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Principal Investigator: Wright, Robert O
Institute Receiving Award Icahn School Of Medicine At Mount Sinai
Location New York, NY
Grant Number R01ES013744
Funding Organization National Institute of Environmental Health Sciences
Award Funding Period 15 Jan 2007 to 31 May 2028
DESCRIPTION (provided by applicant): PROJECT SUMMARY Research shows that environmental exposures during sensitive life periods affect key physiological processes that orchestrate the development of multiple organ systems, including brain development and growth/obesity. The perinatal period is particularly important, as cells and tissues differentiate most rapidly then. Inhibitory control and negative affect (i.e. depression, anxiety) have been linked to obesity, although most research is cross-sectional or in adults. Brain development and later life obesity may have roots in perinatal life- consistent with the Developmental Origins of Health and Disease concept (DOHaD). There is substantial overlap among perinatal environmental risk factors for depression/anxiety, learning disabilities and obesity. Despite shared vulnerabilities, no studies have addressed if perinatal environmental exposures create a temporally dependent network linking obesity with negative affect and inhibitory control, nor have they addressed the sequential nature of their relationships during child life stages that predate adolescent obesity. Bringing all these concepts and observations together, we propose that prevalent, perinatal neurotoxic exposures to air pollution and psychological stress program adolescent obesity by first causing obesity associated neurophenotypes that arise in children prior to adolescence, the age at which obesity incidence peaks. Because neurophenotypes are continuous and overlapping, we use transdiagnostic approaches to better capture the relationships among environment, behavior and obesity. Our proposed framework means that longitudinal pathways from environment to later onset disease should consider other phenotypic traits as intermediates in a larger causal pathway that arises during age dependent developmental stages. We believe this is a paradigm shifting concept in neurodevelopment and obesity research that can unify several widely observed relationships. In addition, the path from environment to behavior to obesity may depend as much on exposure timing as on differences in exposure levels. We combine prospective longitudinal exposure measures of perinatal stress and air pollution with novel statistical approaches to allow us to objectively define susceptibility windows. We conduct this work in PROGRESS, a prospective child health cohort that has collected longitudinal exposure, covariate and phenotype data from pregnancy to age 12 years already. In this proposal, we will assess the role of perinatal environment, negative affect and inhibitory control on obesity phenotypes from 13-16 years, an age during which child obesity rates rise dramatically, ensuring adequate power and justifying data collection in an additional grant cycle. Only a cohort like PROGRESS with longitudinal, prospective measures starting in perinatal life across multiple health domains and across time could address these questions on adolescent health in a single 5 year grant. In sum, we will explain connections among metabolic, neurobehavioral and mental health phenotypes that share vulnerability to similar perinatal environmental factors but are usually studied separately or cross-sectionally.
Science Code(s)/Area of Science(s) Primary: 59 - Social Environment/Built Environment
Secondary: 01 - Basic Cellular or Molecular processes
Publications See publications associated with this Grant.
Program Officer Kimberly Gray
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