Biological Substrates of Maladaptive Stress Response in Early Childhood

NIH RePORTER · NIH · R01 · $720,588 · view on reporter.nih.gov ↗

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
10406368
Project number
5R01MH124266-03
Recipient
WASHINGTON UNIVERSITY
Principal Investigator
Nadine M. Melhem
Activity code
R01
Funding institute
NIH
Fiscal year
2022
Award amount
$720,588
Award type
5
Project period
2020-09-01 → 2025-05-31