Comparing Cortisol and Inflammatory Biomarkers Among Children with High Vs. Low ACEs In Appalachia

Background and Purpose: Adverse childhood experiences (ACEs) are a major contributor to lifelong health disparities and are particularly prevalent in the Appalachian region of the United States. Appalachians experience higher rates of adversity and poorer physical and mental health outcomes than national averages. Less is known about the biological mechanisms through which early adversity may affect child health. To our knowledge, no studies have explored the relationship between ACE exposure, cortisol, and inflammatory immune biomarkers (cytokines) among children in Appalachia. The purpose of this study was to examine the relationship between ACE exposure and biomarkers of stress and immune function among low-income children ages 3–12 (M = 7.72, SD = 2.23) recruited from a school-based health clinic in a mid-sized metropolitan area in south-central Appalachia. We examined differences in cortisol and cytokine levels between children with higher ACE exposure (≥3 ACEs and ≥4 ACEs) and those with lower exposure.

Method: A total of 120 children participated in the study; 54.2% were male, and 45.8% were female. Salivary samples were collected to measure inflammatory biomarkers, including IL-6, IL-1β, IL-12/IL-23p40, TNF-α, and C-reactive protein (CRP). Cortisol was measured from the 3-cm hair segment closest to the scalp, reflecting chronic cortisol exposure. ACE exposure was assessed using a 10-item ACE questionnaire collected during clinic intake. Descriptive statistics included frequencies and measures of central tendency. Bivariate analyses included Pearson’s r correlations, independent samples t-tests with Cohen’s d effect size, and analyses of variance (ANOVA). Multivariate linear regression analyses were conducted in SPSS, controlling for age, race, sex, and ADHD and allergy medication use.

Results:
Children who experienced three or more ACEs had significantly lower cortisol levels (t(33.01) = 2.37, p = .02, d = .63), indicating a blunted cortisol response among children with greater adversity exposure. Exposure to three or more ACEs was significantly associated with all cytokine levels when controlling for covariates. Exposure to four or more ACEs was significantly associated with higher TNF-α (β = .28, p = .02) and lower IL-12/IL-23p40 (β = −.43, p < .001), with age emerging as a significant covariate (β = −.23, p = .02). Among individual ACEs, having an immediate family member incarcerated (β = .22, p = .03) and having an immediate family member who used drugs or alcohol (β = .26, p = .01) were significantly associated with higher TNF-α levels. Cortisol was not significantly associated with cytokine levels; therefore, mediation was not supported.

Conclusions and Implications: Higher ACE exposure was associated with blunted cortisol levels and alterations in inflammatory biomarkers among children. These findings suggest that early adversity may influence immune functioning in childhood and highlight potential biological pathways linking ACE exposure to health disparities. The results underscore the importance of early identification of children exposed to adversity and the use of trauma-informed interventions. Prevention strategies and policies addressing systemic contributors to ACE exposure may help reduce the long-term health impacts of childhood adversity among Appalachian children who are at higher risk for long-term physical and mental health problems.