Common Genetic Contributions to Depressive Symptoms and Inflammatory Markers in Middle-Aged Men: The Twins Heart Study

Abstract

Objective: To examine the extent to which a common genetic pathway is also involved in the relationship between depressive symptoms, in the absence of major depressive disorder (MDD), and inflammation. Recent data suggested that MDD and inflammation share common genes. Methods: We recruited 188 male twins from the Vietnam Era Twin Registry who were free of symptomatic coronary artery disease and MDD, with mean ± standard deviation (SD) age of 55 ± 2.75 years, including 54 monozygotic and 40 dizygotic twin pairs. These pairs were assessed for two inflammatory markers, interleukin (IL)-6 and C-reactive protein (CRP). Current depressive symptoms were measured with the Beck Depression Inventory-II. Generalized estimating equations were used to examine the phenotypic association between depression and inflammatory markers. Biometrical genetic modeling was performed to estimate the genetic and environmental contributions to this association. Results: An association was observed between severity of current depressive symptoms and increased levels of inflammatory markers (p < .001 for IL-6 and p = .005 for CRP). After adjustment for other factors, the association was slightly attenuated but remained statistically significant for IL-6 (p = .002). The heritability of IL-6, CRP, and depressive symptoms were estimated as 0.37, 0.65, and 0.48, respectively. Genetic modeling found a significant genetic correlation between IL-6 and depressive symptoms (r_G = 0.22, p = .046), indicating that about 66% of the covariance between them can be explained by shared genetic influences. Conclusions: Current depressive symptoms are significantly correlated with inflammatory markers. This covariation is due, in large part, to genes that are common to depressive symptoms and inflammation. CAD = coronary artery disease; MDD = major depressive disorder; IL-6 = interleukin-6; CRP = C-reactive protein; THS = Twins Heart Study; VET = Vietnam Era Twin; MZ = monozygotic; DZ = dizygotic; HDL-C = high-density lipoprotein cholesterol; LDL-C = low-density lipoprotein cholesterol; WHR = waist-hip ratio; BDI-II = Beck Depression Inventory-II; GEE = generalized estimating equation; AIC = Akaike's information criterion; CRH = corticotrophin-releasing hormone; HPA = hypothalamic-pituitary-adrenal; SD = standard deviation; Ln = logarithm transformation; CI = Confidence Interval; −2LL = −2×Log (Likelihood).