Skip to main content

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)

  • OSVALDO P. ALMEIDA (a1) (a2), PAUL NORMAN (a1) (a3), GRAEME J. HANKEY (a1) (a4), KONRAD JAMROZIK (a5) and LEON FLICKER (a1) (a4)...

C-reactive protein (CRP) is a non-specific marker of inflammation that has been associated with depression and vascular disease, particularly in men. This study aimed to investigate the association between high CRP concentration and depression while taking physical health into account.


A cross-sectional study of a community-dwelling sample of 5438 men aged 70+. Participants with scores ⩾7 on the 15-item Geriatric Depression Scale (GDS-15) were considered to display clinically significant depressive symptoms. We measured the serum concentration of CRP with a high-sensitivity assay. The assessment of physical co-morbidity included three components: the Charlson weighted index, self-report of major health events on a standardized questionnaire, and the physical component of the 36-item Short-Form Health Survey (SF-36). Other measured factors included age, native language, education, a standardized socio-economic index, smoking, prior or current history of depression treatment, cognitive impairment (Mini-Mental State Examination score <24) and body mass index (BMI).


Participants with depression (n=340) were older than their controls without depression (age in years: 76·6±4·4 v. 75·4±4·1). Men with CRP concentration >3 mg/l had an increased odds ratio (OR) [1·59, 95% confidence interval (CI) 1·20–2·11] of being depressed compared to men with CRP ⩽3 mg/l. This association became non-significant once we adjusted the analysis for the measures of physical co-morbidity and other confounding factors (OR 1·22, 95% CI 0·86–1·73).


The physiological mechanisms that lead to the onset and maintenance of depressive symptoms in older men remain to be determined, but CRP concentration is unlikely to play a significant role in that process.

Corresponding author
*Address for correspondence: Professor Osvaldo P. Almeida, WA Centre for Health and Ageing (M573), University of Western Australia, 35 Stirling Highway, Crawley, Perth, WA 6009, Australia. (Email:
Hide All
Alexopoulos G. S., Meyers B. S., Young R. C., Campbell S., Silbersweig D. & Charlson M. (1997). ‘Vascular depression’ hypothesis. Archives of General Psychiatry 54, 915922.
Almeida O. P. & Almeida S. A. (1999). Short versions of the Geriatric Depression Scale: a study of their validity for the diagnosis of a major depressive episode according to ICD-10 and DSM-IV. International Journal of Geriatric Psychiatry 14, 858865.
Almeida O. P., Flicker L., Norman P. N., Hankey G. J., Vasikaran S., van Bockxmeer F. & Jamrozik K. (2007). Association of ardiovascular risk factors and disease with depression in later life. American Journal of Geriatric Psychiatry. Published online: 8 December 2006. doi: 10.1097/01.JGP.0000246869.49892.77.
Anderson C. S., Jamrozik K. D., Burvill P. W., Chakera T. M., Johnson G. A. & Stewart-Wynne E. G. (1993). Ascertaining the true incidence of stroke: experience from the Perth Community Stroke Study, 1989–1990. Medical Journal of Australia 158, 8084.
ABS (1995). National Health Survey: SF-36 Population Norms, Australia. ABS Catalogue No. 4399.0. Australian Bureau of Statistics: Canberra.
Bray R. B. (2001). Social Indicators for Regional Australia. Department of Family and Community Services: Canberra.
Charlson M. E., Pompei P., Ales K. L. & MacKenzie C. R. (1987). A new method of classifying prognostic comorbidity in longitudinal studies: development and validation. Journal of Chronic Diseases 40, 373383.
Crum R. M., Anthony J. C., Bassett S. S. & Folstein M. F. (1993). Population-based norms for the Mini-Mental State Examination by age and educational level. Journal of the American Medical Association 269, 23862391.
Danesh J., Wheeler J. G., Hirschfield G. M., Eda S., Eiriksdottir G., Rumley A., Lowe G. D. O., Pepys M. B. & Gudnason V. (2004). C-reactive protein and other circulating markers of inflammation in the prediction of coronary heart disease. New England Journal of Medicine 350, 13871397.
Danner M., Kasl S. V., Abramson J. L. & Vaccarino V. (2003). Association between depression and elevated C-reactive protein. Psychosomatic Medicine 65, 347356.
Douglas K. M., Taylor A. J. & O'Malley P. G. (2004). Relationship between depression and C-reactive protein in a screening population. Psychosomatic Medicine 66, 679683.
Elovainio M., Keltikangas-Jarvinen L., Pulkki-Raback L., Kivimaki M., Puttonen S., Viikari L., Rasanen L., Mansikkaniemi K., Viikari J. & Raitakari O. T. (2006). Depressive symptoms and C-reactive protein: the Cardiovascular Risk in Young Finns Study. Psychological Medicine 36, 797805.
Folstein M. F., Folstein S. E. & McHugh P. R. (1975). Mini-mental State: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research 12, 189198.
Ford D. E. & Erlinger T. P. (2004). Depression and C-reactive protein in US adults: data from the Third National Health and Nutrition Examination Study. Archives of Internal Medicine 164, 10101014.
Gruenewald T. L., Seeman T. E., Ryff C. D., Karlamangla A. S. & Singer B. H. (2006). Combinations of biomarkers predictive of later life mortality. Proceedings of the National Academy of Sciences USA 103, 1415814163.
Holman C. D., Bass A. J., Rouse I. L. & Hobbs M. S. (1999). Population-based linkage of health records in Western Australia: development of a health services research linked database. Australian and New Zealand Journal of Public Health 23, 453459.
Jamrozik K., Norman P., Spencer C. A., Parsons R. W., Tuohy R., Lawrence-Brown M. M. & Dickinson J. A. (2000). Screening for abdominal aortic aneurysm: lessons from a population-based study. Medical Journal of Australia 173, 345350.
Kop W. J., Gottdiener J. S., Tangen C. M., Fried L. P., McBurnie M. A., Walston J., Newman A., Hirsch C. & Tracy R. P. (2002). Inflammation and coagulation factors in persons >65 years of age with symptoms of depression but without evidence of myocardial ischemia. American Journal of Cardiology 89, 419424.
Kuo H. K., Yen C. J., Chang C. H., Kuo C. K., Chen J. H. & Sorond F. (2005). Relation of C-reactive protein to stroke, cognitive disorders and depression in the general population: systematic review and meta-analysis. Lancet Neurology 4, 371380.
Lanquillon S., Krieg J. C., Bening-Abu-Shach U. & Vedder H. (2000). Cytokine production and treatment response in major depressive disorder. Neuropsychopharmacology 22, 370379.
Liukkonen T., Silvennoinen-Kassinen S., Jokelainen J., Rasanen P., Leinonen M., Meyer-Rochow V. B. & Timonen M. (2006). The association between C-reactive protein levels and depression: results from the Northern Finland 1966 Birth Cohort Study. Biological Psychiatry 60, 825830.
Loucks E. B., Berkman L. F., Gruenewald T. L. & Seeman T. E. (2006). Relation of social integration to inflammatory marker concentrations in men and women 70 to 79 years. American Journal of Cardiology 97, 10101016.
O'Brien S. M., Scott L. V. & Dinan T. G. (2006). Antidepressant therapy and C-reactive protein levels. British Journal of Psychiatry 188, 449452.
Panagiotakos D. B., Pitsavos C., Chrysohoou C., Tsetsekou E., Papageorgiou C., Christodoulou G. & Stefanadis C.; ATTICA study (2004). Inflammation, coagulation, and depressive symptomatology in cardiovascular disease-free people: the ATTICA study. European Heart Journal 25, 492499.
Pearson T. A., Mensah G. A., Alexander R. W., Anderson J. L., Cannon R. O. 3rd, Criqui M., Fadl Y. Y., Fortmann S. P., Hong Y., Myers G. L., Rifai N., Smith S. C. Jr., Taubert K., Tracy R. P. & Vinicor F. (2003). Markers of inflammation and cardiovascular disease: application to clinical and public health practice: a statement for healthcare professionals from the Centers for Disease Control and Prevention and the American Heart Association. Circulation 107, 499511.
Penninx B. W. J. H., Kritchevsky S. B., Yaffe K., Newman A. B., Simonsick E. M., Rubin S., Ferrucci L., Harris T. & Pahor M. (2003). Inflammatory markers and depressed mood in older persons: results from the Health, Aging and Body Composition Study. Biological Psychiatry 54, 566572.
Quan H., Sundararajan V., Halfon P., Fong A., Burnand B., Luthi J. C., Saunders L. D., Beck C. A., Feasby T. E. & Ghali W. A. (2005). Coding algorithms for defining comorbidities in ICD-9-CM and ICD-10 administrative data. Medical Care 43, 11301139.
Raison C. L., Capuron L. & Miller A. H. (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends in Immunology 27, 2431.
Regier D., Boyd J., Burke J. D. Jr., Rae D. S., Myers J. K., Kramer M., Robins L. N., George L. K., Karno M. & Locke B. Z. (1988). One-month prevalence of mental disorders in the United States. Archives of General Psychiatry 45, 977986.
Ridker P. M., Cushman M., Stampfer M. J., Tracy R. P. & Hennekens C. H. (1997). Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. New England Journal of Medicine 336, 973979.
Ross R. (1999). Atherosclerosis: an inflammatory disease. New England Journal of Medicine 340, 115126.
StataCorp (2006). Intercooled Stata 9.2 for Windows. College Station: TX, USA.
Suarez E. C. (2004). C-reactive protein is associated with psychological risk factors of cardiovascular disease in apparently healthy adults. Psychosomatic Medicine 66, 684691.
Tiemeier H., Hofman A., van Tuijl H. R., Kiliaan A. J., Meijer J. & Breteler M. (2003 a). Inflammatory proteins and depression in the elderly. Epidemiology 14, 103107.
Tiemeier H., van Tuijl H. R., Hofman A., Kiliaan A. J. & Breteler M. (2003 b). Plasma fatty acid composition and depression are associated in the elderly: the Rotterdam Study. American Journal of Clinical Nutrition 78, 4046.
Thomas A. J., Davis S., Morris C., Jackson E., Harrison R. & O'Brien J. T. (2005). Increase in interleukin-1β in late-life depression. American Journal of Psychiatry 162, 175177.
Thomas A. J., Kalaria R. N. & O'Brien J. T. (2004). Depression and vascular disease: what is the relationship? Journal of Affective Disorders 79, 8195.
Verma S., Devaraj S. & Jialal I. (2006). Is C-reactive protein an innocent bystander or proatherogenic culprit? C-reactive protein promotes atherothrombosis. Circulation 113, 21352150.
Walston J., McBurnie A., Newman A., Tracy R. P., Kop W. J., Hirsch C. H., Gottdiener J. & Fried L. P. (2002). Frailty and activation of the inflammation and coagulation systems with and without clinical comorbidities: results from the Cardiovascular Health Study. Archives of Internal Medicine 162, 23332341.
Ware J. E., Kosinski M. & Gandek B. (2000). SF-36 Health Survey: Manual and Interpretation Guide. QualityMetric Incorporated: Lincoln, RI.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Psychological Medicine
  • ISSN: 0033-2917
  • EISSN: 1469-8978
  • URL: /core/journals/psychological-medicine
Please enter your name
Please enter a valid email address
Who would you like to send this to? *


Full text views

Total number of HTML views: 1
Total number of PDF views: 29 *
Loading metrics...

Abstract views

Total abstract views: 161 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 18th November 2017. This data will be updated every 24 hours.