Interpersonal Stress, Epigenetic Indices of Inflammation, and Depressive Symptoms: Longitudinal Associations from Adolescence to Young Adulthood.

Background:Adolescent interpersonal stress increases depression risk, and chronic low-grade inflammation may act as a potential underlying biological mechanism. Methods:We explored longitudinal associations between interpersonal stress, inflammation, and depressive symptoms from adolescence to young adulthood, using DNA methylation (DNAm) indices of C-reactive protein (CRP) from saliva. Data were collected from N = 434 adolescents (RADAR-Y study, 56.4% male) and analyzed in preregistered structural equation models. Interpersonal stress was estimated from repeated measures of parent-adolescent conflict, parental psychological control, parental criticism, and peer victimization. Results:Interpersonal stress was not associated with DNAm indices of CRP at age 17 or age 25, nor with depressive symptoms at age 27. In exploratory analyses examining parent versus peer-related stress separately, higher negative parenting-but not peer victimization-was nominally associated with one out of three DNAm indices of CRP at age 17 (Hillary index, β = .15, p = .035), with no association at age 25. Conclusion:This study did not show an association of either interpersonal stress or inflammation with later depressive symptoms and thereby could not identify inflammation as a potential mediator. Our findings tentatively suggest timing-dependent differential effects of family versus peer-related stress on epigenetic indices of inflammation, which may be further explored in future studies.