Adverse childhood experiences, inflammation, and depressive symptoms in later life: a prospective cohort study

Abstract

BackgroundExposure to adverse childhood experiences (ACEs) has been associated with both inflammation and depression. However, little research has examined the potential mediational role of inflammation in the link between ACEs and depression using longitudinal data. Therefore, we investigated the direct and indirect effects of ACEs on inflammation, depression, and their change trajectories over time. MethodsWe used data from the English Longitudinal Study of Ageing. Four ACE categories were assessed retrospectively at wave 3 (2006–07): abuse (physical or sexual abuse or physical assault), family dysfunction (parent arguments, parent mental illness or substance abuse, or parent separation or divorce), poor parent–child bonding (maternal or paternal), and loss of an attachment figure (separation from mother for >6 months, parent death, foster care or adoption, or institutionalisation). A cumulative ACE score was calculated representing the total number of ACEs experienced by the participants. Concentration of C-reactive protein (CRP), an inflammatory marker, was measured at waves 2 (2004–05), 4 (2008–09), and 6 (2012–13). Depressive symptoms were ascertained using the 8-item Centre for Epidemiological Studies Depression Scale from waves 6 to 8 (2016–17). The longitudinal direct and indirect effects of ACEs were estimated using parallel process latent growth curve modelling. All analyses were adjusted for relevant confounders. Missing data were estimated using multiple imputation. ResultsAmong the study sample (N=4382; mean age 70 years; 56% female), 24% of participants reported one ACE and 13% had two or three ACEs. The percentage of participants with three or more depressive symptoms was 21% at baseline. Greater cumulative exposure to ACEs was associated with increased CRP concentration (β=0·042, p=0·010) and depressive symptoms (β=0·164, p<0·0001) at baseline and predicted a steeper increase in these outcomes throughout the study (βCRP=0·074, p=0·011; βDepression=0·338, p<0·0001). However, indirect effects of ACEs on depression mediated by CRP were not observed, with only weak associations between CRP and depressive symptoms (βiDepression=0·032, p=0·173; βsDepression=0·067, p=0·240). Sensitivity analyses using only somatic depressive symptoms as the outcome revealed a positive association between CRP and somatic symptoms at baseline (βiDepression=0·068, p=0·008), although the indirect effects remained non-significant in this model. InterpretationBiological mechanisms other than inflammation might underlie the relationship between ACEs and depression. Psychosocial interventions to reduce the negative effects of ACEs on children's development could help to reduce the risk of depression and of other medical conditions linked to inflammation. FundingEconomic and Social Research Council–Biotechnology and Biological Sciences Research Council Soc-B Centre for Doctoral Training (ES/P000347/1).