Prenatal and childhood adverse life events, inflammation and depressive symptoms across adolescence

Background: No study has investigated the role of inflammation in explaining the association between early exposures to adverse life events and depressive symptoms in adolescence. Method: Using data from the Avon Longitudinal Study of Parents and Children, we tested if inflammatory markers [serum C-reactive protein (CRP) and interleukin 6 (IL-6)] at age 9 years mediate the association between adverse life events, measured separately for the prenatal (since the beginning of pregnancy) and the childhood (ages 0-9 years) periods, and the development of depressive symptoms at ages 10-17 years. Data (n = 4,263) were analyzed using mediation analysis in a latent growth curve modeling framework. Results: Depressive symptoms at the beginning of adolescence (age 10) were associated with the number of prenatal events, the number of events around birth and the increase in events over time in childhood (ages 0-9), even after adjustment for confounders. IL-6 partially mediated the association between increasing exposure to events over time in childhood and depressive symptoms at the beginning of adolescence. IL-6 did not mediate any other association between events and symptoms. There was no evidence for mediation by CRP, which was generally unrelated to exposure to events. Limitations: The small size of the mediation effect and the robust direct effects of events prenatally and around birth suggest there are multiple routes from early stressors to adolescent depression. Conclusions: In the general adolescent population, increasing exposure to psychosocial stressors over time during childhood is associated with the early onset of depressive symptoms, partly via increasing levels of plasma IL-6.