Maintenance of a positive outlook during acute stress protects against pro-inflammatory reactivity and future depressive symptoms

Abstract

Cognitive and affective responses to acute stress influence pro-inflammatory cytokine reactivity, and peripheral cytokines (particularly interleukin-1 beta (IL-1β)), can act on the brain to promote depressive symptoms. It is unknown whether acute stress-induced changes in positive affect and cognitions (POS) and pro-inflammatory reactivity predict future depressive symptoms. We examined acute stress responses among women, to determine prospective predictors of depressive symptoms.

Hypotheses: (1) Stress-induced decreases in POS will be associated with stress-related increases in circulating IL-1β. (2) Acute stress-induced decreases in POS and increases in IL-1β reactivity will predict increases in depressive symptoms 1 year later. Thirty-five post-menopausal women were exposed to acute stress with the Trier Social Stress Task (TSST) and provided blood samples under resting conditions and 30 min after the conclusion of the TSST, which were assayed for IL-1β. IL-1β reactivity was quantified as post minus pre-TSST. Failure to maintain POS was quantified as the decrease in POS during the TSST. Change in depressive symptoms from the study baseline to the following year was determined. Greater acute stress-induced declines in POS were significantly associated with increased IL-1β reactivity (p≤.02), which significantly predicted increases in depressive symptoms over the following year (p<.01), controlling for age, body mass index, chronic stress, antidepressant use and baseline depressive symptoms. IL-1β reactivity was a significant mediator of the relationship between POS decline and future increases in depressive symptoms (p=.04). Difficulty maintaining positivity under stress and heightened pro-inflammatory reactivity may be markers and/or mechanisms of risk for future increases in depressive symptoms.

Figure 1. The Decrease in a Positive Outlook During Acute Stress is Associated with Greater Pro-Inflammatory Interleukin-1β Reactivity

POS = Positive Affect and Cognitions. The analyses reported in the results use the continuous measures of acute-stress induced change in POS to predict 50-minute IL-1β reactivity (p=.017). In this figure, the effects are represented dichotomously to better illustrate how individuals (n=19) whose POS decreased in resonse to acute stress had a greater increase in IL-1β, relative to individuals (n=16) whose POS increased or stayed the same following the acute stress task.

Figure 2. Pro-inflammatory IL1β Reactivity Mediates the Relationship between Loss of Positivity During Acute Stress & Future Depressive Symptom Increases

**p≤.01, *p≤.05. Bootstrapped linear regression analyses of the indirect effect (Hayes, 2009; Sobel, 1989) were used to test the hypothesis that pro-inflammatory reactivity to acute stress is a significant mediator of the relationship between loss of a positive outlook during acute stress and prospective risk of depressive symptom increases. Loss of a positive outlook was quantified as the decrease in Positive Affect and Cognitions (POS) during the acute stress task. The indirect effect was significant: B(SE)= −1.194 (0.549), p=.030*.