AUTISMO E VACCINI
(articoli scientifici dal 2000 al 2010)
Toxicity Biomarkers in Autism Spectrum Disorder: A Blinded Study of Urinary Porphyrins
Kern JK, Geier DA, Adams JB, Mehta JA, Grannemann BD, Geier MR
Pediatr Int. 2011 Apr;53(2):147-53
Doi: 10.1111/j.1442-200X.2010.03196.x
Abstract
BACKGROUND: Recent studies suggest children diagnosed with an autism spectrum disorder (ASD) have significantly increased levels of urinary porphyrins associated with mercury (Hg) toxicity, including pentacarboxyporphyrin (5cxP), precoproporphyrin (prcP), and coproporphyrin (cP), compared to typically developing controls. However, these initial studies were criticized because the controls were not age- and gender-matched to the children diagnosed with an ASD.
MATERIAL/METHODS: Urinary porphyrin biomarkers in a group of children (2-13 years of age) diagnosed with an ASD (n=20) were compared to matched (age, gender, race, location, and year tested) group of typically developing controls (n = 20).
RESULTS: Participants diagnosed with an ASD had significantly increased levels of 5cxP, prcP, and cP in comparison to controls. No significant differences were found in non-Hg associated urinary porphyrins (uroporphyrins, hexacarboxyporphyrin, and heptacarboxyporphyrin). There was a significantly increased odds ratio for an ASD diagnosis relative to controls among study participants with precoproporphyrin (odds ratio = 15.5, p < 0.01) and coproporphyrin (odds ratio = 15.5, p < 0.01) levels in the second through fourth quartiles in comparison to the first quartile. Conclusion: These results suggest that the levels of Hg-toxicity-associated porphyrins are higher in children with an ASD diagnosis than controls. Although the pattern seen (increased 5cxP, prcP, and cP) is characteristic of Hg toxicity, the influence of other factors, such as genetics and other metals cannot be completely ruled-out.
A Prospective Assessment of Porphyrins in Autistic Disorders: A Potential Marker for Heavy Metal Exposure
Aschner M, Ceccatelli S
Neurotox Res.2006 Aug;10(1):57-64
Abstract
Mercury and mercurial compounds are among the environmentally ubiquitous substances most toxic to both wildlife and humans. Once released into the environment from both natural and anthropogenic sources, mercury exists mainly as three different molecular species: elemental, inorganic, and organic. Potential health risks have been reported from exposure to all forms; however, of particular concern for human exposure relate to the potent neurotoxic effects of methylmercury (MeHg), especially for the developing nervous system. The general population is primarily exposed to MeHg by seafood consumption. In addition, some pharmaceuticals, including vaccines, have been, and some continue to be, a ubiquitous source of exposure to mercurials. A significant controversy has been whether the vaccine preservative ethylmercury thiosalicylate, commonly known as thimerosal, could cause the development of autism. In this review, we have discussed the hypothesis that exposure to thimerosal during childhood may be a primary cause of autism. The conclusion is that there are no reliable data indicating that administration of vaccines containing thimerosal is a primary cause of autism. However, one cannot rule out the possibility that the individual gene profile and/or gene-environment interactions may play a role in modulating the response to acquired risk by modifying the individual susceptibility.
A Case Series of Children with Apparent Mercury Toxic Encephalopathies Manifesting with Clinical Symptoms of Regressive Autistic Disorders
Geier DA, Geier MR.
J Toxicol Environ Health A. 2007 May 15;70(10):837-51
Abstract
Impairments in social relatedness and communication, repetitive behaviors, and stereotypic abnormal movement patterns characterize autism spectrum disorders (ASDs). It is clear that while genetic factors are important to the pathogenesis of ASDs, mercury exposure can induce immune, sensory, neurological, motor, and behavioral dysfunctions similar to traits defining or associated with ASDs. The Institutional Review Board of the Institute for Chronic Illnesses (Office for Human Research Protections, U.S. Department of Health and Human Services, IRB number IRB00005375) approved the present study. A case series of nine patients who presented to the Genetic Centers of America for a genetic/developmental evaluation are discussed. Eight of nine patients (one patient was found to have an ASD due to Rett’s syndrome) (a) had regressive ASDs; (b) had elevated levels of androgens; (c) excreted significant amounts of mercury post chelation challenge; (d) had biochemical evidence of decreased function in their glutathione pathways; (e) had no known significant mercury exposure except from Thimerosal- containing vaccines/Rho(D)-immune globulin preparations; and (f) had alternate causes for their regressive ASDs ruled out. There was a significant dose-response relationship between the severity of the regressive ASDs observed and the total mercury dose children received from Thimerosal-containing vaccines/Rho (D)- immune globulin preparations. Based upon differential diagnoses, 8 of 9 patients examined were exposed to significant mercury from Thimerosal-containing biologic/vaccine preparations during their fetal/infant developmental periods, and subsequently, between 12 and 24 mo of age, these previously normally developing children suffered mercury toxic encephalopathies that manifested with clinical symptoms consistent with regressive ASDs. Evidence for mercury intoxication should be considered in the differential diagnosis as contributing to some regressive ASDs.
Early Downward Trends in Neurodevelopmental Disorders Following Removal of Thimerosal-Containing Vaccines
Geier DA, Geier MR
Med Sci Monit. 2006 Jun;12(6):CR231-9
Abstract
Contemporaneously with the epidemic rise in neurodevelopmental disorders (NDs), first observed in the United States during the 1990s, the childhood immunization schedule was expanded by the U.S. Centers for Disease Control and Prevention (CDC) to include several additional thimerosal-containing vaccines (TCVs). On July 7, 1999, a joint recommendation was made by the American Academy of Pediatrics (AAP) and the U.S. Public Health Service (PHS) to remove thimerosal from vaccines. A two-phase study was undertaken to evaluate trends in diagnosis of new NDs entered into the Vaccine Adverse Event Reporting System (VAERS) and the California Department of Developmental Services (CDDS) databases on a reporting quarter basis, from 1994 through 2005. Significant increasing trends in newly diagnosed NDs were observed in both databases 1994 through mid-2002. Significant decreasing trends in newly diagnosed NDs were observed in both databases from mid-2002 through 2005. The results indicate that the trends in newly diagnosed NDs correspond directly to the expansion and subsequent contraction of the cumulative mercury dose to which children were exposed from TCVs through the U.S. immunization schedule.
Hepatitis B vaccination of male neonates and autism diagnosis, NHIS 1997-2002
Gallagher CM, Goodman MS
J Toxicol Environ Health A. 2010;73(24):1665-77
Abstract
Universal hepatitis B vaccination was recommended for U.S. newborns in 1991; however, safety findings are mixed. The association between hepatitis B vaccination of male neonates and parental report of autism diagnosis was determined. This cross-sectional study used weighted probability samples obtained from National Health Interview Survey 1997-2002 data sets. Vaccination status was determined from the vaccination record. Logistic regression was used to estimate the odds for autism diagnosis associated with neonatal hepatitis B vaccination among boys age 3-17 years, born before 1999, adjusted for race, maternal education, and two-parent household. Boys vaccinated as neonates had threefold greater odds for autism diagnosis compared to boys never vaccinated or vaccinated after the first month of life. Non-Hispanic white boys were 64% less likely to have autism diagnosis relative to nonwhite boys. Findings suggest that U.S. male neonates vaccinated with the hepatitis B vaccine prior to 1999 (from vaccination record) had a threefold higher risk for parental report of autism diagnosis compared to boys not vaccinated as neonates during that same time period. Nonwhite boys bore a greater risk.
A prospective study of prenatal mercury exposure from maternal dental amalgams and autism severity
Geier DA, Kern JKGeier MR
Acta Neurobiol Exp (Wars). 2009;69(2):189-97
Abstract
Dental amalgams containing 50% mercury (Hg) have been used in dentistry for the last 150 years, and Hg exposure during key developmental periods was associated with autism spectrum disorders (ASDs). This study examined increased Hg exposure from maternal dental amalgams during pregnancy among 100 qualifying participants born between 1990–1999 and diagnosed with DSM-IV autism (severe) or ASD (mild). Logistic regression analysis (age, gender, race, and region of residency adjusted) by quintile of maternal dental amalgams during pregnancy revealed the ratio of autism:ASD (severe:mild) were about 1 (no effect) for ≤5 amalgams and increased for ≥6 amalgams. Subjects with ≥6 amalgams were 3.2-fold significantly more likely to be diagnosed with autism (severe), in comparison to ASD (mild), than subjects with ≤5 amalgams. Dental amalgam policies should consider Hg exposure in women before and during the child-bearing age and the possibility of subsequent fetal exposure and adverse outcomes.
Mercury induces inflammatory mediator release from human mast cells
Kempuraj D, Asadi S, Zhang B, Manola A, Hogan J, Peterson E, Theoharides TC.J
Neuroinflammation 2010 Mar 11;7:20
Abstract
BACKGROUND: Mercury is known to be neurotoxic, but its effects on the immune system are less well known. Mast cells are involved in allergic reactions, but also in innate and acquired immunity, as well as in inflammation. Many patients with Autism Spectrum Disorders (ASD) have “allergic” symptoms; moreover, the prevalence of ASD in patients with mastocytosis, characterized by numerous hyperactive mast cells in most tissues, is 10-fold higher than the general population suggesting mast cell involvement. We, therefore, investigated the effect of mercuric chloride (HgCl2) on human mast cell activation.
MATERIAL/METHODS: Human leukemic cultured LAD2 mast cells and normal human umbilical cord blood-derived cultured mast cells (hCBMCs) were stimulated by HgCl2 (0.1-10 μM) for either 10 min for beta-hexosaminidase release or 24 hr for measuring vascular endothelial growth factor (VEGF) and IL-6 release by ELISA.
RESULTS: HgCl2 induced a 2-fold increase in b-hexosaminidase release, and also significant VEGF release at 0.1 and 1 μM (311 ± 32 pg/106 cells and 443 ± 143 pg/106 cells, respectively) from LAD2 mast cells compared to control cells (227 ± 17 pg/106 cells, n = 5, p < 0.05). Addition of HgCl2 (0.1 μM) to the proinflammatory neuropeptide substance P (SP, 0.1 μM) had synergestic action in inducing VEGF from LAD2 mast cells. HgCl2 also stimulated significant VEGF release (360 ± 100 pg/106 cells at 1 μM, n = 5, p < 0.05) from hCBMCs compared to control cells (182 ± 57 pg/106 cells), and IL-6 release (466 ± 57 pg/106 cells at 0.1 μM) compared to untreated cells (13 ± 25 pg/106 cells, n = 5, p < 0.05). Addition of HgCl2 (0.1 μM) to SP (5 μM) further increased IL-6 release.
CONCLUSIONS: HgCl2 stimulates VEGF and IL-6 release from human mast cells. This phenomenon could disrupt the blood-brain-barrier and permit brain inflammation. As a result, the findings of the present study provide a biological mechanism for how low levels of mercury may contribute to ASD pathogenesis.
Fever plus mitochondrial disease could be risk factors for autistic regression
Shoffner J, Hyams L, Langley GN, Cossette S, Mylacraine L, Dale J, Ollis L, Kuoch S, Bennett K, Aliberti A, Hyland K
J Child Neurol. 2010 Apr;25(4):429-34
Abstract
Autistic spectrum disorders encompass etiologically heterogeneous persons, with many genetic causes. A subgroup of these individuals has mitochondrial disease. Because a variety of metabolic disorders, including mitochondrial disease show regression with fever, a retrospective chart review was performed and identified 28 patients who met diagnostic criteria for autistic spectrum disorders and mitochondrial disease. Autistic regression occurred in 60.7% (17 of 28), a statistically significant increase over the general autistic spectrum disorder population (P < .0001). Of the 17 individuals with autistic regression, 70.6% (12 of 17) regressed with fever and 29.4% (5 of 17) regressed without identifiable linkage to fever or vaccinations. None showed regression with vaccination unless a febrile response was present. Although the study is small, a subgroup of patients with mitochondrial disease may be at risk of autistic regression with fever. Although recommended vaccinations schedules are appropriate in mitochondrial disease, fever management appears important for decreasing regression risk.
Urinary porphyrin excretion in neurotypical and autistic children
Woods JS, Armel SE, Fulton DI, Allen J, Wessels K, Simmonds PL, Granpeesheh D, Mumper E, Bradstreet JJ, Echeverria D, Heyer NJ, Rooney JP
Environ Health Perspect. 2010 Oct;118(10):1450-7
Abstract
BACKGROUND: Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU).
OBJECTIVES: This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism.
METHODS: This exploratory study enrolled 278 children 2-12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism.
RESULTS: Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received.
CONCLUSIONS: These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent.
Vaccines and autism: a tale of shifting hypotheses.
Gerber JS, Offit PA
Clin Infect Dis. 2009 Feb 15;48(4):456-61
Abstract
Although child vaccination rates remain high, some parental concern persists that vaccines might cause autism. Three specific hypotheses have been proposed: (1) the combination measles-mumps-rubella vaccine causes autism by damaging the intestinal lining, which allows the entrance of encephalopathic proteins; (2) thimerosal, an ethylmercury-containing preservative in some vaccines, is toxic to the central nervous system; and (3) the simultaneous administration of multiple vaccines overwhelms or weakens the immune system. We will discuss the genesis of each of these theories and review the relevant epidemiological evidence.
Wakefield’s “autistic enterocolitis” under the microscope
Deer B
BMJ. 2010 Apr 15;340:c1127
Doi: 10.1136/bmj.c1127
Abstract
Twelve years ago, a now infamous and retracted paper appeared in the Lancet1 and launched a health scare. In it, researchers at the Royal Free medical school in London reported on 12 children with developmental disorders, and linked their problems to MMR (measles, mumps, and rubella) vaccination.
It was the proposed link between the vaccine and “regressive” autism that caught the headlines and sparked alarm. But the paper also claimed to have discovered a new gut pathology, reported in 11 of the 12 children, which the lead author, Andrew Wakefield, an academic gastroenterologist, would dub “autistic enterocolitis.” “Researchers at the Royal Free Hospital School of Medicine may have discovered a new syndrome in children involving a new inflammatory bowel disease and autism,” the institution announced in a press release in February 1998.2“Their paper . . . also suggests that in a number of cases the onset of behavioural symptoms was associated with MMR vaccination.”
Six years later, the vaccine link was dropped when 10 of the paper’s 13 authors retracted this claim3 in the wake of my investigation for the Sunday Times.4 And last month the entire paper was retracted,5 after a General Medical Council panel decided that Wakefield was “dishonest” and “unethical.”
A biomarker of mercury body-burden correlated with diagnostic domain specific clinical symptoms of autism spectrum disorder.
Kern JK, Geier DA, Adams JB, Geier MR
Biometals. 2010 Dec;23(6):1043-51
Abstract
The study purpose was to compare the quantitative results from tests for urinary porphyrins, where some of these porphyrins are known biomarkers of heavy metal toxicity, to the independent assessments from a recognized quantitative measurement, the Autism Treatment Evaluation Checklist (ATEC), of specific domains of autistic disorders symptoms (Speech/Language, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) in a group of children having a clinical diagnosis of autism spectrum disorder (ASD). After a Childhood Autism Rating Scale (CARS) evaluation to assess the development of each child in this study and aid in confirming their classification, and an ATEC was completed by a parent, a urinary porphyrin profile sample was collected and sent out for blinded analysis. Urinary porphyrins from twenty-four children, 2-13 years of age, diagnosed with autism or PDD-NOS were compared to their ATEC scores as well as their scores in the specific domains (Speech/Language, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) assessed by ATEC. Their urinary porphyrin samples were evaluated at Laboratoire Philippe Auguste (which is an ISO-approved clinical laboratory). The results of the study indicated that the participants' overall ATEC scores and their scores on each of the ATEC subscales (Speech/Language, Sociability, Sensory/Cognitive Awareness, and Health/Physical/Behavior) were linearly related to urinary porphyrins associated with mercury toxicity. The results show an association between the apparent level of mercury toxicity as measured by recognized urinary porphyrin biomarkers of mercury toxicity and the magnitude of the specific hallmark features of autism as assessed by ATEC.
The biological basis of autism spectrum disorders: Understanding causation and treatment by clinical geneticists.
Geier DA, Kern JK, Geier MR
Acta Neurobiol Exp (Wars). 2010;70(2):209-26
Abstract
Autism spectrum disorders (ASDs) also known as pervasive developmental disorders (PDD) are a behaviorally defined group of neurodevelopmental disorders that are usually diagnosed in early childhood. ASDs disproportionately affect male children. Mercury (Hg) a heavy metal, is widespread and persistent in the environment. Mercury is a ubiquitous source of danger in fish, drugs, fungicides/herbicides, dental fillings, thermometers, and many other products. Elevated Hg concentrations may remain in the brain from several years to decades following exposure. This is important because investigators have long recognized that Hg is a neurodevelopmental poison; it can cause problems in neuronal cell migration and division, and can ultimately cause cell degeneration and death. Case-reports of patients have described developmental regressions with ASD symptoms following fetal and/or early childhood Hg exposure, and epidemiological studies have linked exposure to Hg with an elevated risk of a patient being diagnosed with an ASD. Immune, sensory, neurological, motor, and behavioral dysfunctions similar to traits defining or associated with ASDs were reported following Hg intoxication with similarities extending to neuroanatomy, neurotransmitters, and biochemistry. The sexual dimorphism of ASDs may result from synergistic neurotoxicity caused by the interaction of testosterone and Hg; in contrast, estrogen is protective, mitigating the toxicity of Hg. Mercury exposure may significantly increase androgen levels, and as a result, patients diagnosed with an ASD may significantly benefit from anti-androgen therapy. Finally, the clinical geneticist has a wealth of biomarkers to evaluate and treat patients diagnosed with an ASD.