Elsevier

Brain, Behavior, and Immunity

Volume 41, October 2014, Pages 101-108
Brain, Behavior, and Immunity

Race/ethnicity moderates the relationship between depressive symptom severity and C-reactive protein: 2005–2010 NHANES data

https://doi.org/10.1016/j.bbi.2014.04.004Get rights and content

Abstract

Because few studies have examined depression facets or potential moderators of the depression–inflammation relationship, our aims were to determine whether particular depressive symptom clusters are more strongly associated with C-reactive protein (CRP) levels and whether race/ethnicity moderates these relationships. We examined data from 10,149 adults representative of the U.S. population (4858 non-Hispanic White, 1978 non-Hispanic Black, 2260 Mexican American, 1053 Other Hispanic) who participated in the cross-sectional National Health and Nutrition Examination Survey between 2005 and 2010. Depressive symptoms were assessed by the Patient Health Questionnaire-9, and high-sensitivity serum CRP was quantified by latex-enhanced nephelometry. Total (p < .001), somatic (p < .001), and nonsomatic (p = .001) depressive symptoms were each positively related to serum CRP in individual models. However, in the simultaneous model that included both symptom clusters, somatic symptoms (p < .001), but not nonsomatic symptoms (p = .98), remained associated with serum CRP. Evidence of moderation by race/ethnicity was also observed, as six of the nine depressive symptoms × race/ethnicity interactions were significant (ps < .05). Among non-Hispanic Whites, the pattern of results was identical to the full sample; only somatic symptoms (p < .001) remained related to serum CRP in the simultaneous model. No relationships between total, somatic, or nonsomatic symptoms and serum CRP were observed among the non-Hispanic Black, Mexican American, or Other Hispanic groups. Our findings indicate that the link between depressive symptoms and systemic inflammation may be due to the somatic symptoms of sleep disturbance, fatigue, appetite changes, and psychomotor retardation/agitation and may be strongest among non-Hispanic Whites.

Introduction

Considerable evidence suggests that depression is an independent risk factor for atherosclerotic cardiovascular disease (CVD), including coronary artery disease and cerebrovascular disease (Van der Kooy et al., 2007). The longitudinal relationship between depression and incident CVD is consistent, as it has been observed in both genders and in various age and racial/ethnic groups (Rosengren et al., 2004, Van der Kooy et al., 2007). Because depression is a multidimensional construct or disorder composed of affective, cognitive, behavioral, and somatic symptoms (Davidson et al., 2005), recent investigations have compared the relative importance of these symptom clusters in predicting CVD risk. Findings of these studies have been contradictory; some investigators have reported that the somatic symptoms are stronger predictors of CVD risk markers or outcomes (Deverts et al., 2010, Stewart et al., 2007, Stewart et al., 2009), whereas others have observed similar results for the affective and cognitive symptoms (Everson et al., 1996, Kubzansky et al., 2001, Matthews et al., 2004, Stewart et al., 2012). Consequently, whether or not certain depressive symptoms clusters are more cardiotoxic than others remains an open question.

Systemic inflammation is one mechanism that might explain how depression promotes the development of CVD (Kop and Gottdiener, 2005). A recent meta-analysis revealed that various inflammatory markers – i.e., the proinflammatory cytokines, interleukin (IL)-1 and IL-6, and the acute phase reactant, C-reactive protein (CRP) – are upregulated in individuals with depressive disorders or elevated symptoms, although substantial heterogeneity was observed across studies (Howren et al., 2009). In addition, some investigations (Boyle et al., 2007, Stewart et al., 2009), but not all (Gimeno et al., 2009, Kiecolt-Glaser et al., 2003), have found that depression predicts increases in inflammatory marker levels over periods of up to 10 years. Notably, systemic inflammation is thought to play a role in all phases of atherosclerosis (Epstein and Ross, 1999), and several of the inflammatory markers elevated in depression, such as CRP, are predictive of incident CVD after adjustment for conventional cardiovascular risk factors (Kaptoge et al., 2012).

Despite the substantial literature on the depression–inflammation relationship, only four studies have examined whether the strength of this association varies across depressive symptom clusters. In a sample of 263 healthy, older adults most of whom were non-Hispanic White, we found that the somatic-vegetative symptoms of depression, but not cognitive-affective symptoms, predicted increases in IL-6 over six years (Stewart et al., 2009). Neither symptom cluster, however, predicted 6-year change in CRP. In a sample of 2544 healthy, middle-aged adults over 40% of whom were non-Hispanic Black, Deverts et al. (2010) observed that race moderated the prospective association between depressive symptoms and CRP. Among non-Hispanic Blacks, the somatic and positive affect subscales of the depression measure, but not depressed affect and interpersonal problems subscales, were independent predictors of 5-year increases in CRP. In contrast, none of the symptom clusters predicted change in CRP among non-Hispanic Whites. In a population-based sample of 5000 adults aged 35–74 years, Michal and colleagues (2013) found that only somatic depressive symptoms were cross-sectionally associated with various inflammatory markers, including CRP, in age- and sex-adjusted analyses. These relationships, however, did not persist after further adjustment for traditional CVD risk factors. Finally, Duivis et al. (2013) recently reported that, after adjustment for demographic and health factors, the somatic but not the cognitive symptoms were positively related to CRP, IL-6, and tumor necrosis factor-α levels in 2861 Dutch community members aged 18–65 years. Collectively, the available results suggest that the somatic symptoms may be more strongly related to systemic inflammation than other depressive symptom clusters; however, the small number of studies still renders this a tenuous conclusion. In addition, the intriguing findings of Deverts et al. (2010) highlight the need for additional studies examining race/ethnicity as a potential moderator of the depression–inflammation relationship.

Accordingly, the aims of the present study were (1) to determine whether particular depressive symptom clusters are more strongly associated with serum CRP, a nonspecific marker of systemic inflammation predictive of incident CVD (Pearson et al., 2003), and (2) to test whether race/ethnicity is a moderator of the depression–CRP relationship. To achieve these aims, we examined data from a large sample of adults, representative of the U.S. population, who participated in cross-sectional National Health and Nutrition Examination Survey (NHANES) between 2005 and 2010. These survey years provided a good opportunity to accomplish our aims because most of the respondents completed a multidimensional measure of depressive symptoms and underwent a blood draw to quantify high-sensitivity serum CRP. Furthermore, the 2005–2010 sample consists of large numbers of individuals of African American and Latino descent.

Section snippets

Study design and sample

We examined cross-sectional data from the 2005–2010 NHANES survey years. These data were collected by the National Center for Health Statistics of the Centers for Disease Control and Prevention from a nationally representative sample of civilian, non-institutionalized adults and children to assess the health and nutritional status of the U.S. population. Detailed descriptions of the survey design (a stratified, multistage, probability sample) and procedures are available at the study website (//www.cdc.gov/nchs/nhanes.htm

Descriptive statistics and correlations

The mean PHQ-9 Total score for the full sample and each race/ethnicity group (see Table 1) fell in the minimal depression range; however, 645 (6.4%) respondents had a score (⩾10) indicative of clinically significant depressive symptoms (Kroenke et al., 2001). One-way ANOVAs revealed that the PHQ-9 Total score [F (3, 10,145) = 4.55, p = .003] and Nonsomatic score [F (3, 10,145) = 8.30, p < .001] differed across the racial/ethnic groups, with the Other Hispanic group having a higher Total mean than the

Discussion

In a large sample of adults representative of the U.S. population, we found that the cross-sectional relationship between depressive symptom severity and high-sensitivity serum CRP was largely due to the somatic symptoms of depression. The PHQ-9 Somatic and Nonsomatic scores were both positively related to CRP levels in individual models, with effect sizes falling in the small range. Only the somatic score, however, remained associated in the simultaneous model that included both symptom

Conclusions

In summary, we found that the relationship between depressive symptom severity and serum CRP was largely due to the somatic symptoms (sleep disturbance, fatigue, appetite changes, and psychomotor retardation/agitation) and was moderated by race-ethnicity (associations were observed only among non-Hispanic Whites). Our findings raise three intriguing, albeit speculative, possibilities worthy of evaluation in future studies. One, the somatic depressive symptoms may be more predictive of future

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