# Stress-Chemical Interactions and Neurobehavior in School Age Children

> **NIH NIH R01** · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · 2021 · $780,682

## Abstract

PROJECT SUMMARY
Learning disabilities and child obesity are major public health problems and understanding their root causes is
a critical research priority. Inhibitory control has been cross-sectionally linked to obesity, although which
disorder arises first is unclear. In addition, there is substantial overlap among fetal/infant environmental risk
factors for both learning disabilities and for obesity. This may mean that inhibitory control is part of a shared
causal pathway between environment and obesity. To our knowledge, no studies have addressed the
upstream environmental causes that could explain the link between inhibitory control and obesity, nor have
they addressed the temporal relationship between maladaptive behavior and obesity. A large body of research
shows that environmental exposures during sensitive life periods affect key physiological processes and
regulatory systems that orchestrate the development of multiple organ systems, including brain development
and growth/obesity. The perinatal period is particularly important, as this is when cells and tissues differentiate
most rapidly. The role of optimal oxidant balance for proper brain development, as well as its role in obesity is
now increasingly recognized. Bringing all these concepts and observations together, we propose that
prevalent, perinatal, paradigm pro-oxidant exposures –air pollution, metals, and psychological stress- program
child obesity by first causing maladaptive inhibitory control that ultimately leads to obesity. Furthermore, to
better assess the role of oxidative stress (OS) we will measure mitochondrial DNA (mtDNA) damage in cord
blood, as mtDNA is highly sensitive to OS and damage to its DNA propagates via mitosis. Damaged mtDNA
biomarkers act as cumulative records of past oxidative stress, extending our work to include perinatal OS
regardless of its cause. More broadly, our proposed biological framework means that one disease can be a
causal risk factor for another, and that longitudinal pathways from environment to a disease should consider
other disease states as possible intermediates. We believe this is a paradigm shifting concept 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 have therefore developed novel
exposure methods that reconstruct perinatal environments in short time intervals. We combine these exposure
tools with novel statistical approaches to allow us to objectively define susceptibility windows to air pollution
and metals. Finally, we conduct this work in the ELEMENT cohort, a prospective pregnancy cohort study that
has collected longitudinal exposure, covariate and phenotype data from pregnancy to age 7 years. In this
proposal, we propose to assess inhibitory control and obesity phenotypes from 8-11, an age when child obesity
rates rise dramatically, ensuring adequate power for our aims. Our ...

## Key facts

- **NIH application ID:** 10210263
- **Project number:** 5R01ES013744-15
- **Recipient organization:** ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
- **Principal Investigator:** Robert O Wright
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $780,682
- **Award type:** 5
- **Project period:** 2007-01-15 → 2023-08-02

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10210263

## Citation

> US National Institutes of Health, RePORTER application 10210263, Stress-Chemical Interactions and Neurobehavior in School Age Children (5R01ES013744-15). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10210263. Licensed CC0.

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