Journal of Immunotoxicology January 2011; Vol. 8; No. 1; pp. 68 – 79Helen V. Ratajczak FROM ABSTRACT Autism, a member of the pervasive developmental disorders (PDDs), has beenincreasing dramatically since its description by Leo Kanner in 1943. First estimatedto occur in 4 to 5 per 10,000 children, the incidence of autism is now 1 per 110 inthe United States, and 1 per 64 in the United Kingdom, with similar incidencesthroughout the world. Searching information from 1943 to the present in PubMed and Ovid Medlinedatabases, this review summarizes results that correlate the timing of changes inincidence with environmental changes.Autism could result from more than one cause, with different manifestations indifferent individuals that share common symptoms. Documented causes of autism include genetic mutations and/or deletions, viralinfections, and encephalitis following vaccination. Therefore, autism is the result of genetic defects and/or inflammation of the brain.The inflammation could be caused by a defective placenta, immature blood-brainbarrier, the immune response of the mother to infection while pregnant, apremature birth, encephalitis in the child after birth, or a toxic environment. KEY POINTS FROM THIS AUTHOR: 1) Autism is a neuro-developmental disorder. 2) Genetic, environmental, and immunological factors may play a role in thepathogenesis of Autism. 3) Boys have autism 3-4 times more often than girls. 4) 75% of autistic individuals become either institutionalized as adults or areunable to live independently. 5) The estimated lifetime per capita incremental societal cost of autism is $3.2million per case. Greater than the monetary cost, the emotional devastationcaused by the great difficulties posed by the autistic individual, and the strains onthe family. 6) Autism was first described in 1943, with a prevalence of 1/2500 children. 7) In the 1970s, autism was still 1/2500 children. By the 1990s the rate was1/250 children, a 10-fold increase. 8) The Center for Disease Control and Prevention states that the prevalence ofautism is increasing at epidemic rates. 9) In 2002, the rate for autism was 1/150 children (USA). 10) In 2006, the rate for autism was 1/110 children (USA). 11) A 2007 parent survey showed an autism rate of 1/91 children (USA). 12) The incidence of autism in the United Kingdom is also increasing, with higherrates than in the United States, with a current prevalence of 1/64 children. 13) The autism increase is not a result of reclassification; there have been nochanges in prevalence of mental retardation, speech/language impairment, ortraumatic brain injury, which suggests that the increase in autism is real. Changes in rates of autism incidence 1) In 2004, the flu vaccine containing Thimerosal was recommended for allchildren 6 – 23 months old in the United States. In addition, flu vaccination during alltrimesters of pregnancy is now universally recommended in the United States. Mostflu vaccines contain Thimerosal, despite its implication in autism.[Important: the flu vaccine still contains Thimerosal with mercury, and isrecommended for all children and pregnant mothers, every year] 2) The increase in autism incidence began about 1988 – 1990. 3) The new version of the measles, mumps, rubella vaccine (i.e., MMR II) thatdid not contain Thimerosal was introduced in 1979. By 1983, only the new versionwas available. Autism in the United States spiked dramatically between 1983 and1990 from 1/2500 to 1/500. 4) In 1988, two doses of MMR II were recommended to immunize thoseindividuals who did not respond to the first injection. A spike of incidence of autismaccompanied the addition of the second dose of MMR II. 5) In 1988, MMR II was used in the United Kingdom, which reported a dramaticincrease in prevalence of autism to 1/64. Canada, Denmark, and Japan alsoreported dramatic increases in prevalence of autism. 6) The rubella component of MMR II was propagated in a human cell linederived from embryonic lung tissue. The MMR II vaccine is contaminated withhuman DNA from the cell line. This human DNA could be the cause of the spikes inincidence. 7) An additional increased spike in incidence of autism occurred in 1995 whenthe chicken pox vaccine was grown in human fetal tissue. 8) The human DNA from the vaccine can be randomly inserted into therecipients genes. This insertion occurs primarily on the X chromosome in genesinvolved in nerve cell synapse formation, central nervous system development, andmitochondrial function, accounting for autism primarily in boys. These data supportthe hypothesis that residual human DNA in some vaccines might cause autism. 9) The incidence and prevalence data indicate the timing of introduction ofvaccines and changes in the type and increasing number of vaccines given at onetime implicate vaccines as a cause of autism. 10) The current recommended immunization schedule in the United Statesincludes six vaccines at 2 months. The immune system is particularly sensitive at 2months of age. The immune system of an infant is compromised at 2 months. Achallenge by so many vaccines while the immune system is compromised might contribute to an onset of autism. Vaccine antigens 1) Many parents cite normal development of their children until they receivevaccines at about the age of 18 months. 2) A possible cause of autism is that the pertussis toxin in the DPT vaccinecreates chronic autoimmune damage to the gut, altering immune function. 3) When the measles vaccine is given, it depletes the children of their existingsupply of Vitamin A, which negatively impacts the retinoid receptors, accounting forthe distorted vision in autistic individuals. When the natural form (cis) of Vitamin Awas given to autistic subjects for 2 – 3 months, followed by urocholine, many autisticchildren showed immediate improvement in their autistic behaviors, includingimproved eye contact, ability to socialize, ability to sleep through the night, etc. Vaccine Preservative and Environmental Mercury 1) There is evidence that Thimerosal (which is 49% ethyl mercury) is indeedharmful. Thimerosal is an antibacterial agent in vaccines. Thimerosal has beenimplicated as a cause of autism. 2) Not only is every major symptom of autism documented in cases of mercurypoisoning but also biological abnormalities in autism are very similar to the sideeffects of mercury poisoning itself. 3) Autistic brains show neurotransmitter irregularities that are virtually identicalto those arising from mercury exposure. 4) Due to the extensive parallels between autism and mercury poisoning, thelikelihood of a causal relationship is great. More evidence linking autism withmercury poisoning is the timing of inclusion of Thimerosal in vaccines in the 1930sclosely preceding the discovery of autism in 1943. 5) There are dangerous effects of Thimerosal on the immune system,particularly on T-lymphocytes. Mercury induces glutathione depletion, increasedoxidative stress, and apoptosis in these cells. 6) Thimerosal causes toxic effects on brain cells, affects nerve differentiation,and depletes glutathione. 7) Mercury is both neurotoxic and immunotoxic. 8) Autistic individuals have a 10-fold greater number of hyperactive mast cells.Mercury stimulates to release pro-inflammatory cytokines, which may disrupt theblood – brain barrier and cause brain inflammation. 9) Cumulative mercury exposure results from mercury as a pollutant in air, soil,dust, water, consumer products, dental amalgam and lighting fixtures, foodstuffs,fish, and seafood. Concerning air, for every 1,000 pounds of mercury (all forms),there was a 61% increase in the rate of autism. 10) Mercury is found in many foods, including high-fructose corn syrup. Theconsumption of high-fructose corn syrup could impact the behavior of children withattention deficit hyperactivity disorder (ADHD), which is associated with autism. 11) The consumption of some artificial food color additives has been shown tolead to zinc deficiency. Dietary zinc is essential for maintaining the metabolicprocesses required for mercury elimination. Measles Mumps Rubella Vaccine (MMR) An examination of the continuing increase in prevalence in autism in thecontext of the dates of spikes in increase in prevalence which point to the MMR IIvaccine (which did not contain Thimerosal) suggests that something new causedthe increase in incidence of autism. The new component could be the human DNAfrom the preparation of the rubella component of the MMR II vaccine and thechicken pox vaccine. Metal metabolism disorder 85% of autistic patients have severely elevated Cu:Zn ratios. Genetics There is indisputable evidence for a genetic component in autism, because ifone identical twin is autistic, the likelihood that the other twin will have autism is90%. In great contrast, the likelihood that non-identical twins both have autism isonly 2 – 3%. Yet, the genetic cause of autism is only 1 – 2% of the cases. A reasonto discount an overall genetic cause is that autism is now considered an epidemicand there is no such thing as a genetic epidemic. Age of parents 1) Advanced maternal and paternal ages are independently associated with riskof autism-spectrum disorders. 2) A 10-year increase in maternal age is associated with a 38% increase in theodds ratio for autism. A 10-year increase in paternal age is associated with a 22%increase. 3) The trend toward delaying childbearing contributed about a 4.6% increase ofautism over the decade. Ageing increases cumulative toxic exposure, resulting innucleotide repeat instability. Mitochondrial disease and dysfunction Mitochondrial dysfunction is caused by environmental toxins and cancontribute to the altered energy metabolism in the brains of children with autism. Pregnancy 1) A defective blood-brain barrier is common in autistic patients. 2) A mothers immune response(s) to infection during pregnancy includes theformation/release of antibodies and cytokines that could cross the blood-brainbarrier of the fetus and which, over time, could cause autism. Imbalance in neural systems Autism might be caused by an imbalance between excitation and inhibition inkey neural systems including the cortex. Environment Autism may be a disease of very early fetal development (approximately day20 – 24 of gestation), with environmental exposures during pregnancy causing orcontributing to autism based on the neurobiology of developmental genes. Medications are implicated in autism including: 1) Thalidomide by the mother. 2) Misoprostol, a prostaglandin analogue used for prevention of gastric ulcers. 3) Valproic acid, an anti-convulsant. 4) Acetaminophen has also been suggested to cause autism. 5) Children given acetaminophen after the MMR II vaccine were significantlymore likely to become autistic than children given ibuprofen. 6) During pregnancy, mothers of autistic children commonly suffer morebacterial and viral infections and fevers, which could affect the fetus to predisposethe child for autism. These mothers often take acetaminophen to treat theinfections. Acetaminophen overdose depletes the livers supplies of sulfate andglutathione, impairing its ability to detoxify and excrete harmful substances. Therefore, the fetus could be impaired by the mothers consuming acetaminophen.After birth, if acetaminophen were given to the child, and used repeatedly, the drugcould cause depletion of sulfate and glutathione, and the child could regress intoautism. Low Glutathione Glutathione (GSH) is the most important antioxidant for detoxification andelimination of environmental toxins. GSH is decreased in the plasma of autisticsubjects. In addition, GSH plays a major role in methylation and is intimatelyinvolved in detoxification processes. Phthalates, Polychlorinated Biphenyls (PCBs), Environmental Contaminants 1) Phthalates, an environmental toxin, are implicated in autism. 2) Phthalates are synthetic chemicals with widespread human exposure becauseof their use in plastics and other consumer products. 3) Humans are exposed to phthalates through ingestion, inhalation, and dermalroutes. 4) There is a significant relationship between the concentration of urinaryphthalates and the degree of autism. 5) Polychlorinated biphenyls (PCBs) are a suspected as causes of autism. 6) Environmental contaminants, including PCBs, herbicides, perchlorates,mercury, and coal derivatives interfere with thyroid function, and this can affectfetal brain growth, leading to autism. 7) Organophosphate pesticides may contribute to ADHD prevalence. 8) The highest rate of autism is in schools near EPA Superfund sites. SUMMARY 1) Autism has increased to epidemic proportions, affecting four times as manymales and females. 2) With a prevalence of 1/110 in the United States, 1/64 in the UnitedKingdom, and similar ratios in many other countries, [autism is] a very significantthreat to future generations is evident. 3) This review cites documentation of causes of autism, including geneticmutations/deletions, viral infections (i.e., rubella and herpes), and encephalopathyfollowing vaccination. 4) Autism has been documented to be caused by genetic defects and/orinflammation of the brain. The inflammation could be caused by a wide variety ofenvironmental toxicants, infections, and co-morbidities in individuals geneticallyprone to the developmental disorder.