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Impact of Adverse Childhood Experiences on Depression and Biomarkers in Later Life

This study investigates the correlation between adverse childhood experiences (ACE) and stress biomarkers, like C-reactive protein (CRP) and cortisol, with depressive symptoms in later life. It examines how ACE influences CRP and cortisol levels, mediating depressive symptoms longitudinally. The research aims to shed light on the psychobiological processes underlying mental health outcomes in individuals with ACE.

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Impact of Adverse Childhood Experiences on Depression and Biomarkers in Later Life

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  1. Institute of Epidemiology and Health Care Adverse Childhood Experiences, Stress Biomarkers, and Depression in Later Life Eleonora Iob, PhD Candidate Department of Behavioural Science and Health Soc-B CDT (ESRC & BBSRC) University College London APS 77th Annual Scientific Meeting “BODY to MIND”

  2. Outline • Background • Study 1: Relationship of C-reactive Protein (CRP) and Cortisol with Depressive Symptoms • Study 2: Association of Adverse Childhood Experiences (ACE) with CRP and Cortisol • Study 3: Longitudinal mediation analysis of ACE, CRP, and Depressive Symptoms • Conclusions

  3. Outline • Background • Study 1: Relationship of C-reactive Protein (CRP) and Cortisol with Depressive Symptoms • Study 2: Association of Adverse Childhood Experiences (ACE) with CRP and Cortisol • Study 3: Longitudinal mediation analysis of ACE, CRP, and Depressive Symptoms • Conclusions

  4. Background • Adverse Childhood Experiences (ACE) • High prevalence (Bellis et al., 2014) • Associated with several health and disease outcomes (Hughes et al., 2017) • Depression • 50% greater risk of developing depression (McLaughlin et al., 2016) • Worse recovery and treatment outcomes (Nanni et al., 2012) • Psychobiological Processes • Hypothalamic-pituitary-adrenal (HPA)-axis: Cortisol • Inflammation: C-reactive protein • (Danese & McEwen, 2012; Danese & Lewis, 2017)

  5. Background Adverse Childhood Experiences (ACE) • Depression • Psychobiological Processes • Cortisol • C-reactive protein • Limitations • Inconsistent or weak evidence • Methodological differences in measurement of variables • Reverse causality • Lack of evidence for mediation effects

  6. Outline • Background • Study 1: Relationship of C-reactive Protein (CRP) and Cortisol with Depressive Symptoms • Study 2: Association of Adverse Childhood Experiences (ACE) with CRP and Cortisol • Study 3: Longitudinal mediation analysis of ACE, CRP, and Depressive Symptoms • Conclusions

  7. Study 1: Aim and Hypotheses    • Aim:To investigate the relationship of cortisol (i.e. HPA-axis) and C-reactive protein (CRP) (i.e. inflammation) with: • Persistent depressive symptoms • 2) Cognitive-affective versus somatic dimensions

  8. Study 1: Methods • Sample • English Longitudinal Study of Ageing (ELSA) • CRP sample: N = 5,784 • Cortisol sample: N = 4,761 • Measures • Outcome: Depressive symptoms (CES-D 8), w1-8 (14-year period) • Independent variables: Hair cortisol & plasma C-reactive Protein, w6 • Covariates: Demographic, socioeconomic, lifestyle, chronic disease, and medication data COGNITIVE-AFFECTIVE: ‘‘enjoyed life”, ‘‘depressed”, ‘‘happy”, ‘‘lonely” , ‘sad” SOMATIC: ‘‘everything was an effort”, ‘‘sleep was restless”, ‘‘I could not get going”

  9. Study 1: Methods Trait-State Occasion (TSO) model • Statistical Analyses • Trait-State-Occasion (TSO) structural equation modelling • TSO model and missing data estimated using WLSMV estimator in Mplus • Cortisol and CRP (<=10mg/l) were log-transformed C = cognitive-affective; S = somatic

  10. Study 1: Results Effects of Cortisol (N= 4,761) and CRP (N=5,784) on persistent depressive symptoms: Overall, cognitive-affective, and somatic factors

  11. Outline • Background • Study 1: Relationship of C-reactive Protein (CRP) and Cortisol with Depressive Symptoms • Study 2: Association of Adverse Childhood Experiences (ACE) with CRP and Cortisol • Study 3: Longitudinal mediation analysis of ACE, CRP, and Depressive Symptoms • Conclusions

  12. Study 2: Aim and Hypotheses    • Aim:To investigate the effect of exposure to adverse childhood experiences (ACE) on C-reactive protein (CRP) and hair cortisol, distinguishing between: • ACE cumulative exposure • 2) ACE dimensions

  13. Study 2: Methods • Sample • English Longitudinal Study of Ageing (ELSA) • CRP sample: N = 4,198 • Cortisol sample: N = 3,357 • Measures • Independent variable: Adverse childhood experiences (wave 3) • Outcomes: • (1) CRP, wave 4 (log) • (2) High CRP, wave 4+6 (>3mg/l) • (3) Hair Cortisol, wave 6 (log) • Covariates: Demographic characteristics, childhood and adult socioeconomic factors, BMI, health behaviours, and medications

  14. Study 2: Methods CFA model of ACE • Statistical Analyses • ACE cumulative exposure: linear and ordered logistic regression (Rstudio) • ACE dimensions: Confirmatory factor analysis (CFA) (Mplus) • Missing data estimated using multiple imputation (R package ‘mice’) RMSEA: 0.038; CFI: 0.946; TLI: 0.926

  15. Study 2: CRP(log) w4 ACE Cumulative score ACE Dimensions (model 3) • Note. Linear regression model, Ref: ACE(0) • Model 1: sex, age, marital status, medications • Model 2: Model 1 + childhood and adult socioeconomic factors • Model 3: Model 2 + lifestyle indicators C = cognitive-affective; S = somatic

  16. Study 2: High CRP w4+w6 (>3 mg/l) ACE Cumulative score ACE Dimensions (model 3) • Note. Ordered logistic regression, Ref: ACE(0) • Model 1: sex, age, marital status, medications • Model 2: Model 1 + childhood and adult socioeconomic factors • Model 3: Model 2 + lifestyle indicators C = cognitive-affective; S = somatic

  17. Study 2: Hair Cortisol w6 ACE Dimensions (model 3) ACE Cumulative score • Note. Linear regression, Ref: ACE(0) • Model 1: sex, age, marital status, hair data, medications • Model 2: Model 1 + childhood and adult socioeconomic factors • Model 3: Model 2 + lifestyle indicators

  18. Study 2: Hair Cortisol w6 Interaction effect: ACE Cumulative score x Age (Model 3) • Model 3: sex, age, marital status, hair characteristics, medications, childhood and adult socioeconomic factors, lifestyle indicators (bmi, smoking, alcohol, physical activity)

  19. Outline • Background • Study 1: Relationship of C-reactive Protein (CRP) and Cortisol with Depressive Symptoms • Study 2: Effect of Adverse Childhood Experiences (ACE) on C-reactive protein and Cortisol • Study 3: Longitudinal mediation analysis of ACE, CRP, and Depressive Symptoms • Conclusions

  20. Study 3: Aim and Hypotheses    • Aim:To test the mediational role of C-reactive protein (CRP) in the relationship between childhood adverse experiences (ACE) and depression over time: • Direct effects of ACE on depression, CRP, and their trajectories • 2) Indirect effects of ACE on depression through CRP

  21. Study 3: Methods    • Sample • English Longitudinal Study of Ageing (ELSA) • Sample: N = 4,382 • Measures • Independent variable: Adverse childhood experiences (wave 3) • Mediator: CRP (log) waves 2,4,6 • Outcome: Depressive symptoms (CES-D 8) waves 6,7,8 • Covariates: Demographic characteristics, childhood and adult socioeconomic factors, lifestyle indicators, and medications

  22. Study 3: Methods    • Statistical Analyses • Parallel process latent growth curve modelling • (WLSMV estimator in Mplus) • Indirect effects estimated with bias-corrected bootstrap standard errors • Missing data estimated using multiple imputation • (R package ‘mice’) Longitudinal Mediation Model

  23. Study 3: Methods    • Statistical Analyses • Parallel process latent growth curve model • (WLSMV estimator in Mplus) • Indirect effects estimated with bias-corrected bootstrap standard errors • Missing data estimated using multiple imputation • (R package ‘mice’) Longitudinal Mediation Model

  24. Study 3: Methods    • Statistical Analyses • Parallel process latent growth curve model • (WLSMV estimator in Mplus) • Indirect effects estimated with bias-corrected bootstrap standard errors • Missing data estimated using multiple imputation • (R package ‘mice’) Longitudinal Mediation Model

  25. Study 3: Results    Total Depressive Symptoms Somatic Depressive Symptoms • Model 3: Adjusted for sex, age, marital status, childhood and adult socioeconomic factors, lifestyle indicators, and medications

  26. Outline • Background • Study 1: Relationship of C-reactive Protein (CRP) and Cortisol with Depressive Symptoms • Study 2: Effect of Adverse Childhood Experiences (ACE) on C-reactive protein and Cortisol • Study 3: Longitudinal mediation analysis of ACE, CRP, and Depressive Symptoms • Conclusions

  27. Conclusions • STUDY 1 • Higher hair cortisol and CRP levels were associated with more persistent depressive symptoms across a 14-year period • These relationships were driven by somatic symptoms • STUDY 2 • Greater exposure to ACE was associated with elevated CRP levels • Adversities related to loss of an attachment figure had the strongest effects • Greater exposure to ACE was related to a steeper increase in hair cortisol with age • STUDY 3 • Greater exposure to ACE was associated with higher CRP and depression at baseline and with their increase over time • No evidence for mediation effects of CRP

  28. Conclusions • Next steps • 1. ELSA • CRP: reverse mediation model • Cortisol: Moderated mediation model for the interaction between ACE and age • Polygenic scores of depression, cortisol, and CRP: main effects and interaction effects with ACE • 2. ALSPAC • Associations between ACE, stress biomarkers, and depression • Main and interaction effects of polygenic scores • DNA methylation • 3. TEDS • Associations between ACE, salivary cortisol, and depression

  29. Acknowledgments • Supervisors & collaborators: Prof Andrew Steptoe, Dr Rebecca Lacey, Dr Panos Demakakos, Prof Clemens Kirschbaum • Research funders & ELSA participants • Eleonora Iob (PhD Candidate) • Soc-B CDT (ESRC & BBSRC) • University College London • eleonora.iob.17@ucl.ac.uk

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