Parental exposure to severe, threatening stressors is associated with elevated inflammation in adolescent offspring independent of genetic reflatedness

Although parental stressor exposure has been proposed as an intergenerational pathway linking adversity to offspring inflammatory risk, the relative contributions of biological versus postnatal environmental transmission remain unclear. To investigate, we examined whether parental exposure to severe, socially threatening stressors—life-threatening events, legal/criminal victimization, and bereavement—predicted inflammation in late adolescence, and whether this association (a) differed for internationally adopted versus non-adopted youth and (b) varied by the timing of parental stress exposure relative to the child’s placement in the family. Participants were 193 adolescents (97 internationally adopted, 96 non-adopted; mean age = 15.69 years) and their parents. Parents’ lifetime stressor exposure was assessed using the Stress and Adversity Inventory (STRAIN); fasting blood samples were obtained from youth to assess an inflammation composite (z-score sum of IL-6, TNF-α, and CRP) as the primary outcome, with individual marker analyses conducted to identify primary drivers of composite effects. In multivariable linear regression models adjusting for adolescent age, sex, time of blood draw, trunk tissue fat, and adoption status, greater parental life-threatening stressor severity was associated with higher adolescent inflammation composite scores (β = 0.085, SE = 0.038, p = 0.025; R 2 = 0.33), with IL-6 emerging as the primary driver of this effect ( b = 0.034, SE = 0.014, p = 0.015; R 2 = 0.27), robust to adjustment for multiple comparisons ( q = 0.044). This association did not differ by adoption status. Since the majority of parental life-threatening stressors occurred before the child entered the family, we examined timing in exploratory analyses; the association held when restricted to pre-placement stressor severity (β = 0.086, p = 0.027). These findings suggest that parents’ exposure to severe, life-threatening stressors—particularly those preceding the child’s entry into the family—is associated with greater inflammatory activity in adolescence. The comparable effects across adopted and non-adopted youth, combined with the pre-placement timing effect, are most consistent with postnatal environmental transmission mechanisms.