Neurological and Immune Reactive Conditions Affecting Kids: The mercury connection to neurological pervasive developmental dis

Neurological and Immune Reactive Conditions Affecting Kids: The mercury connection to neurological pervasive developmental disorders(autism, schizophrenia, dyslexia, ADD, childhood depression, learning disabilities, OCD, etc.) and developmental immune conditions(eczema, asthma, and allergies) Bernard Windham(Ed)

I. Introduction

The incidence of neurotoxic, allergic, and immune reactive conditions such as autism, schizophrenia, ADD, dyslexia, allergies, asthma, eczema, psoriasis, childhood diabetes, etc. have been increasing rapidly in recent years(1,2,3,5,23,50,52,59,75,82,86,92). A report by the National Research Council in 2000 found that 50% of all pregnancies in the U.S. were resulting in prenatal or postnatal mortality, significant birth defects, developmental disabilities or otherwise chronically unhealthy babies(3a) and a recent study published in JAMA found similar trends continuing with huge increases in children’s chronic conditions (3d). There has been a similar sharp increase in developmental disabilities in Canadian children over the last 2 decades(71), including learning disabilities and behavioral problems, asthma and allergies, and childhood cancer.

The U.S. Dept. Of Education indicates that over 5 million children attending school have neurological related disabilities reported by state agencies, other than ADD(2a). A random sample of Oregon high school students found that over 16% had been diagnosed with depression(75b). According to the American Academy of Pediatrics between 4 to 12 % of all school age children are affected by ADHD(4) and a similar number have some degree of dyslexia(1). However large surveys of elementary level student records finds much higher levels- with over 20% of elementary school boys in some areas being treated for ADD(75a). Studies have found that long term use of stimulant drugs commonly causes significant adverse neurological and health effects (76), and options are available to deal with such conditions without such adverse effects including dealing with the underlying causes. Estimates of the percentage of children with mood or anxiety orders are as much as 20%.

Most of the increase in children’s neurological or developmental conditions have been found to be related to major increases in brain and immune system inflammation related to increased exposure to toxic chemicals or dietary excitoxins of the 4 million U.S. children born each year (598,3,1,2,22,33). At least 1 in 6 had one of the neurological conditions previously listed(1-3). U.S. EPA has estimated that over 3 million of these are related to lead or mercury toxicity, with at least 25% of U.S. children getting mercury exposure at dangerous levels (1,81,499-502).

Studies indicate that over 60,000 children are born each year with neurodevelopmental impairments due to prenatal exposure to methyl mercury (45,46). But two other sources of mercury exposure appear to have been more common and at higher levels than this, ethyl mercury from vaccines(23,33) and mercury vapor from amalgam dental fillings (81,501), with Mom’s mercury fillings being a the largest source of mercury in the fetus and a significant source of mercury in infants(502).

II. A survey of thousands of parents of autistic children or children with Asperger’s by the Autism Association found that chelation/detoxification was by far the most effective treatment for autism and also much safer than most drug treatments for autism spectrum conditions (110). This is consistent with the findings of most autism treatment clinic tests that most autistic children tested are highly mercury and metal toxic.

A study at the U.S. CDC found "statistically significant associations" between neurologic developmental disorders such as autism, attention deficit disorder(ADD) and speech disorders with exposure to mercury from thimerosal‑containing vaccines before the age of 6 months (62,80). An analysis of the U.S. CDC VAERS database for adverse reactions from vaccines regarding effects of the diptheria-tetanus-pertusis vaccine found that those receiving DTaP and DTucP vaccines with thimerosal had significantly higher rates of autism, speech disorders, and heart arrest than those receiving DtaP vaccine without thimerosal, and that the rate of these increase exponentially with dose(81). An analysis of the U.S. Dept. of Education report on the prevalence of various childhood conditions among school children found that the rate of autism and speech disorders increased with increasing levels of thimerosal exposure from vaccines(81).

A followup study using DMSA as a chelator found that overall, urinary mercury concentrations were significantly higher in children with autistic spectrum disorders than in a matched control population, and that vaccinated cases showed significantly higher urinary mercury concentrations than vaccinated controls(81b). This is consistent with other studies that found that those who are poor excreters of mercury are more likely to accumulate mercury and have adverse health effects. Changes in birth procedures in hospitals such as immediate cord clamping has also been found to be a factor in the increase in neurological developmental problems(83). Children with autism had significantly ( 2.1-fold) higher levels of mercury in baby teeth(90) and blood(102), but similar levels of lead and similar levels of zinc. Children with autism also had significantly higher usage of oral antibiotics during their first 12 mo of life. Baby teeth are a good measure of cumulative exposure to toxic metals during fetal development and early infancy(90). A study of environmental mercury levels in Texas school districts found a 61 percent increase in autism and a 43 percent increase in special education cases for every 1,000 pounds of mercury released into the environment(94a). Another similar study found similar results and estimated economic costs due to disability or lower IQ (94b). Fossil fuel-burning power plants were the largest source of the widespread mercury pollution(94) but dental amalgam was the largest source in sewers and a significant source of environmental mercury in water bodies, fish, and air emissions(95).

A new survey released recently indicates a strong correlation between rates of neurological disorders, such as ADHD and autism, and childhood vaccinations. The survey found vaccinated boys were two and a half times (155%) more likely to have neurological disorders compared to their unvaccinated peers. Vaccinated boys were 224% more likely to have Attention Deficit Hyperactivity Disorder (ADHD), and 61% more likely to have autism(93). For older vaccinated boys in the 11-17 age bracket, the results were even more pronounced. Vaccinated boys were 158% more likely to have a neurological disorder, 317% more likely to have ADHD, and 112% more likely to have autism. Other studies have found similar results (92,50).

Also according to the U.S. FDA, at least 26 million have allergies, at least 17 million have asthma( 1b), 15 million have systemic eczema( 82), and childhood diabetes is increasing rapidly(52, etc.). Although Russian and U.S. studies from the 1980s found that thimerosal was highly toxic and recommended thats its use as a medical preservative should be discontinued (70,79) , its use was not discontinued. One study(60a) found 5 times higher rate of allergy among a group vaccinated with pertussis vaccine(DPT) as opposed to an unvaccinated group, and 3 other studies(60bcd) found increased asthma, allergies, and eczema among the vaccinated group. Vaccines given in the first 6 months of infants commonly cause asthma(99).

Over the last 20 years the percent of diabetes cases below 20 years

old has increased from 2% to over 30%, and there was a 70% in cases under 40 years of age between 1990 and 1998(52,50). Studies in the U.S. and Sweden have confirmed vaccinations to be a major factor in the increased diabetes cases(52). Currently over 16 million have diabetes (52).

DPT vaccinations have also been linked to sudden infant death syndrome (SIDS)(61,92a,m). DPT vaccines are mostly given at 2, 4, and 6 months of age and 85% of SIDS cases occur during this age span. One study found babies die at a rate 8 times the normal rate within 3 days of DPT shots(60a), while another found that among SIDS victims 61% had DPT within the 2 previous weeks and 13% within 24 hours of DPT vaccination (60c). According to Dr. Harris Coulter, "Crib death" was so infrequent in the pre-vaccination era that it was not even mentioned in the statistics, but it started to climb in the 1950s with the spread of mass vaccination against diseases of childhood." A monitoring study of infant breathing patterns after DPT vaccinations showed large increases in breathing difficulties including episodes of ceased breathing, which continued for months after DPT in some cases(61b). Some cases of seizures after DPT were also observed. Another study found significantly higher rates of heart arrest in those getting DpaT vaccines with mercury thimerosal compared to those without(81). Prenatal exposure to mercury has also been found to predispose animals and infants to seizures and epilepsy(85).

The computer records from the National Vaccine Injury Compensation Program, obtained by Gannett News Service using the Freedom of Information Act as part of a four-month study of federal immunization policy, reveal:

Of 253 infant death cases awarded more than $61 million by the U.S. Court of Federal Claims in the 1990s under the compensation program, 224, or 86 percent, were attributed to vaccination with DTP, the diphtheria, tetanus and pertussis (whooping cough) shot. In these cases, mortality was originally attributed to SIDS in 90, or 40 percent, of them. (61g)

Of 771 total claims filed by parents from 1990 through mid-1998, 660, or 86 percent, contained assertions that DTP was the cause of death. And 43 percent were classified by medical authorities at time of death as SIDS cases.

A second federal database tends to draw a similar connection. This one, for the 1990s from the Food and Drug Administration, contains 460 reports of children who died within three days of receiving shots containing DTP. Of those 460 reports, 266 -- or 58 percent -- listed SIDS as a ``reaction.''

That database is called VAERS, for Vaccine Adverse Event Reporting System. It was ordered by Congress to track dangerous reactions to the shots all babies must receive as admission to our society. In typical federalese, the FDA refers to death as an ``adverse event'' or a ``reaction.'' By law, reports of reactions to DTP and other vaccines are supposed to be made religiously by doctors, pharmaceutical companies and public health clinics. But former FDA commissioner David A. Kessler has estimated the reports ``represent only a fraction of the serious adverse events'' -- perhaps as few as 10 percent. Dr. Marcel Salive, chief of the FDA's epidemiology staff, says, ``Any number you get, take with a grain of salt.'' (61g)

Vaccines contain immune adjuvants such as aluminum and mercury thimerosal that cause stimulation and activation of the immune system(598). This has been found to cause high levels of brain inflammation with increased free radicals and inflammatory cytokines over prolonged periods of time, as long as a year from one vaccination. Brain inflammation has been found to be a major factor in irritability, anxiety, depression, insomnia, and neurological conditions including ADHD, schizophrenia, and autism(598,22a). With large numbers of vaccines being given in recent years in rapid succession, the brain of infants becomes increasingly overexcited and inflamed, resulting in brain damage and disruption of brain development. Vaccine adjuvants, mercury from mother’s amalgam fillings(502), and dietary excitotoxins such as MSG and soy products have all been found to be major factors in the brain inflammation causing large numbers of developmental neurological conditions in children(598,etc.).

Mercury has been found to cause an increase in inflammatory Th2 cytokines(58,500,22). In the pancreas, the cells responsible for insulin production can be damaged or destroyed by the chronic high levels of cytokines, with the potential of inducing type II diabetes - even in otherwise healthy individuals with no other risk factors for diabetes(52). Mercury inhibits production of insulin and is a factor in diabetes and hypoglycemia, with significant reductions in insulin need after replacement of amalgam filings and normalizing of blood sugar(52,500). In addition to this mechanism, other links between vaccines and diabetes have also been found and there is evidence vaccines are the number one cause of Type I diabetes in young children(52).

The largest increase in neurological and immune conditions has been in infants (1,2,5-7,23,4,50,81,92), with an increase in autism cases to over 500,000 (1,2,23,86), an over 900% increase to a level of approx. 1 per 500 infants in the last decade(2ab), making it the 3rd most common chronic childhood condition. For 1999 through 2002, the number of professionally diagnosed in California with full syndrome autism has doubled(2e,86). There have been similar increases in ADD and dyslexia to over 10 million, similar large numbers(over 10%) with childhood depression or anxiety(75b), and over 10 % of infants- approximately 15 million in the U.S. with systemic eczema(1,2,82). Studies researching the reason for these rapid increases in infant reactive conditions seem to implicate earlier and higher usage of vaccines containing mercury(thimerosal) as a likely connection (2cd,23,30,40,80-82). A recent study comparing pre‑ and post‑vaccination mercury levels, found a significant increase in both preterm and term infants after vaccination(42), with post‑vaccination mercury levels approximately 3 times higher in the preterm infants as compared with term infants. The study found mercury blood levels up to 23.6 ug/L and received an average dose of 16.7 ug/kg. Just this one vaccination gave an exposure to mercury that is many times the U.S. ATSDR adult minimum risk level(MRL) for mercury of .3/ug/kg body weight per day(41,81).

It has been estimated that if all of the vaccines recommended by the American Assoc. of Pediatrics are given and contain thimerosal, then by age 6 months an infant would have received 187 micrograms of ethyl mercury which is more than the EPA/ATSDR health standard for organic mercury (33,41,81) and by age 3 the typical child has received over 235 micrograms of mercury thimerosal from vaccinations which is considerably more than Federal mercury safety guidelines(41,81,501), in addition to significant levels from other sources for many(23). Infants during this period have undeveloped blood brain barriers and much of the mercury goes to the brain, resulting in significant adverse neurological effects in those that are most susceptible (43,3). The bioaccumulation in the brain and toxic effects of ethyl mercury are comparable to that of methyl, with mercury accumulation in the brain and physical effects actually being more extensive (79,88,89).

III. Mechanisms by which vaccines/mercury/toxic metals are documented to cause Autism Spectrum conditions

1. Brain inflammation from exposure to excitotoxins

Brain inflammation has been found to be a major factor in autism, and in the sometimes related metabolic syndrome (598,etc.). Causes of oxidative stress and lipid peroxidative related brain inflammation that have been documented include vaccines, mercury, aluminum, excitotoxins such as MSG, aspartame, food additives, and overconsumption of high-fructose corn sweetener. These cause high glutamate levels in the brain and oxidative damage –resulting in inflammation of the brain and immune system, as well as damage to brain microglia cells and the mitochondrial DNA, high triglycerides, metabolic syndrome, etc. These have been found to be factors in most chronic neurological diseases including autism and diabetes.

Mercury and other toxic metals inhibit astrocyte function in the brain and CNS(22,129), causing increased glutamate and calcium related neurotoxicity (129,333,416,496). Mercury and increased glutamate activate free radical forming processes like xanthine oxidase which produce oxygen radicals and oxidative neurological damage(142,13).

Nitric oxide related toxicty caused by peroxynitrite formed by the reaction of NO with superoxide anions, which results in nitration of tyrosine residues in neurofilaments and manganese Superoxide Dimustase(SOD) has been found to cause inhibition of the mitochondrial respiratory chain, inhibition of the glutamate transporter, and glutamate-induced neurotoxicity (524,521).

These inflammatory processes damage cell structures including DNA, mitochondria, and cell membranes. They also activate microglia cells in the brain, which control brain inflammation and immunity. Once activated, the microglia secrete large amounts of neurotoxic substances such as glutamate, an excitotoxin, which adds to inflammation and stimulates the area of the brain associated with anxiety(598,22). Inflammation also disrupts brain neurotransmitters resulting in reduced levels of serotonin, dopamine, and norepinephrine. Some of the main causes of such disturbances that have been documented include vaccines, mercury, aluminum, other toxic metals, MSG, aspartame, etc. (598,22,500,etc.)

Inflammation induced by vaccine adjuvants like aluminum and mercury or by excitotoxins like MSG has been found to play a significant role in insulin resistance(type-2 diabetes) and in high levels of LDL cholesterol(597,598,etc.). Type 2 diabetes is an epidemic among young Americans and greatly increases the incidence of heart attack, blindness, stoke, infertility, and early death. There is also evidence that the diet drink sweetener aspartame can cause or increase the effects of diabetes and hypoglycemia (450,498). Iron overload has also been found to be a cause of insulin resistance/type 2 diabetes(595).

Reduced levels of magnesium and zinc are related to metabolic syndrome, insulin resistance, and brain inflammation and are protective against these conditions(599,43). Mercury and cadmium inhibiting magnesium and zinc levels as well as inhibiting glucose transfer are other mechanisms by which mercury and toxic metals are factors in metabolic syndrome and insulin resistance/diabetes (43,198,338,597).

2. Impairment of methionine synthase function and impairment of folate-depdendent methylation.

The authors of 2 new studies of thimerosal developmental effects(88) write: "Our studies... provide evidence that mercury, aluminum, other heavy metals and the vaccine preservative thimerosal potently interfere with [methionine synthase] activation and impair folate-dependent methylation. In vitro, mercury and thimerosal in levels found several days after vaccination inhibit methionine synthetase (MS) by 50%. Normal function of MS is crucial in biochemical steps necessary for brain development, attention and production of glutathione, an important antioxidative and detoxifying agent. Repetitive doses of thimerosal leads to neurobehavioral deteriorations in autoimmune susceptible mice, increased oxidative stress and decreased intracellular levels of glutathione in vitro. Subsequent to vaccination, autistic children have significantly decreased level of reduced glutathione. Since each of these agents has been linked to developmental disorders, our findings suggest that impaired methylation, particularly impaired DNA methylation in response to growth factors, may be an important molecular mechanism leading to developmental disorders."

Citing Stajich et al 2002 (J Peds) and Pichichero et al 2002 (Lancet), Waly(88a) et al write: "A single thimerosal-containing vaccination produces acute ethylmercury blood levels of 10-30nM..., and blood samples in 2-month-old infants, obtained 3-20 days after vaccination, contain 3.8-20.6 nM ethylmercury. Our studies therefore indicate the potential for thimerosal to cause adverse effects on [methionine synthase] activity at concentrations well below the levels produced by individual thimerosal-containing vaccines. A second study notes that it has been found that those with autism generally had higher levels of exposure to mercury from their mother’s amalgam fillings or other sources prenatally (88b,50b). Another study on mice supported the autism/thimerosal connection(88c). Many other studies have documented the vaccine/thimerosal connection to autism(91-104).

Because of the evidence the FDA has completed a study and written a letter to vaccine manufacturers asking that mercury be removed from vaccines. The updated letter stated, "The Center for Biologics Evaluation and Research (CBER) has completed its evaluation of the use of thimerosal in vaccines.. Our review concluded that reducing or eliminating thimerosal from vaccines is merited(44). The letter pointed to a joint statement by the American Academy of Pediatrics and the United States Public Health Service in 1999, which "called for the removal of thimerosal from vaccines as soon as possible." A Congressional Committee after holding a hearing has also called for elimination of mercury in vaccines as soon as possible.

3. Mercury and toxic metals block enzymes required to digest milk casein and wheat gluten, resulting in dumping morphine like substances in the blood that are neurotoxic and psychotic, as a major factor in schizophrenia, autism, and ADHD.

A direct mechanism involving mercury’s inhibition of cellular enzymatic processes by binding with the hydroxyl radical(SH) in amino acids appears to be a major part of the connection to these allergic/immune reactive conditions(15-23,36,47,51,98). For example mercury has been found to strongly inhibit the activity of xanthine oxidase and dipeptyl peptidase (DPP IV) which are required in the digestion of the milk protein casein or wheat protein gluten (15,16,17,19,20,500,23-26,98,105), and the same protein that is cluster differentiation antigen 26 (CD26) which helps T lymphocyte activation. CD26 or DPPIV is a cell surface glycoprotein that is very susceptible to inactivation by mercury binding to its cysteinyl domain. Mercury and other toxic metals also inhibit binding of opioid receptor agonists to opioid receptors, while magnesium stimulates binding to opioid receptors(15). Studies involving large samples of patients with autism, schizophrenia, or mania found that over 90 % of those tested had high levels of the milk protein beta-casomorphine-7 in their blood and urine and defective enzymatic processes for digesting milk protein(24,25,27), and similarly for the corresponding enzyme needed to digest wheat gluten(24,26). Like casein, gluten breaks down into molecules with opioid traits, called gluteomorphine or gliadin. As with caseomorphin, it too can retain biological activity if the enzymes needed to digest it are not functioning properly..

Proteins in bovine milk are a common source of bioactive peptides. The peptides are released by the digestion of caseins and whey proteins (105). In vitro the bioactive peptide beta-casomorphin 7 (BCM-7) is yielded by the successive gastrointestinal proteolytic digestion of bovine beta-casein variants A1 and B, but this was not seen in variant A2 or in goats milk. In hydrolysed milk with variant A1 of beta-casein, BCM-7 level is 4-fold higher than in A2 milk. Variants A1 and A2 of beta-casein are common among many dairy cattle breeds. A1 is the most frequent in Holstein-Friesian (0.310–0.660), Ayrshire (0.432–0.720) and Red (0.710) cattle. In contrast, a high frequency of A2 is observed in Guernsey (0.880–0.970) and Jersey (0.490–0.721) cattle(105). In children with autism, most of whom have been found to have been exposed to high levels of toxic metals through vaccines, mother’s dental amalgams, or other sources; higher levels of BCM-7 is found in the blood(24-26).

BCM-7 appears to play a significant role in the aetiology of human diseases(105). Epidemiological evidence from New Zealand claims that consumption of beta-casein A1 is associated with higher national mortality rates from ischaemic heart disease. It appears that the populations that consume milk containing high levels of beta-casein A2 have a lower incidence of cardiovascular disease and type 1 diabetes. Beta-casomorphin-7 has opioid properties including immunosuppression, which account for the specificity of the relation between the consumption of some but not all beta-casein variants and diabetes incidence. BCM-7 has also been suggested as a possible cause of sudden infant death syndrome (SIDS). In addition, neurological disorders, such as autism and schizophrenia, appear to be associated with milk consumption and a higher level of BCM-7 (105).

The studies found high levels of Ig A antigen specific antibodies for casein, lactalbumin and beta-lactoglobulin and IgG and IgM for casein. Beta-casomorphine-7 is a morphine like compound that results in neural disfunction (24,25), as well as being a direct histamine releaser in humans and inducing skin reactions (14,21,25c). Similarly many also had a corresponding form of gluten protein with similar effects(24,26). Elimination of milk and wheat products and sulfur foods from the diet has been found to improve the condition(100,28,etc.). A double blind study using a potent opiate antagonist, naltrexone (NAL), produced significant reduction in autistic symptomology among the 56% most responsive to opioid effects(28). The behavioral improvements was accompanied by alterations in the distribution of the major lymphocyte subsets, with a significant increase in the T-helper-inducers and a significant reduction of the T-cytotoxic-suppressors and a normalization of the CD4/CD8 ratio. Studies have found mercury causes increased levels of the CD8 T-cytotoxic-suppressors(29). As noted previously, such populations of patients have also been found to have high levels of mercury and to recover after mercury detoxification(23,11,500,30,40,100). As mercury levels are reduced the protein binding is reduced and improvement in the enzymatic process occurs (500,11,96).

Studies have also found heavy metals to deplete glutathione and bind

to protein-bound sulfhydryl SH groups, resulting in inhibiting SH-containing enzymes and production of reactive oxygen species such as superoxide ion, hydrogen peroxide, and hydroxyl radical(39,43,45-47, 63-65,89,97,500). In addition to forming strong bonds with SH and other groups like OH,NH2, and Cl in amino acids which interfere with basic enzymatic processes, toxic metals exert part of their toxic effects by replacing essential metals such as zinc at their sites in enzymes. An example of this is mercury’s disabling of the metallothionein protein, which is necessary for the transport and detoxification of metals. Mercury inhibits sulfur ligands in MT and in the case of intestinal cell membranes inactivates MT that normally bind cuprous ions(66), thus allowing buildup of copper to toxic levels in many and malfunction of the Zn/Cu SOD function. Another large study(51) found a high percentage of autistic and PDD children are especially susceptible to metals due to the improper functioning of their metallothionein detoxification process, and that with proper treatment most recover. Mercury has also been found to play a part in neuronal problems through blockage of the P‑450 enzymatic process(67,89). Another study found accelerated lipofuscin deposition--consistent with oxidative injury to autistic brain in cortical areas serving language and communication(97). Compared with controls, children with autism had significantly higher urinary levels of lipid peroxidation. Double-blind, placebo-controlled trials of potent antioxidants--vitamin C or carnosine--significantly improved autistic behavior.

4. Mercury induced reactive oxygen species and lipid peroxidation has been found to be a major factor in mercury’s neurotoxicity, along with leading to decreased levels of glutathione peroxidation and superoxide dismustase (SOD) (63,89). This has been found to be a major factor in neurological and immune damage caused by the heavy metals, including damage to mitochondria and DNA(63,500), as well as chronic autoimmune conditions and diseases(35,104,500)

Another effect of mercury and toxic metals is a reduction in B- lymphocytes (37,38,50,500). Studies(37) dealing with autistic patients and further work with such patients has found this causes a tendency to be more seriously affected by viruses and to develop intestinal disorders including leaky gut, lymphoid modular hyperplasia, and a high incidence of parasites. Gut disease with inflammation has become increasingly evident in autism(37b). Enterocolitis and lymphonodular hyperplasia are found in nearly 90% of regressed autistic children (37d). Widespread inflammatory changes with poor intestinal digestive enzyme activity , abnormal intestinal permeability , and malabsorption have been reported in various autistic subgroups(37e). Studies have found that mercury has similar effects on animals (37b).

Mercury exposure has been shown to disrupt immune system homeostasis making the systems more susceptible to infectious agents such as measles virus and other viruses(22,598).

Autoimmunity

Metals by binding to SH radicals in proteins and other such groups can cause autoimmunity by modifying proteins which via T-cells activate B-cells that target the altered proteins inducing autoimmunity as well as causing aberrant MHC II expression on altered target cells(72).

Studies have also found mercury, aluminum, and lead cause autoantibodies to neuronal proteins, neurofilaments, and myelin basic protein (73,74,104). While zinc binding with MBP stabilizes the association with brain myelin, mercury and cadmium have been found to intefere with zinc binding to MBP and thus cause disfunction and autoimmunities(74). Dr. Stejskal(11) recently began testing children with autism. Her preliminary results on 18 autistic children and 11 controls, found that 5 of 18 autistic children had a positive proliferative ("allergic") response on MELISA to Thimerosal, vs. 1/11 controls. Similar results were recently found for methyl mercury (6/10 autistics vs 0/11 controls) and inorganic mercury (6/18 autistics, vs 0/11 controls). Most importantly, 13/16 autistics tested positive for reactivity to the mercury-MBP vs. only 3/10 controls. The mercury-MBP reactivity is presumed to be caused by the mercury reconfiguring the three-dimensional MBP, to which the body generates the allergic (autoimmune) response. In another study a significant percentage of children with autism developed anti-SK, anti-gliadin and anti-casein peptides and anti-ethyl mercury antibodies, concomitant with the appearance of anti-CD26 and anti-CD69 autoantibodies(89). These antibodies are synthesized as a result of SK, gliadin, casein and ethyl mercury binding to CD26 and CD69, indicating that they are specific. The study found that bacterial antigens (SK), dietary peptides (gliadin, casein) and Thimerosal (ethyl mercury) in individuals with pre-disposing HLA molecules, bind to CD26 or CD69 and induce antibodies against these molecules. Immune mechanisms are thus seen to be a major factor in neurotoxicity of metals seen in conditions such as autism and ADD(112,63,72-74).

7. Parathyroid Hypertensive Factor (PHF) is produced by the parathyroid gland and is measurable by the University of Alberta. Preliminary PHF determinations on over 100 patients through the Pfieffer Treatment Center have revealed very high levels for autistic patients . Heavy metals are known to block calcium L-channels at the cell membrane, whereas PHF is known to open calcium L-channels [84a] and stimulate phosphodiesterase [84b]. Calcium L-channels perform numerous functions, including initiation of transcriptional events which support learning, memory and endocrine secretion. Mercury inhibits L-channels at micromolar concentration [84c] in an irreversible manner in hippocampal neurons. Hypothetically, elevated PHF may serve to at least partially compensate Hg-inhibition of L-channels. Mercury is also a potent inhibitor of cAMP [84d], cellular levels of which presumably further decrease with PHF-stimulation of phosphodiesterase. Thus, in the context of mercury toxicity, PHF may play both adaptive and maladaptive roles. The very mechanism of mercury-induced auto-immune disease in mercury-sensitive rats is related to L-channel signaling. This process involves induction of interleukin-4 gene expression, which is mediated by protein kinase C-dependent calcium influx through L-channels [84e]. PHF hypothetically may affect the auto-immune response

8. An IRB approved study assessing urinary levels of porphyrins found an apparent dose-response effect between autism severity and increased urinary coproporphyrins(91). For patients with non-chelated autism (83% had levels > 2 SD above the control mean) and for children with non-chelated AutismSpectrumDisorders (58% had levels > 2 SD above the control mean), but for patients with non-chelated pervasive developmental delay-not otherwise specified (PDD-NOS) or Asperger's disorder (46% had levels > 2 SD above the control mean). Each group of ASDs had significantly increased median coproporphyrin levels versus controls. A significant increase (1.7-fold) in median coproporphyrin levels was observed among non-chelated ASD patients versus chelated ASD patients. Mercury toxicity was found to be associated with elevations in urinary coproporphyrin (cP), pentacarboxyporphyrin (5cxP), and precoproporphyrin (prcP) (also known as keto-isocoproporphyrin) levels. Two cohorts of autistic patients in the United States and France each had urine porphyrin levels associated with mercury toxicity. Another study using chelation therapy on a group of autistic patients found significant improvement during the study period(96).

Following up other studies showing higher than normal androgen levels in most autistic patients, a study found increased androgen levels in virtually all of a group of autistics. Morning blood samples collected following an overnight fast, compared to the pertinent reference means, showed significantly increased relative mean levels for: serum testosterone (158%), serum free testosterone (214%), percent free testosterone (121%), DHEA (192%), and androstenedione (173%). A medical hypothesis has suggested that some autism spectrum disorders (ASDs) may result from interactions between the methionine cycle-transsulfuration and androgen pathways following exposure to mercury. A study following treatment including chelation using DMSA and Lupron brought significant improvement in the majority of patients(96). A significant (p<0.01) overall improvement from the 70-79th percentile of severity at baseline to the 40-49th percentile of severity at the end of the study was observed for patients treated for a median of approximately 4 months. Significant improvements in sociability, cognitive awareness, behavior, and clinical symptoms/behaviors of hyperandrogenemia were also observed. Significant decreases in blood androgens and increases in urinary heavy metal concentrations were observed. Minimal drug adverse effects were found.

IV. Hypothyroidism during pregnancy as cause of developmental delays, reduced IQs, and autism- the mercury and toxic metal connection.

Studies have documented that mercury causes hypothyroidism (150,84,390,407), damage of thyroid RNA(458), autoimmune thyroiditis (369,382,191), and impairment of conversion of thyroid T4 hormone to the active T3 form(369,382,390,407,150d). These studies and clinical experience indicate that mercury and toxic metal exposures appear to be the most common cause of hypothyroidism and the majority treated by metals detoxification recover or significantly improve (503).

The estimated prevalence of hypothyroidism from a large federal health survey, NHANES III, was 4.6%, but the incidence was twice as high for women as for men and many with sub clinical hypothyroidism are not aware of their condition(113a). Another large study(113b) found that 11.7% tested had abnormal thyroid TSH levels with 9.5% being hypothyroid and 2.1% hyperthyroid. According to survey tests, 8 to 10 % of untreated women were found to have thyroid imbalances so the actual level of hypothyroidism is higher than commonly recognized(508). Even larger percentages of women had elevated levels of antithyroglobulin(anti-TG) or antithyroid peroxidase antibody(anti-TP). Tests have found approx. 30% of pregnant women to have low free T4 in the first trimester(509b).

Thyroid hormones are of primary importance for the perinatal development of the central nervous system, and for normal function of the adult brain (109a). Hypothyroidism of the adults causes most frequently dementia and depression. Nearly all the hyperthyroid patients show minor psychiatric signs, and sometimes psychosis, dementia, confusion state, depression, apathetic thyrotoxicosis, thyrotoxic crisis, seizures, pyramidal signs, or chorea occur(109a). These hormones primarily regulate the transcription of specific target genes. They increase the cortical serotonergic neurotransmission, and play an important role in regulating central noradrenergic and GABA function.

Studies indicate that slight thyroid deficiency/imbalance(sub clinical) during the perinatal period can result in delayed neuropsychological development in neonate and child or permanent neuropsychiatric damage in the developing fetus or autism or mental retardation (109,509,511). Low first trimester levels of free T4 and positive levels of anti-TP antibodies in the mother during pregnancy have been found to result in significantly reduced IQs (509a-e) and causes psychomotor deficits(509f). Women with the highest levels of thyroid-stimulating-hormone(TSH) and lowest free levels of thyroxin 17 weeks into their pregnancies were significantly more likely to have children who tested at least one standard deviation below normal on an IQ test taken at age 8(509a). Based on study findings, maternal hypothyroidism appears to play a role in at least 15% of children whose IQs are more than 1 standard deviation below the mean, millions of children. Overt autoimmune thyroiditis is preceded by a rise in levels of thyroid peroxidase antibodies. "Collectively, reports show that 30-60% of women positive for TPO antibodies in pregnancy develop postpartum thyroiditis," the researchers point out (561,108), calling it "a strong association." Without treatment, many of the women with thyroiditis go on to develop overt clinical hypothyroidism as they age and, eventually, associated complications such as cardiovascular disease. About 7.5% of pregnant women develop thyroiditis after birth(108). Studies have also established a connection between maternal thyroid disease and babies born with heart defects(509h).

Infants of women with hypothyroxinemia at 12 weeks' gestation had significantly lower scores on the Neonatal Behavioral Assessment Scale orientation index compared with subjects(109b). Regression analysis showed that first-trimester maternal free thyroid hormone T4 was a significant predictor of orientation scores. This study confirmed that maternal hypothyroxinemia constitutes a serious risk factor for neurodevelopmental difficulties that can be identified in neonates as young as 3 weeks of age.

Mercury (especially mercury vapor from dental amalgam or organic mercury) rapidly crosses the blood brain barrier and is stored preferentially in the pituitary gland, thyroid gland, hypothalamus, and occipital cortex in direct proportion to the number and extent of dental amalgam surfaces (114,119,185,199,273,274,407), and likewise rapidly crosses the placenta and accumulates in the fetus including the fetal brain and hormone glands at levels commonly higher than the level in the mother(120,122-127). Milk from mothers with 7 or more mercury amalgam dental fillings was found to have levels of mercury approximately 10 times that of amalgam free mothers(1500). The milk sampled ranged from 0.2 to 57 ug/L. In a population of German women, the concentration of mercury in early breast milk ranged from 0.2 to 20.3 ug/L (126). A Japanese study found that the average mercury level in samples tested increased 60% between 1980 and 1990[125]. The study found that prenatal Hg exposure is correlated with lower scores in neurodevelopmental screening, but more so in the linguistic pathway(125). The level of mercury in umbilical cord blood, meconium, and placenta is usually higher than that in mother's blood[123-125].

Alterations of cortical neuronal migration and cerebellar Purkinje cells have been observed in autism. Neuronal migration, via reelin regulation, requires triiodothyronine (T3) produced by deiodination of thyroxine (T4) by fetal brain deiodinases(407). Experimental animal models have shown that transient intrauterine deficits of thyroid hormones (as brief as 3 days) result in permanent alterations of cerebral cortical architecture reminiscent of those observed in brains of patients with autism. Early maternal hypothyroxinemia resulting in low T3 in the fetal brain during the period of neuronal cell migration (weeks 8-12 of pregnancy) may produce morphological brain changes leading to autism. Insufficient dietary iodine intake and a number of environmental antithyroid and goitrogenic agents can affect maternal thyroid function during pregnancy.

Mercury can have significant effects on thyroid function even though the main hormone levels remain in the normal range, so the usual thyroid tests are not adequate in such cases. Prenatal methylmercury exposure severely affects the activity of selenoenzymes, including glutathione peroxidase (GPx) and 5-iodothyronine deiodinases(5-Di and 5'-DI) in the fetal brain, even though thyroxine(T4) levels are normal(390e). Gpx activity is severely inhibited, while 5-DI levels are decreased and 5'-DI increased in the fetal brain, similar to hypothyroidism. Thus normal thyroid tests will not pick up this condition.

Mercury reduces the bloods ability to transport oxygen to fetus and transport of essential nutrients including amino acids, glucose, magnesium, zinc and Vit B12 (143,196,198,263,264,338, 339,427); depresses enzyme isocitric dehydrogenase (ICD) in fetus, causes reduced iodine uptake, autoimmune thyroiditis, & hypothyroidism. (150,191,212,222,369,382,407,135). Because of the evidence of widespread effects on infants, the American Assoc. of Clinical Endocrinologists advises that all women considering becoming pregnant should get a serum thyrotropin test so that hypothyroidism can be diagnosed and treated early(558,17b). Since mercury and toxic metals are common causes of hypothyroidism, another test that should be considered is a hair element test for mercury or toxic metal exposures and essential mineral imbalances.

An ecological study in Texas has correlated higher rates of autism in school districts affected by large environmental releases of mercury from industrial sources.

V. Conclusion

There has been strong suggestive and clinical evidence for a connection between toxic metals and autism spectrum conditions(2bcd,15-40,50,92,103) and recent studies using government databases have confirmed the connection(80,91,92). There also appear to be subgroups of exposure and symptom patterns among the many different types of persuasive developmental disorders (PDD) including autism, Asperger’s syndrome, obsessive compulsive disorder(OCD), dyslexia, ADD/ADHD, learning disabilities, childhood depression, etc.

Some of the apparent subgroups of autism include: the group with blocked enzymatic processes needed to properly digest casein and gluten, a group related to blockage by toxic metals of methionine synthase function, a group related to mother’s hypothyroid condition during the first trimester of pregnancy(other due to metals effects), a group of general brain-related encephalies and/or immune effects of toxic exposures(23), the Singh subgroup of autoimmune reactions to brain myelin sheath or other autoimmunity (112), the reduced B lymphocyte/MMR subgroup with intestional leaky gut and/or involvement of measles virus(37), and the Megson/DPT visual abnormality related group(49). Since most children have been been found to have high levels of toxic exposure, most of those affected appear to have symptoms related to both the first subgroup plus often one or more of the other exposures/subgroups. The Megson group are often helped significantly by treatment with Vitamin A from cod liver oil and urocholine. Thousands of autistic children are being treated for metals toxicity using chelation protocols after tests have documented high exposures to mercury and other toxic metals, and the majority have shown significant improvement (23,40,51,96,100). In a large survey of parents of autistic children by the Autism Research Institute of treatment success in treating autism, chelation/detoxification with nutritional support was found to be by far the most effective and least harmful treatment of all treatments surveyed, with over 73% of those using chelation protocol improving significantly after treatment(100). Autism treatment clinics testing and treating autism usually find high toxic metal body burdens and successful cognitive and behavioral treatment results as toxic metal body burden declines and metabolic imbalances are improved(101). Most of those using chelation/nutrition protocol recovered or significantly improved and are doing well in school.

In addition to large numbers of cases affecting infants, allergic contact eczema is the most frequent occupational disease(1,500,82); and the most common cause of contact eczema is exposure to toxic metals(1, 6-12,500). The metals most commonly causing allergic immune reactivity are nickel, mercury, chromium, cobalt, and palladium(1,6-14,500). The highest level of sensitization is to Infants, who are most reactive to thimerosal, a form of mercury that has been used as a preservative in vaccines and eye drops(6,7). Many with immune reactive conditions like eczema and psoriasis recover after tests and treatment for the cause of the immune reactivity(11,500 ).

References

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