Depressive symptoms and levels of C-reactive protein

A population-based study
  • Hynek Pikhart
  • Jaroslav A. Hubacek
  • Ruzena Kubinova
  • Amanda Nicholson
  • Anne Peasey
  • Nada Capkova
  • Rudolf Poledne
  • Martin Bobak



Depression and depressive symptoms have been repeatedly linked to elevated levels of C-reactive protein (CRP) but questions remain as to the statistical robustness of the association and particularly whether the association between depression and CRP reflects the presence of a chronic disease.


A random sample of 6,126 men and women aged 45–69 years was examined in a cross-sectional study in seven towns in the Czech Republic. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression (CESD) scale.


Center for Epidemiologic Studies Depression score was significantly related to increased levels of CRP in a linear fashion. After controlling for a range of potential confounders, subjects with depressive symptoms (CESD score ≥ 16) had CRP concentrations 0.43 mg/l (95% CI 0.16–0.72) higher than those without symptoms. The association remained significant when study sample was restricted to healthy subjects; among individuals who did not report any chronic disease, the difference between those with and without depressive symptoms was 0.44 mg/l (95% CI 0.14–0.74), and among persons who did not visit a doctor in the last 12 months the difference was 1.20 mg/l (95% CI 0.52–1.87).


These results confirm that there is a statistically robust association between depressive symptoms and increased levels of CRP. We did not find evidence that the association is due presence of a chronic condition.


depressive symptoms CRP inflammation 



This study is funded by grants from the Wellcome Trust “Determinants of Cardiovascular Diseases in Eastern Europe: A multi-centre cohort study” (reference number 064947/Z/01/Z) and “Determinants of Cardiovascular Diseases in Eastern Europe: Longitudinal follow-up of a multi-centre cohort study (The HAPIEE Project)” (reference number 081081/Z/06/Z); a grant from the National Institute on Aging “Health disparities and aging in societies in transition (the HAPIEE study)”, grant number 1R01 AG23522-01; and a grant from MacArthur Foundation “Health and Social Upheaval (a research network)”. We would like to thank local collaborators and interviewers in Havirov, Karvina, Jihlava, Usti nad Labem, Liberec, Hradec Kralove, Kromeriz and Prague.

Competing interests None of the authors have any competing interest in connection with this work.


  1. 1.
    Almeida OP, Norman P, Hankey GJ, Jamrozik K, Flicker L (2007) The association between C-reactive protein concentration and depression in later life is due to poor physical health: results from the Health in Men Study (HIMS). Psychol Med 37:1775–1786PubMedCrossRefGoogle Scholar
  2. 2.
    Ayuso-Mateos JL, Vazquez-Barquero JL, Dowrick C et al (2001) Depressive disorders in Europe: prevalence figures from the ODIN study. Br J Psychiatry 179:308–316PubMedCrossRefGoogle Scholar
  3. 3.
    Beekman AT, Deeg DJ, Van Limbeek J, Braam AW, De Vries MZ, Van Tilburg W (1997) Criterion validity of the Center for Epidemiologic Studies Depression scale (CES-D): results from a community-based sample of older subjects in The Netherlands. Psychol Med 27:231–235PubMedCrossRefGoogle Scholar
  4. 4.
    Bierhaus A, Wolf J, Andrassy M et al (2003) A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci 100:1920–1925PubMedCrossRefGoogle Scholar
  5. 5.
    Black PH, Garbutt LD (2002) Stress, inflammation and cardiovascular disease. J Psychosom Res 52:1–23PubMedCrossRefGoogle Scholar
  6. 6.
    Blake GJ, Ridker P (2002) Inflammatory biomarkers and cardiovascular risk prediction. J Intern Med 252:283–294PubMedCrossRefGoogle Scholar
  7. 7.
    Boekholdt S, Hack C, Sandhu M et al (2006) C-reactive protein levels and coronary artery disease incidence and mortality in apparently healthy men and women: the EPIC-Norfolk prospective population study 1993–2003. Atherosclerosis 187:415–422PubMedCrossRefGoogle Scholar
  8. 8.
    Casas JP, Shah T, Cooper J et al (2006) Insight into the nature of the CRP-coronary event association using Mendelian randomization. Int J Epidemiol 35:922–931PubMedCrossRefGoogle Scholar
  9. 9.
    Danesh J, Wheeler JG, Hirschfield GM et al (2004) C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. N Engl J Med 350:1387–1397PubMedCrossRefGoogle Scholar
  10. 10.
    Danner M, Kasl SV, Abramson JL, Vaccarino V (2003) Association between depression and elevated C-reactive protein. Psychosom Med 65:347–356PubMedCrossRefGoogle Scholar
  11. 11.
    Douglas KM, Taylor AJ, O’Malley PG (2004) Relationship between depression and C-reactive protein in a screening population. Psychosom Med 66:679–683PubMedCrossRefGoogle Scholar
  12. 12.
    Elovainio M, Keltikangas-Jarvinen L, Pulkki-Raback L et al (2006) Depressive symptoms and C-reactive protein: the Cardiovascular Risk in Young Finns Study. Psychol Med 36:797–805PubMedCrossRefGoogle Scholar
  13. 13.
    Fountoulakis K, Iacovides A, Kleanthous S et al (2001) Reliability, validity and psychometric properties of the Greek translation of the Center for Epidemiological Studies-Depression (CES-D) Scale. BMC Psychiatry 1:3PubMedCrossRefGoogle Scholar
  14. 14.
    Gump BB, Matthews KA, Eberly LE, Chang YF (2005) Depressive symptoms and mortality in men. Results from the multiple risk factors intervention trial. Stroke 36:98–102PubMedCrossRefGoogle Scholar
  15. 15.
    Hemingway H, Marmot M (1999) Evidence based cardiology: psychosocial factors in the aetiology and prognosis of coronary heart disease. Systematic review of prospective cohort studies. BMJ 318:1460–1467PubMedGoogle Scholar
  16. 16.
    Hilton ME (1989) A comparison of a prospective diary and two summary recall techniques for recording alcohol consumption. Br J Addict 84:1085–1092PubMedCrossRefGoogle Scholar
  17. 17.
    Kamphuis MH, Kalmijn S, Tijhuis MAR et al (2006) Depressive symptoms as risk factor of cardiovascular mortality in older European men: the Finland, Italy and Netherlands Elderly (FINE) study. Eur J Cardiovasc Prev Rehabil 13:199–206PubMedCrossRefGoogle Scholar
  18. 18.
    Kessler RC, McGonagle KA, Zhao S et al (1994) Lifetime and 12-month prevalence of DSM-II-R psychiatric disorders in the United States. Results from the National Comorbidity Survey. Arch Gen Psychiatry 51:8–19PubMedGoogle Scholar
  19. 19.
    Kop WJ (2003) The integration of cardiovascular behavioral medicine and psychoneuroimmunology: new developments based on converging research fields. Brain Behav Immun 17:233–237PubMedCrossRefGoogle Scholar
  20. 20.
    Liukkonen T, Silvennoinen-Kassinen S, Jokelainen J et al (2006) The association between C-reactive protein levels and depression: results from the Northern Finland 1966 Birth Cohort Study. Biol Psychiatry 60:825–830PubMedCrossRefGoogle Scholar
  21. 21.
    Lorant V, Deliege D, Eaton W, Robert A, Philippot P, Ansseau M (2003) Socioeconomic inequalities in depression: a meta-analysis. Am J Epidemiol 157:98–112PubMedCrossRefGoogle Scholar
  22. 22.
    Lyness JM, Noel TK, Cox C, King DA, Conwell Y, Caine ED (1997) Screening for depression in elderly primary care patients. Arch Intern Med 157:449–454PubMedCrossRefGoogle Scholar
  23. 23.
    Mathers CD, Loncar D (2006) Projections of global mortality and burden of disease from 2002 to 2030. PLoS Med 3:e442PubMedCrossRefGoogle Scholar
  24. 24.
    Meijer A, Zakay-Rones Z, Morag A (1988) Post-influenzal psychiatric disorder in adolescents. Acta Psychiatr Scand 78:176–181PubMedCrossRefGoogle Scholar
  25. 25.
    Nicholson A, Kuper H, Hemingway H (2006) Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur Heart J 27:2763–2774PubMedCrossRefGoogle Scholar
  26. 26.
    Osecká L (1999) Škála deprese CESD—psychometrická analýza. Akademie ved Ceské republiky–Psychologický ústav, BrnoGoogle Scholar
  27. 27.
    Peasey A, Bobak M, Kubinova R et al (2006) Determinants of cardiovascular disease and other non-communicable diseases in Central and Eastern Europe: rationale and design of the HAPIEE study. BMC Public Health 6:255PubMedCrossRefGoogle Scholar
  28. 28.
    Radloff LS (1977) The CES-D scale: a self-report depression scale for research in the general population. Appl Psychol Meas 1:385–401CrossRefGoogle Scholar
  29. 29.
    Rehm J (1998) Measuring quantity, frequency and volume drinking. Alcohol Clin Exp Res 22:4S–14SPubMedCrossRefGoogle Scholar
  30. 30.
    Rehm J, Greenfield TK, Walsh G, Xie X, Robson L, Single E (1999) Assessment methods for alcohol consumption, prevalence of high risk drinking and harm: a sensitivity analysis. Int J Epidemiol 28:219–224PubMedCrossRefGoogle Scholar
  31. 31.
    Ridker P, Hennekens CH, Buring JE, Rifai N (2000) C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 342:836–843PubMedCrossRefGoogle Scholar
  32. 32.
    Roberts RE, Vernon SW (1983) The Center for Epidemiologic Studies Depression Scale: its use in a community sample. Am J Psychiatry 140:41–46PubMedGoogle Scholar
  33. 33.
    Segerstrom S, Miller G (2004) Psychological stress and the human immune system: a meta-analytic study of 30 years of inquiry. Psychol Bull 130:601–630PubMedCrossRefGoogle Scholar
  34. 34.
    Sher L (2000) Psychological factors, immunity, and heart disease psychosomatics. Psychosomatics 41:372–373PubMedCrossRefGoogle Scholar
  35. 35.
    Suarez EC (2004) C-reactive protein is associated with psychological risk factors of cardiovascular disease in apparently healthy adults. Psychosom Med 66:684–691PubMedCrossRefGoogle Scholar
  36. 36.
    Toker S, Shirom A, Shapira I, Berliner S, Melamed S (2005) The association between burnout, depression, anxiety, and inflammation biomarkers: C-reactive protein and fibrinogen in men and women. J Occup Health Psychol 10:344–362PubMedCrossRefGoogle Scholar
  37. 37.
    Ustun TB, Ayuso-Mateos JL, Chatterji S, Mathers C, Murray CJ (2004) Global burden of depressive disorders in the year 2000. Br J Psychiatry 184:386–392PubMedCrossRefGoogle Scholar
  38. 38.
    Vaccarino V, Johnson BD, Sheps DS et al (2007) 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 50:2044–2050PubMedCrossRefGoogle Scholar
  39. 39.
    Watson D, Clark LA (1984) Negative affectivity; the disposition to experience aversive emotional states. Psychol Bull 96:465–490PubMedCrossRefGoogle Scholar
  40. 40.
    Zorrilla EP, Luborsky L, McKay JR et al (2001) The relationship of depression and stressors to immunological assays: a meta-analytic review. Brain Behav Immun 15:199–226PubMedCrossRefGoogle Scholar

Copyright information

© Steinkopff Verlag Darmstadt 2008

Authors and Affiliations

  • Hynek Pikhart
    • 1
  • Jaroslav A. Hubacek
    • 2
  • Ruzena Kubinova
    • 3
  • Amanda Nicholson
    • 1
  • Anne Peasey
    • 1
  • Nada Capkova
    • 3
  • Rudolf Poledne
    • 2
  • Martin Bobak
    • 1
  1. 1.Dept. of Epidemiology and Public HealthUniversity College LondonLondonUK
  2. 2.Institute for Clinical and Experimental MedicinePragueCzech Republic
  3. 3.National Institute of Public HealthPragueCzech Republic

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