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

Abstract

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 mediated 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 analysed using mediation analysis in a latent growth curve modelling 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 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.

Youth Depression Alleviation with Anti-inflammatory Agents (YoDA-A): a randomised clinical trial of rosuvastatin and aspirin

“…Depression is associated with a complex picture of increased immune activation, impaired immune function, and inflammation [14][15][16], including in young people [17]. Depression not only is associated with depression in youth, but risk factors for depression themselves, such as trauma and obesity, are associated with inflammation [18,19]. Higher levels of C-reactive protein are associated with risk for the development of de novo depression, suggesting that inflammation contributes at least in part to the genesis and progression of depression [20].…”

Involvement of Oxytocin Receptor/Erk/MAPK Signaling in the mPFC in Early Life Stress-Induced Autistic-Like Behaviors

“…Early life stress confers lifelong stress susceptibility ( Pena et al, 2017 ) and causes psychiatric diseases and cognitive impairment later in life, including social deficits relevant to ASD, anxiety, and depression ( Chapman et al, 2004 ; Carr et al, 2013 ; Flouri et al, 2020 ). To examine the effects of ELS during the stress hyporesponsive period on social and cognitive–behavioral changes in juvenile rats, we used NMS as the ELS.…”

“…Early life, including early childhood, neonatal, or even infant period, is a time of significant brain development and, therefore, a time when early social experiences influence the development of the central nervous system and expression of behaviors in subsequent adolescence and adulthood ( Cushing and Kramer, 2005 ; Anda et al, 2006 ; Tian et al, 2018 ). Emerging pieces of evidence suggest that adversities during early life may contribute to a greater risk of developing mental disorders such as autism spectrum disorder (ASD), anxiety, and depression ( Chapman et al, 2004 ; Carr et al, 2013 ; Flouri et al, 2020 ). Thus, early life stress (ELS) events are a cause or a predisposing factor for psychiatric diseases later in life.…”

Commentary: Neurobiology and Therapeutic Potential of Cyclooxygenase-2 (COX-2) Inhibitors for Inflammation in Neuropsychiatric Disorders

“…For example, childhood trauma is associated with significantly elevated peripheral levels of C-reactive protein, interleukin (IL)-6, tumor necrosis factor-a, and soluble urokinase plasminogen activator receptor (44,45). Elevated IL-6 in childhood is in turn associated with increased risk of future depressive and psychotic symptoms in adolescence (46,47). Stress-related epigenetic dysregulation in immune networks represents one mechanism by which childhood experiences may become biologically embedded (48), and a potential target for early intervention.…”