decades, further research in this area is in dire need. Furthermore, as rates increase, advocating for increased awareness about the disorder is desperately needed as well. Autism creates new educational/social challenges which will require novel methods of interpersonal interaction and treatment for these individuals.
http://www.morphonix.com/software/education/science/brain/game/specimens/wet_brain.html
http://www.boloji.com/index.cfm?md=Content&sd=Articles&ArticleID=1098
http://www.webmd.com/brain/autism/autism-symptoms
Deth, R., Muratore, C., Benzecry, J., Power-Charnitsky, V., and Waly, M. How environmental and genetic factors combine to cause autism: A redox/methylation hypothesis. Neurotoxicology 2008;29:190-201.
http://www.nationalautismassociation.org/thimerosal.php