Adverse childhood experiences and severity levels of inflammation and depression from childhood to young adulthood: a longitudinal cohort study

Abstract

Adverse childhood experiences (ACEs) are associated with depression and systemic inflammation in adults. However, limited longitudinal research has tested these relationships in children and young people, and it is unclear whether inflammation is an underlying mechanism through which ACEs influence depression. We examined the longitudinal associations of several ACEs across different early-life periods with longitudinal patterns of early-life inflammation and depression in young adulthood and assessed the mediating role of inflammation. The data came from the Avon Longitudinal Study of Parents and Children (N = 3931). ACEs from the prenatal period through to adolescence were operationalised using cumulative scores, single adversities, and dimensions derived through factor analysis. Inflammation (C-reactive protein) was measured on three occasions (9-18 years) and depressive symptoms were ascertained on four occasions (18-23 years). Latent class growth analysis was employed to delineate group-based trajectories of inflammation and depression. The associations between ACEs and the inflammation/depression trajectories were tested using multinomial logistic regression analysis. Most types of ACEs across all early-life periods were associated with elevated depression trajectories, with larger associations for threat-related adversities compared with other ACEs. Bullying victimisation and sexual abuse in late childhood/adolescence were associated with elevated CRP trajectories, while other ACEs were unrelated to inflammation. Inflammation was also unrelated to depression and did not mediate the associations with ACEs. These results suggest that ACEs are consistently associated with depression, whereas the associations of inflammation with ACEs and depression are weak in young people. Interventions targeting inflammation in this population might not offer protection against depression.

Fig. 1. Flowchart of the statistical analyses.

(i) Data preparation and multiple imputation of missing data were conducted in R; (ii) Factor analysis of ACEs was performed in Mplus, and Latent class growth analysis of CRP and depression was performed in Stata; (iii) Multinomial logistic regression analysis was conducted in Stata; (iv) Model-based causal mediation analysis was conducted in R.

Fig. 2. Group-based trajectories of depressive symptoms and CRP.

Sample: ALSPAC (N = 3931). The latent class growth analysis resulted in the following trajectories: (1) Depression: Class 1—low depressive symptoms (68.9%), representing participants with low depressive symptoms at all assessments; Class 2—moderate depressive symptoms (23.8%), representing participants with moderate depressive symptoms at all assessments; Class 3—severe depressive symptoms (7.4%), representing participants with high levels of depressive symptoms at all assessments; (2) CRP: Class 1—low-moderate CRP (69.8%), representing participants with low levels in late childhood and moderate levels in adolescence; Class 2—moderate-high CRP (19.5%), representing participants with moderate levels in late childhood and high levels in adolescence; Class 3—high-moderate CRP (10.6%), representing participants with high levels in late childhood but lower levels in adolescence. The ‘low depression’ and ‘low-moderate CRP’ trajectories were used as reference categories in multinomial logistic regression analysis.

Fig. 3. Associations between ACEs (prenatal to 18 years) and CRP trajectories (9–18 years).

Sample: ALSPAC (N = 3931). Pooled estimates and 95% confidence intervals from multinomial logistic regression models across 20 imputed datasets. Model 1—adjusted for sex, ethnicity, maternal smoking during pregnancy, mother’s marital status, mother’s education, and household’s social class; Model 2—Model 1 + ACEs experienced during previous early-life periods. The associations are statistically significant at the 95% confidence level if the confidence interval does not cross 1 (dotted line of graph), and those marked with an asterisk symbol (*) were no longer significant following the correction for multiple comparisons. Reference trajectory: low-moderate CRP levels.

Fig. 4. Associations between ACEs (prenatal to 18 years) and depression trajectories (18–23 years).

Sample: ALSPAC (N = 3931). Pooled estimates and 95% confidence intervals from multinomial logistic regression models across 20 imputed datasets. Model 1—adjusted for sex, ethnicity, maternal smoking during pregnancy, mother’s marital status, mother’s education, and household’s social class; Model 2—Model 1 + ACEs experienced during previous early-life periods. The associations are statistically significant at the 95% confidence level if the confidence interval does not cross 1, and those marked with an asterisk symbol (*) were no longer significant following the correction for multiple comparisons. Reference trajectory: low depressive symptoms.

Fig. 5. Associations of single and multiple exposures to ACEs (prenatal to 18 years) with depression trajectories (18–23 years).

Sample: ALSPAC (N = 3931). Pooled estimates and 95% confidence intervals from multinomial logistic regression models across 20 imputed datasets. Model 4—adjusted for sex, ethnicity, maternal smoking during pregnancy, mother’s marital status, mother’s education, and household’s social class. The associations are statistically significant at the 95% confidence level if the confidence interval does not cross 1 (dotted line of graph). The reference group for both single and multiple exposures to ACEs is ‘no ACE exposure’. The multiple-exposure group was not tested for sexual abuse as only a few participants reported experiences of sexual abuse twice during childhood. Reference trajectory: low depressive symptoms.