Primed to feel, not to flare: Early life adversity and psychological sensitivity to interleukin-6 in a randomized trial among middle-aged female breast cancer survivors.
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BACKGROUND: There have been recent calls to investigate potential moderators of inflammation's psychological effects in humans. In a small observational study, Kuhlman et al. (2020b) found that individuals with higher early life adversity (ELA) showed heightened psychological sensitivity (i.e., more depressed mood and poorer cognition but not decreased social connection) in response to influenza vaccine-induced increases in interleukin-6 (IL-6). In a larger cohort with a placebo-controlled experimental design, we examined ELA's moderating effects on (1) vaccine-induced IL-6 reactivity, (2) increases in IL-6 reactivity and psychological outcomes, and (3) the effect of injection type on psychological outcomes. METHOD: Female breast cancer survivors (N = 172) received the typhoid vaccine and saline placebo injection in a randomized sequence at two separate visits. At screening, early life adversity was indexed using two measures: the Childhood Trauma Questionnaire-Short Form and the Kessler Childhood Adversity Index. During each visit, IL-6 was measured six times over 7.5 h, and psychological outcomes (sadness, focus difficulty, memory difficulty, social connection) were repeatedly assessed across 8.5 h. RESULTS: Neither ELA index moderated vaccine-induced IL-6 reactivity (ps > 0.17) nor moderated the effect of injection type on psychological outcomes (ps > 0.25). Instead, those with more ELA had greater psychological sensitivity to inflammatory increases. Among individuals with higher ELA exposure (≥2 adverse events), increases in IL-6 were associated with greater sadness (p = 0.030) and focus difficulty (p = 0.048), marginally greater memory difficulty (p = 0.067), but were unrelated to feelings of social connection (ps > 0.81). These associations were nonsignificant among individuals who reported zero or one adverse event. CONCLUSION: Our findings suggest that among individuals with greater exposure to early life adversity, those with heightened inflammatory reactivity may be particularly vulnerable to IL-6's psychological effects, highlighting a potential target for identifying and supporting individuals at risk for inflammation-associated depression.