Abstract
Objective
Depression is very prevalent in rheumatoid arthritis (RA) compared with the general population and may be associated with poor clinical outcomes. Identifying factors associated with depression could improve outcomes for this at risk group. However, few studies have comprehensively examined the association of contextual and disease-related factors as well as pro inflammatory cytokines interleukin 6 (IL-6) and interleukin 17 (IL-17) with depression in RA. Therefore, we aimed to identify the factors significantly associated with depression and severe depression in RA, thus providing a reference for applying clinical care interventions for patients with RA.
Methods
An observational cross-sectional study was conducted on 120 RA patients. Potential determinants included contextual and disease-related factors and laboratory variables. Enzyme-linked immunosorbent assay was used to measure serum IL-6 and IL-17 levels. Depression was assessed using the Arabic version of the Beck Depression Inventory-II questionnaire.
Results
A total of 120 patients were included, and up to 67.5% had some degree of depression with 60% having moderate to severe depression. The severity of disease activity of RA (DAS28-ESR (OR, 1.63; 95% CI, 0.899-3.755), HAQ scores (OR, 1.27; 95% CI, 0.702-2.933), and VAS scores for pain (OR, 2.2; 95% CI, 1.251–5.223)), besides elevated serum IL-6 (OR, 1.51; 95% CI, 0.832-3.475), IL-17 (OR, 1.28; 95% CI, 0.706-2.947), and CRP levels (OR, 1.20; 95% CI, 0.923-2.882) were significantly associated with depression and its severity in the multivariate analysis.
Conclusion
Depression is frequent in RA and is strongly associated to elevated serum IL-6, IL-17, CRP levels, and disease activity-related factors.
Key Points • RA patients are at increased risk of developing depression, particularly if their level of disease activity scores, serum IL-6, and IL-17 levels increases. • Patient characteristics associated with depression in RA include living without family, without employments, and with co-morbid hypertension, while RA disease factors are pain, functional disability, and high disease activity. • A multidisciplinary cooperative approach to RA patient care with regular assessments of these factors associated with depression should be incorporated into routine care programs to improve patients’ self care capabilities and mitigate or prevent depression in these patients. |
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References
Alamanos Y, Voulgari PV, Drosos AA (2006) Incidence and prevalence of rheumatoid arthritis, based on the 1987 American College of Rheumatology criteria: a systematic review. Semin Arthritis Rheum 36:182–188
Žagar I, Delimar V, Pap M, Peri D, Laktaši N, Žerjavi LN, Per P (2018) Prevalence and correlation of depressive symptoms with functional scores, therapy and disease activity among Croatian patients with rheumatoid arthritis: a preliminary study. Psychiatr Danub 30(4):452–458. https://doi.org/10.24869/psyd.2018.452
Matcham F, Rayner L, Steer S, Hotopf M (2013) The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology (Oxford) 52:2136–2148
Covic T, Cumming SR, Pallant JF, Manolios N, Emery P, Conaghan PG et al (2012) Depression and anxiety in patients with rheumatoid arthritis: prevalence rates based on a comparison of the Depression, Anxiety and Stress Scale (DASS) and the Hospital Anxiety and Depression Scale (HADS). BMC Psychiatry 12:6
Sturgeon JA, Finan PH, Zautra AJ (2016) Affective disturbance in rheumatoid arthritis: psychological and disease-related pathways. Nat Rev Rheumatol 12(9):532–542
Nerurkar L, Siebert S, McInnes IB, Cavanagh J (2018) Rheumatoid arthritis and depression: an inflammatory perspective. Lancet Psychiatry 6(2):164–173. https://doi.org/10.1016/S2215-0366(18)30255-4
Margaretten M, Julian L, Katz P, Yelin E (2011) Depression in patients with rheumatoid arthritis: description, causes and mechanisms. Int J Clin Rheumtol 6(6):617–623. https://doi.org/10.2217/IJR.11.6
Joyce AT, Smith P, Khandker R, Melin JM, Singh A (2009) Hidden cost of rheumatoid arthritis (RA): estimating cost of comorbid cardiovascular disease and depression among patients with RA. J Rheumatol 36:743–752
Ang DC, Choi H, Kroenke K, Wolfe F (2005) Comorbid depression is an independent risk factor for mortality in patients with rheumatoid arthritis. J Rheumatol 32:1013–1019
Baillet A, Gossec L, Carmona L, Wit M, van Eijk-Hustings Y, Bertheussen H et al (2016) Points to consider for reporting, screening for and preventing selected comorbidities in chronic inflammatory rheumatic diseases in daily practice: a EULAR initiative. Ann Rheum Dis 75(6):965–973
Wang Y-P, Gorenstein C (2013) Assessment of depression in medical patients: a systematic review of the utility of the Beck Depression InventoryII. Clinics 68(9):1274–1287
American Psychiatric Association (2013) Diagnostic and statistical manual of mental disorders, 5th edn. Author, Washington, DC. https://doi.org/10.1176/appi.books.9780890425596
Aletaha D, Neogi T, Silman AJ, Funovits J, Felson DT, Bingham CO, Birnbaum NS, Burmester GR, Bykerk VP, Cohen MD (2010) Rheumatoid arthritis classification criteria: an American College of Rheumatology/European League Against Rheumatism collaborative initiative. Ann Rheum Dis 69:1580–1588
Prevoo ML, Van’t Hof MA, Kuper HH, van Leeuwen MA, van de Putte LB, van Riel PL (1995) Modified disease activity scores that include twenty-eight joint counts: development and validation in a prospective longitudinal study of patients with rheumatoid arthritis. Arthritis Rheum 38:44–48
Wolfe F, Kleinheksel SM, Cathey MA, Hawley DJ, Spitz PW, Fries JF (1988) The clinical value of the stanford health assessment questionnaire functional disability index in patients with rheumatoid arthritis. J Rheumatol 15(10):1480–1488
Bruce B, Fries JF (2003) The Stanford health assessment questionnaire (HAQ): a review of its history, issues, progress, and documentation. J Rheumatol 30(1):167–178
Beck AT, Steer RA, Brown GK, San Antonio TX (1996) Psychological Corporation; 1996. Manual for the Beck Depression Inventory–II
Ghareeb A, Cairo G (2000) Egypt: Angle Press. Manual of the Arabic BDI-II
Alansari BM (2005) Kuwait: The New Book Home Co., Kuwait University. Beck Depression Inventory (BDI-II) Sourcebook of Personality disorders Scales
Masood A, Salim B, Nasim A, Khalid Z, Afzal A (2017) Are we missing the diagnosis of depression in patients with rheumatoid arthritis at a tertiary care facility? Pak J Med Sci 33(2):300–305. https://doi.org/10.12669/pjms.332.11856
Rezaei F, Doost HT, Molavi H, Abedi MR, Karimifar M (2014) Depression and pain in patients with rheumatoid arthritis: mediating role of illness perception. Egypt Rheumatol 36(2):57–64
Mostafa H, Radwan A (2013) The relationship between disease activity and depression in Egyptian patients with rheumatoid arthritis. Egypt Rheumatol 35(4):193–199
Dalia A, ElSherbiny DA, Saad WE (2019) Depression in rheumatoid arthritis patients: screening for a frequent yet underestimated comorbidity. Egypt Rheumatol. https://doi.org/10.1016/j.ejr.2019.07.002
Hassan AA, Nasr MH, Mohamed AL, Kamal AM, Elmoghazy AD (2019) Psychological affection in rheumatoid arthritis patients in relation to disease activity. Medicine (Baltimore) 98(19):e15373
Sambamoorthi U, Shah D, Zhao X (2017) Healthcare burden of depression in adults with arthritis. Expert Rev Pharmacoecon Outcomes Res 17(1):53–65. https://doi.org/10.1080/14737167.2017.1281744
Tekaya R, Saadi F, Mahmoud I, Saidane O, Abdelmoula LC, Chaabouni L, Zouari R (2012) Assessment of depression in rheumatoid arthritis: a cross sectional study on 60 patients. Presse Med 415:e220–e225
GEO-RA Group (2017) Latitude gradient influences the age of onset of rheumatoid arthritis: a worldwide survey. Clin Rheumatol 36(3):485–497. https://doi.org/10.1007/s10067-016-3481-9
Gabra RH, Ebrahim OS, Osman DMM et al (2020) Knowledge, attitude and health-seeking behavior among family caregivers of mentally ill patients at Assiut University Hospitals: a cross-sectional study. Middle East Curr Psychiatry 27:10 (2020). https://doi.org/10.1186/s43045-020-0015-6
Guerrero-López JB, Cabrera DM, Lara-Mu MDC, García RO (2017) Evaluation of quality of life and depression in patients with rheumatoid arthritis in a General Hospital. Rev Colomb Reumatol 24:199–204
Kwiatkowska B, Kłak A, Maślińska M, Mańczak M, Raciborski F (2018) Factors of depression among patients with rheumatoid arthritis. Reumatologia 56(4):219–227
Steiner G, Smolen J (2002) Autoantibodies in rheumatoid arthritis and their clinical significance. Arthritis Res 4(Suppl 2):S1–S5. https://doi.org/10.1186/ar551
Yousefi F, Mansor MB, Juhari RB (2010) The relationship between gender, age, depression and academic achievement. Curr Res Psychol 6:61–66
Dickens C, McGowan L, Clark D, Creed F (2002) Depression in rheumatoid arthritis: a systematic review of the literature with meta- analysis. Psychosom Med 64:52–60
Maldonado G, Ríos C, Paredes C, Ferro C, Intriago MJ, Aguirre C et al (2017) Depression in rheumatoid arthritis. Rev Colomb Reumatol 24:84–91
Zabsonré WJ, Kaboré F, Nanema D, Savadogo B, Dravé A, Sompougdou C, Ouedraogo M, Ouédraogo D (2019) Frequency and factors associated with depression in rheumatoid arthritis in African Black Patients: case-control study. Open J Rheumatol Autoimmun Dis 09:35–41
Li YC, Chou YC, Chen HC, Lu CC, Chang DM (2019) Interleukin-6 and interleukin-17 are related to depression in patients with rheumatoid arthritis. Int J Rheum Dis 22(6):980–985. https://doi.org/10.1111/1756-185X.13529
Lee CH, Giuliani F (2019) The role of inflammation in depression and fatigue. Front Immunol. 19 10:1696. https://doi.org/10.3389/fimmu.2019.01696
Matcham F, Davies R, Hotopf M, Hyrich K, Norton S, Steer S (2018) Galloway J (2018) The relationship between depression and biologic treatment response in rheumatoid arthritis: an analysis of the British Society for Rheumatology Biologics Register. Rheumatology (Oxford). https://doi.org/10.1093/rheumatology/kex528
Bechman K, Sin FE, Ibrahim F et al (2018) Mental health, fatigue and function are associated with increased risk of disease flare following TNF inhibitor tapering in patients with rheumatoid arthritis: an exploratory analysis of data from the Optimizing TNF Tapering in RA (OPTTIRA) trial. RMD Open 4:e000676
Yayikci Y, Karadag A (2019) Effects of conventional and biological drugs used for the treatment of rheumatoid arthritis on the quality of life and depression. Euras J Med 51(1):12–16. https://doi.org/10.5152/eurasianjmed.2018.18018
Lwin MN, Serhal L, Holroyd C, Edwards CJ (2020, 2020) Rheumatoid arthritis: the impact of mental health on disease: a narrative review. Rheumatol Ther. https://doi.org/10.1007/s40744-020-00217-4
US National Institute of Mental Health (2015) National Survey on Drug Use and Health (NSDUH). https://www.nimh.nih.gov/health/topics/depression/index.shtml. Accessed 25 May 2017
Dworkin RH, O'Connor AB, Audette J, Baron R, Gourlay GK, Haanpaa ML, Kent JL, Krane EJ, Lebel AA, Levy RM, Mackey SC, Mayer J, Miaskowsk C, Raja SN, Rice AS, Schmader KE, Stacey B, Stanos S, Treede RD, Turk DC, Walco GA, Wells CD (2009) Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc 2010 85:S3–S14. https://doi.org/10.4065/mcp.2009.0649
Krishnadas R, Krishnadas R, Cavanagh J (2011) Sustained remission of rheumatoid arthritis with a specific serotonin reuptake inhibitor antidepressant: a case report and review of the literature. J Med Case Rep 5(1):1–5
Wada K, Yamada N, Sati T et al (2001) Corticosteroid-induced psychotic and mood disorders:diagnosis definef by DSM-IV and clinical picture. Psychosomatics 42:461–466
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Participants were in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments and approved by the Research Ethics Committee of Faculty of Medicine for Girls, Al-Azhar University, Cairo, Egypt (approval number 202005250, May 2020).
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Albeltagy, E.S., Elaziz, S.Y.A., Abozaid, S.Y. et al. Interleukin 6, interleukin 17, disease-related and contextual factor association with depression, and its severity in patients with rheumatoid arthritis. Clin Rheumatol 40, 895–904 (2021). https://doi.org/10.1007/s10067-020-05326-7
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DOI: https://doi.org/10.1007/s10067-020-05326-7