Associations between Social Adversity and Biomarkers of Inflammation, Stress, and Aging in Children.

BACKGROUND: Prior work has found relationships between childhood social adversity and biomarkers of stress, but knowledge gaps remain. To help address these gaps, we explored associations between social adversity and biomarkers of inflammation (interleukin-1ß [IL-1ß], IL-6, IL-8, tumor necrosis factor-alpha [TNF-α], and salivary cytokine hierarchical "clusters" based on the three interleukins), neuroendocrine function (cortisol, cortisone, dehydroepiandrosterone, testosterone, and progesterone), neuromodulation (N-arachidonoylethanolamine, stearoylethanolamine, oleoylethanolamide, and palmitoylethanolamide), and epigenetic aging (Pediatric-Buccal-Epigenetic clock). METHODS: We collected biomarker samples of children ages 0-17 recruited from an acute care pediatrics clinic and examined their associations with caregiver-endorsed education, income, social risk factors, and cumulative adversity. We calculated regression-adjusted means for each biomarker and compared associations with social factors using Wald tests. We used logistic regression to predict being in the highest cytokine cluster based on social predictors. RESULTS: Our final sample included 537 children but varied based on each biomarker. Cumulative social adversity was significantly associated with having higher levels of all inflammatory markers and with cortisol, displaying a U-shaped distribution. There were no significant relationships between cumulative social adversity and cortisone, neuromodulation biomarkers or epigenetic aging. CONCLUSION: Our findings support prior work suggesting that social stress exposures contribute to increased inflammation in children. IMPACT: Our study is one of the largest studies examining associations between childhood social adversity and biomarkers of inflammation, neuroendocrine function, neuromodulation, and epigenetic aging. It is one of the largest studies to link childhood social adversity to biomarkers of inflammation, and the first of which we are aware to link cumulative social adversity to cytokine clusters. It is also one of the largest studies to examine associations between steroids and epigenetic aging among children, and one of the only studies of which we are aware to examine associations between social adversity and endocannabinoids among children. CLINICAL TRIAL REGISTRATION: NCT02746393.

Salivary cytokine cluster moderates the association between caregivers perceived stress and emotional functioning in youth.

Some individuals exposed to early life stress show evidence of enhanced systemic inflammation and are at greater risk for psychopathology. In the current study, caregivers and their offspring (0-17 years) were recruited at a pediatric clinic visit at the University of California, San Francisco (UCSF). Mothers and seven-year-old children from the Growing Up inSingaporeTowards healthy Outcomes (GUSTO) prospective birth cohort were used as a replication cohort. Caregivers perceived stress was measured to determine potential intergenerational effects on the children's functioning and inflammation levels. Children's emotional functioning in the UCSF cohort was evaluated using the Pediatric Quality of Life (PedsQL) inventory. Child emotional and behavioral functioning was measured using the Child Behavior Checklist (CBCL) in GUSTO. Saliva was collected from the children and salivary levels of IL-6, IL-1ß, IL-8 and TNF-α were measured using an electrochemiluminescent cytokine multiplex panel. Child IL-6, IL-1ß, IL-8 cytokine levels were clustered into low, average, and high cytokine cluster groups using hierarchical cluster analysis. We did not find that salivary cytokine clusters were significantly associated with children's emotional or behavioral function. However, cytokine clusters did significantly moderate the association between increased caregiver perceived stress and reduced child emotional functioning (UCSF cohort) and increased Attention-Deficit-Hyperactivity (ADH) problems (GUSTO cohort, uncorrected Cohen's F2 = 0.02). Using a cytokine clustering technique may be useful in identifying those children exposed to increased caregiver perceived stress that are at risk of emotional and attention deficit hyperactivity problems.