Abstract :
This study examined whether the interaction between inflammatory genetic risk and serum interleukin-6 (IL-6) moderates the association between diet quality and depressive symptoms among community-dwelling older adults. A cross-sectional quantitative study was conducted among 486 community-dwelling adults aged 60 years and older. Diet quality was assessed using the Healthy Eating Index-2020 depressive symptoms were measured using the Patient Health Questionnaire-9 and inflammatory status was evaluated through serum IL-6 concentrations. A pro-inflammatory Genetic Risk Score was constructed using eight single-nucleotide polymorphisms within the IL6, TNF, CRP, and IL1B genes. Hierarchical multiple regression analyses were performed to examine the independent and interactive effects of diet quality, inflammatory genetic risk, and IL-6 while controlling for demographic and health-related covariates. Higher diet quality was significantly associated with lower depressive symptoms (? = ?0.24, p < .001). Serum IL-6 independently predicted depressive symptoms (? = 0.19, p < .001), while the interaction between diet quality and IL-6 was also significant (? = ?0.12, p = .008). Most importantly, the three-way interaction among HEI-2020, inflammatory GRS, and IL-6 significantly improved the prediction of depressive symptoms (?R² = .03, ? = ?0.16, p = .006). Simple-slope analyses demonstrated that the inverse association between diet quality and depressive symptoms was strongest among participants with high inflammatory genetic risk and elevated IL-6 levels (? = ?0.41, p < .001), whereas no significant association was observed among individuals with low genetic risk and low IL-6 levels (? = ?0.08, p = .31).The findings indicate that the mental health benefits of healthy dietary patterns differ according to an individual's inflammatory genetic susceptibility and inflammatory status. Gene–inflammation interaction significantly moderates the relationship between diet quality and depressive symptoms, highlighting the importance of integrating nutrigenomic and immunological biomarkers into precision nutrition and personalized public health strategies for the prevention and management of late-life depression.