The association between obsessive–compulsive disorder (OCD) and Tourette’s/chronic tic disorders (TD/CTD) with autoimmune diseases (ADs) is uncertain. In this nationwide study, we sought to clarify the patterns of comorbidity and familial clustering of a broad range of ADs in individuals with OCD, individuals with TD/CTD and their biological relatives. From a birth cohort of 7 465 455 individuals born in Sweden between 1940 and 2007, we identified 30 082 OCD and 7279 TD/CTD cases in the National Patient Register and followed them up to 31 December 2013. The risk of 40 ADs was evaluated in individuals with OCD, individuals with TD/CTD and their first- (siblings, mothers, fathers), second- (half siblings) and third-degree (cousins) relatives, compared with population controls. Individuals with OCD and TD/CTD had increased comorbidity with any AD (43% and 36%, respectively) and many individual ADs. The risk of any AD and several individual ADs was consistently higher among first-degree relatives than among second- and third-degree relatives of OCD and TD/CTD probands. The risk of ADs was very similar in mothers, fathers and siblings of OCD probands, whereas it tended to be higher in mothers and fathers of TD/CTD probands (compared with siblings). The results suggest a familial link between ADs in general (that is, not limited to Streptococcus-related conditions) and both OCD and TD/CTD. Additional mother-specific factors, such as the placental transmission of antibodies, cannot be fully ruled out, particularly in TD/CTD.
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Atladottir HO, Pedersen MG, Thorsen P, Mortensen PB, Deleuran B, Eaton WW et al. Association of family history of autoimmune diseases and autism spectrum disorders. Pediatrics 2009; 124: 687–694.
Eaton WW, Byrne M, Ewald H, Mors O, Chen CY, Agerbo E et al. Association of schizophrenia and autoimmune diseases: linkage of Danish national registers. Am J Psychiatry 2006 163: 521–528.
Eaton WW, Pedersen MG, Nielsen PR, Mortensen PB. Autoimmune diseases, bipolar disorder, and non-affective psychosis. Bipolar Disord 2010; 12: 638–646.
Swedo SE, Leonard HL, Garvey M, Mittleman B, Allen AJ, Perlmutter S et al. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections: clinical description of the first 50 cases. Am J Psychiatry 1998; 155: 264–271.
Macerollo A, Martino D. Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): an evolving concept. Tremor Other Hyperkinet Mov (N Y) 2013; 3: pii: tre-03-167-4158-7.
Brown RS. Autoimmune thyroid disease: unlocking a complex puzzle. Curr Opin Pediatr 2009; 21: 523–528.
Lernmark A. Environmental factors in the etiology of type 1 diabetes, celiac disease, and narcolepsy. Pediatr Diabetes 2016; 17(Suppl 22): 65–72.
Anaya JM. Common mechanisms of autoimmune diseases (the autoimmune tautology). Autoimmun Rev 2012; 11: 781–784.
Restrepo NA, Butkiewicz M, McGrath JA, Crawford DC. Shared genetic etiology of autoimmune diseases in patients from a biorepository linked to de-identified electronic health records. Front Genet 2016; 7: 185.
Cardenas-Roldan J, Rojas-Villarraga A, Anaya JM. How do autoimmune diseases cluster in families? A systematic review and meta-analysis. BMC Med 2013; 11: 73.
Cooper GS, Bynum ML, Somers EC. Recent insights in the epidemiology of autoimmune diseases: improved prevalence estimates and understanding of clustering of diseases. J Autoimmun 2009; 33: 197–207.
Somers EC, Thomas SL, Smeeth L, Hall AJ. Autoimmune diseases co-occurring within individuals and within families: a systematic review. Epidemiology 2006; 17: 202–217.
Pérez-Vigil A, Fernández de la Cruz L, Brander G, Isomura K, Gromark C, Mataix-Cols D. The link between autoimmune diseases and obsessive-compulsive and tic disorders: a systematic review. Neurosci Biobehav Rev 2016; 71: 542–562.
de Alvarenga PG, Floresi AC, Torres AR, Hounie AG, Fossaluza V, Gentil AF et al. Higher prevalence of obsessive-compulsive spectrum disorders in rheumatic fever. Gen Hosp Psychiatry 2009; 31: 178–180.
Foroughipour M, Behdani F, Hebrani P, Marvast MN, Esmatinia F, Akhavanrezayat A. Frequency of obsessive-compulsive disorder in patients with multiple sclerosis: a cross-sectional study. J Res Med Sci 2012; 17: 248–253.
Toren P, Toren A, Weizman A, Mozes T, Eldar S, Magor A et al. Tourette's disorder: is there an association with the antiphospholipid syndrome? Biol Psychiatry 1994; 35: 495–498.
Murphy T, Storch E, Turner A, Reid J, Tan J, Lewin A. Maternal history of autoimmune disease in children presenting with tics and/or obsessive-compulsive disorder. J Neuroimmunol 2010; 229: 243–247.
Dalsgaard S, Waltoft BL, Leckman JF, Mortensen PB. Maternal history of autoimmune disease and later development of Tourette syndrome in offspring. J Am Acad Child Adolesc Psychiatry 2015; 54: 495–501.
Hounie AG, Pauls DL, do Rosario-Campos MC, Mercadante MT, Diniz JB, De Mathis MA et al. Obsessive-compulsive spectrum disorders and rheumatic fever: a family study. Biol Psychiatry 2007; 61: 266–272.
Seixas AA, Hounie AG, Fossaluza V, Curi M, Alvarenga PG, De Mathis MA et al. Anxiety disorders and rheumatic Fever: is there an association? CNS Spectr 2008; 13: 1039–1046.
Burke PM, Kocoshis S, Neigut D, Sauer J, Chandra R, Orenstein D. Maternal psychiatric disorders in pediatric inflammatory bowel disease and cystic fibrosis. Child Psychiatry Hum Dev 1994; 25: 45–52.
Lee JY, Huerta PT, Zhang J, Kowal C, Bertini E, Volpe BT et al. Neurotoxic autoantibodies mediate congenital cortical impairment of offspring in maternal lupus. Nat Med 2009; 15: 91–96.
Palmeira P, Quinello C, Silveira-Lessa AL, Zago CA, Carneiro-Sampaio M. IgG placental transfer in healthy and pathological pregnancies. Clin Dev Immunol 2012; 2012: 985646.
Lunde AS, Lundeborg S, Lettenstrom GS, Thygesen L, Huebner J. The person-number systems of Sweden, Norway, Denmark, and Israel. Vital Health Stat 2 1980; 84: 1–59.
Rück C, Larsson KJ, Lind K, Pérez-Vigil A, Isomura K, Sariaslan A et al. Validity and reliability of chronic tic disorder and obsessive-compulsive disorder diagnoses in the Swedish National Patient Register. BMJ Open 2015; 5: e007520.
World Health OrganisationManual of International Statistical Classification of Diseases, Injuries, and Causes of Death, Vol I, 8th revision. World Health Organisation: Geneva, 1967.
World Health OrganisationManual of International Statistical Classification of Diseases, Injuries, and Causes of Death, Vol I, 9th revision. World Health Organization: Geneva, 1977.
World Health OrganisationManual of International Statistical Classification of Diseases, Injuries, and Causes of Death, Vol I, 10th revision. World Health Organization: Geneva, 1993.
Ludvigsson JF, Andersson E, Ekbom A, Feychting M, Kim JL, Reuterwall C et al. External review and validation of the Swedish national inpatient register. BMC Public Health 2011; 11: 450.
American Autoimmune Related Diseases Association [Internet] [accessed 10 October 2015]. Available from https://www.aarda.org/disease-list/AARDA.
Waldenlind K, Eriksson JK, Grewin B, Askling J. Validation of the rheumatoid arthritis diagnosis in the Swedish National Patient Register: a cohort study from Stockholm County. BMC Musculoskelet Disord 2014; 15: 432.
Arkema EV, Jonsen A, Ronnblom L, Svenungsson E, Sjowall C, Simard JF. Case definitions in Swedish register data to identify systemic lupus erythematosus. BMJ Open 2016; 6: e007769.
Pettersson E, Larsson H, Lichtenstein P. Common psychiatric disorders share the same genetic origin: a multivariate sibling study of the Swedish population. Mol Psychiatry 2016; 21: 717–721.
Tylee DS, Sun J, Hess JL, Tahir MA, Sharma E, Malik R et al. Genetic correlations among brain-behavioral and immune-related phenotypes based on genome-wide association data. bioRxiv, 070730; doi: https://doi.org/10.1101/070730.
Stewart SE, Yu D, Scharf JM, Neale BM, Fagerness JA, Mathews CA et al. Genome-wide association study of obsessive-compulsive disorder. Mol Psychiatry 2013; 18: 788–798.
Mattheisen M, Samuels JF, Wang Y, Greenberg BD, Fyer AJ, McCracken JT et al. Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS. Mol Psychiatry 2015; 20: 337–344.
Scharf JM, Yu D, Mathews CA, Neale BM, Stewart SE, Fagerness JA et al. Genome-wide association study of Tourette's syndrome. Mol Psychiatry 2013; 18: 721–728.
Roessner V, Hoekstra PJ. European Multicenter Tics in Children Studies (EMTICS): exploring the onset and course of tic disorders. Eur Child Adolesc Psychiatry 2013; 22: 451–452.
Georgitsi M, Willsey AJ, Mathews CA, State M, Scharf JM, Paschou P. The genetic etiology of Tourette syndrome: large-scale collaborative efforts on the precipice of discovery. Front Neurosci 2016; 10: 351.
Network and Pathway Analysis Subgroup of Psychiatric Genomics Consortium. Psychiatric genome-wide association study analyses implicate neuronal, immune and histone pathways. Nat Rev Neurol 2015; 18: 199–209.
Knuesel I, Chicha L, Britschgi M, Schobel SA, Bodmer M, Hellings JA et al. Maternal immune activation and abnormal brain development across CNS disorders. Nat Rev Neurol 2014; 10: 643–660.
Estes ML, McAllister AK. Maternal immune activation: implications for neuropsychiatric disorders. Science 2016; 353: 772–777.
We are grateful to Daniel S Tylee and Stephen J Glatt (Psychiatric Genetic Epidemiology & Neurobiology Laboratory; Departments of Psychiatry and Behavioral Sciences & Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA) for sharing their unpublished data. The study was partly supported by a grant from the Tourette Association of America (DM-C). EF was supported by the Swedish Brain Foundation. APV was supported by a grant from the Alicia Koplowitz Foundation. LFdlC is supported by a Junior Researcher grant from the Swedish Research Council for Health, Working Life and Welfare (FORTE Grant Number 2015-00569). JJC was supported by NIMH Grants R01MH105500 and R01MH110427. CR was supported by a grant from the Swedish Research Council (K2013-61P-22168). We also acknowledge financial support from the Swedish Research Council through the SIMSAM (Swedish Initiative for Research on Microdata in the Social And Medical Sciences) framework Grant No. 340-2013-5867. PL is supported by grants from the Swedish Research Council for Health, Working Life and Welfare and the Swedish Research Council. The funders had no role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decisions to submit the manuscript for publication.
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