title: Developmental pesticide exposure reproduces features of attention deficit hyperactivity disorder.
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.
authors: *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.
authors: Jason R
authors: JR
authors: Richardson
authors: *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.
authors: Michele M
authors: MM
authors: Taylor
authors: *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.
authors: Stuart L
authors: SL
authors: Shalat
authors: *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.
authors: Thomas S
authors: TS
authors: Guillot
authors: *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.
authors: W Michael
authors: WM
authors: Caudle
authors: *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.
authors: Muhammad M
authors: MM
authors: Hossain
authors: *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.
authors: Tiffany A
authors: TA
authors: Mathews
authors: *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.
authors: Sara R
authors: SR
authors: Jones
authors: *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.
authors: Deborah A
authors: DA
authors: Cory-Slechta
authors: *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.
authors: Gary W
authors: GW
authors: Miller
mesh_terms: D000293:Adolescent; D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology*; D001362:Avoidance Learning / Q000187:drug effects; D015153:Blotting, Western; D016022:Case-Control Studies; D002648:Child; D002851:Chromatography, High Pressure Liquid; D003430:Cross-Sectional Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000378:metabolism*; D005260:Female; D006801:Humans; D007306:Insecticides / Q000633:toxicity; D008124:Locomotion / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008569:Memory Disorders / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009570:Nitriles / Q000633:toxicity*; D011722:Pyrethrins / Q000009:adverse effects / Q000633:toxicity / Q000652:urine*; D017447:Receptors, Dopamine D1 / Q000378:metabolism*
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; D017447:Receptors, Dopamine D1; C017180:decamethrin
keywords: ADHD; dopamine receptor; dopamine transporter; impulsivity; pyrethyroid
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