Within-subject associations between inflammation and features of depression: Using the flu vaccine as a mild inflammatory stimulus

Abstract

Minor increases in inflammation were associated with corresponding increases in features of depression, and these associations occurred in the absence of any physical symptoms. The influenza vaccine could be used to probe causal relationships with a high degree of ecological validity, even in high-risk and vulnerable populations, to better understand the role of inflammation in the pathogenesis of depression.

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

“…Participants were recruited as part of a project on the feasibility of using the influenza vaccine as a model for interrogating the role of inflammation in depression (Kuhlman et al, ). Participants were recruited during the Fall of 2015 and 2016 using flyers on a university campus.…”

“…For our primary analyses, we ran three regression models predicting change in depressed mood, cognitive difficulty, and social disconnection as a function of ΔIL‐6 from pre‐ to post‐vaccine, ELS, and the interaction between ΔIL‐6 and ELS. Each model covaried for pre‐vaccine concentrations of IL‐6, female sex, and BMI based on best practices in psychoneuroimmunology (O’Connor et al, ), as well as whether the participant was part of the first or second cohort (See Kuhlman et al, for details). It should be noted that the results of our models are similar and conclusions the same when post‐vaccine IL‐6 was our dependent variable while controlling for pre‐vaccine IL‐6 (See Wainer, for more on the theoretical and statistical importance of this issue).…”

“…Several manifestations of sickness behavior, including depressed mood, difficulty with attention and memory, and withdrawal from social activities overlap with depressive symptoms. Indeed, we recently demonstrated that mild increases in inflammation following receipt of the annual influenza vaccine were associated with corresponding increases in daily depressed mood, problems with memory and attention, and to a lesser extent social disconnection (Kuhlman et al, ). This is important because inflammation is considered to be one putative mechanism through which depression develops (Raison, Capuron, & Miller, ).…”

“…In this study, we tested these competing hypotheses in a sample of healthy young adults. To do this, we examined three depression‐related psychological domains associated with increases in peripheral inflammation following exposure to the annual flu vaccine: self‐reported depressed mood, cognitive difficulty, and feelings of social disconnection (Kuhlman et al, ). Consistent with the literature demonstrating that ELS leads to exaggerated inflammatory responses, we hypothesized that individuals with greater self‐reported exposure to ELS would demonstrate a larger increase in inflammation from pre‐ to post‐vaccine.…”

“…This may suggest that individuals exposed to greater ELS may be more sensitive to the cognitive effects of inflammation than the mood effects. Indeed, the main effect of change in IL‐6 on confusion was larger with less variability, b = 0.20 ( SE = 0.06), than on depressed mood, b = 0.17 ( SE = 0.08) (Kuhlman et al, ). However, the relatively small sample size and high correlation between Δ depressed mood and Δ cognitive difficulty lead us to interpret the results of this sensitivity analysis with caution.…”