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

Abstract

Background: Inflammation plays a role in mood and behavior that may be relevant to identifying risk factors and treatment for depression and other stress-related illnesses. The purpose of this study was to examine whether fluctuations in inflammation following a mild immune stimulus were associated with changes in daily reported features of depression for up to a week in a healthy sample of young adults.

Methods: Forty-one undergraduate students completed daily diaries of mood, feelings of social disconnection, sleep, and physical symptoms for one week before and after receiving the seasonal influenza vaccine. Circulating plasma interleukin-6 (IL-6) was measured via blood samples taken immediately before and one day after vaccination.

Results: There was a significant increase in circulating IL-6 from pre- to post-intervention (p = .008), and there was significant variability in the magnitude of IL-6 change. Greater increases in IL-6 were associated with greater mood disturbance on post-vaccine days, specifically depressed mood and cognitive symptoms.

Conclusions: 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.

Keywords: Depression; IL-6; Inflammation; Influenza vaccine; Interleukin-6; Mood; Sickness behavior.

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Figure 1. Change in IL-6 from pre- to one-day post-vaccine administration

IL-6 at pre- and post-vaccine for all participants. Black lines indicate participants with an increase in IL-6 from pre- to post-vaccine (n = 32), dashed grey lines indicate participants who did not show an increase in IL-6 (n = 9), and the red line indicates the mean change in IL-6 across the sample.

Figure 2. Change in depressed mood and confusion over week following vaccine by IL-6 response

Within-subject change in (a) depressed mood and (b) confusion from pre-vaccine to post-vaccine days by within-subject change in IL-6. Estimates of fixed effects for the Time*ΔIL-6 term in each model are presented in the bottom right corner of each panel.

Figure 3. Daily reported depressed mood for participants who did and did not demonstrate an inflammatory response to the flu vaccine

Daily mean (SE) of depressed mood following vaccine administration by participants demonstrating an increase in IL-6 from immediately before to 1-day after the vaccine.