Early life stress sensitizes individuals to the psychological correlates of mild fluctuations in inflammation

Abstract

Background Early life stress (ELS) has been linked to health disparities across the human lifespan, particularly increased risk for depression and its recurrence. In this study we explore two plausible and competing pathways through which ELS may lead to depression via inflammation. Methods Participants (ages 18–22; n = 41) completed the Early Trauma Inventory as a measure of ELS. Participants then completed consecutive daily diaries of mood and other sickness behavior for the 7 days prior to and 7 days after receiving the annual influenza vaccine. Circulating concentrations of plasma interleukin‐6 (IL‐6) were measured immediately before and 24 hr after vaccination. Results ELS was not associated with the magnitude of change in IL‐6 from pre‐ to post‐vaccine, however, exposure to ELS moderated the association between change in IL‐6 from pre‐ to post‐vaccine and changes in both cognitive difficulty and depressed mood. Individuals exposed to greater ELS showed greater psychological sensitivity to increases in IL‐6. Conclusions Exposure to ELS may increase sensitivity to peripheral inflammation in the central nervous system. Future studies elaborating on the impact of ELS on the sensitivity of specific neural circuits and cells to inflammation are needed.

Inflammation and depression in young people: a systematic review and proposed inflammatory pathways

“…For example, the longitudinal ACE cohort study found that proinflammatory proteins CRP and IL-6 moderated the association between prior stressful events and depression at follow-up [90]. Early life adversity may also interact with inflammation, with 6 [66,97,[103][104][105]132] of 7 studies showing that early life adversity is strongly associated with inflammation in young people, particularly CRP; however, this association was often independent of depressive symptoms. These findings are consistent with a meta-analysis in adults on the effect of early life trauma on inflammation, in which higher CRP, IL-6 and TNF-α was found, suggesting long-lasting effects [133].…”

The Psychobiology of Bereavement and Health: A Conceptual Review From the Perspective of Social Signal Transduction Theory of Depression

“…These responses, either directly or via interaction with the social environment, can cause alterations in biological functioning that include the onset of chronic low-grade inflammation, which can increase risk for sickness behaviors, infections, mental and physical health problems, and premature mortality in vulnerable individuals (26,(47)(48)(49). Consistent with this thinking, several lines of evidence indicate that stressful life events are strongly associated with altered immune function and the development of depression, especially for persons living in a high-risk environment (e.g., trauma exposure) who possess a genetic predisposition to depression (20,(50)(51)(52). Moreover, clinical studies have shown that depressive symptoms are prevalent in widows and widowers during the first 2 years of bereavement, with a particular high risk for individuals with a history of depression (53,54).…”

Early life stress sensitizes youth to the influence of stress‐induced cortisol on memory for affective words

“…Stress activates a number of physiological processes (e.g., autonomic nervous system, immune system), which may have played a role in affective attention and memory in this sample. Indeed, ELS has recently been linked to greater behavioral sensitivity to inflammation (Kuhlman et al, 2020). Additionally, HPA axis functioning and reactivity is robustly modulated by gonadal hormones such as estrogens and testosterone (Heck & Handa, 2019).…”