Psychosomatic Medicine Tips for Better Browsing
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Figures Only
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Danner, M.
Right arrow Articles by Vaccarino, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Danner, M.
Right arrow Articles by Vaccarino, V.
Related Collections
Right arrow Coronary Artery Disease
Right arrow Other Cardiovascular Medicine
Right arrow Other Epidemiology
Right arrow Immunology
Right arrow Depression
Psychosomatic Medicine 65:347-356 (2003)
© 2003 American Psychosomatic Society

ORIGINAL ARTICLES

Association Between Depression and Elevated C-Reactive Protein

Marion Danner, MPH, Stanislav V. Kasl, PhD, Jerome L. Abramson, PhD and Viola Vaccarino, MD, PhD

From the Department of Medicine, Division of Cardiology, Emory University School of Medicine (V.V., J.L.A.), Atlanta, Georgia; and the Department of Epidemiology and Public Health, Yale University School of Medicine (M.D., S.V.K.), New Haven, Connecticut.

Address reprint requests to: Viola Vaccarino, MD, PhD, Emory University School of Medicine, Department of Medicine, Division of Cardiology, 1256 Briarcliff Road, Suite 1 North, Atlanta, GA 30306. Email: lvaccar{at}emory.edu


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
OBJECTIVE: Depression has been related to a higher risk of developing coronary heart disease, but the mechanism that accounts for this association is unclear. Because atherosclerosis is an inflammatory process, depression could increase the risk of coronary heart disease by inducing or promoting inflammation. The objective of the present study was to investigate the association between history of major depressive episode and presence of low-grade systemic inflammation as measured by serum C-reactive protein (CRP).

METHODS: We analyzed data from the Third National Health and Nutrition Examination Survey, a representative sample of the US population from 1988 to 1994. Participants included a total of 6149 individuals aged 17 to 39 years who were free of cardiovascular diseases and chronic inflammatory conditions. The main predictor variable of interest was lifetime history of a major depressive episode as assessed by means of the Diagnostic Interview Schedule. The main outcome variable was the presence or absence of an elevated CRP level (>=22 mg/dl).

RESULTS: Among men, history of a major depressive episode was associated with elevated CRP, particularly for recent episodes (up to 6 months before assessment). In multivariate analyses, men with a history of major depressive episode had 2.77 times higher odds of elevated CRP compared with never-depressed men (95% confidence interval, 1.43–5.26). The adjusted odds ratio was 3.81, 3.98, 1.51, and 1.52 for men who had their last major depressive episode less than 1 month before, 1 to 6 months before, 7 to 12 months before, and more than 12 months before assessment, respectively (p for trend = .004). In women, a comparable association between depression and CRP was quite weak and not significant.

CONCLUSIONS: A recent history of major depressive episode is strongly associated with elevated CRP in men aged 17 to 39. In this group, low-grade systemic inflammation could represent a mechanism linking depression to cardiovascular risk.

Key Words: depression, • inflammation, • epidemiology, • risk factors, • population studies.

Abbreviations: CHD = coronary heart disease;; CRP = C-reactive protein;; DIS = Diagnostic Interview Schedule;; DSM = Diagnostic and Statistical Manual of Mental Disorders;; HDL = high-density lipoprotein;; MEC = mobile examination center;; NHANES III = Third National Health and Nutrition Examination Survey.


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Major depressive disorder is a highly prevalent disease in the United States and has been associated with all-cause and especially cardiovascular morbidity and mortality (1–6). A host of studies indicate that depression is related to a higher incidence of cardiovascular events and mortality in patients with cardiac disease (7–14) as well as to a higher incidence of fatal and nonfatal cardiovascular events in individuals initially free of cardiovascular diseases (9, 15–24). However, the mechanisms underlying the association between depression and cardiovascular diseases have not been established.

Growing evidence suggests that atherosclerosis is fundamentally an inflammatory disease (25) and that inflammatory markers are powerful predictors of coronary heart disease (CHD) events (26–32). Therefore, it would be reasonable to argue that the link between depression and CHD might be mediated by inflammation. In support of this argument, some studies have reported that depression is associated with higher levels of C-reactive protein (CRP) (33–37), a marker of systemic inflammation that has been shown consistently to predict CHD risk (26–30). However, these previous studies of depression and CRP have been limited to selected clinical samples and/or have failed to control for important confounding factors. To clarify the association between depression and CRP, studies based on wider population samples with more extensive control of confounding factors are needed.

The primary objective of the present study was to investigate the association between history of major depressive episodes and the presence of a low-grade systemic inflammation as measured by serum CRP levels in a sample of 6149 persons who took part in the Third National Health and Nutrition Examination Survey (NHANES III). We hypothesized that after adjustment for confounding factors, individuals with a history of major depressive episodes would be more likely to have elevated CRP compared with individuals without such a history and that the more recent the last depressive episode, the higher the probability of elevated CRP. We also examined whether an association between depressive symptoms and CRP could be found in the absence of major depressive episodes.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Study Population
Details of the NHANES III survey methods have been previously described (38, 39). Briefly, the survey was based on a complex multistage, clustered population sample with oversampling of certain subgroups, such as African and Mexican Americans. Data were collected by means of face-to-face interviews, physical examinations in a mobile examination center (MEC), and laboratory analyses. In the MEC, adults aged 17 to 39 years were also administered the depression and mania subsections of the Diagnostic Interview Schedule (DIS) developed by the National Institute of Mental Health in 1981 (40). The DIS was designed to allow trained lay interviewers to obtain reliable psychiatric diagnoses according to the Diagnostic and Statistical Manual of Mental Disorders, revised third edition (DSM-III-R) (41). The DIS has been shown to be a valid instrument for the diagnosis of major depression (42) and has been used in numerous large population studies (43–46).

Of the 7681 individuals aged 17 to 39 who received the DIS in NHANES III, we excluded pregnant women (N = 321, 4.2%), individuals whose interviews were coded as unreliable by the NHANES III file documentation (N = 9, 0.1%), and individuals with missing information on CRP (N = 458, 6.0%). Comparison of characteristics between subjects with and without missing data showed only minor differences. Persons with missing CRP tended to be more often white, more likely to have a normal body mass index (<25 kg/m2), and less often users of birth control pills. There were no significant differences in other risk factors or in previous history of major depressive episode. Individuals with diseases that are known to influence CRP (cardiovascular diseases, diabetes, and chronic inflammatory diseases) (40, 47–50) were also excluded (N = 744). Exclusion of persons with cardiovascular diseases was based on self-reported information of prior stroke, myocardial infarction, or angina using standard questions for population surveys, including the Rose Questionnaire (51). The latter has been shown to have a sensitivity of 82% and a specificity of 100% when compared with a diagnosis of angina pectoris performed by two independent physicians (52); it is a strong predictor of fatal and nonfatal CHD (53–55), and it is associated with standard CHD risk factors and carotid intima-media thickness measured by B-mode ultrasound (56). Exclusion of persons with diabetes mellitus was based on self-reported diabetes as well as on a fasting plasma glucose greater than or equal to 126 mg/dl (7.0 mmol/liter) (57). Exclusions resulting from chronic inflammatory disorders were based on self-reported recent diagnosis of one of the following: chronic bronchitis, asthma, emphysema, or rheumatoid arthritis. Finally, we excluded 49 persons with a history of bipolar disorder. After these exclusions, 6100 persons were included in this study.

Study Variables
Serum CRP was measured with a latex-enhanced Behring Nephelometer Analyzer System. The coefficient of variation was between 3.2% and 16.1% throughout the period of data collection. This system was able to detect a minimal CRP concentration of 0.22 mg/dl. Because most persons had values less than this minimum detectable concentration, CRP was treated as a categorical rather than a continuous variable and dichotomized into either undetectable (<0.22 mg/dl) or elevated (>=0.22 mg/dl) consistent with previous work (58). Because only 5% of the women and 2% of the men had clinically raised CRP according to the conventional clinical cutoff point for inflammation (>1.00 mg/dl), this level was not considered as a separate category. Therefore, elevated levels of CRP (>=0.22 mg/dl) in this study are mostly indicative of a subtle and persistent increase in systemic inflammation, a response that has been linked to cardiovascular risk (27, 30, 59, 60).

Depression was assessed by means of the DIS (40), which yields clinical diagnoses of major depression and major depressive episodes based on DSM-III-R (41).

Race-ethnicity was self-reported as non-Hispanic white, non-Hispanic black, or Mexican American, representing the three major ethnic groups in NHANES III. People outside these categories were classified as "other." Body mass index was computed as weight in kilograms divided by the square of standing height in meters (kg/m2) and was categorized as normal (<25 kg/m2), overweight (25 to <30 kg/m2), or obese (30 kg/m2 or above) (61). Participants were classified into current, former, and never smokers based on self-reported information on smoking patterns. Irrespective of self-report, individuals with a serum cotinine concentration greater than 57 nmol/liter (62) were classified as current smokers. A small proportion of individuals (4.9%) who classified themselves as nonsmokers were, in fact, smokers according to cotinine values. Education was categorized into less than high school (<12 years of education), high school degree (12 years), and at least some college (>12 years). Women were classified as being contraception users if they reported current use of birth control pills or contraceptive implant and as hormone replacement users if they reported current use of estrogens or other female hormone treatment. The presence of acute infection or inflammation was based on a positive answer to the question, "In the past few days have you had a cough, cold, or other acute illness?" or on the examining physicians’ diagnosis of a possible active infection. Use of antidepressants in the past month was self-reported. Total serum cholesterol was categorized as <200 mg/dl, 200 to 239 mg/dl, and >=240 mg/dl. High-density lipoprotein cholesterol was categorized as <35 mg/dl, 35 to 60 mg/dl, and >60 mg/dl (63). Hypertension was defined as a systolic blood pressure of >=140 mm Hg, a diastolic blood pressure of >=90 mm Hg, or the current use of antihypertensive medication.

Statistical Analyses
The first step in the analysis was to calculate the proportion of individuals with elevated CRP according to depression and other important sample characteristics. Differences in proportions were tested with chi-square statistics, and Mantel tests for trend were performed for ordinal variables with more than two levels. Two-sided p values were always generated. Consistent with previous studies of depression and CHD (18), our main predictor was lifetime history of major depressive episode. In our main analyses, this definition included a small number of individuals in whom a major depressive episode was related to bereavement (N = 58). We examined the association between depression and CRP with depression as a dichotomous variable (ever had major depressive episode vs. never had major depressive episode). Additionally, to investigate whether the presence of elevated CRP levels depended on how recently the last major depressive episode had occurred, we constructed a series of dummy variables indicating the time since the last major depressive episode (<1 month, 1–6 months, 7–12 months, >12 months, and never had one). A Mantel test for trend was performed to determine whether the prevalence of elevated CRP differed according to the levels of this variable. The percentages were weighted to represent the total civilian, noninstitutionalized US population and, therefore, are population prevalence estimates.

The multivariate association between a major depressive episode and elevated CRP was examined by means of logistic regression models, which were adjusted for all the variables listed in Table 1. Odds ratios and 95% confidence intervals (CIs) were calculated with the never-depressed individuals used as the reference category. Because the prevalence of elevated CRP was above 10%, odds ratios do not approximate risk ratios and should not be interpreted as risk ratios in this study. The use of antidepressant medications was included among the adjustment factors because both positive (64, 65) and negative (66–68) effects have been described with the use of these drugs in relation to cardiovascular disease and because antidepressant use can reduce CRP levels irrespective of response to therapy (69). However, because of a concern of overadjustment, we repeated the analyses after excluding this variable from the multivariable models. These analyses, however, yielded very similar results and therefore are omitted from this report.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Proportion of Individuals With Elevated CRP According to Sample Characteristics (Based on Unweighted Counts)
 
Additional analyses were performed to determine whether the inclusion of the following variables in the model, in addition to the variables listed in Table 1, would change the study results: glucose levels, use of antiinflammatory drugs, and physical activity. Because of a potential link between depression and diabetes, possibly due to the effects of catecholamine and serotonin levels on glucose control (70), and because fasting glucose and insulin levels are associated with CRP even in the absence of diabetes (71), it is possible that depression might influence CRP by influencing glucose levels in absence of overt diabetes. In this analysis, fasting blood glucose was added to the models as a continuous variable. Regarding the use of antiinflammatory drugs, the adult NHANES III questionnaire contains a question about whether, in the past month, the responder took nonsteroid antiinflammatory medications such as ibuprofen. A variable indicator of the use of any of these medications was included in the model. Finally, we considered the impact of physical activity in our analysis because higher levels of physical activity have been associated with lower concentrations of inflammatory markers, including CRP (72, 73). We constructed a three-level variable indicator of the total number of times that a participant engaged in any leisure-time physical activity in the month before the household interview: 0 to 3 times per month, 4 to 21 times per month, and 22 or more times per month (73).

Analyses were conducted in SUDAAN (74), which incorporates sampling weights to account for oversampling and nonresponse. Variance estimation in SUDAAN allowed for the complex sampling design of NHANES III (75). All analyses were conducted separately by gender, given the important gender differences in the prevalence of depression (76) and elevated CRP (58) as well as gender differences in the strength of the association between depression and CHD (16, 19, 77).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Elevated values of CRP (>=0.22 mg/dl) were found in 13.29% of men (N = 474) and 24.5% of women (N = 925). As expected, higher body mass index and acute inflammatory conditions were associated with a higher prevalence of elevated CRP in both men and women. Older age and smoking status were associated with CRP levels in men (Table 1). Race-ethnicity was also associated with the prevalence of elevated CRP, with non-Hispanic whites having the lowest prevalence and African Americans the highest prevalence. Hypertension and lower levels of HDL cholesterol tended to be associated with a higher likelihood of elevated CRP.

History of a major depressive episode was present in 134 men (5.2%) and 324 women (10.6%). Men with a history of a major depressive episode were about twice as likely to have elevated CRP compared with men without a history of depression: 24.0% vs. 12.6% (unadjusted odds ratio, 2.17; 95% CI, 1.81–4.00). No association between history of a major depressive episode and elevated CRP, however, was found in women (Tables 1 and 2).


View this table:
[in this window]
[in a new window]
  		TABLE 2. Proportion of Individuals With a History of Major Depression According to Sample Characteristics (Based on Unweighted Counts)
 
Few significant associations were found comparing sociodemographic characteristics and other factors according to history of major depressive episode (Table 2). In men, history of major depressive episode was inversely related to total serum cholesterol levels, whereas in women it was significantly related to older age, race/ethnicity (being more prevalent in non-Hispanic white women), and hypertension. A correlation matrix involving all the variables under study showed that the highest correlation was between age and total cholesterol in men (r = 0.32) and between elevated CRP and body mass index in women (r = 0.37). Other variables showing relatively strong correlations were, in men, age and education (r = 0.26), smoking status and education (r = -0.24), high-density lipoprotein (HDL) cholesterol and body mass index (r = -0.24), and age and body mass index (r = 0.21). In women, they were HDL cholesterol and body mass index (r = -0.29), age and use of contraception (r = -0.27), and total cholesterol and body mass index (r = 0.26). All the other correlations had a correlation coefficient less than <=0.20.

In men, the prevalence of elevated CRP was related to the time of the occurrence of the last major depressive episode (Table 3 and Fig. 1). About one third of the men who reported a major depressive episode within the past month or between 1 and 6 months had an elevated CRP. If the major depressive episode occurred more than 6 months before, however, the prevalence of elevated CRP was considerably lower and close to the levels of men with no history of depression. These associations were not weakened in multivariable analyses that adjusted for all the variables listed in Table 1 (Table 3). The overall adjusted odds ratio was 2.77 comparing men with a history of major depressive episode to those who had never been depressed (95% CI, 1.43–5.26).


View this table:
[in this window]
[in a new window]
  		TABLE 3. Association Between Major Depressive Episode and Elevated CRP (>=0.22 mg/dl) in Men Before and After Adjusting for Study Variablesa
 


View larger version (23K):
[in this window]
[in a new window]
  		Fig. 1. Prevalence of elevated C-reactive protein (>=0.22 mg/dl) by sex and depression category.

 
Similar results were not observed in women (Fig. 1 and Table 4) with the possible exception of women who had had a major depressive episode within the past month. The latter had a nonsignificantly higher probability of elevated CRP compared with their nondepressed counterparts that did not persist in multivariable analysis.


View this table:
[in this window]
[in a new window]
  		TABLE 4. Association Between Major Depressive Episode and Elevated CRP (>=0.22 mg/dl) in Women Before and After Adjusting for Study Variablesa
 
To address the possibility that fasting plasma glucose could play a role in our results, analyses were repeated with fasting glucose added to the model. These analyses, however, yielded similar results, indicating that glucose levels do not explain the relationship between depression and CRP in our data. When we adjusted for use of nonsteroid antiinflammatory drugs, these analyses also yielded results that were similar to those reported above. Similarly, level of leisure-time physical activity did not seem to play a role in our findings. When this variable was added to the model, the association between depressive episode in the past month and elevated CRP actually became slightly stronger among men.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
This is the first population-based study to clearly demonstrate an association between depression and serum CRP levels in men. In particular, we found that compared with men with no history of depression, men reporting a history of a major depressive episode had significantly higher odds of having elevated CRP levels after adjustment for a number of other factors. Furthermore, we found evidence that the more recent the depressive episode in men, the higher the odds of having an elevated CRP level. In contrast to the results for men, we failed to find that depression was significantly related to CRP levels in women.

Previous studies investigating the association between depression and CRP were conducted mostly in clinical populations (33–37). Many of these studies have suggested that depression promotes systemic inflammation and increases plasma levels of inflammatory cytokines such as interleukin-6 (IL-6) (34, 36, 37, 78) as well as a number of acute-phase proteins such as CRP (34–36). Reported results, however, have not been entirely consistent. Rothermundt et al. (79) found that {alpha}2-macroglobulin and monocyte counts, but not CRP, were increased in patients with nonmelancholic depression compared with control subjects and that none of these inflammatory markers was elevated in patients with melancholic depression. Most of the patients studied (86%), however, were receiving pharmacological treatment for depression. Lanquillon et al. (69) found that although pretreatment CRP levels were significantly elevated in patients with major depressive disorder compared with control subjects, antidepressive treatment decreased these values to levels similar to those of control subjects irrespective of response to treatment.

Many of these previous reports were limited by small sample sizes, selected samples, and/or failure to control for important confounding variables. By using a broad, population-based sample and by controlling extensively for potential confounding factors, the present study provides the strongest evidence to date of an association between depression and an increase in systemic inflammation. A particular strength of our study is the fact that our population was composed of young individuals, aged 17 to 39 years. In this group, the prevalence of clinical and subclinical disease can be expected to be very low; therefore, confounding by unmeasured disease status should be minimal in our results.

Depression might promote an inflammatory response by activating the immune response (80). Alternatively, the effects of depression on inflammation might be due to its links to psychological stress (81–83). The latter has also been associated with excessive production of IL-6 (36, 78, 80, 84). IL-6 and IL-1ß synergistically induce a systemic immune response. IL-6 is also the main proinflammatory cytokine inducing synthesis of type 1 acute-phase proteins such as CRP. Psychological stress has been shown to increase oxidative state (85–89), which in turn, through modified lipids and lipoproteins, is thought to initiate an inflammatory response in the artery wall (85, 86) . It may also be that depression leads to higher CRP levels, but that it does so through some indirect, nonbiological mechanism such as a health behavior. For example, depression may lead to higher smoking levels, which in turn would lead to higher CRP levels. Our finding in men was adjusted for smoking, so it seems unlikely that smoking could explain the association we observed, but we cannot rule out that it was due to some other intervening factor.

Low-grade systemic inflammation may play a role in the initiation and progression of atherosclerosis, plaque destabilization, or thrombosis (59, 90). Atherosclerosis itself is now recognized to be predominantly an inflammatory process (25). Consistent with this view, in recent epidemiological studies serum markers of inflammation have come to the fore as important indicators of cardiovascular risk in both individuals with established coronary heart disease (31, 32, 91) and in individuals initially free of the disease (26, 27, 29). CRP, in particular, has been proposed as a potential candidate for coronary risk screening (92, 93).

In general, there is little doubt that the link between CRP and CHD is a chronic inflammatory state that predisposes to atherosclerosis and to plaque rupture (93). For example, recent studies have shown that CRP predicts coronary events only among patients not pretreated with aspirin (94); conversely, aspirin reduces coronary event rates only among individuals with CRP in the highest quartile (27). However, the exact role of CRP in the pathogenesis of atherosclerosis is not clear. CRP could be only a marker of inflammation with no direct role in the pathogenesis of atherosclerosis. A direct proinflammatory effect of CRP on the endothelium, however, has been described (90), as has an ability of CRP to induce the production of tissue factor, a potent procoagulant, in monocytes (95). Whatever the exact role of CRP in inflammation, the results of our study suggest that in men, the link between depression and higher CHD risk may be mediated by a depression-induced increase in inflammation (1–6).

An intriguing finding of our study is that an association between depressive episodes and CRP was found in men but not in women. One possible explanation is that women, particularly if premenopausal, are protected from the pathophysiological consequences of psychological stress because of their estrogen levels (96, 97). However, estrogen has complex effects on inflammation, including both antiinflammatory and proinflammatory effects (98). The proinflammatory properties of estrogen may explain the higher prevalence of elevated CRP in women than in men even in the absence of depression.

Another explanation for the sex-based difference in the effect of depression on CRP is that because women have relatively high levels of CRP even in absence of depression, it may be more difficult to detect an effect of depression on CRP in this group. Whatever the reason for this sex-based difference, if inflammation is truly an important mechanism linking depression to CHD risk, depression should be more strongly related to cardiovascular disease in men than in women. In general, this does seem to be the case (16, 19, 24, 77).

Our study has a number of limitations. First, it was based on observational data; thus we cannot rule out unmeasured confounding factors. For example, there might be unmeasured medical conditions that might explain the association between depression and CRP. However, given the young age of our sample, and the fact that we are dealing with a presumably healthy community sample as opposed to a clinical population, this potential confounding may be less of an issue in our analysis than in other observational studies.

Second, our finding was based on cross-sectional data; therefore, the temporal ordering of the association between depression and CRP cannot be definitively established. It is possible that instead of depression leading to inflammation, inflammation leads to depression. Indeed, IL-6 may induce production of corticotropin-releasing hormone, resulting in hypercortisolemia (1, 2, 36, 80, 84, 99), which in turn might contribute to depression. The latter might also represent a vicious cycle ultimately leading to an exacerbation of depression, immunosuppression, and inflammation.

Third, the CRP assay used in NHANES III was not a high-sensitivity assay and was not able to detect CRP concentrations less than 0.22 mg/dl. Because of this assay limitation, and because of the small proportion of persons in the category of clinically elevated CRP (CRP >1.00 mg/dl), we were unable to examine more than one cutoff point of the CRP values. For example, we were unable to verify that a history of major depression would be related also to clinically raised CRP according to the conventional clinical cutoff point of >1.00 mg/dl. This limitation, however, should not diminish the importance of our results because recent epidemiological studies have shown an increased cardiovascular risk for CRP levels of 0.2 mg and higher, corresponding to a low-grade inflammation (27, 30, 59, 60).

Finally, in our study, depression was measured by means of the DIS, an interview instrument designed to provide psychiatric diagnoses according to the DSM-III-R in epidemiological studies (40). Although a clinician-administered structured psychiatric interview might have been the ideal method, such an approach is unfeasible in large community-based studies. In these settings the DIS has been shown to provide accurate diagnoses of major depression, and it is the tool used in most large psychiatric epidemiology studies (43–46).

In conclusion, our study demonstrated for the first time in a large representative US sample of younger adults a strong association between recent major depressive episodes and CRP, a marker of systemic inflammation and a strong risk factor for atherosclerotic heart disease. This association was noted in men only. Because of the young age of our study population, subclinical disease is unlikely to explain our findings. These results may have important implications in explaining the pathophysiological mechanisms linking depression to cardiovascular disease in men. Future studies should link depression and systemic inflammation with higher risk of cardiovascular events using a longitudinal design.

Received for publication August 1, 2001.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

  1. Musselman DL, Evans DL, Nemeroff CB. The relationship of depression to cardiovascular disease: epidemiology, biology, and treatment. Arch Gen Psychiatry 1998; 55: 580–92.[Abstract/Free Full Text]
  2. Barrett-Barrick C. Sad, glad, or mad hearts? Epidemiological evidence for a causal relationship between mood disorders and coronary artery disease. J Affect Disord 1999; 53: 193–201.[CrossRef][Medline]
  3. Murphy JM, Monson RR, Olivier DC, Sobol AM, Leighton AH. Affective disorders and mortality: a general population study. Arch Gen Psychiatry 1987; 44: 473–80.[Abstract]
  4. Wulsin LR, Vaillant GE, Wells VE. A systematic review of the mortality of depression. Psychosom Med 1999; 61: 6–17.[Abstract/Free Full Text]
  5. Glassman AH, Shapiro PA. Depression and the course of coronary artery disease. Am J Psychiatry 1998; 155: 4–11.[Abstract/Free Full Text]
  6. Hemingway H, Marmot M. Psychosocial factors in the aetiology and prognosis of coronary heart disease: systematic review of prospective cohort studies. BMJ 1999; 318: 1460–7.[Free Full Text]
  7. Frasure-Smith N, Lesperance F, Talajic M. Depression following myocardial infarction: impact on 6-month survival. JAMA 1993; 270: 1819–25.[Abstract]
  8. Frasure-Smith N, Lesperance F, Juneau M, Talajic M, Bourassa MG. Gender, depression and one-year prognosis after myocardial infarction. Psychosom Med 1999; 61: 26–37.[Abstract/Free Full Text]
  9. Barefoot J, Schroll M. Symptoms of depression, acute myocardial infarction, and total mortality in a community sample. Circulation 1996; 93: 1976–80.[Abstract/Free Full Text]
  10. Ahern DK, Gorkin L, Anderson JL, Tierney C, Hallstrom A, Ewart C, Capone RJ, Schron E, Kornfeld D, Herd JA, Richardson DW, Follick MJ. Biobehavioral variables and mortality or cardiac arrest in the Cardiac Arrhythmia Pilot Study (CAPS). Am J Cardiol 1990; 66: 59–62.[CrossRef][Medline]
  11. Carney RM, Rich MW, Freedland KE, Saini J, TeVelve A, Simeone C, Clark K. Major depressive disorder predicts cardiac events in patients with coronary artery disease. Psychosom Med 1988; 50: 627–33.[Abstract/Free Full Text]
  12. Denollet J, Brutsaert DL. Personality, disease severity, and risk of long-term cardiac events in patients with a decreased ejection fraction after myocardial infarction. Circulation 1998; 97: 167–73.[Abstract/Free Full Text]
  13. Silverstone PH. Depression and outcome in acute myocardial infarction. BMJ 1987; 294: 219–20.
  14. Lesperance F, Frasure-Smith N, Juneau M, Theroux P. Depression and 1-year prognosis in unstable angina. Arch Intern Med 2000; 160: 1354–60.[Abstract/Free Full Text]
  15. Anda R, Williamson D, Jones D, Macera C, Eaker E, Glassman A, Marks J. Depressed affect, hopelessness, and the risk of ischemic heart disease in a cohort of U.S. adults. Epidemiology 1993; 4: 285–94.[Medline]
  16. Aromaa A, Raitasalo R, Reunanen A, Impivaara O, Heliovaara M, Knekt P, Lehtinen V, Joukamaa M, Maatela J. Depression and cardiovascular diseases. Acta Psychiatr Scand Suppl 1994; 377: 77–82.[Medline]
  17. Everson SA, Goldberg DE, Kaplan GA, Cohen RD, Pukkala E, Tuomilehto J, Salonen J. Hopelessness and risk of mortality and incidence of myocardial infarction and cancer. Psychosom Med 1996; 58: 113–21.[Abstract/Free Full Text]
  18. Pratt LA, Ford DE, Crum RM, Armenian HK, Gallo JJ, Eaton WW. Depression, psychotropic medication, and risk of myocardial infarction: prospective data from the Baltimore ECA follow-up. Circulation 1996; 94: 3123–9.[Abstract/Free Full Text]
  19. Hippisley-Cox J, Fielding K, Pringle M. Depression as a risk factor for ischemic heart disease in men: population based case-control study. BMJ 1998; 316: 1714–9.[Abstract/Free Full Text]
  20. Ford DE, Mead LA, Chang PP, Cooper-Patrick L, Wang N, Klag MJ. Depression is a risk factor for coronary artery disease in men. Arch Intern Med 1998; 158: 1422–6.[Abstract/Free Full Text]
  21. Fredman L, Magaziner J, Hebel JR, Hawkes W, Zimmerman SI. Depressive symptoms and 6-year mortality among elderly community-dwelling women. Epidemiology 1999; 10: 54–9.[CrossRef][Medline]
  22. Whooley MA, Browner WS. Association between depressive symptoms and mortality in older women. Arch Intern Med 1998; 158: 2129–35.[Abstract/Free Full Text]
  23. Everson SA, Roberts RE, Goldberg DE, Kaplan GA. Depressive symptoms and increased risk of stroke mortality over a 29-year period. Arch Intern Med 1998; 158: 1133–8.[Abstract/Free Full Text]
  24. Ferketich AK, Schwartzbaum JA, Frid DJ, Moeschberger ML. Depression as an antecedent to heart disease among men and women in the NHANES I study. National Health and Nutrition Examination Survey. Arch Intern Med 2000; 160: 1261–8.[Abstract/Free Full Text]
  25. Ross R. Atherosclerosis—an inflammatory disease. N Engl J Med 1999; 340: 115–26.[Free Full Text]
  26. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342: 836–43.[Abstract/Free Full Text]
  27. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens CH. Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. N Engl J Med 1997; 336: 973–9.[Abstract/Free Full Text]
  28. Kuller LH, Tracy RP, Shaten J, Meilahn EN, for the MRFIT Research Group. Relationships of C-reactive protein and coronary heart disease in the MRFIT nested case control study. Am J Epidemiol 1996; 144: 537–47.[Abstract/Free Full Text]
  29. Tracy RP, Lemaitre RN, Psaty BM, Ives DG, Evans RW, Cushman M, Meilahn EN, Kuller LH. Relationship of C-reactive protein to risk of cardiovascular disease in the elderly: results from the Cardiovascular Health Study and the Rural Health Promotion Project. Atheroscler Thromb Vasc Biol 1997; 17: 1121–7.[Abstract/Free Full Text]
  30. Koenig W, Sund M, Frohlich M, Fischer HG, Lowel H, Doring A, Hutchinson WL, Pepys MB. C-reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. Circulation 1999; 99: 237–42.[Abstract/Free Full Text]
  31. Liuzzu G, Biasucci LM, Gallimore JR, Grillo RL, Rebuzzi AG, Pepys MB, Maseri A. The prognostic value of C-reactive protein and serum amyloid A protein in severe unstable angina. N Engl J Med 1994; 331: 417–24.[Abstract/Free Full Text]
  32. Haverkate F, Thompson SG, Pyke SDM, Gallimore JR, Pepys MB, for the European Concerted Action on Thrombosis and Disabilities Angina Pectoris Study Group. Production of C-reactive protein and risk of coronary events in stable and unstable angina. Lancet 1997; 349: 462–6.[CrossRef][Medline]
  33. Gabay C, Kushner I. Acute-phase proteins and other systemic responses to inflammation. N Engl J Med 1999; 340: 448–54.[Free Full Text]
  34. Sluzewska A, Rybakowski L, Bosmans E, Sobieska M, Berghmans R, Maes M, Wiktorowicz K. Indicators of immune activation in major depression. Psychiatry Res 1996; 64: 161–7.[CrossRef][Medline]
  35. Hornig M, Goodman DBP, Kamoun M, Amsterdam JD. Positive and negative acute phase proteins in affective subtypes. J Affect Disord 1998; 49: 9–18.[CrossRef][Medline]
  36. Berk M, Wadee AA, Kuschke RH, O’Neill-Kerr A. Acute-phase proteins in major depression. J Psychosom Res 1997; 43: 529–34.[CrossRef][Medline]
  37. Maes M, Scharpe S, Meltzer HY, Bosmans E, Suy E, Calabrese J, Cosyns P. Relationships between interleukin-6 activity, acute phase proteins, and function of the hypothalamic-pituitary-adrenal axis in severe depression. Psychiatry Res 1993; 49: 11–27.[CrossRef][Medline]
  38. National Center for Health Statistics. Plan and operation of the Third National Health and Nutrition Examination Survey, 1988–94. Hyattsville (MD): National Center for Health Statistics; 1994.
  39. National Center for Health Statistics, Centers for Disease Control and Prevention. Analytic and reporting guidelines: the Third National Health and Nutrition Examination Survey, NHANES III. Hyattsville (MD): National Center for Health Statistics; 1996.
  40. Robins LM, Helzer JE, Croughan J, Ratcliff KS. National Institute of Mental Health Diagnostic Interview Schedule: its history, characteristics, and validity. Arch Gen Psychiatry 1981; 38: 381–9.[Abstract]
  41. DSM-III-R. Diagnostic and statistical manual of mental disorders. 3rd ed revised. Washington DC: American Psychiatric Association; 1987.
  42. Helzer JE, Robins LN, McEvoy LT, Spitznagel EL, Stoltzman RK, Farmer A, Brockington IF. A comparison of clinical and diagnostic interview schedule diagnoses. Arch Gen Psychiatry 1985; 42: 657–66.[Abstract]
  43. Centers for Disease Control Vietnam Experience Study. Health status of Vietnam veterans: psychosocial characteristics. JAMA 1988; 259: 2701–7.[Abstract]
  44. Helzer JE, Robins LN, McEvoy L. Post-traumatic stress disorder in the general population. N Engl J Med 1987; 317: 1630–4.[Abstract]
  45. Kulka RA, Schlenger WE, Fairbank JA, Hough RL, Jordan BK, Marmar CR, Weiss DS. Trauma and the Vietnam War generation: report of findings from the National Vietnam Veterans Readjustment Study. New York: Brunner/Mazel; 1990.
  46. Regier DA, Myers JK, Kramer M, Robins LN, Blazer DG, Hough RL, Eaton WW, Locke BZ. The NIMH Epidemiologic Catchment Area Program: historical context, major objectives, and study population characteristics. Arch Gen Psychiatry 1984; 41: 934–41.[Abstract]
  47. Danesh J, Collins R, Appleby P, Peto R. Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease. JAMA 1998; 279: 1477–82.[Abstract/Free Full Text]
  48. Fischer CL, Gill CW. Acute-phase proteins. Boston: Little, Brown & Co; 1975.
  49. Pickup JC, Mattock MB, Chusney GD, Burt D. NIDDM as a disease of the innate immune system. Diabetologia 1997; 40: 1286–92.[CrossRef][Medline]
  50. Morley JJ, Kushner I. Serum C-reactive protein levels in disease. Ann N Y Acad Sci 1982; 389: 406–17.[Medline]
  51. Rose GA, Blackburn HB, Gillum RF, Prineas RJ. Cardiovascular survey methods. Geneva: World Health Organization; 1982.
  52. Rose GA. The diagnosis of ischemic heart pain and intermittent claudication in field surveys. Bull WHO 1962; 27: 645–58.[Medline]
  53. Rose G, Reid DD, Hamilton PJS, McCartney P, Keen H, Jarrett RJ. Myocardial ischemia, risk factors and death from coronary heart disease. Lancet 1977; 1: 105–9.[CrossRef][Medline]
  54. Feinleib M, Lambert PM, Zeiner-Hemriksen T, Rogot E, Hunt BM, Ingster-Moore L. The British-Norwegian migrant study: analysis of parameters of mortality differentials associated with angina. Biometrics 1982; 38 (suppl): 1–120.
  55. LaCroix AZ, Guralnik JM, Curb JD, Wallace RB, Ostfeld AM, Hennekens CH. Chest pain and coronary heart disease mortality among older men and women in three communities. Circulation 1990; 81: 436–66.
  56. Sorlie PD, Cooper L, Schreiner PJ, Rosamond W, Szklo M. Repeatability and validity of the Rose questionnaire for angina pectoris in the Atherosclerosis Risk in Communities Study. J Clin Epidemiol 1996; 49: 719–25.[CrossRef][Medline]
  57. Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus. Diabetes Care 1997; 20: 1183–90.[Medline]
  58. Visser M, Bouter L, McQuillan GM, Wener MH, Harris T. Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999; 282: 2131–5.[Abstract/Free Full Text]
  59. Danesh J, Whincup P, Walker M, Lennon L, Thompson A, Appleby P, Gallimore JR. Low grade inflammation and coronary disease: prospective study and updated meta-analyses. Br Heart J 2000; 321: 199–204.
  60. Ridker PM, Cushman M, Stampfer MJ, Tracy RP, Hennekens C. Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease. Circulation 1998; 97: 425–8.[Abstract/Free Full Text]
  61. National Heart, Lung, and Blood Institute. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults. Bethesda (MD): National Heart, Lung, and Blood Institute; 1998.
  62. Pirkle JL, Flegal KM, Bernert JT, Brody DJ, Etzel RA, Maurer KR. Exposure of the US population to environmental tobacco smoke: the Third National Health and Nutrition Examination Survey, 1988 to 1991. JAMA 1996; 275: 1233–40.[Abstract]
  63. National Cholesterol Education Program. Second report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel II). Circulation 1994; 89: 1329–445.
  64. Sauer WH, Berlin JA, Kimmel SE. Selective serotonin reuptake inhibitors and myocardial infarction. Circulation 2001; 104: 1894–8.[Abstract/Free Full Text]
  65. Serebruany VL, O’Connor CM, Gurbel PA. Effect of selective serotonin reuptake inhibitors on platelets in patients with coronary artery disease. Am J Cardiol 2001; 87: 1398–400.[CrossRef][Medline]
  66. Cohen HW, Gibson G, Alderman MH. Excess risk of myocardial infarction in patients treated with antidepressant medications: association with use of tricyclic agents. Am J Med 2000; 108: 2–8.[Medline]
  67. Heard K, Cain BS, Dart RC, Cairns CB. Tricyclic antidepressants directly depress human myocardial mechanical function independent of effects on the conduction system. Acad Emerg Med 2001; 8: 1122–7.[Medline]
  68. Hippisley-Cox J, Pringle M, Hammersley V, Crown N, Wynn A, Meal A, Coupland C. Antidepressants as risk factor for ischaemic heart disease: case-control study in primary care. BMJ 2001; 323: 666–9.[Abstract/Free Full Text]
  69. Lanquillon S, Krieg JC, Bening-Abu-Shach U, Vedder H. Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 2000; 22: 370–9.[CrossRef][Medline]
  70. Talbot F, Nouwen A. A review of the relationship between depression and diabetes in adults: is there a link? Diabetes Care 2000; 23: 1556–62.[Abstract]
  71. Wu T, Dorn JP, Donahue RP, Sempos CT, Trevisan M. Associations of serum C-reactive protein with fasting insulin, glucose, and glycosylated hemoglobin: the Third National Health and Nutrition Examination Survey, 1988–1994. Am J Epidemiol 2001; 155: 65–71.
  72. Geffken D, Cushman M, Burke G, Polak J, Sakkinen P, Tracy R. Association between physical activity and markers of inflammation in a healthy elderly population. Am J Epidemiol 2001; 153: 242–50.[Abstract/Free Full Text]
  73. Abramson J, Vaccarino V. Relationship between physical activity and inflammation among apparently healthy middle-aged and older US adults. Arch Intern Med 2002; 162: 1286-92.[Abstract/Free Full Text]
  74. SUDAAN survey data analysis software. Research Triangle Park (NC): Research Triangle Institute; 1991.
  75. Centers for Disease Control and Prevention. The Third National Health and Nutrition Examination Survey (NHANES III, 1988–1994) reference manuals and reports [CD-ROM]. Bethesda (MD): National Center for Health Statistics; 1996.
  76. Kessler RC, McGonagle KA, Zhao S, Nelson CB, Hughes M, Eshleman S, Wittchen HU, Kendler KS. Lifetime and 12-month prevalence of DSM-III-R psychiatric disorders in the United States. Arch Gen Psychiatry 1994; 51: 8–19.[Abstract]
  77. Penninx BW, Guralnik JM, Mendes de Leon CF, Pahor M, Visser M, Corti M, Wallace RB. Cardiovascular events and mortality in newly and chronically depressed persons >70 years of age. Am J Cardiol 1998; 81: 988–94.[CrossRef][Medline]
  78. Dentino AN, Pieper CF, Rao MK, Currie MS, Harris T, Blazer DG, Cohen HJ. Association of interleukin-6 and other biological variables with depression in older people living in the community. J Am Geriatr Soc 1999; 47: 6–11.[Medline]
  79. Rothermundt M, Arolt V, Fenker J, Gutbrodt H, Peters M, Kirchner H. Different immune patterns in melancholic and non-melancholic major depression. J Affect Disord 2001; 63: 93–102.[CrossRef][Medline]
  80. Maes M. Evidence for an immune response in major depression: a review and hypothesis. Prog Neuropsychopharmacol Biol Psychiatry 1995; 19: 11–38.[CrossRef][Medline]
  81. Kendler KS, Karkowski LM, Prescott CA. Stressful life events and major depression: risk period, long-term contextual threat, and diagnostic specificity. J Nerv Ment Dis 1998; 186: 661–9.[CrossRef][Medline]
  82. Kendler KS, Karkowski LM, Prescott CA. Causal relationship between stressful life events and the onset of major depression. Am J Psychiatry 1999; 156: 837–41.[Abstract/Free Full Text]
  83. Kendler KS, Karkowski-Shuman L. Stressful life events and genetic liability to major depression: genetic control of exposure to the environment? Psychol Med 1997; 27: 539–47.[CrossRef][Medline]
  84. Gold PW, Goodwin FK, Chrousous GP. Clinical and biochemical manifestations of depression: relation to the neurobiology of stress. N Engl J Med 1988; 319: 348–53, 413–20.[Abstract]
  85. Dhalla N, Temsah RM, Netticadan T. Role of oxidative stress in cardiovascular disease. J Hypertens 2000; 18: 655–73.[CrossRef][Medline]
  86. Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL, Edwards PA, Watson AD, Lusis AJ. Atherosclerosis. Basic mechanisms. Oxidation, inflammation, and genetics. Circulation 1995; 91: 2488–96.[Abstract/Free Full Text]
  87. Kang D-H, McCarthy DO. The effect of psychological stress on neutrophil superoxide release. Res Nurs Health 1994; 17: 363–70.[Medline]
  88. Haggendal J, Jonsson L, Johansson G, Bjurstrom S, Carlsten J, Thoren-Tolling K. Catecholamine-induced free radicals in myocardial cell necrosis on experimental stress in pigs. Acta Physiol Scand 1987; 131: 447–52.[Medline]
  89. Irie M, Asami S, Nagata S, Masakazu M, Kasai H. Relationship between perceived workload, stress and oxidative DNA damage. Int Arch Occup Environ Health 2001; 74: 153–7.[CrossRef][Medline]
  90. Pasceri V, Willerson JT, Yeh E. Direct pro-inflammatory effects of C-reactive protein on human endothelial cells. Circulation 2000; 102: 2165–8.[Abstract/Free Full Text]
  91. Kuller LH, Tracy RP, Shaten J, Meilahn EN. Relationship of C-reactive protein and coronary heart disease in the MRFIT nested case-control study. Am J Epidemiol 1996; 144: 537–47.
  92. Ridker PM. Evaluating novel cardiovascular risk factors: can we better predict heart attacks? Ann Intern Med 1999; 130: 933–7.[Abstract/Free Full Text]
  93. Libby PL, Ridker PM. Novel inflammatory markers of coronary risk: theory versus practice. Circulation 1999; 100: 1148–50.[Free Full Text]
  94. Kennon S, Price CP, Mills PG, Ranjadayalan K, Cooper J, Clarke H, Timmis AD. The effect of aspirin on C-reactive protein as a marker of risk in unstable angina. J Am Coll Cardiol 2001; 37: 1266–70.[Abstract/Free Full Text]
  95. Cermak J, Key NS, Bach RR, Balla J, Jacob HS, Vercellotti GM. C-reactive protein induces human peripheral blood monocytes to synthesize tissue factor. Blood 1993; 82: 513–20.[Abstract/Free Full Text]
  96. Stoney CM, Matthews KA, McDonald RH, Johnson CS. Sex differences in lipid, lipoprotein, cardiovascular, and neuroendocrine responses to acute stress. Psychophysiology 1988; 25: 645–56.[Medline]
  97. Matthews K. Interactive effects of behavior and reproductive hormones in sex differences in risk for coronary heart disease. Health Psychol 1989; 8: 373–87.[CrossRef][Medline]
  98. Cushman M, Legault C, Barrett-Connor E, Stefanick ML, Kessler C, Judd HL, Sakkinen PA, Tracy RP. Effect of postmenopausal hormones on inflammation-sensitive proteins: the Postmenopausal Estrogen/Progestin Interventions (PEPI) study. Circulation 1999; 100: 717–22.[Abstract/Free Full Text]
  99. Mitchell AJ. The role of corticotropin releasing factor in depressive illness: a critical review. Neurosci Biobehav Rev 1998; 22: 635–51.[CrossRef][Medline]



This article has been cited by other articles:


Home page
 Eur Heart JHome page
B. Bankier, J. Barajas, A. Martinez-Rumayor, and J. L. Januzzi
Association between C-reactive protein and generalized anxiety disorder in stable coronary heart disease patients
Eur. Heart J., July 4, 2008; (2008) ehn326v1.
[Abstract] [Full Text] [PDF]

Home page
 J Am Coll CardiolHome page
V. Vaccarino, B. D. Johnson, D. S. Sheps, S. E. Reis, S. F. Kelsey, V. Bittner, T. Rutledge, L. J. Shaw, G. Sopko, and C. N. Bairey Merz
Depression, Inflammation, and Incident Cardiovascular Disease in Women With Suspected Coronary Ischemia: The National Heart, Lung, and Blood Institute Sponsored WISE Study
J. Am. Coll. Cardiol., November 20, 2007; 50(21): 2044 - 2050.
[Abstract] [Full Text] [PDF]

Home page
 Psychosom. Med.Home page
T. Liukkonen, P. Rasanen, A. Ruokonen, J. Laitinen, J. Jokelainen, M. Leinonen, V. B. Meyer-Rochow, and M. Timonen
C-reactive protein Levels and Sleep Disturbances: Observations Based on The Northern Finland 1966 Birth Cohort Study
Psychosom Med, October 1, 2007; 69(8): 756 - 761.
[Abstract] [Full Text] [PDF]

Home page
 PsychosomaticsHome page
A. M. Andrei, R. Fraguas Jr., R. M.S. Telles, T. C.T.F. Alves, C. M.C. Strunz, A. Nussbacher, J. Rays, D. V. Iosifescu, and M. Wajngarten
Major Depressive Disorder and Inflammatory Markers in Elderly Patients With Heart Failure
Psychosomatics, August 1, 2007; 48(4): 319 - 324.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Public HealthHome page
C. H. van Gool, G. I.J.M. Kempen, H. Bosma, M. P.J. van Boxtel, J. Jolles, and J. T.M. van Eijk
Associations Between Lifestyle and Depressed Mood: Longitudinal Results From the Maastricht Aging Study
Am J Public Health, May 1, 2007; 97(5): 887 - 894.
[Abstract] [Full Text] [PDF]

Home page
 Psychosom. Med.Home page
K. A. Matthews, L. L. Schott, J. Bromberger, J. Cyranowski, S. A. Everson-Rose, and M. F. Sowers
Associations Between Depressive Symptoms and Inflammatory/Hemostatic Markers in Women During the Menopausal Transition
Psychosom Med, February 1, 2007; 69(2): 124 - 130.
[Abstract] [Full Text] [PDF]

Home page
 Psychosom. Med.Home page
S. H. Boyle, J. E. Michalek, and E. C. Suarez
Covariation of Psychological Attributes and Incident Coronary Heart Disease in U.S. Air Force Veterans of the Vietnam War
Psychosom Med, November 1, 2006; 68(6): 844 - 850.
[Abstract] [Full Text] [PDF]

Home page
 Psychosom. Med.Home page
J. M. McCaffery, N. Frasure-Smith, M.-P. Dube, P. Theroux, G. A. Rouleau, Q. Duan, and F. Lesperance
Common genetic vulnerability to depressive symptoms and coronary artery disease: a review and development of candidate genes related to inflammation and serotonin.
Psychosom Med, March 1, 2006; 68(2): 187 - 200.
[Abstract] [Full Text] [PDF]

Home page
 Psychosom. Med.Home page
J. A. Wagner, H. Tennen, G. A. Mansoor, and G. Abbott
History of Major Depressive Disorder and Endothelial Function in Postmenopausal Women
Psychosom Med, January 1, 2006; 68(1): 80 - 86.
[Abstract] [Full Text] [PDF]

Home page
 Eur Heart JHome page
K.-H. Ladwig, B. Marten-Mittag, H. Lowel, A. Doring, and W. Koenig
C-reactive protein, depressed mood, and the prediction of coronary heart disease in initially healthy men: results from the MONICA-KORA Augsburg Cohort Study 1984-1998
Eur. Heart J., December 1, 2005; 26(23): 2537 - 2542.
[Abstract] [Full Text] [PDF]