Bidirectional relationship between eating disorders and autoimmune diseases
Anna Hedman
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorLauren Breithaupt
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Department of Psychology, George Mason University, Fairfax, VA, USA
Search for more papers by this authorChristopher Hübel
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
Search for more papers by this authorLaura M. Thornton
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Search for more papers by this authorAnnika Tillander
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Department of Computer and Information Science, Linköping University, Linköping, Sweden
Search for more papers by this authorClaes Norring
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
Search for more papers by this authorAndreas Birgegård
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
Search for more papers by this authorHenrik Larsson
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
School of Medical Sciences, Örebro University, Örebro, Sweden
Search for more papers by this authorJonas F. Ludvigsson
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
Search for more papers by this authorLars Sävendahl
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorCatarina Almqvist
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Pediatric Allergy and Pulmonology Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
Search for more papers by this authorCorresponding Author
Cynthia M. Bulik
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Correspondence
Cynthia M. Bulik, Department of Psychiatry, University of North Carolina at Chapel Hill, CB #7160, 101 Manning Drive, Chapel Hill, NC 27599-7160, USA; Email: [email protected]
Search for more papers by this authorAnna Hedman
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorLauren Breithaupt
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Department of Psychology, George Mason University, Fairfax, VA, USA
Search for more papers by this authorChristopher Hübel
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, UK
Search for more papers by this authorLaura M. Thornton
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Search for more papers by this authorAnnika Tillander
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Department of Computer and Information Science, Linköping University, Linköping, Sweden
Search for more papers by this authorClaes Norring
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
Search for more papers by this authorAndreas Birgegård
Department of Clinical Neuroscience, Centre for Psychiatry Research, Karolinska Institutet, & Stockholm Health Care Services, Stockholm County Council, Stockholm, Sweden
Search for more papers by this authorHenrik Larsson
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
School of Medical Sciences, Örebro University, Örebro, Sweden
Search for more papers by this authorJonas F. Ludvigsson
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Department of Pediatrics, Örebro University Hospital, Örebro, Sweden
Search for more papers by this authorLars Sävendahl
Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
Search for more papers by this authorCatarina Almqvist
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Pediatric Allergy and Pulmonology Unit, Astrid Lindgren Children's Hospital, Karolinska University Hospital, Stockholm, Sweden
Search for more papers by this authorCorresponding Author
Cynthia M. Bulik
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
Correspondence
Cynthia M. Bulik, Department of Psychiatry, University of North Carolina at Chapel Hill, CB #7160, 101 Manning Drive, Chapel Hill, NC 27599-7160, USA; Email: [email protected]
Search for more papers by this authorAbstract
Background
Immune system dysfunction may be associated with eating disorders (ED) and could have implications for detection, risk assessment, and treatment of both autoimmune diseases and EDs. However, questions regarding the nature of the relationship between these two disease entities remain. We evaluated the strength of associations for the bidirectional relationships between EDs and autoimmune diseases.
Methods
In this nationwide population-based study, Swedish registers were linked to establish a cohort of more than 2.5 million individuals born in Sweden between January 1, 1979 and December 31, 2005 and followed up until December 2013. Cox proportional hazard regression models were used to investigate: (a) subsequent risk of EDs in individuals with autoimmune diseases; and (b) subsequent risk of autoimmune diseases in individuals with EDs.
Results
We observed a strong, bidirectional relationship between the two illness classes indicating that diagnosis in one illness class increased the risk of the other. In women, the diagnoses of autoimmune disease increased subsequent hazards of anorexia nervosa (AN), bulimia nervosa (BN), and other eating disorders (OED). Similarly, AN, BN, and OED increased subsequent hazards of autoimmune diseases.Gastrointestinal-related autoimmune diseases such as, celiac disease and Crohn's disease showed a bidirectional relationship with AN and OED. Psoriasis showed a bidirectional relationship with OED. The previous occurence of type 1 diabetes increased the risk for AN, BN, and OED. In men, we did not observe a bidirectional pattern, but prior autoimmune arthritis increased the risk for OED.
Conclusions
The interactions between EDs and autoimmune diseases support the previously reported associations. The bidirectional risk pattern observed in women suggests either a shared mechanism or a third mediating variable contributing to the association of these illnesses.
Supporting Information
| Filename | Description |
|---|---|
| jcpp12958-sup-0001-TableS1-S5.docxWord document, 55.1 KB |
Table S1. Table of references of previous association of autoimmune diseases and eating disorders. Table S2. Autoimmune disease diagnostic codes for Swedish ICD-Revisions 8 and 9 and for ICD-10. Table S3a. Hazard ratios evaluating subsequent risk of eating disorders in men with autoimmune diseases. Table S3b. Hazard ratios evaluating subsequent risk of eating disorders in women with autoimmune diseases. Table S4a. Hazard ratios evaluating subsequent risk of autoimmune diseases in men with eating disorders. Table S4b. Hazard ratios evaluating subsequent risk of autoimmune diseases in women with eating disorders. Table S5. Temporal proximity between first and second diagnosis. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- Abella, V., Scotece, M., Conde, J., Pino, J., Gonzalez-Gay, M.A., Gómez-Reino, J.J., … & Gualillo, O. (2017). Leptin in the interplay of inflammation, metabolism and immune system disorders. Nature Reviews Rheumatology, 13, 100–109.
- Ackard, D.M., Vik, N., Neumark-Sztainer, D., Schmitz, K.H., Hannan, P., & Jacobs, D.R., Jr (2008). Disordered eating and body dissatisfaction in adolescents with type 1 diabetes and a population-based comparison sample. Pediatric Diabetes, 9, 312–319.
- Almagro, J.R., Almagro, D.R., Ruiz, C.S., González, J.S., & Martínez, A.H. (2018). The experience of living with a gluten-free diet. Gastroenterology Nursing, 41, 189–200.
- American Psychiatric Association (2005). Diagnostic and statistical manual of mental disorders ( 4th edn, text rev.). Washington, DC: Author.
- Araia, E., Hendrieckx, C., Skinner, T., Pouwer, F., Speight, J., & King, R.M. (2017). Gender differences in disordered eating behaviors and body dissatisfaction among adolescents with type 1 diabetes: Results from diabetes MILES youth-Australia. International Journal of Eating Disorders, 50, 1183–1193.
- Arigo, D., Anskis, A.M., & Smyth, J.M. (2012). Psychiatric comorbidities in women with celiac disease. Chronic Illness, 8, 45–55.
- Barrett, J.C., Clayton, D.G., Concannon, P., Akolkar, B., Cooper, J.D., Erlich, H.A., … & Type 1 Diabetes Genetics Consortium (2009). Genome-wide association study and meta-analysis find that over 40 loci affect risk of type 1 diabetes. Nature Genetics, 41, 703–707.
- Benjamini, Y., & Hochberg, Y. (2000). On the adaptive control of the false discovery rate in multiple testing with independent statistics. Journal of Educational and Behavioral Statistics, 25, 60–83.
- Benros, M.E., Pedersen, M.G., Rasmussen, H., Eaton, W.W., Nordentoft, M., & Mortensen, P.B. (2014). A nationwide study on the risk of autoimmune diseases in individuals with a personal or a family history of schizophrenia and related psychosis. American Journal of Psychiatry, 171, 218–226.
- Birgegård, A., Björck, C., & Clinton, D. (2010). Quality assurance of specialised treatment of eating disorders using large-scale Internet-based collection systems: Methods, results and lessons learned from designing the Stepwise database. European Eating Disorders Review, 18, 251–259.
- Bryden, K.S., Neil, A., Mayou, R.A., Peveler, R.C., Fairburn, C.G., & Dunger, D.B. (1999). Eating habits, body weight, and insulin misuse. Diabetes Care, 22, 1956–1960.
- Bulik, C.M., Sullivan, P.F., Tozzi, F., Furberg, H., Lichtenstein, P., & Pedersen, N.L. (2006). Prevalence, heritability, and prospective risk factors for anorexia nervosa. Archives of General Psychiatry, 63, 305–312. Erratum in: (2008). Archives of General Psychiatry, 65, 1061.
- Carr, J., Kleiman, S.C., Bulik, C.M., Bulik-Sullivan, E.C., & Carroll, I.M. (2016). Can attention to the intestinal microbiota improve understanding and treatment of anorexia nervosa? Expert Review of Gastroenterology and Hepatology, 10, 565–569.
- Chiaroni-Clarke, R.C., Munro, J.E., & Ellis, J.A. (2016). Sex bias in paediatric autoimmune disease - Not just about sex hormones? Journal of Autoimmunity, 69, 12–23.
- Colton, P.A., Olmsted, M.P., Daneman, D., Farquhar, J.C., Wong, H., Muskat, S., & Rodin, G.M. (2015). Eating disorders in girls and women with type 1 diabetes. Diabetes Care, 38, 1212–1217.
- Crosta, M.L., Caldarola, G., Fraietta, S., Craba, A., Benedetti, C., Coco, V., … & De Simone, C. (2014). Psychopathology and eating disorders in patients with psoriasis. Giornale Italiano Di Dermatologia E Venereologia, 149, 355–361.
- Duncan, L., Yilmaz, Z., Gaspar, H., Walters, R., Goldstein, J., Anttila, V., … & Bulik, C.M. (2017). Significant locus and metabolic genetic correlations revealed in genome-wide association study of anorexia nervosa. American Journal of Psychiatry, 174, 850–858.
- Eaton, W.W., Byrne, M., Ewald, H., Mors, O., Chen, C.-Y., Agerbo, E., & Mortensen, P.B. (2006). Association of schizophrenia and autoimmune diseases: Linkage of Danish national registers. American Journal of Psychiatry, 163, 521–528.
- Emilsson, L., Lindahl, B., Köster, M., Lambe, M., & Ludvigsson, J.F. (2015). Review of 103 Swedish healthcare quality registries. Journal of Internal Medicine, 277, 94–136.
- Euesden, J., Danese, A., Lewis, C.M., & Maughan, B. (2017). A bidirectional relationship between depression and the autoimmune disorders - New perspectives from the National Child Development Study. PLoS ONE, 12, e0173015.
- Ferreira, B.I., Abreu, J.L., Reis, J.P., & Figueiredo, A.M. (2016). Psoriasis and associated psychiatric disorders. Journal of Clinical and Aesthetic Dermatology, 9, 36–43.
- Fetissov, S.O., Hallman, J., Oreland, L., af Klinteberg, B., Grenbäck, E., Hulting, A.-L., & Hökfelt, T. (2002). Autoantibodies against α-MSH, ACTH, and LHRH in anorexia and bulimia nervosa patients. Proceedings of the National Academy of Sciences, 99, 17155–17160.
- Fetissov, S.O., Hamze Sinno, M., Coquerel, Q., Do Rego, J.C., Coëffier, M., Gilbert, D., … & Déchelotte, P. (2008). Emerging role of autoantibodies against appetite-regulating neuropeptides in eating disorders. Nutrition, 24, 854–859.
- Fetissov, S.O., Harro, J., Jaanisk, M., Järv, A., Podar, I., Allik, J., … & Hökfelt, T. (2005). Autoantibodies against neuropeptides are associated with psychological traits in eating disorders. Proceedings of the National Academy of Sciences of the United States of America, 102, 14865–14870.
- Frick, L., & Pittenger, C. (2016). Microglial dysregulation in OCD, Tourette Syndrome, and PANDAS. Journal of Immunology Research, 2016, 8606057.
- Golden, N.H., & Park, K.T. (2017). Celiac disease and anorexia nervosa—an association well worth considering. Pediatrics, 139, e20170545.
- Hafström, I., Ringertz, B., Gyllenhammar, H., Palmblad, J., & Harms-Ringdahl, M. (1988). Effects of fasting on disease activity, neutrophil function, fatty acid composition, and leukotriene biosynthesis in patients with rheumatoid arthritis. Arthritis and Rheumatism, 31, 585–592.
- Hudson, J.I., Hiripi, E., Pope, H.G., Jr, & Kessler, R.C. (2007). The prevalence and correlates of eating disorders in the National Comorbidity Survey Replication. Biological Psychiatry, 61, 348–358.
- Ilzarbe, L., Fàbrega, M., Quintero, R., Bastidas, A., Pintor, L., García-Campayo, J., … & Ilzarbe, D. (2017). Inflammatory bowel disease and eating disorders. Journal of Psychosomatic Research, 102, 47–53.
- Javaras, K.N., Runfola, C.D., Thornton, L.M., Agerbo, E., Birgegård, A., Norring, C., … & Bulik, C.M. (2015). Sex- and age-specific incidence of healthcare-register-recorded eating disorders in the complete Swedish 1979-2001 birth cohort. International Journal of Eating Disorders, 48, 1070–1081.
- Karwautz, A., Wagner, G., Berger, G., Sinnreich, U., Grylli, V., & Huber, W.D. (2008). Eating pathology in adolescents with celiac disease. Psychosomatics, 49, 399–406.
- Khan, D., & Ansar Ahmed, S. (2015). The immune system is a natural target for estrogen actions. Frontiers in Immunology, 6, 635.
- Klein, S.L., & Flanagan, K.L. (2016). Sex differences in immune responses. Nature Reviews Immunology, 16, 626–638.
- Klump, K.L., Culbert, K.M., & Sisk, C.L. (2017). Sex differences in binge eating: Gonadal hormone effects across development. Annual Review of Clinical Psychology, 13, 183–207.
- Lane, E.R., Zisman, T.L., & Suskind, D.L. (2017). The microbiota in inflammatory bowel disease. Journal of Inflammation Research, 10, 63–73.
- Lindevall, O. (2009). Pastill—a comprehensive clinical database for child and adolescent psychiatry in Stockholm. Budapest: European Society for Child and Adolescent Psychiatry.
- Ludvigsson, J.F., Almqvist, C., Bonamy, A.-K.E., Ljung, R., Michaëlsson, K., Neovius, M., … & Ye, W. (2016). Registers of the Swedish total population and their use in medical research. European Journal of Epidemiology, 31, 125–136.
- Ludvigsson, J.F., Andersson, E., Ekbom, A., Feychting, M., Kim, J.-L., Reuterwall, C., … & Olausson, P.O. (2011). External review and validation of the Swedish national inpatient register. BMC Public Health, 11, 450.
- Ludvigsson, J.F., Otterblad-Olausson, P., Pettersson, B.U., & Ekbom, A. (2009). The Swedish personal identity number: Possibilities and pitfalls in healthcare and medical research. European Journal of Epidemiology, 24, 659–667.
- Mårild, K., Størdal, K., Bulik, C.M., Rewers, M., Ekbom, A., Liu, E., & Ludvigsson, J.F. (2017). Celiac disease and anorexia nervosa. Pediatrics, 139, e20164367.
- Mazzone, L., Reale, L., Spina, M., Guarnera, M., Lionetti, E., Martorana, S., & Mazzone, D. (2011). Compliant gluten-free children with celiac disease: an evaluation of psychological distress. BMC Pediatrics, 11, 46.
- McAllister, B.P., Williams, E., & Clarke, K. (2018). A comprehensive review of celiac disease/gluten-sensitive enteropathies. Clinical Reviews in Allergy and Immunology. https://doi.org/10.1007/s12016-018-8691-2
- McCarthy, M.M., Nugent, B.M., & Lenz, K.M. (2017). Neuroimmunology and neuroepigenetics in the establishment of sex differences in the brain. Nature Reviews Neuroscience, 18, 471–484.
- Monteleone, P., Maes, M., Fabrazzo, M., Tortorella, A., Lin, A., Bosmans, E., … & Maj, M. (1999). Immunoendocrine findings in patients with eating disorders. Neuropsychobiology, 40, 115–120.
- Okada, Y., Wu, D., Trynka, G., Raj, T., Terao, C., Ikari, K., … & Plenge, R.M. (2014). Genetics of rheumatoid arthritis contributes to biology and drug discovery. Nature, 506, 376–381.
- Raevuori, A., Haukka, J., Vaarala, O., Suvisaari, J.M., Gissler, M., Grainger, M., … & Suokas, J.T. (2014). The increased risk for autoimmune diseases in patients with eating disorders. PLoS ONE, 9, e104845.
- Rooks, M.G., & Garrett, W.S. (2016). Gut microbiota, metabolites and host immunity. Nature Reviews Immunology, 16, 341–352.
- Smedby, B. (2006). Health classifications in the Nordic countries: Historic development in a national and international perspective. Copenhagen, Denmark: Nordisk Medicinalstatistisk Komité.
- Solmi, F., Hotopf, M., Hatch, S.L., Treasure, J., & Micali, N. (2016). Eating disorders in a multi-ethnic inner-city UK sample. Social Psychiatry and Psychiatric Epidemiology, 51, 369–381.
- Solmi, M., Veronese, N., Favaro, A., Santonastaso, P., Manzato, E., Sergi, G., & Correll, C.U. (2015). Inflammatory cytokines and anorexia nervosa. Psychoneuroendocrinology, 51, 237–252.
- Stice, E., Marti, C.N., & Rohde, P. (2013). Prevalence, incidence, impairment, and course of the proposed DSM-5 eating disorder diagnoses in an 8-year prospective community study of young women. Journal of Abnormal Psychology, 122, 445–457.
- Straub, R.H., & Cutolo, M. (2016). Glucocorticoids and chronic inflammation. Rheumatology, 55(suppl 2), ii6–ii14.
- Swanson, S.A., Crow, S.J., Le Grange, D., Swendsen, J., & Merikangas, K.R. (2011). Prevalence and correlates of eating disorders in adolescents. Archives of General Psychiatry, 68, 714–723.
- Symmons, D.P.M. (2002). Epidemiology of rheumatoid arthritis. Clinical Rheumatology, 16, 707–722.
- Theofilopoulos, A.N., Kono, D.H., & Baccala, R. (2017). The multiple pathways to autoimmunity. Nature Immunology, 18, 716–724.
- Tokatly Latzer, I., Rachmiel, M., Zuckerman Levin, N., Mazor-Aronovitch, K., Landau, Z., Ben-David, R.F., … & Pinhas-Hamiel, O. (2018). Increased prevalence of disordered eating in the dual diagnosis of type 1 diabetes mellitus and celiac disease. Pediatric Diabetes, 19, 749–755.
- Tylee, D.S., Sun, J., Hess, J.L., Tahir, M.A., Sharma, E., Malik, R., … & Glatt, S.J. (2017 August 13). Genetic correlations among neuro-behavioral and immune-related phenotypes based on genome-wide association data. bioRxiv, 070730. https://doi.org/10.1101/070730.
- Ungaro, R., Mehandru, S., Allen, P.B., Peyrin-Biroulet, L., & Colombel, J.-F. (2017). Ulcerative colitis. Lancet, 389, 1756–1770.
- Wagner, G., Zeiler, M., Berger, G., Huber, W.D., Favaro, A., Santonastaso, P., & Karwautz, A. (2015). Eating disorders in adolescents with celiac disease. European Eating Disorders Review, 23, 361–370.
- Wotton, C.J., James, A., & Goldacre, M.J. (2016). Coexistence of eating disorders and autoimmune diseases: Record linkage cohort study, UK. International Journal of Eating Disorders, 49, 663–672.
- Yao, S., Kuja-Halkola, R., Thornton, L.M., Runfola, C.D., D'Onofrio, B.M., Almqvist, C., … & Bulik, C.M. (2016). Familial liability for eating disorders and suicide attempts: Evidence from a population registry in Sweden. JAMA Psychiatry, 73, 284–291.
- Yilmaz, Z., Hardaway, J.A., & Bulik, C.M. (2015). Genetics and epigenetics of eating disorders. Advances in Genomics and Genetics, 5, 131–150.
- Young-Hyman, D.L., & Davis, C.L. (2010). Disordered eating behavior in individuals with diabetes: Importance of context, evaluation, and classification. Diabetes Care, 33, 683–689.
- Zallot, C., Quilliot, D., Chevaux, J.-B., Peyrin-Biroulet, C., Guéant-Rodriguez, R.M., Freling, E., … & Peyrin-Biroulet, L. (2013). Dietary beliefs and behavior among inflammatory bowel disease patients. Inflammatory Bowel Diseases, 19, 66–72.
- Zerwas, S., Larsen, J.T., Petersen, L., Thornton, L.M., Quaranta, M., Koch, S.V., … & Bulik, C.M. (2017). Eating disorders, autoimmune, and autoinflammatory disease. Pediatrics, 140, e20162089.
