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Associations of C-reactive protein and interleukin-6 with cognitive symptoms of depression: 12-year follow-up of the Whitehall II study

Published online by Cambridge University Press:  04 June 2008

D. Gimeno ,
M. Kivimäki ,
E. J. Brunner ,
M. Elovainio ,
R. De Vogli ,
A. Steptoe ,
M. Kumari ,
G. D. O. Lowe ,
A. Rumley  and
M. G. Marmot
...Show all authors
D. Gimeno*
Affiliation:
International Institute for Society and Health, Department of Epidemiology and Public Health, UCL Medical School, London, UK
M. Kivimäki
Affiliation:
International Institute for Society and Health, Department of Epidemiology and Public Health, UCL Medical School, London, UK Finnish Institute of Occupational Health, Helsinki, Finland
E. J. Brunner
Affiliation:
International Institute for Society and Health, Department of Epidemiology and Public Health, UCL Medical School, London, UK
M. Elovainio
Affiliation:
Finnish Institute of Occupational Health, Helsinki, Finland National Research and Development Centre of Welfare and Health (STAKES), Helsinki, Finland
R. De Vogli
Affiliation:
International Institute for Society and Health, Department of Epidemiology and Public Health, UCL Medical School, London, UK
A. Steptoe
Affiliation:
Psychobiology Group, Department of Epidemiology and Public Health, UCL Medical School, London, UK
M. Kumari
Affiliation:
International Institute for Society and Health, Department of Epidemiology and Public Health, UCL Medical School, London, UK
G. D. O. Lowe
Affiliation:
Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow, UK
A. Rumley
Affiliation:
Division of Cardiovascular and Medical Sciences, University of Glasgow, Royal Infirmary, Glasgow, UK
M. G. Marmot
Affiliation:
International Institute for Society and Health, Department of Epidemiology and Public Health, UCL Medical School, London, UK
J. E. Ferrie
Affiliation:
International Institute for Society and Health, Department of Epidemiology and Public Health, UCL Medical School, London, UK
*
*Address for correspondence: D. Gimeno, Ph.D., International Institute for Society and Health, Department of Epidemiology and Public Health, University College London, 1–19 Torrington Place, London WC1E 6BT, UK. (Email: d.gimeno@ucl.ac.uk)
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Abstract

Background

A lack of longitudinal studies has made it difficult to establish the direction of associations between circulating concentrations of low-grade chronic inflammatory markers, such as C-reactive protein and interleukin-6, and cognitive symptoms of depression. The present study sought to assess whether C-reactive protein and interleukin-6 predict cognitive symptoms of depression or whether these symptoms predict inflammatory markers.

Method

In a prospective occupational cohort study of British white-collar civil servants (the Whitehall II study), serum C-reactive protein, interleukin-6 and cognitive symptoms of depression were measured at baseline in 1991–1993 and at follow-up in 2002–2004, an average follow-up of 11.8 years. Symptoms of depression were measured with four items describing cognitive symptoms of depression from the General Health Questionnaire. The number of participants varied between 3339 and 3070 (mean age 50 years, 30% women) depending on the analysis.

Results

Baseline C-reactive protein (β=0.046, p=0.004) and interleukin-6 (β=0.046, p=0.005) predicted cognitive symptoms of depression at follow-up, while baseline symptoms of depression did not predict inflammatory markers at follow-up. After full adjustment for sociodemographic, behavioural and biological risk factors, health conditions, medication use and baseline cognitive systems of depression, baseline C-reactive protein (β=0.038, p=0.036) and interleukin-6 (β=0.041, p=0.018) remained predictive of cognitive symptoms of depression at follow-up.

Conclusions

These findings suggest that inflammation precedes depression at least with regard to the cognitive symptoms of depression.

Keywords

Cohort studyepidemiologyinflammatory markersmental health

Information

Type
Original Articles
Information
Psychological Medicine , Volume 39 , Issue 3 , March 2009 , pp. 413 - 423
Copyright
Copyright © 2008 Cambridge University Press

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References

Bremmer, MA, Beekman, AT, Deeg, DJ, Penninx, BW, Dik, MG, Hack, CE, Hoogendijk, WJ (2008). Inflammatory markers in late-life depression: results from a population-based study. Journal of Affective Disorders 106, 249–255.CrossRefGoogle ScholarPubMed
Brunner, E, Davey Smith, G, Marmot, M, Canner, R, Beksinska, M, O'Brien, J (1996). Childhood social circumstances and psychosocial and behavioural factors as determinants of plasma fibrinogen. Lancet 347, 1008–1013.CrossRefGoogle ScholarPubMed
Brunner, E, Shipley, MJ, Blane, D, Smith, GD, Marmot, MG (1999). When does cardiovascular risk start? Past and present socioeconomic circumstances and risk factors in adulthood. Journal of Epidemiology and Community Health 53, 757–764.CrossRefGoogle ScholarPubMed
Carney, RM, Freedland, KE, Miller, GE, Jaffe, AS (2002). Depression as a risk factor for cardiac mortality and morbidity: a review of potential mechanisms. Journal of Psychosomatic Research 53, 897–902.CrossRefGoogle ScholarPubMed
Cyranowski, JM, Marsland, AL, Bromberger, JT, Whiteside, TL, Chang, Y, Matthews, KA (2007). Depressive symptoms and production of proinflammatory cytokines by peripheral blood mononuclear cells stimulated in vitro. Brain, Behavior, and Immunity 21, 229–237.CrossRefGoogle ScholarPubMed
Danese, A, Pariante, CA, Caspi, A, Taylor, A, Poulton, R (2007). Childhood maltreatment predicts adult inflammation in a life-course study. Proceedings of the National Academy of Sciences USA 104, 1319–1324.CrossRefGoogle Scholar
Danesh, J, Wheeler, JG, Hirschfield, GM, Eda, S, Eiriksdottir, G, Rumley, A, Lowe, GD, Pepys, MB, 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, 1387–1397.CrossRefGoogle Scholar
Dantzer, R, Castanon, N, Lestage, J, Moreau, M, Capuron, L (2006). Inflammation, sickness behaviour and depression. In Depression and Physical Illness (ed. Steptoe, A.), pp. 265–279. Cambridge University Press: Cambridge.CrossRefGoogle Scholar
Dantzer, R, Kelley, KW (2007). Twenty years of research on cytokine-induced sickness behavior. Brain, Behavior, and Immunity 21, 153–160.CrossRefGoogle ScholarPubMed
Dentino, AN, Pieper, CF, Rao, MK, Currie, MS, Harris, T, Blazer, DG, Cohen, HJ (1999). Association of interleukin-6 and other biologic variables with depression in older people living in the community. Journal of the American Geriatrics Society 47, 6–11.CrossRefGoogle ScholarPubMed
Elovainio, M, Keltikangas-Jarvinen, L, Pulkki-Raback, L, Kivimaki, M, Puttonen, S, Viikari, L, Rasanen, L, Mansikkaniemi, K, Viikari, J, Raitakari, OT (2006). Depressive symptoms and C-reactive protein: the Cardiovascular Risk in Young Finns Study. Psychological Medicine 36, 797–805.CrossRefGoogle ScholarPubMed
Fogel, J, Eaton, WW, Ford, DE (2006). Minor depression as a predictor of the first onset of major depressive disorder over a 15-year follow-up. Acta Psychiatrica Scandinavica 113, 36–43.CrossRefGoogle Scholar
Ford, DE, Erlinger, TP (2004). Depression and C-reactive protein in US adults: data from the Third National Health and Nutrition Examination Survey. Archives of Internal Medicine 164, 1010–1014.CrossRefGoogle ScholarPubMed
Frasure-Smith, N, Lesperance, F (2006). Recent evidence linking coronary heart disease and depression. Canadian Journal of Psychiatry 51, 730–737.CrossRefGoogle Scholar
Gabay, C, Kushner, I (1999). Acute-phase proteins and other systemic responses to inflammation. New England Journal of Medicine 340, 448–454.CrossRefGoogle ScholarPubMed
Goldberg, D (1972). The Detection of Psychiatric Illness by Questionnaire. Maudsley Monograph no. 21. Oxford University Press: London.Google Scholar
Goldberg, DP, Hillier, VF (1979). A scaled version of the General Health Questionnaire. Psychological Medicine 9, 139–145.CrossRefGoogle ScholarPubMed
Kiecolt-Glaser, JK, McGuire, L, Robles, TF, Glaser, R (2002). Emotions, morbidity, and mortality: new perspectives from psychoneuroimmunology. Annual Review of Psychology 53, 83–107.CrossRefGoogle ScholarPubMed
Kingman, A, Zion, G (1994). Some power considerations when deciding to use transformations. Statistics in Medicine 13, 769–783.CrossRefGoogle ScholarPubMed
Kumari, M, Head, J, Marmot, M (2004). Prospective study of social and other risk factors for incidence of type 2 diabetes in the Whitehall II study. Archives of Internal Medicine 164, 1873–1880.CrossRefGoogle ScholarPubMed
Kuo, HK, Yen, CJ, Chang, CH, Kuo, CK, Chen, JH, 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, 371–380.CrossRefGoogle ScholarPubMed
Kuper, H, Marmot, M (2003). Job strain, job demands, decision latitude, and risk of coronary heart disease within the Whitehall II study. Journal of Epidemiology and Community Health 57, 147–153.CrossRefGoogle ScholarPubMed
Li, CY, Sung, FC (1999). A review of the healthy worker effect in occupational epidemiology. Occupational Medicine 49, 225–229.CrossRefGoogle ScholarPubMed
Liukkonen, T, Silvennoinen-Kassinen, S, Jokelainen, J, Rasanen, P, Leinonen, M, Meyer-Rochow, VB, Timonen, M (2006). The association between C-reactive protein levels and depression: results from the northern Finland 1966 birth cohort study. Biological Psychiatry 60, 825–830.CrossRefGoogle ScholarPubMed
Maes, M, Meltzer, HY, Bosmans, E, Bergmans, R, Vandoolaeghe, E, Ranjan, R, Desnyder, R (1995 a). Increased plasma concentrations of interleukin-6, soluble interleukin-6, soluble interleukin-2 and transferrin receptor in major depression. Journal of Affective Disorders 34, 301–309.CrossRefGoogle ScholarPubMed
Maes, M, Vandoolaeghe, E, Ranjan, R, Bosmans, E, Bergmans, R, Desnyder, R (1995 b). Increased serum interleukin-1-receptor-antagonist concentrations in major depression. Journal of Affective Disorders 36, 29–36.CrossRefGoogle ScholarPubMed
Mancini, GB, Dahlof, B, Diez, J (2004). Surrogate markers for cardiovascular disease: structural markers. Circulation 109 (Suppl. 1), IV22–IV30.CrossRefGoogle ScholarPubMed
Marmot, M, Brunner, E (2005). Cohort profile: the Whitehall II study. International Journal of Epidemiology 34, 251–256.CrossRefGoogle ScholarPubMed
Marmot, MG, Smith, GD, Stansfeld, S, Patel, C, North, F, Head, J, White, I, Brunner, E, Feeney, A (1991). Health inequalities among British civil servants: the Whitehall II study. Lancet 337, 1387–1393.CrossRefGoogle ScholarPubMed
Myers, GL, Rifai, N, Tracy, RP, Roberts, WL, Alexander, RW, Biasucci, LM, Catravas, JD, Cole, TG, Cooper, GR, Khan, BV, Kimberly, MM, Stein, EA, Taubert, KA, Warnick, GR, Waymack, PP (2004). CDC/AHA Workshop on Markers of Inflammation and Cardiovascular Disease: Application to Clinical and Public Health Practice: report from the laboratory science discussion group. Circulation 110, e545–e549.CrossRefGoogle Scholar
Nicholson, A, Fuhrer, R, Marmot, M (2005). Psychological distress as a predictor of CHD events in men: the effect of persistence and components of risk. Psychosomatic Medicine 67, 522–530.CrossRefGoogle ScholarPubMed
Office for National Statistics (2005). Labour Force Survey, Spring 2005 (http://www.statistics.gov.uk/cci/nugget.asp?id=1654). Accessed 21 February 2008.Google Scholar
Pace, TW, Mletzko, TC, Alagbe, O, Musselman, DL, Nemeroff, CB, Miller, AH, Heim, CM (2006). Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. American Journal of Psychiatry 163, 1630–1633.CrossRefGoogle ScholarPubMed
Patel, V, Araya, R, Chowdhary, N, King, M, Kirkwood, B, Nayak, S, Simon, G, Weiss, HA (2008). Detecting common mental disorders in primary care in India: a comparison of five screening questionnaires. Psychological Medicine 38, 221–228.CrossRefGoogle ScholarPubMed
Penninx, BW, Kritchevsky, SB, Yaffe, K, Newman, AB, Simonsick, EM, 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, 566–572.CrossRefGoogle ScholarPubMed
Pradhan, AD, Manson, JE, Rifai, N, Buring, JE, Ridker, PM (2001). C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. Journal of the American Medical Association 286, 327–334.CrossRefGoogle ScholarPubMed
Raison, CL, Capuron, L, Miller, AH (2006). Cytokines sing the blues: inflammation and the pathogenesis of depression. Trends in Immunology 27, 24–31.CrossRefGoogle ScholarPubMed
Ranjit, N, Diez-Roux, AV, Shea, S, Cushman, M, Seeman, T, Jackson, SA, Ni, H (2007). Psychosocial factors and inflammation in the multi-ethnic study of atherosclerosis. Archives of Internal Medicine 167, 174–181.CrossRefGoogle ScholarPubMed
Rasul, F, Stansfeld, SA, Smith, GD, Shlomo, YB, Gallacher, J (2007). Psychological distress, physical illness and risk of myocardial infarction in the Caerphilly study. Psychological Medicine 37, 1305–1313.CrossRefGoogle ScholarPubMed
Ross, R (1999). Atherosclerosis – an inflammatory disease. New England Journal of Medicine 340, 115–126.CrossRefGoogle ScholarPubMed
Royal College of Physicians, Royal College of Psychiatrists, Royal College of General Practitioners (1995). Alcohol and the Heart in Perspective: Sensible Limits Reaffirmed. Royal College of Physicians, Royal College of Psychiatrists, Royal College of General Practitioners: London.Google Scholar
Sothern, RB, Roitman-Johnson, B, Kanabrocki, EL, Yager, JG, Roodell, MM, Weatherbee, JA, Young, MR, Nenchausky, BM, Scheving, LE (1995). Circadian characteristics of circulating interleukin-6 in men. Journal of Allergy and Clinical Immunology 95, 1029–1035.CrossRefGoogle ScholarPubMed
Stansfeld, SA, Head, J, Fuhrer, R, Wardle, J, Cattell, V (2003). Social inequalities in depressive symptoms and physical functioning in the Whitehall II study: exploring a common cause explanation. Journal of Epidemiology and Community Health 57, 361–367.CrossRefGoogle ScholarPubMed
Stansfeld, SA, Marmot, MG (1992). Social class and minor psychiatric disorder in British civil servants: a validated screening survey using the General Health Questionnaire. Psychological Medicine 22, 739–749.CrossRefGoogle ScholarPubMed
Stewart, JC, Janicki, DL, Muldoon, MF, Sutton-Tyrrell, K, Kamarck, TW (2007). Negative emotions and 3-year progression of subclinical atherosclerosis. Archives of General Psychiatry 64, 225–233.CrossRefGoogle ScholarPubMed
Tiemeier, H, Hofman, A, van Tuijl, HR, Kiliaan, AJ, Meijer, J, Breteler, MM (2003). Inflammatory proteins and depression in the elderly. Epidemiology 14, 103–107.CrossRefGoogle ScholarPubMed
Watson, R, Deary, IJ, Shipley, B (2008). A hierarchy of distress: Mokken scaling of the GHQ-30. Psychological Medicine 38, 575–579.CrossRefGoogle ScholarPubMed
Wener, MH, Daum, PR, McQuillan, GM (2000). The influence of age, sex, and race on the upper reference limit of serum C-reactive protein concentration. Journal of Rheumatology 27, 2351–2359.Google ScholarPubMed
Wichers, M, Maes, M (2002). The psychoneuroimmuno-pathophysiology of cytokine-induced depression in humans. International Journal of Neuropsychopharmacology 5, 375–388.CrossRefGoogle ScholarPubMed
Woodward, M, Rumley, A, Lowe, GD, Tunstall-Pedoe, H (2003). C-reactive protein: associations with haematological variables, cardiovascular risk factors and prevalent cardiovascular disease. British Journal of Haematology 122, 135–141.CrossRefGoogle ScholarPubMed
Woodward, M, Rumley, A, Tunstall-Pedoe, H, Lowe, GD (1999). Associations of blood rheology and interleukin-6 with cardiovascular risk factors and prevalent cardiovascular disease. British Journal of Haematology 104, 246–257.CrossRefGoogle ScholarPubMed
Yaffe, K, Kanaya, A, Lindquist, K, Simonsick, EM, Harris, T, Shorr, RI, Tylavsky, FA, Newman, AB (2004). The metabolic syndrome, inflammation, and risk of cognitive decline. Journal of the American Medical Association 292, 2237–2242.CrossRefGoogle ScholarPubMed