A Comparison of Urinary Mercury between Children with Autism Spectrum Disorders and Control Children

Wright, Barry; Pearce, Helen; Allgar, Victoria; Miles, Jeremy N. V.; Whitton, Clare; Leon, Irene de; Jardine, Jenny; McCaffrey, Nikki; Smith, Rob; Holbrook, Ian; Lewis, John D.; Goodall, David M.; Alderson-Day, Ben

doi:10.1371/journal.pone.0029547

Cited by 32 publications

(8 citation statements)

References 44 publications

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“…Overall, the finding of increased levels of several toxic metals in urine of children with ASD agrees with two previous studies [15, 77], but disagrees with one large study [78] and one small study [79]. This disagreement is similar to that of the 40 case-control studies discussed in the introduction, in which about half observed levels of increased toxic metals.…”

Section: Discussionsupporting

confidence: 69%

“…A study by Wright et al [78] in the United Kingdom investigated urinary levels of several toxic metals in 56 children with ASD compared to 121 neurotypical children, and did not find significant differences in levels of mercury, antimony, cadmium, or lead. The results for mercury and cadmium are consistent with the present study, but the results for antimony and lead are not.…”

Section: Discussionmentioning

confidence: 99%

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Significant Association of Urinary Toxic Metals and Autism-Related Symptoms—A Nonlinear Statistical Analysis with Cross Validation

et al. 2017

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IntroductionA number of previous studies examined a possible association of toxic metals and autism, and over half of those studies suggest that toxic metal levels are different in individuals with Autism Spectrum Disorders (ASD). Additionally, several studies found that those levels correlate with the severity of ASD.MethodsIn order to further investigate these points, this paper performs the most detailed statistical analysis to date of a data set in this field. First morning urine samples were collected from 67 children and adults with ASD and 50 neurotypical controls of similar age and gender. The samples were analyzed to determine the levels of 10 urinary toxic metals (UTM). Autism-related symptoms were assessed with eleven behavioral measures. Statistical analysis was used to distinguish participants on the ASD spectrum and neurotypical participants based upon the UTM data alone. The analysis also included examining the association of autism severity with toxic metal excretion data using linear and nonlinear analysis. “Leave-one-out” cross-validation was used to ensure statistical independence of results.Results and DiscussionAverage excretion levels of several toxic metals (lead, tin, thallium, antimony) were significantly higher in the ASD group. However, ASD classification using univariate statistics proved difficult due to large variability, but nonlinear multivariate statistical analysis significantly improved ASD classification with Type I/II errors of 15% and 18%, respectively. These results clearly indicate that the urinary toxic metal excretion profiles of participants in the ASD group were significantly different from those of the neurotypical participants. Similarly, nonlinear methods determined a significantly stronger association between the behavioral measures and toxic metal excretion. The association was strongest for the Aberrant Behavior Checklist (including subscales on Irritability, Stereotypy, Hyperactivity, and Inappropriate Speech), but significant associations were found for UTM with all eleven autism-related assessments with cross-validation R2 values ranging from 0.12–0.48.

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Section: Discussionsupporting

confidence: 69%

Section: Discussionmentioning

confidence: 99%

Significant Association of Urinary Toxic Metals and Autism-Related Symptoms—A Nonlinear Statistical Analysis with Cross Validation

et al. 2017

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“…Several recent studies have shown no link between mercury body burdens and autism (Ip, Wong et al 2004; Hertz-Picciotto, Green et al 2010; Albizzati, More et al 2012; Wright, Pearce et al 2012). However, a reanalysis of data generated by Ip et al showed there was in fact an association between mercury levels and autism that had been overlooked due to a statistical error (Desoto and Hitlan 2007).…”

Section: Environmental Factors In Autism and Immune Dysfunctionmentioning

confidence: 99%

Cytokine dysregulation in autism spectrum disorders (ASD): Possible role of the environment

Goines

Ashwood

2013

Neurotoxicology and Teratology

260

177

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Autism spectrum disorders (ASD) are neurodevelopmental diseases that affect an alarming number of individuals. The etiological basis of ASD is unclear, and evidence suggests it involves both genetic and environmental factors. There are many reports of cytokine imbalances in ASD. These imbalances could have a pathogenic role, or they may be markers of underlying genetic and environmental influences. Cytokines act primarily as mediators of immunological activity, but they also have significant interactions with the nervous system. They participate in normal neural development and function, and inappropriate activity can have a variety of neurological implications. It is therefore possible that cytokine dysregulation contributes directly to neural dysfunction in ASD. Further, cytokine profiles change dramatically in the face of infection, disease, and toxic exposures. Therefore, imbalances may represent an immune response to environmental contributors to ASD. The following review is presented in two main parts. First, we discuss select cytokines implicated in ASD, including IL-1Β, IL-6, IL-4, IFN-γ, and TGF-Β, and focus on their role in the nervous system. Second, we explore several neurotoxic environmental factors that may be involved in the disorders, and focus on their immunological impacts. This review represents an emerging model that recognizes the importance of both genetic and environmental factors in ASD etiology. We propose that the immune system provides critical clues regarding the nature of the gene by environment interactions that underlie ASD pathophysiology.

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“…Several recent studies have also failed to find a relationship between a higher body burden of toxic metals and an ASD diagnosis [14,15,16,17]. Although studies have shown an association between an ASD diagnosis and various toxic metals, such as cadmium (Cd), lead (Pb), and arsenic (As), the bulk of the research has focused on mercury (Hg).…”

Section: Introductionmentioning

confidence: 99%

Hair Toxic Metal Concentrations and Autism Spectrum Disorder Severity in Young Children

Geier¹,

Kern

King³

et al. 2012

IJERPH

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Previous studies have found a higher body-burden of toxic metals, particularly mercury (Hg), among subjects diagnosed with an autism spectrum disorder (ASD) in comparison to neurotypical controls. Moreover, Hg body-burden was associated with ASD severity. This cross-sectional study examined the potential correlation between hair toxic metal concentrations and ASD severity in a prospective cohort of participants diagnosed with moderate to severe ASD. The Institutional Review Board at the University of Texas Southwestern Medical Center at Dallas (Dallas, TX) approved the present study. Qualifying study participants (n = 18) were evaluated for ASD severity using the Childhood Autism Rating Scale (CARS) and quantitatively for arsenic, Hg, cadmium, lead, chromium, cobalt, nickel, aluminum, tin, uranium, and manganese using hair toxic element testing by Doctor’s Data (a CLIA-approved laboratory). CARS scoring and hair toxic element testing were blinded to one another. Increasing hair Hg concentrations significantly correlated with increased ASD severity. In contrast, no significant correlations were observed between any other of the hair toxic metals examined and ASD severity. This study helps to provide additional mechanistic support for Hg in the etiology of ASD severity, and is supported by an increasing number of recent critical reviews that provide biological plausibility for the role of Hg exposure in the pathogenesis of ASDs.

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A Comparison of Urinary Mercury between Children with Autism Spectrum Disorders and Control Children

Cited by 32 publications

References 44 publications

Significant Association of Urinary Toxic Metals and Autism-Related Symptoms—A Nonlinear Statistical Analysis with Cross Validation

Significant Association of Urinary Toxic Metals and Autism-Related Symptoms—A Nonlinear Statistical Analysis with Cross Validation

Cytokine dysregulation in autism spectrum disorders (ASD): Possible role of the environment

Hair Toxic Metal Concentrations and Autism Spectrum Disorder Severity in Young Children

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