Objective: Proinflamatory biomarkers such as C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) have been linked to the pathophysiology of depression. Depressive states encompass affective (both negative & positive affect) and somatic symptoms. The association of affective and somatic factors of depression with inflammation has not been examined in a multi-ethnic cohort.
Methods: Data were derived from 6,818 participants aged 45-84 years from the Multi-Ethnic Study of Atherosclerosis (MESA).Depressive symptoms, as measured by the Center for Epidemiologic Studies Depression Scale (CES-D), and inflammatory markers (i.e., CRP, IL-6 and TNF-α) were collected from visit 1 from the MESA cohort. Inflammatory markers were log-transformed to reduce skewness. A confirmatory factor analysis supported a 3-factor model of the CES-D comprised of: somatic symptoms (poor appetite, could not get going, poor sleep, excessive effort, trouble concentrating), negative affect (feeling blue, depressed, crying spells, sadness, felt like a failure, fearful and lonely), and positive affect (feeling happy, good, hopeful, enjoy life). In cross-sectional analyses, structural equation modeling (SEM) was performed to examine the associations between affective and somatic latent variables of the CES-D with the inflammatory biomarkers (CRP, IL-6 and TNF-α) after controlling for age, gender, ethnicity, BMI, lipids, systolic blood pressure, smoking, alcohol use, physical activity, diabetes, lipid-lowering medications and antihypertensives.
Results: The mean age was 62.15 (SD=1.23) and mean CES-D score was 7.57 (SD=7.59). The 3-factor model of the CES-D exhibited good fit with root mean square-error of approximation <0.05 and standardized root mean square residual <0.07. In the fully adjusted models, the SEM showed a significant association between the somatic factor and IL-6 (β=0.18;p<0.01)and TNF-α (β=0.21;p=0.006) but not CRP (β=-0.12; p=0.16). The negative affect factor was significantly associated with IL-6 (β=0.05;p=0.006), CRP (β=0.04; p=0.03) but not with TNF-α (β=-0.02;p=0.18), while the positive factor was significantly associated with IL-6 (β=0.20;p=0.006), CRP (β=0.65;p<0.001) and TNF-α (β=-0.17;p=0.01).
Conclusion: This cross-sectional study showed that inflammatory markers are significantly associated with somatic and both positive and affective factors of depressive symptomatology in a multi-ethnic cohort.