The role of mercury in the pathogenesis of autism

The role of mercury in the pathogenesis of autism

Molecular Psychiatry
S Bernard, A Enayati, H Roger, T Binstock and L Redwood
2002


Autistic spectrum disorder (ASD) is a neurological development disorder of unknown etiology in most cases. Monozygotic twins studies report an average concordance rate of 60%, indicating a role for both genetic and environmental factors in the expression of the disease. Recent reviews on environmental health have suggested that early exposure to hazardous substances may underlie some cases of neurological development disorders, including ADHD, learning difficulties and linguistic / linguistic difficulties. In 1999, thimerosal used as a vaccine preservative was identified as a widespread source of mercury exposure in infants. Mercury (Hg), a heavy metal, is considered highly neurotoxic. The amount of mercury in the vaccines, although small in size, exceeded USEPA safety guidelines on a cumulative basis. Some individuals may experience severe adverse reactions at low doses of Hg which are mostly largely benign to most exposed people. Some individuals with idiopathic autism spectrum disorder may represent such a sensitive population. As summarized in this article, the characteristics of the disease suggest this possibility: (a) ASD traits are known for mercury exposure; (b) the onset of ASD symptoms is temporarily associated with the administration of immunizations; (c) the reported increase in the prevalence of autism in the 90s closely follows the introduction of two mercury-containing vaccines; and (d) elevated mercury was detected in biological samples from autistic patients. Since ASD can now affect at least one in 150 U.S. children, and since thimerosal is still used in many products around the world, the confirmation of thimerosal as an environmental agent in the pathogenesis of autism has important social and therapeutic implications.

49,6% of thimerosal is made up of ethylmercury (EtHg) by weight. Until the beginning of 2001, it was a component of most hepatitis B, Haemophilus influenzae type B (HiB) and diphtheria / tetanus / pertussis (DTP or DTaP) vaccines. These vaccines were routinely administered to babies at birth and at 2, 4, 6 and 15-18 months. The cumulative amount of mercury injected in the first 6 months of life was 187,5 μg. Although the pharmacokinetics of EtHg have not been well studied, its toxicity is believed to be similar to MeHg, for which pharmacokinetic models have been developed to estimate the risk of adverse outcomes based on Hg levels in standard hair or blood biomarkers . Using this model, the EtHg of the recommended vaccines is expected to increase hair mercury levels above USEPA guidelines by 1 ppm up to one year and, in some infants, to raise Hg levels to 10 ppm, which is the lowest threshold for adverse outcomes in children prenatally exposed to MeHg. That thimerosal-containing vaccines can significantly increase blood Hg levels in infants has been shown in vivo. The end points for the adverse effects at low doses of MeHg have been in the characteristic domains of ASD and include reduced performance in tests of attention, memory, language and fine motor skills. A CDC analysis of computerized HMO medical records found statistically significant associations between increased exposure to thimerosal from childhood immunization and attention deficit disorder, language / language delay and tics. characteristic features of these disorders are common features of ASD.

A review of the medical literature has shown that exposure to mercury, whether organic or inorganic, can give rise to the symptoms and traits that define or are commonly found in individuals with ASD. Mercury can cause impairments in social interaction, communication difficulties and repetitive and stereotyped patterns of behavior, which include the three diagnostic criteria of DSM-IV autism. In addition, mercury can induce significant characteristics in ASD such as sensory abnormalities, emotional / psychological changes, movement disorders, impairments in abstract or complex thinking, severe sleep disturbances and self-injurious behaviors. Males are more affected than females in both conditions. Physiological abnormalities most common in ASD populations and known to be caused by mercury exposure include gastrointestinal problems, autonomic nervous system disorders, unusual EEG activity, immune system abnormalities, irregularities in neurotransmitter systems, and nonspecific brain injury.

The discovery and increase in the reported prevalence of autism parallels the introduction and spread of thimerosal-containing vaccines. Autism was first described in 1943 among children born in the 30s. Thimerosal was first added to childhood vaccines in the 30s. Before 1970, classical autism was estimated to be around 1 in 2000 children, while the average prevalence reported from the studies from 1970 to 1990 is 1 in 1000. This period was a period of greatest immunization in the developed world. In 1995, the National Institutes of Health reported an autism prevalence of 1 in 500 children, and in 2000 the CDC identified approximately 1 in 250 children with classic autism in a city in New Jersey. In the early 90s, vaccines containing HiB and hepatitis B containing thimerosal became part of the children's routine program.

The onset of autistic symptoms generally follows the administration of thimerosal in vaccines and the emergence of symptoms is consistent with the expression of mercury toxicity. As noted earlier, mercury exposure from vaccines started at birth and continued at around 2, 4, 6 and 15 months. The vast majority of autistic children appear normal at birth, but subtle abnormalities in movement have been observed starting from 4 months of age and sensory-motor disorders detected at 9-12 months. The full range of diagnostic impairments is generally evident in 15-24 months. Symptoms of mercury toxicity may arise suddenly in particularly sensitive or sensitized individuals, but the expression is usually gradual. I Autistic symptoms usually emerge gradually even if there are cases of sudden onset.

Almost all American children are immunized, but less than 1% have ASD. This model is consistent with the response to low-dose mercury exposure, which is characterized by a large interindividual variation. Acrodynia, a serious early childhood disease prevalent 50 years ago, illustrates this phenomenon. Acrodynia was caused by small amounts of mercuric chloride in the toothpaste powders. Although the use of powders was widespread, only a small percentage of children developed the disease. Occasionally siblings of acrodynia patients also succumbed and a genetic link was suggested. Studies in mice and rats have demonstrated the role of genetics in interindividual differences in Hg sensitivity, with most resistant strains, some strains responding highly and others intermediate. Some strains with a high response rate are those prone to autoimmune disorders. ASD is highly heritable 1 and occurs more frequently than expected in families with autoimmune diseases.

Doctors treating autistic patients have reported high levels of post-challenge urine mercury with standard heavy metal chelators and improved function after removing mercury from chelation.

In a case study, the only known mercury exposure came from vaccines. These preliminary reports suggest that mercury may persist in the tissue in some autistic individuals and may contribute to autistic symptoms.

These results support the hypothesis that mercury in vaccines may be a factor in the pathogenesis of autism. Understanding the biological mechanisms underlying thimerosal toxicity in populations genetically susceptible to the effects of mercury could lead to effective medical treatments for autistic individuals. A positive discovery of a role of thimerosal would also give further impetus to the removal of this non-essential compound from the health and medical products where it can still be found. These products include many pediatric vaccines used in developing countries, all U.S. influenza vaccines, all diphtheria and tetanus mono- and divalent vaccines, some immunoglobulins routinely administered to Rh negative pregnant women and some over-the-counter drops and nasal sprays counter top.


Source: Nature.com