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Teresa Binstock
Researcher in Developmental & Behavioral Neuroanatomy
August 12, 2009
A study by James Adams, Ph.D., and colleagues explored levels of toxic
metals and levels of glutathione in relation to the severity of
autistic symptoms (1). The study is free online and provides
information useful for clinicians evaluating and biomedically treating
autistic children. Several of the new study's primary citations are
available free online (2-4). Previously, several other studies have
documented mercury and other toxic metals in relation to autism and are
available free online (5-8). Furthermore, mercury is associated with
attention deficit and with ADHD (9).
Students in high school and college are encouraged to write essays
using these studies and citations (1-9) as the basis for term papers written for
class credit. News reporters are invited to peruse these peer-reviewed
articles.
References:
1. Severity of Autism Is Associated With Toxic Metal Body Burden and Red
Blood Cell Glutathione Levels
Adams J et al
Journal of Toxicology, 2009
Provisional PDF:
http://www.hindawi.com/journals/jt/aip.532640.pdf
Abstract: This study investigated the relationship of children’s autism
symptoms with their toxic metal body burden and red blood cell (RBC)
glutathione levels. In children ages 3-8 years, the severity of autism
was assessed using four tools: ADOS, PDD-BI, ATEC, and SAS. Toxic metal
body burden was assessed by measuring urinary excretion of toxic
metals, both before and after oral dimercaptosuccinic acid (DMSA).
Multiple positive correlations were found between the severity of
autism and the urinary excretion of toxic metals. Variations in the
severity of autism measurements could be explained, in part, by
regression analyses of urinary excretion of toxic metals before and
after DMSA and the level of RBC glutathione (adjusted R2 of 0.22-0.45,
p<0.005 in all cases). This study demonstrates a significant
positive association between the severity of autism and the relative
body burden of toxic metals.
2. Autism spectrum disorders in relation to distribution of hazardous air pollutants in the san francisco bay area
Windham GC et al. Environ Health Perspect. 2006 Sep;114(9):1438-44.
{free online}
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=1570060&blobtype=pdf
OBJECTIVE: To explore possible associations between autism spectrum
disorders (ASD) and environmental exposures, we linked the California
autism surveillance system to estimated hazardous air pollutant (HAP)
concentrations compiled by the U.S. Environmental Protection Agency.
METHODS: Subjects included 284 children with ASD and 657 controls, born
in 1994 in the San Francisco Bay area. We assigned exposure level by
census tract of birth residence for 19 chemicals we identified as
potential neurotoxicants, developmental toxicants, and/or endocrine
disruptors from the 1996 HAPs database. Because concentrations of many
of these were highly correlated, we combined the chemicals into
mechanistic and structural groups, calculating summary index scores. We
calculated ASD risk in the upper quartiles of these group scores or
individual chemical concentrations compared with below the median,
adjusting for demographic factors. RESULTS: The adjusted odds ratios
(AORs) were elevated by 50% in the top quartile of chlorinated solvents
and heavy metals [95% confidence intervals (CIs) , 1.1-2.1], but not
for aromatic solvents. Adjusting for these three groups simultaneously
led to decreased risks for the solvents and increased risk for metals
(AORs for metals: fourth quartile = 1.7 ; 95% CI, 1.0-3.0 ; third
quartile = 1.95 ; 95% CI, 1.2-3.1) . The individual compounds that
contributed most to these associations included mercury, cadmium,
nickel, trichloroethylene, and vinyl chloride. CONCLUSIONS: Our results
suggest a potential association between autism and estimated metal
concentrations, and possibly solvents, in ambient air around the birth
residence, requiring confirmation and more refined exposure assessment
in future studies.
3. Metabolic biomarkers of increased oxidative stress and impaired methylation capacity in children with autism
James SJ et al. Am J Clin Nutr. 2004 Dec;80(6):1611-7.
{free online}
http://www.ajcn.org/cgi/content/full/80/6/1611
BACKGROUND: Autism is a complex neurodevelopmental disorder that
usually presents in early childhood and that is thought to be
influenced by genetic and environmental factors. Although abnormal
metabolism of methionine and homocysteine has been associated with
other neurologic diseases, these pathways have not been evaluated in
persons with autism. OBJECTIVE: The purpose of this study was to
evaluate plasma concentrations of metabolites in the methionine
transmethylation and transsulfuration pathways in children diagnosed
with autism. DESIGN: Plasma concentrations of methionine,
S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), adenosine,
homocysteine, cystathionine, cysteine, and oxidized and reduced
glutathione were measured in 20 children with autism and in 33 control
children. On the basis of the abnormal metabolic profile, a targeted
nutritional intervention trial with folinic acid, betaine, and
methylcobalamin was initiated in a subset of the autistic children.
RESULTS: Relative to the control children, the children with autism had
significantly lower baseline plasma concentrations of methionine, SAM,
homocysteine, cystathionine, cysteine, and total glutathione and
significantly higher concentrations of SAH, adenosine, and oxidized
glutathione. This metabolic profile is consistent with impaired
capacity for methylation (significantly lower ratio of SAM to SAH) and
increased oxidative stress (significantly lower redox ratio of reduced
glutathione to oxidized glutathione) in children with autism. The
intervention trial was effective in normalizing the metabolic imbalance
in the autistic children. CONCLUSIONS: An increased vulnerability to
oxidative stress and a decreased capacity for methylation may
contribute to the development and clinical manifestation of autism.
4. Metabolic endophenotype and related genotypes are associated with oxidative stress in children with autism
James SJ et al. Am J Med Genet B Neuropsychiatr Genet. 2006 Dec 5;141B(8):947-56.
{free online}
http://www.pubmedcentral.nih.gov/picrender.fcgi?artid=2610366&blobtype=pdf
Autism is a behaviorally defined neurodevelopmental disorder usually
diagnosed in early childhood that is characterized by impairment in
reciprocal communication and speech, repetitive behaviors, and social
withdrawal. Although both genetic and environmental factors are thought
to be involved, none have been reproducibly identified. The metabolic
phenotype of an individual reflects the influence of endogenous and
exogenous factors on genotype. As such, it provides a window through
which the interactive impact of genes and environment may be viewed and
relevant susceptibility factors identified. Although abnormal
methionine metabolism has been associated with other neurologic
disorders, these pathways and related polymorphisms have not been
evaluated in autistic children. Plasma levels of metabolites in
methionine transmethylation and transsulfuration pathways were measured
in 80 autistic and 73 control children. In addition, common polymorphic
variants known to modulate these metabolic pathways were evaluated in
360 autistic children and 205 controls. The metabolic results indicated
that plasma methionine and the ratio of S-adenosylmethionine (SAM) to
S-adenosylhomocysteine (SAH), an indicator of methylation capacity,
were significantly decreased in the autistic children relative to
age-matched controls. In addition, plasma levels of cysteine,
glutathione, and the ratio of reduced to oxidized glutathione, an
indication of antioxidant capacity and redox homeostasis, were
significantly decreased. Differences in allele frequency and/or
significant gene-gene interactions were found for relevant genes
encoding the reduced folate carrier (RFC 80G > A), transcobalamin II
(TCN2 776G > C), catechol-O-methyltransferase (COMT 472G > A),
methylenetetrahydrofolate reductase (MTHFR 677C > T and 1298A >
C), and glutathione-S-transferase (GST M1). We propose that an
increased vulnerability to oxidative stress (endogenous or
environmental) may contribute to the development and clinical
manifestations of autism.
5. Environmental mercury release, special education rates, and autism disorder: an ecological study of Texas
Palmer RF et al. Health Place. 2006 Jun;12(2):203-9.
{free online}
http://www.generationrescue.org/pdf/seed.pdf
The association between environmentally released mercury, special
education and autism rates in Texas was investigated using data from
the Texas Education Department and the United States Environmental
Protection Agency. A Poisson regression analysis adjusted for school
district population size, economic and demographic factors was used.
There was a significant increase in the rates of special education
students and autism rates associated with increases in environmentally
released mercury. On average, for each 1,000 lb of environmentally
released mercury, there was a 43% increase in the rate of special
education services and a 61% increase in the rate of autism. The
association between environmentally released mercury and special
education rates were fully mediated by increased autism rates. This
ecological study suggests the need for further research regarding the
association between environmentally released mercury and developmental
disorders such as autism. These results have implications for policy
planning and cost analysis.
6. Proximity to point sources of environmental mercury release as a predictor of autism prevalence
Palmer RF et al. Health Place. 2009 Mar;15(1):18-24.
{free online}
http://images.huffingtonpost.com/2009-01-29-Palmer2008.pdf
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.
7. Treatment of autism spectrum children with thiamine tetrahydrofurfuryl disulfide: a pilot study
Lonsdale D et al. Neuro Endocrinol Lett. 2002 Aug;23(4):303-8.
{free online}
http://www.feingold.org/Research/PDFstudies/Lonsdale2002.pdf
OBJECTIVES: In a Pilot Study, the clinical and biochemical effects of
thiamine tetrahydrofurfuryl disulfide (TTFD) on autistic spectrum
children were investigated. SUBJECTS AND METHODS: Ten children were
studied. Diagnosis was confirmed through the use of form E2, a computer
assessed symptom score. For practical reasons, TTFD was administered
twice daily for two months in the form of rectal suppositories, each
containing 50 mg of TTFD. Symptomatic responses were determined through
the use of the computer assessed Autism Treatment Evaluation Checklist
(ATEC) forms. The erythrocyte transketolase (TKA) and thiamine
pyrophosphate effect (TPPE), were measured at outset and on completion
of the study to document intracellular thiamine deficiency. Urines from
patients were examined at outset, after 30 days and after 60 days of
treatment and the concentrations of SH-reactive metals, total protein,
sulfate, sulfite, thiosulfate and thiocyanate were determined. The
concentrations of metals in hair were also determined. RESULTS: At the
beginning of the study thiamine deficiency was observed in 3 out of the
10 patients. Out of 10 patients, 6 had initial urine samples containing
arsenic in greater concentration than healthy controls. Traces of
mercury were seen in urines from all of these autistic children.
Following administration of TTFD an increase in cadmium was seen in 2
children and in lead in one child. Nickel was increased in the urine of
one patient during treatment. Sulfur metabolites in urine did not
differ from those measured in healthy children. CONCLUSIONS: Thiamine
tetrahydrofurfuryl disulfide appears to have a beneficial clinical
effect on some autistic children, since 8 of the 10 children improved
clinically. We obtained evidence of an association of this increasingly
occurring disease with presence of urinary SH-reactive metals, arsenic
in particular.
8.
Hepatitis B triple series vaccine and developmental disability in US
children aged 1-9 years
Gallagher C, Goodman M. Toxicol Environ Chem 2008 90(5):997-1008.
{free online}
http://fourteenstudies.org/pdf/hep_b.pdf
This study investigated the association between vaccination with the
Hepatitis B triple series vaccine prior to 2000 and developmental
disability in children aged 1-9 years (n = 1824), proxied by parental
report that their child receives early intervention or special
education services (EIS). National Health and Nutrition Examination
Survey 1999-2000 data were analyzed and adjusted for survey design by
Taylor Linearization using SAS version 9.1 software, with SAS callable
SUDAAN version 9.0.1. The odds of receiving EIS were approximately nine times as great for vaccinated boys (n
= 46) as for unvaccinated boys (n = 7), after adjustment for
confounders. This study found statistically significant evidence to
suggest that boys in United States who were vaccinated with the triple
series Hepatitis B vaccine, during the time period in which vaccines
were manufactured with thimerosal, were more susceptible to
developmental disability than were unvaccinated boys.
9. Mercury (Hg) and Lead (Pb) etc in AD and ADHD
Citations compiled by Teresa Binstock, June 2008
http://www.generationrescue.org/adhd/adhd-HgPbEtc.htm
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