# Biological Substrates of Maladaptive Stress Response in Early Childhood

> **NIH NIH R01** · WASHINGTON UNIVERSITY · 2020 · $799,702

## Abstract

Early life stress is associated with increased risk for psychiatric disorders that is long lasting into adulthood.
Much of the research has focused on middle childhood and adolescence, however, there is mounting evidence
that stressful life experiences occurring in early childhood set the foundation for dysregulation in biological
stress responses that put children at risk for psychopathology. Our overarching aims are to examine the
biological pathways through which early life stress affects risk for psychopathology in early childhood, and by
which caregiving can alter biological and psychological stress responses . We propose to recruit 150 children,
aged 4-6 years, within 3 months of parental divorce (stress group) and compare them to 75 control children
from families with no history of parental divorce. Stress and control children will be followed at 6 and 18 months
later. We choose divorce as a stressor because it is common in early childhood; represents the exacerbation of
multiple stressful family processes; disrupts the caregiving environment; and is associated with internalizing
and externalizing problems and long-lasting psychopathology in children. This population will allow us to study
the unfolding of stress responses, which is almost impossible to capture for other more severe stressors. We
focus on the 4-6 years period because it is a period of heightened neural plasticity and a transitional period
from family to peer and teacher relationships, which makes children especially sensitive to a stressor that could
disrupt their caregiving environment. We assess biological stress responses using: 1) hair cortisol
concentrations (HCC), a retrospective measure of chronic HPA axis activity; 2) salivary cortisol, a measure of
current HPA axis activity; and 3) MRI structural and functional connectivity in areas implicated in stress
responses. We will assess pre-divorce factors (e.g., parental history of psychopathology, parental conflict),
post-divorce parental adjustment using self-report and biological measures (HCC); parent-child behavioral and
brain synchrony, a biological measure of the parent-child relationship; other post-divorce factors (e.g., ongoing
conflict); and internalizing and externalizing symptoms in children. We hypothesize that the stress group will
show higher HCC, salivary cortisol, and structural and functional connectivity early on following divorce
compared to control children; and that pre-divorce factors will moderate these relationships. The stress group
will show decreased HCC, salivary cortisol, and structural and functional connectivity over time; and parental
reduced cortisol and increased psychiatric symptoms and decreased parent-child behavioral and brain
synchrony and other post-divorce factors will mediate these relationships. Finally, early biological responses
and changes in these responses over time will predict internalizing and externalizing symptoms. This study will
examine the neurobiology of stress r...

## Key facts

- **NIH application ID:** 10070377
- **Project number:** 1R01MH124266-01
- **Recipient organization:** WASHINGTON UNIVERSITY
- **Principal Investigator:** Nadine M. Melhem
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $799,702
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10070377

## Citation

> US National Institutes of Health, RePORTER application 10070377, Biological Substrates of Maladaptive Stress Response in Early Childhood (1R01MH124266-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10070377. Licensed CC0.

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