Tipping the Balance of Autism Risk: Potential Mechanisms Linking Pesticides and Autism
Shelton, Janie F., Hertz-Picciotto, Irva, Pessah, Isaac N., Environmental Health Perspectives
BACKGROUND: Autism spectrum disorders (ASDs) have been increasing in many parts of the world and a portion of cases are attributable to environmental exposures. Conclusive replicated findings have yet to appear on any specific exposure; however, mounting evidence suggests gestational pesticides exposures are strong candidates. Because multiple developmental processes are implicated in ASDs during gestation and early life, biological plausibility is more likely if these agents can be shown to affect core pathophysiological features.
OBJECTIVES: Our objectives were to examine shared mechanisms between autism pathophysiology and the effects of pesticide exposures, focusing on neuroexcitability, oxidative stress, and immune functions and to outline the biological correlates between pesticide exposure and autism risk.
METHODS: We review and discuss previous research related to autism risk, developmental effects of early pesticide exposure, and basic biological mechanisms by which pesticides may induce or exacerbate pathophysiological features of autism.
DISCUSSION: On the basis of experimental and observational research, certain pesticides may be capable of inducing core features of autism, but little is known about the timing or dose, or which of various mechanisms is sufficient to induce this condition.
CONCLUSIONS: In animal studies, we encourage more research on gene x environment interactions, as well as experimental exposure to mixtures of compounds. Similarly, epidemiologic studies in humans with exceptionally high exposures can identify which pesticide classes are of greatest concern, and studies focused on gene x environment are needed to determine if there are susceptible subpopulations at greater risk from pesticide exposures.
KEY WORDS: autism spectrum disorders, carbamate, gene--environment interaction, immune, mitochondria, neuroexcitation, organochlorine, organophosphate, oxidative stress, pesticide, pyrethroid. Environ Health Perspect 120:944-951 (2012). http://dx.cloi.org/10.1289/ehp.1104553 [Online 25 April 2012]
Causes for the recent rise in autism diagnoses throughout the United States remain largely unknown. In California, a 600% increased incidence in autism was observed among children up to 5 years of age for births from 1990 to 2001, yet only one-third of the rise could be explained by identified factors such as changing diagnostic criteria and a younger age at diagnosis (Hertz-Picciotto and Delwiche 2009). Across the United States, autism spectrum disorders (ASD) are now estimated to affect 1 in 88 eight-year-olds, with much higher prevalence in boys (1 in 54) than girls (1 in 252) (Centers for Disease Control and Prevention 2012). Autism is a heterogeneous, behaviorally defined condition often diagnosed in children prior to age 3 years. Although each individual diagnosis must meet specific criteria related to deficits in social interaction and language and to the presence of repetitive behaviors or restricted interests, autism phenotypes vary widely, even among concordant twins (Le Couteur et al. 1996).
Idiopathic autisms are diagnosed 4-5 times more often in boys than girls and frequently involve a wide range of genes that confer susceptibility as opposed to a singular heritable factor (Geschwind 2011). Genetic contributions to autism risks involve rare mutations, complex gene x gene interactions, and copy number variants (CNVs) including deletions and duplications (Stankiewicz and Lupski 2010). In a recent series of papers, rare de nova point mutations were associated with autism in parent--child trios with sporadic ASD (Neale et al. 2012; O'Roak et al. 2012; Sanders et al. 2012), and those mutations were more frequently derived from fathers, increasing with paternal age (O'Roak et al. 2012). Although twin studies have demonstrated evidence of heritability--a stronger concordance among monozygotic than dizygotic twins (Bailey et al. …