Elevated interleukin-6 levels significantly amplified the association between greater social strain and higher future depressive symptoms over a nine-year period (d = 0.18, p = 0.003).
Cohort (n=1,054)
Yes
Do IL-6 levels moderate the associations between social support and strain with future MDD symptoms in community adults?
Elevated IL-6 levels exacerbate the risk of future depressive symptoms associated with social strain, highlighting a neuroimmune interaction in depression risk.
Effect estimate: d 0.18
p-value: p=0.003
Inflammation has been increasingly implicated in major depressive disorder (MDD), with interleukin-6 (IL-6) emerging as a key biomarker. How this relates to psychosocial risk factors, such as social support and strain, remains underexplored. IL-6 levels, social support, and strain may interact through shared underlying mechanisms in conferring depression risk. The study examined whether IL-6 levels moderate the associations between social support and strain with future MDD symptoms. Longitudinal data from 1,054 community adults in the Midlife Development in the United States (MIDUS) study were analyzed. Multiple linear regression models examined the main and interactive effects of social support, social strain, and IL-6 on future MDD symptoms. Serum IL-6 levels were measured using both ELISA and MSD immunoassays, with results cross-examined. Sensitivity analyses, including generalized additive models (GAM) and covariate-adjusted models, were conducted to account for potential nonlinearities and confounders. Lower social support and greater social strain predicted higher future MDD symptoms, particularly among individuals with elevated IL-6 levels. The interaction between social strain and IL-6 levels was robust across both ELISA ( d = 0.18, p = .003) and MSD-derived ( d = 0.12, p = .048) assay methods. In contrast, the interaction between social support and IL-6 was observed only in ELISA-based measurements ( d = -0.13, p = .033). IL-6 levels may moderate the relationship between social support, strain, and future MDD symptoms. Interpersonally-focused interventions enhancing social support or mitigating strain may consider the potential interacting role of inflammation in alleviating the psychosocial risk of depression. • IL-6 increases the 9-year social strain-to-depression link across assay methods. • Social support mitigates MDD severity risk at medium-to-high IL-6 levels. • The 9-year design detects interactions between inflammation and social strain. • MSD assays show independent impacts of both social strain and support. • IL-6 may moderate the risk of MDD via the HPA axis and neuroimmune pathways.
Aw et al. (Wed,) conducted a cohort in Major depressive disorder symptoms (n=1,054). Interleukin-6 (IL-6) levels, social support, and social strain was evaluated on Future MDD symptoms at Wave 2 (d 0.18, p=0.003). Elevated interleukin-6 levels significantly amplified the association between greater social strain and higher future depressive symptoms over a nine-year period (d = 0.18, p = 0.003).