Comorbid depression in rheumatoid arthritis: Pathophysiology and clinical implications


Rheumatoid arthritis (RA) is a chronic inflammatory illness that primarily affects the joints. It is associated with symptoms of fatigue, pain, and sleep disturbances that can overlap with or mimic symptoms of depression. Depressive symptoms are highly comorbid with RA and may occur with at least mild severity in up to 42% of RA patients. RA and depression contribute to mortality, decreased quality of life, increased health care costs, and disability. Inflammatory pathways may hold the key to a link between depression and RA, and cytokines have been a major target of research in this area. This article reviews some of the most recent research and commentary on this complex relationship.

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References and Recommended Reading

  1. 1.

    Covic T, Tyson G, Spencer D, Howe G: Depression in rheumatoid arthritis patients: demographic, clinical, and psychological predictors. J Psychosom Res 2006, 60:469–476.

    PubMed  Article  Google Scholar 

  2. 2.

    Isik A, Koca SS, Ozturk A, Mermi O: Anxiety and depression in patients with rheumatoid arthritis. Clin Rheumatol 2007, 26:872–878.

    PubMed  Article  Google Scholar 

  3. 3.

    Nakajima A, Kamitsuji S, Saito A, et al.: Disability and patient’s appraisal of general health contribute to depressed mood in rheumatoid arthritis in a large clinical study in Japan. Mod Rheumatol 2006, 16:151–157.

    PubMed  Article  Google Scholar 

  4. 4.

    Sheehy C, Murphy E, Barry M: Depression in rheumatoid arthritis—underscoring the problem. Rheumatology (Oxford) 2006, 45:1325–1327.

    Article  CAS  Google Scholar 

  5. 5.

    Rifkin A: Depression in physically ill patients: don’t dismiss it as ‘understandable.’ Postgrad Med 1992, 92:147–151.

    PubMed  CAS  Google Scholar 

  6. 6.

    Ang DC, Choi H, Kroenke K, Wolfe F: Comorbid depression is an independent risk factor for mortality in patients with rheumatoid arthritis. J Rheumatol 2005, 32:1013–1019.

    PubMed  Google Scholar 

  7. 7.

    Kinder LS, Bradley KA, Katon WJ, et al.: Depression, post-traumatic stress disorder, and mortality. Psychosom Med 2008, 70:20–26.

    PubMed  Article  Google Scholar 

  8. 8.

    Gallo JJ, Bogner HR, Morales KH, et al.: The effect of a primary care practice-based depression intervention on mortality in older adults. Ann Intern Med 2007, 14:689–698.

    Google Scholar 

  9. 9.

    Spring TR, Yanni LM, Levenson JL: A shot in the dark: failing to recognize the link between physical and mental illness. J Gen Intern Med 2006, 22:677–680.

    Article  Google Scholar 

  10. 10.

    Timonen M, Viilo K, Särkioja T, et al.: Suicides in persons suffering from rheumatoid arthritis. Rheumatology (Oxford) 2003, 42:287–291.

    Article  CAS  Google Scholar 

  11. 11.

    Druss B, Pincus H: Suicidal ideation and suicide attempts in general medical illness. Arch Intern Med 2000, 160:1522–1526.

    PubMed  Article  CAS  Google Scholar 

  12. 12.

    Pollard L, Choy EH, Scott DL: The consequences of rheumatoid arthritis: quality of life measures in the individual patient. Clin Exp Rheumatol 2005, 23(Suppl 39):S43–S52.

    PubMed  CAS  Google Scholar 

  13. 13.

    Cadena J, Vinaccia S, Pérez A, et al.: The impact of disease activity on the quality of life, mental health status, and family dysfunction in Colombian patients with rheumatoid arthritis. J Clin Rheumatol 2003, 9:142–150.

    PubMed  Article  Google Scholar 

  14. 14.

    Rupp I, Boshuizen HC, Dinant HJ, et al.: Disability and health-related quality of life among patients with rheumatoid arthritis: association with radiographic joint damage, disease activity, pain, and depressive symptoms. Scand J Rheumatol 2006, 35:175–181.

    PubMed  Article  CAS  Google Scholar 

  15. 15.

    Bazzichi L, Maser J, Piccinni A, et al.: Quality of life in rheumatoid arthritis: impact of disability and lifetime depressive spectrum symptomatology. Clin Exp Rheumatol 2005, 23:783–788.

    PubMed  CAS  Google Scholar 

  16. 16.

    Heiberg T, Kvien T: Preferences for improved health examined in 1024 patients with rheumatoid arthritis: pain has the highest priority. Arthritis Rheum 2002, 15:391–397.

    Article  Google Scholar 

  17. 17.

    Dickens C, Creed F: The burden of depression in patients with rheumatoid arthritis. Rheumatology (Oxford) 2001, 40:1327–1330.

    Article  CAS  Google Scholar 

  18. 18.

    Magni G, Moreschi C, Rigatti Luchini S, et al.: Prospective study on the relationship between depressive symptoms and chronic musculo-skeletal pain. Pain 1994, 56:289–297.

    PubMed  Article  CAS  Google Scholar 

  19. 19.

    Groarke A, Curtis R, Coughlan R, Gsel A: The role of perceived and actual disease status in adjustment to rheumatoid arthritis. Rheumatology (Oxford) 2004, 43:1142–1149.

    Article  CAS  Google Scholar 

  20. 20.

    Häkkinen A, Kautiainen H, Hannonen P, et al.: Pain and joint mobility explain individual subdimensions of the health assessment questionnaire (HAQ) disability index in patients with rheumatoid arthritis. Ann Rheum Dis 2005, 64:59–63.

    PubMed  Article  Google Scholar 

  21. 21.

    Fifield J, Tennen H, Reisine S, McQuillan J: Depression and the long-term risk of pain, fatigue, and disability in patients with rheumatoid arthritis. Arthritis Rheum 1998, 41:1851–1857.

    PubMed  Article  CAS  Google Scholar 

  22. 22.

    Tennen H, Affleck G, Zautra A: Depression history and coping with chronic pain: a daily process analysis. Health Psychol 2006, 25:370–379.

    PubMed  Article  Google Scholar 

  23. 23.

    Connor TS, Tennen H, Zatra AJ, et al.: Coping with rheumatoid arthritis pain in daily life: within-person analyses reveal hidden vulnerability for the formerly depressed. Pain 2006, 126:198–209.

    Article  Google Scholar 

  24. 24.

    Zautra AJ, Parrish BP, Van Puymbroeck CM, et al.: Depression history, stress, and pain in rheumatoid arthritis. J Behav Med 2007, 30:187–197.

    PubMed  Article  Google Scholar 

  25. 25.

    Rupp I, Boshiuzen HC, Jacobi CE, et al.: Impact of fatigue on health-related quality of life in rheumatoid arthritis. Arthritis Rheum 2004, 51:578–585.

    PubMed  Article  Google Scholar 

  26. 26.

    Ahlmén M, Nordenskiöld U, Archenholtz B, et al.: Rheumatology outcomes: the patient’s perspective. A multicentre focus group interview study of Swedish rheumatoid arthritis patients. Rheumatology (Oxford) 2005, 44:105–110.

    Article  Google Scholar 

  27. 27.

    Wolfe F, Hawley DJ, Wilson K: The prevalence and meaning of fatigue in rheumatic disease. J Rheumatol 1996, 23:1407–1417.

    PubMed  CAS  Google Scholar 

  28. 28.

    Mancuso CA, Rincon M, Sayles W, Paget SA: Psychosocial variables and fatigue: a longitudinal study comparing individuals with rheumatoid arthritis and healthy controls. J Rheumatol 2006, 33:1496–1502.

    PubMed  Google Scholar 

  29. 29.

    Katz PP, Yelin EH: Prevalence and correlates of depressive symptoms among persons with rheumatoid arthritis. J Rheumatol 1993, 20:790–796.

    PubMed  CAS  Google Scholar 

  30. 30.

    Ozminkowski RJ, Burton WN, Goetzel RZ, et al.: The impact of rheumatoid arthritis and medical expenditures, absenteeism, and short-term disability benefits. J Occup Environ Med 2006, 48:135–148.

    PubMed  Article  Google Scholar 

  31. 31.

    Michaud K, Wolfe F: Comorbidities in rheumatoid arthritis. Best Pract Res Clin Rheumatol 2007, 21:885–906.

    PubMed  Article  Google Scholar 

  32. 32.

    Katz PP, Yelin EH: The development of depressive symptoms among women with rheumatoid arthritis: the role of function. Arthritis Rheum 1995, 38:49–56.

    PubMed  Article  CAS  Google Scholar 

  33. 33.

    Hawley DJ, Wolfe F: Effect of light and season on pain and depression in subjects with rheumatic disorders. Pain 1994, 59:227–234.

    PubMed  Article  CAS  Google Scholar 

  34. 34.

    Hawley DJ, Wolfe F, Lue FA, Moldofsky H: Seasonal symptom severity in patients with rheumatic diseases: a study of 1424 patients. J Rheumatol 2001, 28:1900–1909.

    PubMed  CAS  Google Scholar 

  35. 35.

    Hyphantis TN, Bai M, Siafaka V, et al.: Psychological distress and personality trait in early rheumatoid arthritis: a preliminary survey. Rheumatol Int 2006, 26:828–836.

    PubMed  Article  CAS  Google Scholar 

  36. 36.

    Pincus T: Psychological factors and rheumatoid arthritis. Int J Adv Rheumatol 2003, 1:58–63.

    Google Scholar 

  37. 37.

    Maes M, Vandoolaeghe E, Ranjan R, et al.: Increased serum interleukin-1-receptor-antagonist concentrations in major depression. J Affect Disord 1995, 36:29–36.

    PubMed  Article  CAS  Google Scholar 

  38. 38.

    van den Biggelar AH, Gussekloo J, de Craen AJ, et al.: Inflammation and interleukin-1 signaling network contribute to depressive symptoms but not cognitive decline in old age. Exp Gerontol 2007, 42:693–701.

    Article  Google Scholar 

  39. 39.

    Kop WJ, Gottdiener JS, Tangen CM, et al.: Inflammation and coagulation factors in persons > 65 years of age with symptoms of depression but without evidence of myocardial ischemia. Am J Cardiol 2002, 89:419–424.

    PubMed  Article  CAS  Google Scholar 

  40. 40.

    Vaccarino V, Johnson BD, Sheps DS, et al.: Depression, inflammation, and incident cardiovascular disease in women with suspected coronary ischemia. J Am Coll Cardiol 2007, 50:2044–2050.

    PubMed  Article  Google Scholar 

  41. 41.

    Shimbo D, Chaplin W, Crossman D, et al.: Role of depression and inflammation in incident coronary heart disease events. Am J Cardiol 2005, 96:1016–1021.

    PubMed  Article  Google Scholar 

  42. 42.

    Dantzer R, Aubert A, Bluthe RM, et al.: Mechanisms of the behavioural effects of cytokines. Adv Exp Med Biol 1999, 461:83–105.

    PubMed  Article  CAS  Google Scholar 

  43. 43.

    Matsuzaki T, Nakajima A, Ishigami S, et al.: Mirthful laughter differentially affects serum pro-and anti-inflammatory cytokine levels depending on the level of disease activity in patients with rheumatoid arthritis. Rheumatology (Oxford) 2006, 45:182–186.

    Article  CAS  Google Scholar 

  44. 44.

    Neuberger GB, Aaronson LS, Gajewski B, et al.: Predictors of exercise and effects of exercise on symptoms, function, aerobic fitness, and disease outcomes of rheumatoid arthritis. Arthritis Rheum 2007, 57:943–952.

    PubMed  Article  Google Scholar 

  45. 45.

    Sokka T, Häkkinen A, Kautiainen H, et al.: Physical inactivity in patients with rheumatoid arthritis: data from twenty-one countries in a cross-sectional, international study. Arthritis Rheum 2008, 59:42–50.

    PubMed  Article  Google Scholar 

  46. 46.

    Sharpe L, Sensky T, Timberlake N, et al.: A blind, randomized, controlled trial of cognitive-behavioural intervention for patients with recent onset rheumatoid arthritis: preventing psychological and physical morbidity. Pain 2001, 89:275–283.

    PubMed  Article  CAS  Google Scholar 

  47. 47.

    Evers AW, Kraaimaat FW, van Riel PL, de Jong AJ: Tailored cognitive behavioral therapy in early rheumatoid arthritis for patients at risk: a randomized controlled trial. Pain 2002, 100:141–153.

    PubMed  Article  Google Scholar 

  48. 48.

    Parker JC, Hart ES, Walker S: Psychological factors in rheumatoid arthritis. Int J Adv Rheumatol 2007, 5:40–43.

    Google Scholar 

  49. 49.

    Bird H, Broggini M: Paroxetine versus amitriptyline for treatment of depression associated with rheumatoid arthritis: a randomized, double blind, parallel group study. J Rheumatol 2000, 27:2791–2797.

    PubMed  CAS  Google Scholar 

  50. 50.

    Masand PS, Narasimhan M, Patkar AA: Paroxetine for somatic pain associated with physical illness: a review. Prim Care Companion J Clin Psychiatry 2006, 8:122–130.

    PubMed  Google Scholar 

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Correspondence to Travis O. Bruce.

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Bruce, T.O. Comorbid depression in rheumatoid arthritis: Pathophysiology and clinical implications. Curr Psychiatry Rep 10, 258–264 (2008).

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  • Rheumatoid Arthritis
  • Depressive Symptom
  • Suicidal Ideation
  • Rheumatol
  • Illness Perception