Association between C-reactive protein and depression: modulated by gender and mediated by body weight
Introduction
Depression is multifactorial and has been linked to multiple biological, physical, and behavioral factors (Ford and Erlinger, 2004, Lamers et al., 2013). Several lines of evidences emerged that depression might be associated with neuro-inflammation (Vogelzangs et al., 2012, Lamers et al., 2013), and recent research has specifically focused on the relationship between depression and C-reactive protein (CRP), interleukin-6, tumor necrosis factor-α (TNF-α) and other biological indicators of systematic inflammations (Vogelzangs et al., 2012); among them CRP being the most extensively examined (Vogelzangs et al., 2012). Different patterns of associations between depression and CRP have been identified in previous studies. Multiple and recurrent episodes of depression were consistently reported to be associated with elevated CRP level (Liukkonen et al., 2006, Copeland et al., 2012); lifetime diagnosis or presence of depression was also associated with high CRP from multiple studies (Ford and Erlinger, 2004, Vogelzangs et al., 2012), and high CRP was also observed among adult suffering from moderate to severe depression (De Berardis et al., 2008). However, the association of current episode of depression and CRP was detected only from one study (Liukkonen et al., 2006), and no relationship was also reported (Chaiton et al., 2010, Bjerkeset et al., 2011).
It is well documented that chronic medical illnesses are comorbid with depression (Manning and Jackson, 2013), and systematic inflammation is a part of pathophysiological changes of chronic medical illnesses (Jensen, 2008). Therefore, elevated CRP observed among depressed individuals might be the result of pre-existing medical illnesses, in particular, heart diseases, stroke and cancers (Kuo et al., 2005). However, majority of previous studies were not able to adequately control for this confounding effect largely because some of them were conducted in clinical settings (Rommel et al., 2013, Zahn et al., 2013) or with a relatively older study population (Baune et al., 2012, Hamer et al., 2012). In addition, several previous studies dichotomized the CRP level with a consumption of threshold-effect from CRP on depression (Ford and Erlinger, 2004, Chaiton et al., 2010). Inadequately adjusting for confounding effects from major medical illnesses and an inappropriate assumption of a threshold-effect may explain a part of inconsistency from previous studies. Gender is a well-established risk factor for mood disorders (Zhang et al., 2005, Quill, 2008) and CRP was higher in women compared with men (Lakoski et al., 2006, Laugsand et al., 2012, Morita and Okita, 2013). However, the gender difference has not yet been sufficiently addressed in previous studies, and residual confounding or moderating effects from gender remained a concern if gender was included as a simple covariate instead of a variable for stratification (Kuo et al., 2005, Howren et al., 2009, Zahn et al., 2013). To address these limitations, we analyzed the data from the latest releases of national survey with a relatively young population. The comparatively large sample size and comprehensive data made it possible to consider men and women separately, to control for the history of major medical illnesses, and to test the association without a presumption of a threshold effect.
Section snippets
Study participants
The NHANES, conducted by the U.S. Centers for Disease Control and Prevention, is a national survey designed to assess the health and nutritional status of adults and children in the United States. It began in the early 1960s, and has been conducted as a series of surveys to monitor the national trends of various health issues, from seroprevalence of herpes simplex virus, use of prescription Medications (Bertisch et al., 2014), to smoking behaviors. A unique feature of NHANES is that the
Results
The mean age of men and women was 46.17(SE: 0.38) years and 47.16(0.39) years (Table 1). On average, CRP was significantly higher among women than men, 0.45(0.01) vs. 0.32(0.01) mg/dL. The prevalence of minimal–mild and moderate–severe depression among women was 22.88% and 3.33%, both significantly higher than these among men, which were 15.88% and 1.62% respectively. Consistent with the national population profile, about 72% of men and women were non-Hispanic whites, and Mexican or other
Discussion
The major finding of the current study is that the association between CRP and depression was effect-modified by gender, and elevated CRP was strongly associated with depression among men but women. This is consistent with a recent study conducted among 390 participants with a BMI of 30–50 kg/m2 who were enrolled in a weight loss intervention trial in an obese clinical population (Vetter et al., 2013). What factors contributed to this gender variation remains controversy. The hormonal difference
Conclusions
The current study offers a new explanation for the inconsistent literature, insufficiently controlling for gender and body weight that might account for a part of the inconsistency. The current study also provides additional lines of evidence indicating that gender and abnormal body weight, major modifiable risk factors, are playing a critical role on the relationship between CRP and depression. Clarifying the neuro-inflammation pathways involved, examining the gender difference, and
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