Stressful life events, inflammation and emotional and behavioural problems in children: A population-based study

Abstract

Objective: To test the hypothesis that higher plasma levels of inflammatory markers due to exposure to adverse life events may lead to internalising and externalising symptoms in children. Method: Using data from the Avon Longitudinal Study of Parents and Children, a general population birth cohort, we explored if inflammatory markers [serum C-reactive protein (CRP) and interleukin-6 (IL-6)] at age 9 years explain the longitudinal association between adverse life events (at ages 1-9 and 9-11 years) and internalising and externalising symptoms (at ages 9 and 11 years). Data (n=4,583) were analysed using cross-lagged panel modelling to take into account reciprocal associations and reverse causality, and path analyses to test for mediation. Gender, ethnicity, body mass index, maternal education, paternal social class and maternal depression were used as potential confounders. Results: CRP was not associated with adverse life events. There was evidence for partial mediation by IL-6 such that exposure to adverse life events was associated with increased levels of IL-6 later, in turn associated with later internalising symptoms. These associations were robust to adjustment for confounders. IL-6 did not explain part of the opposite association, that of earlier internalising symptoms and later life events, nor did it explain either direction of the association between life events and externalising symptoms. Conclusion: Our findings suggest a pathway that may connect early psychosocial adversity and childhood internalising symptoms via higher plasma levels of inflammatory markers such as IL-6. Highlights

Biological embedding of maternal postpartum depressive symptoms: The potential role of cortisol and telomere length

“…Telomeres shorten with every cell division, and telomeres that are shortened past a critical length can become senescent (Harley et al, 1990). These senescent cells can exert harmful effects on the tissue micro-environment, including an increase in the secretion of pro-inflammatory cytokines (Davalos, Coppe, Campisi, & Desprez, 2010), which in turn could impact brain functioning and behavior (Flouri, Francesconi, Papachristou, Midouhas, & Lewis, 2019). Alternatively, as our present study did not include an earlier measure of behavior problems, it is also possible that telomeres do not contribute to the development, but are a result, of behavior problems.…”

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

“…15 Thus, the link from early stressful life events to depression via inflammation is plausible but, to our knowledge, still unexplored in adolescence. One study tested the role of inflammation in the association between stressful life events and internalising symptoms, but did not investigate links beyond childhood, did not consider the role of prenatal life events and did not explore depressive symptomatology specifically 49 . No study has yet investigated if prenatal and childhood stressful life events are related to the development of depression across adolescence via increasing levels of inflammatory markers.…”

Challenges in researching the immune pathways between early life adversity and psychopathology

“…However, IL-6 did not explain the association between ELA and externalizing symptoms. A separate study on this cohort found that IL-6 levels at 9 years partially mediated the association between ELA in childhood and depressive symptoms at the beginning of adolescence (Flouri et al, 2019). Internalizing symptoms at age 9 years fully mediated the association between levels of IL-6 in childhood and subclinical psychotic symptoms (psychotic-like experiences, PLEs) at age 18 (Flouri et al, 2020).…”

“…However, childhood sexual abuse was significantly associated with IL-6 and CRP for nonwhites only (Pinto Pereira et al, 2019). In studies of pediatric populations, threat experiences of maltreatment and victimization are positively associated with inflammation in some studies (Baldwin et al, 2018; Bucker et al, 2015; Danese et al, 2007; Flouri et al, 2019; Kilic et al, 2017) but not all (Bernard et al, 2019; Cicchetti et al, 2015; Miller & Cole, 2012).…”

“…One analysis found that prospective measures of adversity predicted IL-6 but not CRP in 9-year-olds (Flouri et al, 2020). IL-6 partially mediated the relationship between ELA and later internalizing symptoms (Flouri et al, 2019). However, IL-6 did not explain the association between ELA and externalizing symptoms.…”