The purpose of this study is to assess the effects of pre- and postnatal exposure to the organophosphorus (OP) pesticide chlorpyrifos (CPF) on neurobehavioral functioning in a cohort of inner-city children who have reached 9 years of age. This work builds on, and shares a cohort with, a prospective cohort study of ambient air pollutant effects on child development and respiratory health, being conducted by the Columbia Center for Children's Environmental Health (NIEHS R01 ES08977, P.I. Perera:11/01/03-10/31/08;5 P01 ES09600/EPA RD-83214101, P.I. Perera, Co-I Rauh:11/01/03-10/31/08). Previous findings from the Children's Center study reveal adverse effects of prenatal exposure to CPF (validated with biomarkers in cord blood) on birth weight (Whyatt et al., 2004), cognitive and motor development, and neuro-behavioral problems at 3 years (Rauh et al., 2006). Affected neurobehavioral areas include attention and ADHD-- conditions with serious long-term clinical implications. Based on these findings, and evidence from the experimental literature showing long-term, possibly irreversible effects of CPF exposure on brain development and sensorimotor activity (Dam et al, 2000;Levin et al, 2002;Slotkin et al, 2005), we now propose to evaluate the longer-term neurodevelopmental effects of CPF in 300 9-year-old children. We will use Magnetic Resonance Imaging (MRI) to define the intermediary neurobiological effects of CPF exposure on the structure, metabolism, and anatomical connectivity of the brain in all 300 children. CPF was selected as a model for translational research because it is representative of the class of OP pesticides, well characterized, and well-studied in animals. Furthermore, agricultural and commercial uses continue, despite the 2001 residential ban by EPA. Specifically, we propose to: (1) assess the 9- year effects of prenatal and early childhood exposures to CPF on neurobehavioral (inattention, hyperactivity and depression) and neuropsychological functioning (attentional capacity, memory, impulse control and sensory motor functioning);and (2) assess the 9-year effects of prenatal and early childhood exposures to CPF on measures of brain structure (using anatomical MRI), brain chemistry/cellular metabolism (using magnetic resonance spectroscopy), and anatomical connectivity (using diffusion tensor imaging) in the same children.

Public Health Relevance

This application is for a 5-year study to assess the effects of exposure to the organophosphorus pesticides, chlorpyrifos and diazinon, on neurobehavioral functioning in a cohort of inner-city children (n=400) who have reached 8-9 years of age. This work shares a cohort with a longitudinal study of ambient air pollutant effects on child development, from the prenatal period to 9 years of age, being conducted by the Columbia Center for Children's Environmental Health. The project has access to biomarkers of exposure, includes neuroimaging assessments on a subset of 60 children, and has potential for further informing regulatory safety standards for OP use in the United States.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
5R01ES015579-05
Application #
8391755
Study Section
Child Psychopathology and Developmental Disabilities Study Section (CPDD)
Program Officer
Gray, Kimberly A
Project Start
2009-03-11
Project End
2014-11-30
Budget Start
2012-12-01
Budget End
2014-11-30
Support Year
5
Fiscal Year
2013
Total Cost
$501,943
Indirect Cost
$76,930
Name
Columbia University (N.Y.)
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
621889815
City
New York
State
NY
Country
United States
Zip Code
10032
Horga, Guillermo; Kaur, Tejal; Peterson, Bradley S (2014) Annual research review: Current limitations and future directions in MRI studies of child- and adult-onset developmental psychopathologies. J Child Psychol Psychiatry 55:659-80
Goodman, Jarid; Marsh, Rachel; Peterson, Bradley S et al. (2014) Annual research review: The neurobehavioral development of multiple memory systems--implications for childhood and adolescent psychiatric disorders. J Child Psychol Psychiatry 55:582-610
Yan, Xu; Zhou, Minxiong; Ying, Lingfang et al. (2013) Evaluation of optimized b-value sampling schemas for diffusion kurtosis imaging with an application to stroke patient data. Comput Med Imaging Graph 37:272-80
Posner, Jonathan; Rauh, Virginia; Gruber, Allison et al. (2013) Dissociable attentional and affective circuits in medication-naive children with attention-deficit/hyperactivity disorder. Psychiatry Res 213:24-30
Hao, Xuejun; Xu, Dongrong; Bansal, Ravi et al. (2013) Multimodal magnetic resonance imaging: The coordinated use of multiple, mutually informative probes to understand brain structure and function. Hum Brain Mapp 34:253-71
Zhou, Zhenyu; Liu, Wei; Cui, Jiali et al. (2011) Automated artifact detection and removal for improved tensor estimation in motion-corrupted DTI data sets using the combination of local binary patterns and 2D partial least squares. Magn Reson Imaging 29:230-42
Hao, Xuejun; Xu, Dongrong; Bansal, Ravi et al. (2011) An improved representation of regional boundaries on parcellated morphological surfaces. Comput Med Imaging Graph 35:206-19