Stress-induced IL-6 response patterns amplify the link between daily negative affect and later depressive symptoms during bereavement

Depressive symptoms frequently follow exposure to major life stressors, such as spousal bereavement. However, long-term mental well-being varies considerably. Previously, daily negative affect significantly predicted future depressive symptoms. Higher daily negative affect may signify worse long-term mental health for individuals who also show enhanced inflammatory responses to acute stress, as heightened physiological reactivity to acute stress has been linked with increased susceptibility to depression. Among widow(er)s, we examined whether stress-induced inflammatory responses altered the magnitude of the association between daily negative affect and future depressive symptoms. In exploratory analyses, we examined whether these patterns differed between bereaved and nonbereaved adults. Participants (143 bereaved, 69 nonbereaved) completed the Trier Social Stress Test (TSST) and a 7-day affect survey at baseline (4 months post-loss). Subjects self-reported depressive symptoms at baseline and at an 8-month follow-up. Stress-induced IL-6 responses (IL-6 slope) were characterized as the change in serum IL-6 across 3 timepoints (pre-TSST, 45-min post-TSST, 120-min post-TSST). SEM path analysis was used to test hypotheses. Among widow(er)s, we observed a significant negative affect × IL-6 slope effect on future depressive symptoms, after controlling for baseline depressive symptoms and covariates. Widow(er)s with larger stress-induced IL-6 increases showed the strongest, positive association between negative affect and future depressive symptoms. This pattern was not observed in nonbereaved adults. Findings suggest that more daily negative affect in conjunction with heightened stress-induced IL-6 activity may forecast future increases in depressive symptoms. The study identifies possible psychobiological patterns indicative of future maladjustment to stressful life events.