Autism spectrum disorder (ASD) is a neurodevelopmental disorder defined by behavioral observations and characterized by core impairments in speech and social interaction along with restricted and repetitive patterns of behaviors. Many children with ASD have additional behavioral impairments, including inattention, aggression, and hyperactivity. The prevalence of ASD in the US is estimated to be 1 in 68 children.1 The diagnosis of ASD was recently revised and now includes a rating of ASD severity based on the required level of support for the individual needs of the child.
A number of physiological abnormalities are implicated in ASD, including oxidative stress; immune dysregulation; inflammation; mitochondrial dysfunction; disorders of folate, cobalamin, tetrahydrobiopterin, and carnitine metabolism; gastrointestinal abnormalities; and seizures. When viewed in this light, ASD might arise from these comorbidities, as treatment of these abnormalities may improve symptoms of ASD.2
A better understanding of these comorbidities may lead to future diagnostic tests and treatments, but may also better target research toward the underlying causes of these issues. Potential causes of ASD include genetic abnormalities, but to date, only a minority of ASD cases have been shown to be caused by single gene or chromosomal abnormalities. Recent studies suggest that the etiology of ASD is most consistent with oligogenic inheritance patterns along with non-shared environmental effects. Findings from a recent systematic review indicate an association between ASD and environmental toxicants, which could potentially lead to neurotoxicity and subsequent neurological and psychiatric symptoms.3
Exposures to environmental toxicants during susceptible periods of neurodevelopment may lead to alterations in normal developmental patterns and impaired neurotransmitter function. Several environmental toxicants—including mercury, lead, arsenic, polychlorinated biphenyls, and toluene—cause neurodevelopmental disorders, such as autism, cerebral palsy, ADHD, and mental retardation.4 This may be because the developing brain is more susceptible to injury from toxicants than the adult brain.
Environmental toxicants can also have adverse effects on physiology and could account for some of the physiological abnormalities reported in individuals with ASD. For example, toxicants are known to inhibit mitochondrial function, deplete glutathione, contribute to immune dysregulation, and increase oxidative stress. Mitochondrial dysfunction, depleted glutathione, oxidative stress, and immune dysregulation have been seen in persons with ASD.5-7
A concern when evaluating adverse effects of toxicants in patients is a potential difference in the ability to detoxify and neutralize environmental toxicants, which might vary from person to person depending on genetic susceptibility. Polymorphisms in genes involved with detoxification can lead to impairments in detoxification. In many cases, the exposure to the toxicant may have occurred many years earlier, which makes the identification of the toxicant and a connection between exposure and a particular neurodevelopment disorder difficult at best.
Dr. Rossignol is a family practice physician, Rossignol Medical Center, Aliso Viejo. CA. Dr. Frye is Director of Autism Research, Arkansas Children’s Hospital Research Institute, Little Rock, AR, and Associate Professor, Division of Neurology, Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, AR. The authors report no conflicts of interest concerning the subject matter of this article.
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