Association of subsyndromal and depressive symptoms with inflammatory markers among different ethnic groups: The multi-ethnic study of atherosclerosis (MESA)

Abstract

Objective

Depressive symptoms are associated with inflammation yet the association between inflammation and different levels of depression remains unclear. Therefore, we studied the association of subsyndromal and depressive symptoms with inflammatory markers in a large multi-ethnic cohort.

Methods

C-reactive protein (CRP) (n=6269), interleukin-6 (IL-6) (n=6135) and tumor necrosis factor-alpha (TNF-α) (n=1830) were measured in selected participants from the multi-ethnic study of atherosclerosis (MESA). Subsyndromal depressive symptoms were defined as a CES-D value from 8 to 15, depressive symptoms as a CES-D≥16 and normal as a CES-D≤7. Depressive states (subsyndromal and depressed) were entered into multivariable linear regression models incrementally adjusting for demographic, behavioral, biologic and comorbidities.

Results

Among 6289 participants not taking antidepressants and free from CVD, the mean age was 62.2, while 52% were women, 36.4% were Caucasian, 28.9% African-American, 22.3% Hispanics and 12.4% Chinese-American. Of the total, 24.2% had subsyndromal depression and 11.8% had depressive symptoms. Compared to the non-depressed group and after controlling for demographics, there was no association between both subsyndromal and depressive symptoms with log CRP (β=−0.01, p=0.80 and β=−0.05, p=0.25 respectively), log IL-6 (β=0.01, p=0.71 and β=−0.04, p=0.07 respectively) and log TNF-α (β=−0.03, p=0.29 and β=0.06, p=0.18 respectively). Moreover, fully adjusted models showed no significant associations for log IL-6 and log TNF-α and the different depressive categories. However, with full adjustment, we found a significant inverse association between depressive symptoms and ln CRP (β=−0.10, p=0.01) that was not present for subsyndromal depression (β=−0.05, p=0.11).

Conclusion

Among participants not taking anti-depressants, subsyndromal depression is not associated with inflammation. However, depressive symptoms measured by CES-D≥16 are associated with a lower inflammation (CRP).

Introduction

For more than 5 decades, research has identified that inflammation and negative emotional states are recognized risk factors for the development of cardiovascular disease (CVD) (Amyre Morris et al., 2011, Libby and Ridker, 1999, Dinan, 2009, Musselman et al., 1998). Notably, depression is associated with inflammation among patients without CVD and studies have postulated that depression could be an inflammatory condition (Whooley et al., 2007, Dinan, 2009, Tiemeier et al., 2003, Kop et al., 2002, Maes et al., 2009, Camacho, 2013). For instance, in the Third National Health and Nutrition Examination Survey (NHANES), men with a history of major depression had a 2.77 higher adjusted odds (95% CI; 1.43–5.26) of elevated C-reactive protein compared to controls (Danner et al., 2003).

Subsyndromal depression is a condition where depressive symptoms are present, yet the full criteria for a major depressive episode have not been met. Subsyndromal depression affects 15–20% of patients older than 65 years, is undertreated and frequently associated with functional disability and chronic medical conditions comparable to major depressive disorder (Judd et al., 2002, Vahia et al., 2010, VanItallie, 2005, Bruce, 2010). Subsyndromal depressive symptoms are measured categorically by lowering the established cut-off point from validated scales that screen for depression, such as the center for epidemiologic scale for depression (CES-D) (Vahia et al., 2010). For example, subsyndromal depressive states have scores between 8 and 16 in the CES-D scale (Vahia et al., 2010). Other studies report that subsyndromal depression could also be defined by the presence of only one or two symptoms of depression (Vahia et al., 2010, Judd et al., 2002). Furthermore, the core symptoms required to diagnose a major depressive episode, which are depressed mood and anhedonia, are not required to define subsyndromal depression (Vahia et al., 2010, American Psychiatric Association, 2000).

To understand the association of different depressive states with chronic medical conditions such as cardiovascular disease, studies have examined the role of inflammation as a possible common pathway (Ranjit et al., 2007, Ross, 1999). Proinflamatory cytokines and acute phase proteins, such as CRP, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), are higher among individuals with depressive states and cardiovascular disease (Liukkonen et al., 2006, Amyre Morris et al., 2011, Matthews et al., 2007), although results are inconsistent. Even though the literature has frequently reported an association between depression and inflammation (Dinan, 2009, Amyre Morris et al., 2011, Miller et al., 2009), several studies found no associations between depression and inflammation (Whooley et al., 2007, Janszky et al., 2005, Schins et al., 2005). Different methodological approaches for defining depression (depressive symptoms/states vs. major depressive disorder) might account for the different results (Steptoe et al., 2003, Amyre Morris et al., 2011, Matthews et al., 2007, Whooley et al., 2007).

In the current study, we tested the hypothesis that compared to individuals with no depressive symptoms, depressive states (subsyndromal and depressive symptoms) are associated with selected inflammatory markers among individuals from different ethnic groups participating in a large epidemiologic study. To our knowledge, this is the first study that looks at the association of subsyndromal depression with inflammatory markers in a large ethnically diverse cohort.