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FASEB J. 2015 May;29(5):1960-72. doi: 10.1096/fj.14-260901. Epub 2015 Jan 28.

Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder.

Author information

1
*Department of Environmental and Occupational Medicine and Environmental and Occupational Health Sciences Institute, Rutgers-Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA; Center for Neurodegenerative Disease, School of Medicine, and Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA; Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA; Department of Chemistry, Wayne State University, Detroit, Michigan, USA; and Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York, USA jricha3@eohsi.rutgers.edu.
2
*Department of Environmental and Occupational Medicine and Environmental and Occupational Health Sciences Institute, Rutgers-Robert Wood Johnson Medical School, Rutgers, The State University of New Jersey, Piscataway, New Jersey, USA; Center for Neurodegenerative Disease, School of Medicine, and Department of Environmental and Occupational Health, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA; Department of Physiology and Pharmacology, Wake Forest University Health Sciences, Winston-Salem, North Carolina, USA; Department of Chemistry, Wayne State University, Detroit, Michigan, USA; and Department of Environmental Medicine, University of Rochester Medical Center, Rochester, New York, USA.

Abstract

Attention-deficit hyperactivity disorder (ADHD) is estimated to affect 8-12% of school-age children worldwide. ADHD is a complex disorder with significant genetic contributions. However, no single gene has been linked to a significant percentage of cases, suggesting that environmental factors may contribute to ADHD. Here, we used behavioral, molecular, and neurochemical techniques to characterize the effects of developmental exposure to the pyrethroid pesticide deltamethrin. We also used epidemiologic methods to determine whether there is an association between pyrethroid exposure and diagnosis of ADHD. Mice exposed to the pyrethroid pesticide deltamethrin during development exhibit several features reminiscent of ADHD, including elevated dopamine transporter (DAT) levels, hyperactivity, working memory and attention deficits, and impulsive-like behavior. Increased DAT and D1 dopamine receptor levels appear to be responsible for the behavioral deficits. Epidemiologic data reveal that children aged 6-15 with detectable levels of pyrethroid metabolites in their urine were more than twice as likely to be diagnosed with ADHD. Our epidemiologic finding, combined with the recapitulation of ADHD behavior in pesticide-treated mice, provides a mechanistic basis to suggest that developmental pyrethroid exposure is a risk factor for ADHD.

KEYWORDS:

ADHD; dopamine receptor; dopamine transporter; impulsivity; pyrethyroid

PMID:
25630971
PMCID:
PMC4415012
DOI:
10.1096/fj.14-260901
[Indexed for MEDLINE]
Free PMC Article

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