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Query: UMLS:C0004352 (autism)
 32,579 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence and prevalence of autism have increased during the past two decades. Despite comprehensive genetic studies the cause of autism remains unknown. This review emphasizes the potential importance of environmental factors in its causation. 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. 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. I postulate that 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. The most common causes could include inhibition of deiodinases D2 or D3 from maternal ingestion of dietary flavonoids or from antithyroid environmental contaminants. Some plant isoflavonoids have profound effects on thyroid hormones and on the hypothalamus-pituitary axis. Genistein and daidzein from soy (Glycine max) inhibit thyroperoxidase that catalyzes iodination and thyroid hormone biosynthesis. Other plants with hypothyroid effects include pearl millet (Pennisetum glaucum) and fonio millet (Digitaria exilis); thiocyanate is found in Brassicae plants including cabbage, cauliflower, kale, rutabaga, and kohlrabi, as well as in tropical plants such as cassava, lima beans, linseed, bamboo shoots, and sweet potatoes. Tobacco smoke is also a source of thiocyanate. Environmental contaminants interfere with thyroid function including 60% of all herbicides, in particular 2,4-dichlorophenoxyacetic acid (2,4-D), acetochlor, aminotriazole, amitrole, bromoxynil, pendamethalin, mancozeb, and thioureas. Other antithyroid agents include polychlorinated biphenyls (PCBs), perchlorates, mercury, and coal derivatives such as resorcinol, phthalates, and anthracenes. A leading ecological study in Texas has correlated higher rates of autism in school districts affected by large environmental releases of mercury from industrial sources. Mercury is a well known antithyroid substance causing inhibition of deiodinases and thyroid peroxidase. The current surge of autism could be related to transient maternal hypothyroxinemia resulting from dietary and/or environmental exposure to antithyroid agents. Additional multidisciplinary epidemiological studies will be required to confirm this environmental hypothesis of autism.
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PMID:Autism: transient in utero hypothyroxinemia related to maternal flavonoid ingestion during pregnancy and to other environmental antithyroid agents. 1896 27

Porphyrins are derivatives formed in the heme synthesis pathway and porphyrins afford a measure of xenobiotic exposure. The steps in the heme pathway most vulnerable to heavy metal inhibition are uroporphyrin decarboxylase (UROD) and coproporphyrinogen oxidase (CPOX) reactions. Mercury toxicity was 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 had urine porphyrin levels associated with mercury toxicity. A prospective study of urinary porphyrin testing at LabCorp (United States) and the Laboratoire Philippe Auguste (France) involving 71 autism spectrum disorder (ASD) patients, neurotypical sibling controls, and general population controls was undertaken. ASD patients had significant elevations in urinary levels of cP, 5cxP, and prcP relative to controls, and > 50% of ASD patients had urinary cP levels more than 2 standard deviations above the mean values for neurotypical sibling controls. Significant reductions in urinary 5cxP and cP levels were observed in ASD patients following chelation. A significant correlation was found between urinary porphyrins measured at LabCorp and those measured at the Laboratoire Philippe Auguste on individual ASD patients. The established developmental neurotoxicity attributed to mercury and biochemical/genomic evidence for mercury susceptibility/toxicity in ASDs indicates a causal role for mercury. Urinary porphyrin testing is clinically available, relatively inexpensive, and noninvasive. Porphyrins need to be routinely measured in ASDs to establish if mercury toxicity is a causative factor and to evaluate the effectiveness of chelation therapy.
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PMID:A prospective study of mercury toxicity biomarkers in autistic spectrum disorders. 1788 29

Ethylmercury in thimerosal-preserved childhood vaccines has been suggested to be neurotoxic and to contribute to the etiology of neurodevelopmental disorders, including autism. Immune system function may be an important factor influencing vulnerability of the developing nervous system to thimerosal. This possibility is based in part on a report by Hornig et al. (2004, Mol. Psychiatry 9, 833-845) of neurodevelomental toxicity in SJL/J mice that develop autoantibodies when exposed to organic mercury. The present study reexamined this possibility by injecting neonatal SJL/J mice with thimerosal, with and without combined HiB and DTP vaccines. Injections modeled childhood vaccination schedules, with mice injected on postnatal days 7, 9, 11, and 15 with 14.2, 10.8, 9.2, and 5.6 mug/kg mercury from thimerosal, respectively, or vehicle. Additional groups received vaccine only or a 10 times higher thimerosal + vaccine dose. Low levels of mercury were found in blood, brain, and kidneys 24 h following the last thimerosal injection. Survival, body weight, indices of early development (negative geotaxis, righting) and hippocampal morphology were not affected. Performance was unaffected in behavioral tests selected to assess behavioral domains relevant to core deficits in neurodevelopmental disorders such as autism (i.e., social interaction, sensory gating, anxiety). In an open-field test the majority of behaviors were unaffected by thimerosal injection, although thimerosal-injected female mice showed increased time in the margin of an open field at 4 weeks of age. Considered together the present results do not indicate pervasive developmental neurotoxicity following vaccine-level thimerosal injections in SJL mice, and provide little if any support for the hypothesis that thimerosal exposure contributes to the etiology of neurodevelopmental disorders.
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PMID:Low-level neonatal thimerosal exposure: further evaluation of altered neurotoxic potential in SJL mice. 1836 66

Impairments in social relatedness and communication, repetitive behaviors, abnormal movement patterns, and sensory dysfunction characterize autism spectrum disorders (ASDs). Seventy consecutive patients with an ASD diagnosis (DSM-IV criteria, >/= 6 years-old) who presented to the Genetic Centers of America for outpatient genetic/developmental evaluations from 2005-2007 were examined. Patients were evaluated using CLIA-approved Laboratory Cooperation of America (LabCorp) testing for: serum testosterone, serum free testosterone, % free testosterone, serum/plasma dehydroepiandrosterone (DHEA), androstendione, and follicle-stimulating hormone (FSH). 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%). By contrast, compared to the pertinent reference mean, the relative mean level of FSH (51%) was significantly decreased. Additionally, at least one of the androgen attributes examined exceeded its recognized laboratory age- and sex-specific reference range in 81.4% (57 of 70) of the patients examined. With respect to their age- and sex-specific reference ranges, females had significantly higher overall mean relative testosterone and relative free testosterone levels than males. Increased androgens in patients diagnosed with ASDs may involve cyclical interactions between the androgen and the transsulfuration pathways, particularly following mercury exposure. A review of therapies that have significantly improved clinical outcomes in ASD patients indicates they share commonality in helping lower androgens. Thus, androgens should be routinely clinically measured in patients with an ASD diagnosis and appropriate androgen-lowering therapies considered for those who have significantly elevated levels.
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PMID:A prospective assessment of androgen levels in patients with autistic spectrum disorders: biochemical underpinnings and suggested therapies. 1798 58

The question of what is leading to the apparent increase in autism is of great importance. Like the link between aspirin and heart attack, even a small effect can have major health implications. If there is any link between autism and mercury, it is absolutely crucial that the first reports of the question are not falsely stating that no link occurs. We have reanalyzed the data set originally reported by Ip et al. in 2004 and have found that the original p value was in error and that a significant relation does exist between the blood levels of mercury and diagnosis of an autism spectrum disorder. Moreover, the hair sample analysis results offer some support for the idea that persons with autism may be less efficient and more variable at eliminating mercury from the blood.
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PMID:Blood levels of mercury are related to diagnosis of autism: a reanalysis of an important data set. 1840 Oct 39

The controversy regarding the once widely used mercury-containing preservative thimerosal in childhood vaccines has raised many historical questions that have not been adequately explored. Why was this preservative incorporated in the first place? Was there any real evidence that it caused harm? And how did thimerosal become linked in the public mind to the "autism epidemic"? I examine the origins of the thimerosal controversy and their legacy for the debate that has followed. More specifically, I explore the parallel histories of three factors that converged to create the crisis: vaccine preservatives, mercury poisoning, and autism. An understanding of this history provides important lessons for physicians and policymakers seeking to preserve the public's trust in the nation's vaccine system.
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PMID:Mercury, vaccines, and autism: one controversy, three histories. 1855 96

The objective of this study was to determine if proximity to sources of mercury pollution in 1998 were related to autism prevalence in 2002. Autism count data from the Texas Educational Agency and environmental mercury release data from the Environmental Protection Agency were used. We found that for every 1000 pounds of industrial release, there was a corresponding 2.6% increase in autism rates (p<.05) and a 3.7% increase associated with power plant emissions(P<.05). Distances to these sources were independent predictors after adjustment for relevant covariates. For every 10 miles from industrial or power plant sources, there was an associated decreased autism Incident Risk of 2.0% and 1.4%, respectively (p<.05). While design limitations preclude interpretation of individual risk, further investigations of environmental risks to child development issues are warranted.
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PMID:Proximity to point sources of environmental mercury release as a predictor of autism prevalence. 1835 3

Metallothioneins (MTs) are a family of small proteins containing 61-68 amino acids with an unusually high concentration of cysteine. MT-1, the most functional and active MT in humans, has the ability to react with and enhance the detoxification of a number of metals including zinc, mercury, copper and cadmium. MT dysfunction may result, then, in many of the aetiological syndromes observed in autistic children, such as the leaky gut. It has been proposed that allergic autoimmune reactions occurring after exposure to heavy metals, may contribute to some symptoms associated with autism. Therefore abnormalities in MT concentration and/or structure, as well as the presence of anti-MT antibodies, may be associated with autism. We used direct ELISAs to quantitate the concentration of serum anti-metallothionein IgG in 66 individuals (parents and children) from 14 families with autistic children, as well as 11 controls from families with no history of autism. We measured the concentration of serum metallothionein in 39 of the above family members from 8 families. Our results indicate that a significantly high number (23 of 66) of autistic family members had high levels of anti-metallothionein IgG, when compared to controls (1 ) and the production of these antibodies correlated with levels of metallothionein, suggesting that the production of these antibodies is inherited. However, the presence of these antibodies does not correlate with autism, types of autism, including regression, or demographics such as allergies, respiratory problems or GI disease. This suggests that the presence of anti-metallothionein antibodies is not causative to autism and may be the result of other immunological pathology seen in many autistics.
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PMID:Anti-metallothionein IgG and levels of metallothionein in autistic families. 1836 50

Methylmercury (MeHg) has cytotoxic effects on animals and humans, and a major target organ for MeHg is the central nervous system (CNS). It is well known that the developing CNS is extremely vulnerable to MeHg-induced changes in comparison to the mature brain. Most studies have concentrated on the direct effects of high levels of prenatal MeHg exposure. Surprisingly, behavioral outcomes found in adult offspring exposed developmentally to the neurotoxic effects of chronic, low-dose mercury more akin to ingestion in humans are not well characterized. The objective of this study was to determine whether such exposure produces deleterious effects on behavior in adult mice, including motor/coordination abilities, overall activity and mnemonic function. Developing mouse fetuses were exposed in utero during gestational days 8-18 by giving pregnant C57Bl/6J female mice food containing MeHg at a daily dose of 0.01 mg/kg body weight. Adult mice prenatally exposed to MeHg exhibited significant deficits in motor abilities, coordination, and overall activity, as measured by rotarod, footprint analysis and open field. In addition, MeHg-exposed mice were impaired with respect to reference memory but not in a visible, cued version of the Morris water maze task. These results indicate that prenatal exposure to the lowest dose of MeHg examined to date can have long-lasting motor and cognitive consequences on adult offspring. These findings have far reaching implications related to putative safe levels of MeHg ingestion, particularly during pregnancy, and increasing rates of cognitive and psychological disorders (e.g. attention hyperactivity deficit disorder, autism) in our society.
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PMID:Chronic, low-dose prenatal exposure to methylmercury impairs motor and mnemonic function in adult C57/B6 mice. 1843 14

The study evaluated possible associations between neurodevelopmental disorders (NDs) and exposure to mercury (Hg) from Thimerosal-containing vaccines (TCVs) by examining the automated Vaccine Safety Datalink (VSD). A total of 278,624 subjects were identified in birth cohorts from 1990-1996 that had received their first oral polio vaccination by 3 months of age in the VSD. The birth cohort prevalence rate of medically diagnosed International Classification of Disease, 9th revision (ICD-9) specific NDs and control outcomes were calculated. Exposures to Hg from TCVs were calculated by birth cohort for specific exposure windows from birth-7 months and birth-13 months of age. Poisson regression analysis was used to model the association between the prevalence of outcomes and Hg doses from TCVs. Consistent significantly increased rate ratios were observed for autism, autism spectrum disorders, tics, attention deficit disorder, and emotional disturbances with Hg exposure from TCVs. By contrast, none of the control outcomes had significantly increased rate ratios with Hg exposure from TCVs. Routine childhood vaccination should be continued to help reduce the morbidity and mortality associated with infectious diseases, but efforts should be undertaken to remove Hg from vaccines. Additional studies should be conducted to further evaluate the relationship between Hg exposure and NDs.
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PMID:Thimerosal exposure in infants and neurodevelopmental disorders: an assessment of computerized medical records in the Vaccine Safety Datalink. 1848 37


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