Increased risks of psychiatric disorders in patients with primary Sjögren’s syndrome—a secondary cohort analysis of nationwide, population-based health claim data

  • Min-Chih Hsieh
  • Chia-Wen Hsu
  • Ming-Chi LuEmail author
  • Malcolm KooEmail author
Original Article



Primary Sjögren’s syndrome (pSS) is a chronic systemic autoimmune disease. The aim of this study was to investigate the risk of five common psychiatrist-diagnosed disorders in patients with pSS.


Using Taiwan’s National Health Insurance Research Database, 688 patients with newly diagnosed pSS between 2000 and 2012 were identified. Two comparison cohorts were assembled, namely, 3440 patients without pSS and 1302 newly diagnosed patients with rheumatoid arthritis. The incidences of depressive disorder, anxiety disorder, bipolar disorder, sleep disorder, and schizophrenia between the pSS cohort and the comparison cohorts were compared using Poisson regression models.


Patients with pSS exhibited a significantly higher risk of developing depressive disorder (adjusted incidence rate ratio [aIRR] = 2.11, p < 0.001), anxiety disorder (aIRR = 2.20, p < 0.001), and sleep disorder (aIRR = 1.76, p = 0.012) when compared with the non-pSS cohort. The risks of developing depressive, anxiety, and sleep disorders were also significantly increased when compared to the rheumatoid arthritis comparison cohort. When the analyses were stratified by sex, depressive disorder (aIRR = 2.10, p < 0.001), anxiety disorder (aIRR = 2.02, p = 0.001), and sleep disorder (aIRR = 1.74, p = 0.022) were found to be significantly increased in female patients with pSS. However, only anxiety disorder (aIRR = 4.88, p = 0.044) was also significantly increased in male patients with pSS. The peak age group of developing depressive disorder was 65–80 years old (aIRR = 3.46, p < 0.001).


In this retrospective cohort study based on population-based claim data, significantly increased incidences of depressive disorder, anxiety disorder, and sleep disorder were observed in patients with pSS.

Key Points

• Patients, particularly women, with primary Sjögren’s syndrome exhibited a significantly higher risk of developing depressive disorder, anxiety disorder, and sleep disorder.

• The peak age group of developing depressive disorder was 65–80 years old.


Anxiety Depression Primary Sjögren’s syndrome Sleep disorder 



This study is based in part on data from the National Health Insurance Research Database provided by the National Health Insurance Administration, Ministry of Health and Welfare and managed by the National Health Research Institutes, Taiwan. The interpretation and conclusions contained herein do not represent those of the National Health Insurance Administration, Ministry of Health and Welfare or the National Health Research Institutes, Taiwan.

Compliance with ethical standards

The study protocol was reviewed and approved by the Institutional Review Board of the Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taiwan (Nos. B10104020 and B10004021).




  1. 1.
    Fox RI (2005) Sjögren’s syndrome. Lancet 366(9482):321–331CrossRefPubMedGoogle Scholar
  2. 2.
    Bowman SJ (2018) Primary Sjögren’s syndrome. Lupus 27(1_suppl):32–35CrossRefPubMedGoogle Scholar
  3. 3.
    Weng MY, Huang YT, Liu MF, Lu TH (2011) Incidence and mortality of treated primary Sjögren's syndrome in Taiwan: a population-based study. J Rheumatol 38(4):706–708CrossRefPubMedGoogle Scholar
  4. 4.
    Kang JH, Lin HC (2010) Comorbidities in patients with primary Sjögren’s syndrome: a registry-based case-control study. J Rheumatol 37(6):1188–1194CrossRefPubMedGoogle Scholar
  5. 5.
    Cui Y, Li L, Yin R, Zhao Q, Chen S, Zhang Q, Shen B (2018) Depression in primary Sjögren’s syndrome: a systematic review and meta-analysis. Psychol Health Med 23(2):198–209CrossRefPubMedGoogle Scholar
  6. 6.
    Wan KH, Chen LJ, Young AL (2016) Depression and anxiety in dry eye disease: a systematic review and meta-analysis. Eye (Lond) 30(12):1558–1567CrossRefGoogle Scholar
  7. 7.
    Tishler M, Barak Y, Paran D, Yaron M (1997) Sleep disturbances, fibromyalgia and primary Sjögren’s syndrome. Clin Exp Rheumatol 15(1):71–74PubMedGoogle Scholar
  8. 8.
    Wang LY, Chiang JH, Chen SF, Shen YC (2018) Systemic autoimmune diseases are associated with an increased risk of bipolar disorder: a nationwide population-based cohort study. J Affect Disord 227:31–37CrossRefPubMedGoogle Scholar
  9. 9.
    Lin CE (2016) One patient with Sjögren’s syndrome presenting schizophrenia-like symptoms. Neuropsychiatr Dis Treat 12:661–663CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Eaton WW, Byrne M, Ewald H, Mors O, Chen CY, Agerbo E, Mortensen PB (2006) Association of schizophrenia and autoimmune diseases: linkage of Danish national registers. Am J Psychiatry 163(3):521–528CrossRefPubMedGoogle Scholar
  11. 11.
    Shen CC, Yang AC, Kuo BI, Tsai SJ (2015) Risk of psychiatric disorders following primary Sjögren syndrome: a nationwide population-based retrospective cohort study. J Rheumatol 42(7):1203–1208CrossRefPubMedGoogle Scholar
  12. 12.
    National Health Insurance Administration. Ministry of Health and Welfare, Taiwan. Handbook of Taiwan’s National Health Insurance. 2018–2019. Accessed 20 May 2019
  13. 13.
    Vitali C, Bombardieri S, Moutsopoulos HM, Balestrieri G, Bencivelli W, Bernstein RM, Bjerrum KB, Braga S, Coll J, de Vita S et al (1993) Preliminary classification criteria for Sjögren’s syndrome. Results of a prospective concerted action supported by the European community. Arthritis Rheum 36(3):340–347CrossRefPubMedGoogle Scholar
  14. 14.
    Vitali C, Bombardieri S, Jonsson R, Moutsopoulos HM, Alexander EL, Carsons SE, Daniels TE, Fox PC, Fox RI, Kassan SS, Pillemer SR, Talal N, Weisman MH, European Study Group on Classification Criteria for Sjögren’s Syndrome (2002) Classification criteria for Sjögren’s syndrome: a revised version of the European criteria proposed by the American-European Consensus Group. Ann Rheum Dis 61(6):554–558CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, Healey LA, Kaplan SR, Liang MH, Luthra HS et al (1988) The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 31(3):315–324CrossRefGoogle Scholar
  16. 16.
    Shen CC, Hu LY, Yang AC, Kuo BI, Chiang YY, Tsai SJ (2016) Risk of psychiatric disorders following ankylosing spondylitis: a nationwide population-based retrospective cohort study. J Rheumatol 43(3):625–631CrossRefPubMedGoogle Scholar
  17. 17.
    Lass P, Krajka-Lauer J, Homziuk M, Iwaszkiewicz-Bilikiewicz B, Koseda M, Hebanowski M, Lyczak P (2000) Cerebral blood flow in Sjögren’s syndrome using 99Tcm-HMPAO brain SPET. Nucl Med Commun 21(1):31–35CrossRefPubMedGoogle Scholar
  18. 18.
    Pertovaara M, Silvennoinen O, Isomäki P (2016) Cytokine-induced STAT1 activation is increased in patients with primary Sjögren’s syndrome. Clin Immunol 165:60–67CrossRefPubMedGoogle Scholar
  19. 19.
    Grygiel-Górniak B, Limphaibool N, Puszczewicz M (2019) Cytokine secretion and the risk of depression development in patients with connective tissue diseases. Psychiatry Clin Neurosci 73(6):302–316CrossRefPubMedGoogle Scholar
  20. 20.
    Hou R, Garner M, Holmes C, Osmond C, Teeling J, Lau L, Baldwin DS (2017) Peripheral inflammatory cytokines and immune balance in generalised anxiety disorder: case-controlled study. Brain Behav Immun 62:212–218CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    de Oliveira FR, Fantucci MZ, Adriano L, Valim V, Cunha TM, Louzada-Junior P, Rocha EM (2018) Neurological and inflammatory manifestations in Sjögren’s syndrome: the role of the kynurenine metabolic pathway. Int J Mol Sci 19(12):3953CrossRefPubMedCentralGoogle Scholar
  22. 22.
    Hackett KL, Gotts ZM, Ellis J, Deary V, Rapley T, Ng WF, Newton JL, Deane KH (2016) An investigation into the prevalence of sleep disturbances in primary Sjögren’s syndrome: a systematic review of the literature. Rheumatology (Oxford) 56(4):570–580Google Scholar
  23. 23.
    Milin M, Cornec D, Chastaing M, Griner V, Berrouiguet S, Nowak E, Marhadour T, Saraux A, Devauchelle-Pensec V (2016) Sicca symptoms are associated with similar fatigue, anxiety, depression, and quality-of-life impairments in patients with and without primary Sjogren’s syndrome. Joint Bone Spine 83(6):681–685CrossRefPubMedGoogle Scholar
  24. 24.
    Kuehner C (2017) Why is depression more common among women than among men? Lancet Psychiatry 4(2):146–158CrossRefPubMedGoogle Scholar
  25. 25.
    Li SH, Graham BM (2017) Why are women so vulnerable to anxiety, trauma-related and stress-related disorders? The potential role of sex hormones. Lancet Psychiatry 4(1):73–82CrossRefPubMedGoogle Scholar
  26. 26.
    Michael T, Zetsche U, Margraf J (2007) Epidemiology of anxiety disorders. Psychiatry 6(4):136–142CrossRefGoogle Scholar
  27. 27.
    Kessler RC, Bromet EJ (2013) The epidemiology of depression across cultures. Annu Rev Public Health 34:119–138CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Seror R Ravaud P, Bowman SJ, Baron G, Tzioufas A, Theander E, Gottenberg JE, Bootsma H, Mariette X, Vitali C, EULAR Sjögren’s Task Force (2010) EULAR Sjogren’s syndrome disease activity index: development of a consensus systemic disease activity index for primary Sjogren’s syndrome. Ann Rheum Dis 69(6):1103–1109CrossRefPubMedGoogle Scholar
  29. 29.
    Seror R, Ravaud P, Mariette X, Bootsma H, Theander E, Hansen A, Ramos-Casals M, Dörner T, Bombardieri S, Hachulla E et al (2011) EULAR Sjogren’s syndrome patient reported index (ESSPRI): development of a consensus patient index for primary Sjogren’s syndrome. Ann Rheum Dis 70(6):968–972CrossRefPubMedGoogle Scholar

Copyright information

© International League of Associations for Rheumatology (ILAR) 2019

Authors and Affiliations

  1. 1.Division of Obstetrics and Gynecology, Dalin Tzu Chi HospitalBuddhist Tzu Chi Medical FoundationChiayiTaiwan
  2. 2.School of MedicineTzu Chi UniversityHualienTaiwan
  3. 3.Department of Medical Research, Dalin Tzu Chi HospitalBuddhist Tzu Chi Medical FoundationChiayiTaiwan
  4. 4.Division of Allergy, Immunology and Rheumatology, Dalin Tzu Chi HospitalBuddhist Tzu Chi Medical FoundationChiayiTaiwan
  5. 5.Graduate Institute of Long-term CareTzu Chi University of Science and TechnologyHualienTaiwan
  6. 6.Dalla Lana School of Public HealthUniversity of TorontoTorontoCanada

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