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Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood.

ABSTRACT: BACKGROUND:Childhood risk factors are associated with elevated inflammatory biomarkers in adulthood, but it is unknown whether these risk factors are associated with increased adult levels of the chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR). We aimed to test the hypothesis that childhood exposure to risk factors for adult disease is associated with elevated suPAR in adulthood and to compare suPAR with the oft-reported inflammatory biomarker C-reactive protein (CRP). METHODS:Prospective study of a population-representative 1972-1973 birth cohort; the Dunedin Multidisciplinary Health and Development Study observed participants to age 38 years. Main childhood predictors were poor health, socioeconomic disadvantage, adverse childhood experiences (ACEs), low IQ, and poor self-control. Main adult outcomes were adulthood inflammation measured as suPAR and high-sensitivity CRP (hsCRP). RESULTS:Participants with available plasma samples at age 38 were included (N = 837, 50.5% male). suPAR (mean 2.40 ng/ml; SD 0.91) was positively correlated with hsCRP (r 0.15, p < .001). After controlling for sex, body mass index (BMI), and smoking, children who experienced more ACEs, lower IQ, or had poorer self-control showed elevated adult suPAR. When the five childhood risks were aggregated into a Cumulative Childhood Risk index, and controlling for sex, BMI, and smoking, Cumulative Childhood Risk was associated with higher suPAR (b 0.10; SE 0.03; p = .002). Cumulative Childhood Risk predicted elevated suPAR, after controlling for hsCRP (b 0.18; SE 0.03; p < .001). CONCLUSIONS:Exposure to more childhood risk factors was associated with higher suPAR levels, independent of CRP. suPAR is a useful addition to studies connecting childhood risk to adult inflammatory burden.

SUBMITTER: Rasmussen LJH

PROVIDER: S-EPMC6342676 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood.

Rasmussen Line Jee Hartmann LJH Moffitt Terrie E TE Eugen-Olsen Jesper J Belsky Daniel W DW Danese Andrea A Harrington HonaLee H Houts Renate M RM Poulton Richie R Sugden Karen K Williams Benjamin B Caspi Avshalom A

Journal of child psychology and psychiatry, and allied disciplines 20180509 2

<h4>Background</h4>Childhood risk factors are associated with elevated inflammatory biomarkers in adulthood, but it is unknown whether these risk factors are associated with increased adult levels of the chronic inflammation marker soluble urokinase plasminogen activator receptor (suPAR). We aimed to test the hypothesis that childhood exposure to risk factors for adult disease is associated with elevated suPAR in adulthood and to compare suPAR with the oft-reported inflammatory biomarker C-react ...[more]

PMID: 29741788

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Project description:BackgroundAdverse childhood experiences (ACEs) have long been known to be related to poorer health across the life course. Previous studies typically relied on cumulative risk scores or individual adversities measured through retrospective self-reports. However, these approaches have important limitations. Cumulative risk scores assume equal weighting of adversities and the single adversity approach ignores the high probability that adversities co-occur. In contrast, latent class analysis (LCA) offers an alternative approach to operationalise ACEs that respects the clustering of adversities and may identify specific patterns of ACEs important for health outcomes. Furthermore, prospective and retrospective reports of ACEs show poor agreement. Therefore, it is important to compare findings based on prospective and retrospective measures in the same individuals. Despite an increasing number of studies applying LCA to ACEs data, no studies have yet simultaneously investigated LCA to cumulative risk and single adversity approaches in their relationships with adult inflammation. Identifying the specific ACEs or combinations of ACEs which are strongly related to inflammation is important for investigating the mechanisms involved and the planning of effective interventions.MethodsUsing data on 8810 members of the 1958 British birth cohort we investigated 12 ACEs - physical, psychological and sexual abuse, physical and emotional neglect, parental mental health problems, witnessing abuse, parental conflict, parental divorce, parental offending, parental substance misuse and parental death. LCA was applied to explore the clustering of prospectively and retrospectively reported ACEs separately. Associations between latent classes, cumulative risk scores and individual adversities with three inflammatory markers (C-Reactive Protein, fibrinogen and von Willebrand Factor) were tested using linear regression.ResultsThere was co-occurrence between adversities, and particularly for retrospectively reported adversities. Three latent classes were identified in the prospective data - 'Low ACEs' (95.7%), 'Household dysfunction' (2.8%) and 'Parental loss' (1.5%) which were related to increased inflammation in mid-life, as were high ACE scores and individual measures of offending, death, divorce, physical neglect and family conflict. Four latent classes were identified in the retrospective data - 'Low ACEs', 'Parental mental health and substance misuse', 'Maltreatment and conflict' and 'Polyadversity.' The latter two (5.2%) were related to raised inflammation in mid-life, as was a retrospective ACE score of 4+ (8.3%) and individual measures of family conflict, psychological and physical abuse, emotional neglect and witnessing abuse.ConclusionsSpecific ACEs or ACE combinations might be important for chronic inflammation. LCA is an alternative approach to operationalising ACEs data but further research is needed.

Project description:Importance:Childhood adversity (CA) is associated with an increased risk of suicide in young adulthood that might be explained by maladaptive trajectories during adolescence. Although adolescent violent offending is linked with suicide, little is known about its role in the association between CA and suicide. Objective:To examine whether adolescent violent offending mediates the association between CA and suicide in early adulthood. Design, Setting, and Participants:This population-based, longitudinal cohort study with a follow-up time spanning 5 to 9 years included 476?103 individuals born in Sweden between 1984 and 1988. The study population was prospectively followed up from 20 years of age until December 31, 2013, with respect to suicide. Data analysis was performed from January 1, 1984, to December 31, 2013. Exposures:Register-based CAs included parental death, parental substance abuse and psychiatric disorder, parental criminal offending, parental separation, public assistance recipiency, child welfare intervention, and residential instability. Adolescent violent offending was defined as being convicted of a violent crime between the ages of 15 and 19 years. Main Outcomes and Measures:Estimates of risk of suicide after 20 years of age (from 2004 if born in 1984 and from 2008 if born in 1988) until the end of 2013 were calculated as incidence rate ratios (IRRs) with 95% CIs using Poisson regression analysis. Adjustments were made for demographics and psychiatric disorder. In addition, binary mediation analysis with logistic regression was used. Results:A total of 476?103 individuals (231 699 [48.7%] female) were included in the study. Those with a conviction for violent offending had been exposed to all CAs to a greater extent than those with no violent offending. Cumulative CA was associated with risk of suicide in nonconvicted (adjusted IRR, 2.4; 95% CI, 1.5-3.9) and convicted youths, who had a higher risk of suicide (adjusted IRR, 8.5; 95% CI, 4.6-15.7). Adolescent violent offending partly mediated the association between CA and suicide. Conclusions and Relevance:Individuals with a history of CA who also engage in violent offending in adolescence have a high risk of suicide. Interventions to prevent externalizing behavior during childhood and increased support to youths with delinquent behavior may have the potential to prevent suicide related to CA.

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Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood.

Publications

Cumulative childhood risk is associated with a new measure of chronic inflammation in adulthood.

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