Abstract
Purpose
Studies suggested autoimmunity plays a role in the etiology of obsessive–compulsive disorder (OCD). The purpose of this study was to determine if a history of systemic autoimmune diseases (SADs) is associated with an increased risk of subsequent onset of OCD.
Methods
Patients with or without SADs were identified in the Taiwan National Health Insurance Program. The SADs cohort consisted of 63,165, while the comparison cohort consisted of 315,825 patients. The incidence rates of OCD with a maximum follow-up period of 10 years between patients with and without SADs were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI).
Results
The major finding was the discovery of a higher incidence of subsequent OCD among patients with SADs (HR: 1.85; 95% CI 1.41–2.43) after adjusted for other demographic characteristics. Specifically, the risk of OCD was observed to be significant increase in systemic lupus erythematosus (1.65, 1.07–2.54) dermatomyositis (3.25, 1.04–10.17), and Sjögren’s syndrome (2.38, 1.53–3.72). Also, this study revealed some potential risk factors for developing OCD, including younger age (less than or equal to 50-year-old) and some comorbidities (alcohol use disorder, liver cirrhosis, and malignancies). Conversely, this study found that steroid use was a potential protective factor for the development of OCD.
Conclusions
This study confirms that SADs are associated with higher incidence of OCD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.
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References
Veale D, Roberts A (2014) Obsessive-compulsive disorder. BMJ 348:g2183. https://doi.org/10.1136/bmj.g2183
Huang LC, Tsai KJ, Wang HK, Sung PS, Wu MH, Hung KW, Lin SH (2014) Prevalence, incidence, and comorbidity of clinically diagnosed obsessive-compulsive disorder in Taiwan: a national population-based study. Psychiatry Res 220(1–2):335–341. https://doi.org/10.1016/j.psychres.2014.08.011
Mataix-Cols D, Boman M, Monzani B, Ruck C, Serlachius E, Langstrom N, Lichtenstein P (2013) Population-based, multigenerational family clustering study of obsessive-compulsive disorder. JAMA Psychiatry 70(7):709–717. https://doi.org/10.1001/jamapsychiatry.2013.3
den Braber A, Zilhao NR, Fedko IO, Hottenga JJ, Pool R, Smit DJ, Cath DC, Boomsma DI (2016) Obsessive-compulsive symptoms in a large population-based twin-family sample are predicted by clinically based polygenic scores and by genome-wide SNPs. Transl Psychiatry 6:e731. https://doi.org/10.1038/tp.2015.223
Stewart SE, Yu D, Scharf JM, Neale BM, Fagerness JA, Mathews CA, Arnold PD, Evans PD, Gamazon ER, Davis LK, Osiecki L, McGrath L, Haddad S, Crane J, Hezel D, Illman C, Mayerfeld C, Konkashbaev A, Liu C, Pluzhnikov A, Tikhomirov A, Edlund CK, Rauch SL, Moessner R, Falkai P, Maier W, Ruhrmann S, Grabe HJ, Lennertz L, Wagner M, Bellodi L, Cavallini MC, Richter MA, Cook EH Jr, Kennedy JL, Rosenberg D, Stein DJ, Hemmings SM, Lochner C, Azzam A, Chavira DA, Fournier E, Garrido H, Sheppard B, Umana P, Murphy DL, Wendland JR, Veenstra-VanderWeele J, Denys D, Blom R, Deforce D, Van Nieuwerburgh F, Westenberg HG, Walitza S, Egberts K, Renner T, Miguel EC, Cappi C, Hounie AG, Conceicao do Rosario M, Sampaio AS, Vallada H, Nicolini H, Lanzagorta N, Camarena B, Delorme R, Leboyer M, Pato CN, Pato MT, Voyiaziakis E, Heutink P, Cath DC, Posthuma D, Smit JH, Samuels J, Bienvenu OJ, Cullen B, Fyer AJ, Grados MA, Greenberg BD, McCracken JT, Riddle MA, Wang Y, Coric V, Leckman JF, Bloch M, Pittenger C, Eapen V, Black DW, Ophoff RA, Strengman E, Cusi D, Turiel M, Frau F, Macciardi F, Gibbs JR, Cookson MR, Singleton A, North American Brain Expression C, Hardy J, Database UKBE, Crenshaw AT, Parkin MA, Mirel DB, Conti DV, Purcell S, Nestadt G, Hanna GL, Jenike MA, Knowles JA, Cox N, Pauls DL (2013) Genome-wide association study of obsessive-compulsive disorder. Mol Psychiatry 18(7):788–798. https://doi.org/10.1038/mp.2012.85
Taylor S (2013) Molecular genetics of obsessive-compulsive disorder: a comprehensive meta-analysis of genetic association studies. Mol Psychiatry 18(7):799–805. https://doi.org/10.1038/mp.2012.76
Harrison BJ, Soriano-Mas C, Pujol J, Ortiz H, Lopez-Sola M, Hernandez-Ribas R, Deus J, Alonso P, Yucel M, Pantelis C, Menchon JM, Cardoner N (2009) Altered corticostriatal functional connectivity in obsessive-compulsive disorder. Arch Gen Psychiatry 66(11):1189–1200. https://doi.org/10.1001/archgenpsychiatry.2009.152
Greenberg BD, Rauch SL, Haber SN (2010) Invasive circuitry-based neurotherapeutics: stereotactic ablation and deep brain stimulation for OCD. Neuropsychopharmacology 35(1):317–336. https://doi.org/10.1038/npp.2009.128
Murphy DL, Timpano KR, Wheaton MG, Greenberg BD, Miguel EC (2010) Obsessive-compulsive disorder and its related disorders: a reappraisal of obsessive-compulsive spectrum concepts. Dialogues Clin Neurosci 12(2):131–148
Arnold PD, Richter MA (2001) Is obsessive-compulsive disorder an autoimmune disease? CMAJ 165(10):1353–1358
Murphy TK, Sajid M, Soto O, Shapira N, Edge P, Yang M, Lewis MH, Goodman WK (2004) Detecting pediatric autoimmune neuropsychiatric disorders associated with streptococcus in children with obsessive-compulsive disorder and tics. Biol Psychiatry 55(1):61–68
Perez-Vigil A, Fernandez de la Cruz L, Brander G, Isomura K, Gromark C, Mataix-Cols D (2016) The link between autoimmune diseases and obsessive-compulsive and tic disorders: a systematic review. Neurosci Biobehav Rev 71:542–562. https://doi.org/10.1016/j.neubiorev.2016.09.025
Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S, Lougee L, Dow S, Zamkoff J, Dubbert BK (1998) Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 155(2):264–271. https://doi.org/10.1176/ajp.155.2.264
Cunningham MW (2014) Rheumatic fever, autoimmunity, and molecular mimicry: the streptococcal connection. Int Rev Immunol 33(4):314–329. https://doi.org/10.3109/08830185.2014.917411
Esposito S, Bianchini S, Baggi E, Fattizzo M, Rigante D (2014) Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: an overview. Eur J Clin Microbiol Infect Dis 33(12):2105–2109. https://doi.org/10.1007/s10096-014-2185-9
Slattery MJ, Dubbert BK, Allen AJ, Leonard HL, Swedo SE, Gourley MF (2004) Prevalence of obsessive-compulsive disorder in patients with systemic lupus erythematosus. J Clin Psychiatry 65(3):301–306
Miller AH, Maletic V, Raison CL (2009) Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biol Psychiatry 65(9):732–741. https://doi.org/10.1016/j.biopsych.2008.11.029
Rao NP, Venkatasubramanian G, Ravi V, Kalmady S, Cherian A, Yc JR (2015) Plasma cytokine abnormalities in drug-naive, comorbidity-free obsessive-compulsive disorder. Psychiatry Res 229(3):949–952. https://doi.org/10.1016/j.psychres.2015.07.009
Lougee L, Perlmutter SJ, Nicolson R, Garvey MA, Swedo SE (2000) Psychiatric disorders in first-degree relatives of children with pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS). J Am Acad Child Adolesc Psychiatry 39(9):1120–1126. https://doi.org/10.1097/00004583-200009000-00011
Hounie AG, Pauls DL, do Rosario-Campos MC, Mercadante MT, Diniz JB, De Mathis MA, De Mathis ME, Chacon P, Shavitt RG, Curi M, Guilherme L, Miguel EC (2007) Obsessive-compulsive spectrum disorders and rheumatic fever: a family study. Biol Psychiatry 61(3):266–272. https://doi.org/10.1016/j.biopsych.2006.02.021
Seixas AA, Hounie AG, Fossaluza V, Curi M, Alvarenga PG, De Mathis MA, De Mathis ME, Vallada H, Pauls D, de Braganca Pereira CA, Miguel EC (2008) Anxiety disorders and rheumatic fever: is there an association? CNS Spectr 13(12):1039–1046
Murphy TK, Storch EA, Turner A, Reid JM, Tan J, Lewin AB (2010) Maternal history of autoimmune disease in children presenting with tics and/or obsessive-compulsive disorder. J Neuroimmunol 229(1–2):243–247. https://doi.org/10.1016/j.jneuroim.2010.08.017
Callen JP, Wortmann RL (2006) Dermatomyositis. Clin Dermatol 24(5):363–373. https://doi.org/10.1016/j.clindermatol.2006.07.001
Achtman J, Kling MA, Feng R, Okawa J, Werth VP (2016) A cross-sectional study of untreated depression and anxiety in cutaneous lupus erythematosus and dermatomyositis. J Am Acad Dermatol 74(2):377–379. https://doi.org/10.1016/j.jaad.2015.09.016
Mavragani CP, Moutsopoulos HM (2014) Sjogren’s syndrome. Annu Rev Pathol 9:273–285. https://doi.org/10.1146/annurev-pathol-012513-104728
Cox PD, Hales RE (1999) CNS Sjogren’s syndrome: an underrecognized and underappreciated neuropsychiatric disorder. J Neuropsychiatry Clin Neurosci 11(2):241–247. https://doi.org/10.1176/jnp.11.2.241
Shen CC, Yang AC, Kuo BI, Tsai SJ (2015) Risk of psychiatric disorders following primary sjogren syndrome: a nationwide population-based retrospective cohort study. J Rheumatol 42(7):1203–1208. https://doi.org/10.3899/jrheum.141361
Fedoroff I, Sobell LC, Agrawal S, Sobell MB, Gavin DR (1999) Evaluation of the Yale-Brown Obsessive Compulsive Scale (YBOCS-hd) for heavy drinking with mild to moderately dependent alcohol abusers. Alcohol Clin Exp Res 23(9):1477–1483
Campos LM, Yoshimi NT, Simao MO, Torresan RC, Torres AR (2015) Obsessive-compulsive symptoms among alcoholics in outpatient treatment: prevalence, severity and correlates. Psychiatry Res 229(1–2):401–409. https://doi.org/10.1016/j.psychres.2015.05.111
Ko FY, Tsai SJ, Yang AC, Zhou Y, Xu LM (2013) Association of CD8 T cells with depression and anxiety in patients with liver cirrhosis. Int J Psychiatry Med 45(1):15–29. https://doi.org/10.2190/PM.45.1.b
Kocabayoglu P, Friedman SL (2013) Cellular basis of hepatic fibrosis and its role in inflammation and cancer. Front Biosci (Schol Ed) 5:217–230
Shen CC, Hu LY, Hu YW, Chang WH, Tang PL, Chen PM, Chen TJ, Su TP (2016) The risk of cancer in patients with obsessive-compulsive disorder: a nationwide population-based retrospective cohort study. Medicine (Baltimore) 95(9):e2989. https://doi.org/10.1097/MD.0000000000002989
Acknowledgements
The authors would like to thank Shinn-Zong Lin for the cross-hospital integration.
Funding
This study is supported in part by Taiwan Ministry of Health and Welfare Clinical Trial Center (MOHW107-TDU-B-212-123004), China Medical University Hospital (DMR-107-192), Academia Sinica Taiwan Biobank Stroke Biosignature Project (BM10701010021), NRPB Stroke Clinical Trial Consortium (MOST 106-2321-B-039-005), Tseng-Lien Lin Foundation, Taichung, Taiwan, Taiwan Brain Disease Foundation, Taipei, Taiwan, and Katsuzo and Kiyo Aoshima Memorial Funds, Japan.
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Wang, LY., Chen, SF., Chiang, JH. et al. Systemic autoimmune diseases are associated with an increased risk of obsessive–compulsive disorder: a nationwide population-based cohort study. Soc Psychiatry Psychiatr Epidemiol 54, 507–516 (2019). https://doi.org/10.1007/s00127-018-1622-y
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DOI: https://doi.org/10.1007/s00127-018-1622-y