Clear differences were observed in the relationship between depression and hs-CRP in men and women in the present study. Depression was significantly correlated with log-transformed hs-CRP concentrations in men, but not in women, in both primary and secondary analyses. Few studies have reported results separately for men and women, and results have been discrepant.20,23,36
Depression and elevated CRP concentrations were found to be more strongly associated in men than women in two large population-based studies.20,23
In a study of 6,914 US adults who participated in the Third National Health and Nutrition Survey (NHANES III), Ford et al.
found that major depression was strongly associated with increased CRP levels in men after controlling for obesity, but not in women.20
Similarly, this relationship was also observed in a study of 6,005 Finnish men and women in which the Beck Depression Inventory (BDI) and the Composite International Diagnostic Interview (CIDI) were used to assess a range of symptoms of depression and clinical depression, respectively.23
In contrast to our findings and others, Ma et al.
found that depression was associated with hs-CRP only in women, in a population-based study of 508 healthy adults living in Massachusetts.37
However, the authors failed to control for important confounding variables such as estrogen therapy and oral contraceptive use that may influence this relationship.
The mechanisms for sex-specific differences in the relationship between hs-CRP and depression are likely multifactorial, but it has been hypothesized that CRP levels may vary by hormonal environment.20
In women, menopausal status and estrogen replacement have been shown to impact adiposity38
which could potentially confound the relationship. Few women in the present study took hormone replacement therapy or oral contraceptive pills. Even when this subset was excluded, no relationship between depression and hs-CRP was observed in women. Gender may also influence CRP-related genetic variation, which has been found to moderate the association between depressive symptomatology and circulating CRP levels.39
Thus, it is possible that symptoms of depression might interact with genetic variation to predict the inflammatory marker differently in men and women.
The present investigation has several strengths. First, we performed a robust analysis that included important factors known to affect hs-CRP concentrations, including medications such as statins and anti-inflammatory therapies, estrogen use, and conditions associated with increased inflammation (such as diabetes and metabolic syndrome). Previous studies have failed to adjust for many of these confounding variables,37,40
which may explain why our findings differed from others. Second, our study population is generally representative of patients seen in the primary care setting and may be more generalizable than studies performed in specific clinical populations. For example, Dixon et al.
reported a positive association between depression and CRP in obese individuals with a BMI range of 31 to 91 kg/m2
, who presented for bariatric surgery.41
However, these individuals had a higher BMI and greater adiposity than obese individuals in the general population, which has significant effects on inflammation.8–10
This study also had several limitations. First, relatively few men participated in the study, compared to women. Despite the small number of males, the relationship between symptoms of depression and increasing hs-CRP remained significant in men. Second, our findings were based on cross-sectional data. Thus, the temporal relationship between hs-CRP and depression cannot be definitively established. Furthermore, CRP is an acute phase reactant and can vary considerably depending on the underlying inflammatory state at the time of measurement (i.e., infections, acute attack of gout). Thus, serial measurement of hs-CRP over time provides more clinically useful information than a single measurement and may have yielded a stronger relationship between hs-CRP and symptoms of depression. Finally, diagnoses of depression were made based on an 8-item questionnaire rather than by using a structured clinical interview (for the DSM-IV), the preferred method.
In summary, symptoms consistent with major depression were significantly associated with hs-CRP in men only, even after adjusting for age, obesity class, metabolic variables, and medications known to affect inflammation. This finding suggests that there are biologic differences between men and women that may modify the relationship between hs-CRP and depression. Further studies are needed to elucidate the biologic basis for these findings.