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Association of Adverse Experiences and Exposure to Violence in Childhood and Adolescence With Inflammatory Burden in Young People

Authors
  • Rasmussen, Line Jee Hartmann1, 2
  • Moffitt, Terrie E.1, 3, 4, 5
  • Arseneault, Louise5
  • Danese, Andrea5, 6, 7
  • Eugen-Olsen, Jesper2
  • Fisher, Helen L.5
  • Harrington, HonaLee1
  • Houts, Renate1
  • Matthews, Timothy5
  • Sugden, Karen1
  • Williams, Benjamin1
  • Caspi, Avshalom1, 3, 4, 5
  • 1 Department of Psychology and Neuroscience, Duke University, Durham, North Carolina
  • 2 Clinical Research Centre, Copenhagen University Hospital Amager and Hvidovre, Hvidovre, Denmark
  • 3 Department of Psychiatry and Behavioral Sciences, Duke University School of Medicine, Durham, North Carolina
  • 4 Center for Genomic and Computational Biology, Duke University, Durham, North Carolina
  • 5 Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, United Kingdom
  • 6 Department of Child and Adolescent Psychiatry, Institute of Psychiatry, Psychology, and Neuroscience, King’s College London, London, United Kingdom
  • 7 National and Specialist Child and Adolescent Mental Health Services Trauma, Anxiety, and Depression Clinic, South London and Maudsley National Health Service Foundation Trust, London, United Kingdom
Type
Published Article
Journal
JAMA Pediatrics
Publisher
American Medical Association
Publication Date
Nov 04, 2019
Volume
174
Issue
1
Pages
38–47
Identifiers
DOI: 10.1001/jamapediatrics.2019.3875
PMID: 31682707
PMCID: PMC6830440
Source
PubMed Central
License
Green
External links

Abstract

Importance Childhood stress exposure is associated with inflammation as measured by C-reactive protein (CRP) and interleukin 6 (IL-6). However, findings are inconsistent and effect sizes are small. The addition of soluble urokinase plasminogen activator receptor (suPAR), a new biomarker of chronic inflammation, may improve measurement of stress-related inflammatory burden. Objectives To assess whether exposure to adverse experiences, stress, and violence is associated with an increase in suPAR levels in young people and to test the hypothesis that measuring suPAR in addition to CRP or IL-6 levels improves the assessment of the inflammatory burden associated with early-life stress. Design, Setting, and Participants This cohort study included 1391 participants from a 1994 to 1995 birth cohort of twins from the nationally representative Environmental Risk Longitudinal Twin Study in the United Kingdom. Participants were followed up until 18 years of age (93% retention). Plasma samples were analyzed in July 2018, and statistical analysis was performed from October 1, 2018, to May 31, 2019. Exposures Adverse childhood experiences and childhood and adolescent experience of stress and violence exposure. Main Outcomes and Measures Plasma CRP, IL-6, and suPAR levels at 18 years of age. Results Among 1391 young people (mean [SD] age, 18.4 [0.36] years; 733 [52.7%] female), those who had been exposed to stressful experiences had elevated suPAR levels by 18 years of age after controlling for sex, body mass index, and smoking: 0.03-ng/mL (95% CI, 0.01-0.05 ng/mL) increase in suPAR per each additional adverse childhood experience, 0.09-ng/mL (95% CI, 0.01-0.17 ng/mL) increase in suPAR per each additional severe childhood experience of stress or violence, and 0.04-ng/mL (95% CI, −0.02 to 0.10 ng/mL) increase in suPAR per each additional severe adolescent experience of stress or violence. Individuals exposed to multiple types of violence in both childhood and adolescence had 0.26-ng/mL (95% CI, 0.07-0.45 ng/mL) higher suPAR levels compared with children who did not experience stress or violence. These stress-exposed young people were significantly more likely to have elevated suPAR levels at 18 years of age even if they did not have elevated CRP or IL-6 levels. Measuring suPAR in addition to CRP or IL-6 increased the association between stress exposure and inflammatory burden. For example, after adjusting for CRP and IL-6 levels, each additional adverse childhood experience was associated with a 0.05-mL (95% CI, 0.03-0.07 ng/mL) increase in suPAR, each additional severe childhood experience of stress or violence was associated with a 0.14-ng/mL (95% CI, 0.06-0.22 ng/mL) increase in suPAR, and each additional severe adolescent experience of stress or violence was associated with a 0.10-ng/mL (95% CI, 0.04-0.16 ng/mL) increase in suPAR. Conclusions and Relevance The results suggest that adult inflammation is associated with childhood exposure to stress. Adding information about suPAR to traditional biomarkers of inflammation may improve the measurement of inflammatory burden associated with exposure to stress and violence.

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