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

Matthew S Pantell; Patricia P Silveira; Euclides José de Mendonça Filho; Holly Wing; Erika M Brown; Victoria F Keeton; Irina Pokhvisneva; Kieran J O'Donnell; John Neuhaus; Danielle Hessler; Michael J Meaney; Nancy E Adler; Laura M Gottlieb

doi:10.1038/s41390-023-02992-6

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

Pediatr Res. 2024 Jan 17. doi: 10.1038/s41390-023-02992-6. Online ahead of print.

Authors

Matthew S Pantell^{1

2

3}, Patricia P Silveira^{4

5}, Euclides José de Mendonça Filho^{4

5}, Holly Wing^{6

7}, Erika M Brown⁸, Victoria F Keeton⁹, Irina Pokhvisneva⁴, Kieran J O'Donnell^{4

5

10}, John Neuhaus¹¹, Danielle Hessler^{7

12}, Michael J Meaney^{4

5

13}, Nancy E Adler⁶, Laura M Gottlieb^{6

7

12}

Affiliations

¹ Division of Pediatric Hospital Medicine, Department of Pediatrics, University of California, San Francisco, CA, USA. Matt.Pantell@ucsf.edu.
² Center for Health and Community, University of California, San Francisco, San Francisco, CA, USA. Matt.Pantell@ucsf.edu.
³ Social Interventions Research and Evaluation Network, University of California, San Francisco, CA, USA. Matt.Pantell@ucsf.edu.
⁴ Douglas Mental Health University Institute, Douglas Research Center, McGill University, Montreal, QC, Canada.
⁵ Ludmer Centre for Neuroinformatics and Mental Health and Department of Psychiatry, Faculty of Medicine, McGill University, Montreal, QC, Canada.
⁶ Center for Health and Community, University of California, San Francisco, San Francisco, CA, USA.
⁷ Social Interventions Research and Evaluation Network, University of California, San Francisco, CA, USA.
⁸ California Policy Lab, Berkeley, CA, USA.
⁹ Department of Obstetrics, Gynecology, and Reproductive Sciences, University of California, San Francisco, 490 Illinois St, Box 2930, 94143, San Francisco, CA, USA.
¹⁰ Yale Child Study Center & Department of Obstetrics, Gynecology & Reproductive Sciences, Yale School of Medicine, New Haven, CT, USA.
¹¹ Department of Epidemiology and Biostatistics, University of California, San Francisco, CA, USA.
¹² Department of Family and Community Medicine, University of California, San Francisco, CA, USA.
¹³ Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Republic of Singapore.

PMID: 38233512
DOI: 10.1038/s41390-023-02992-6

Abstract

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-1β [IL-1β], 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.

Associated data

ClinicalTrials.gov/NCT02746393