TY - JOUR
T1 - Association of Adverse Experiences and Exposure to Violence in Childhood and Adolescence with Inflammatory Burden in Young People
AU - Rasmussen, Line Jee Hartmann
AU - Moffitt, Terrie E.
AU - Arseneault, Louise
AU - Danese, Andrea
AU - Eugen-Olsen, Jesper
AU - Fisher, Helen L.
AU - Harrington, Honalee
AU - Houts, Renate
AU - Matthews, Timothy
AU - Sugden, Karen
AU - Williams, Benjamin
AU - Caspi, Avshalom
PY - 2020/1
Y1 - 2020/1
N2 - 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..
AB - 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..
UR - http://www.scopus.com/inward/record.url?scp=85074493993&partnerID=8YFLogxK
U2 - 10.1001/jamapediatrics.2019.3875
DO - 10.1001/jamapediatrics.2019.3875
M3 - Article
C2 - 31682707
AN - SCOPUS:85074493993
SN - 2168-6203
VL - 174
SP - 38
EP - 47
JO - JAMA Pediatrics
JF - JAMA Pediatrics
IS - 1
ER -