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Depression and the risk of autoimmune disease: a nationally representative, prospective longitudinal study

Published online by Cambridge University Press:  14 August 2015

N. W. Andersson ,
L. N. Gustafsson ,
N. Okkels ,
F. Taha ,
S. W. Cole ,
P. Munk-Jørgensen  and
R. D. Goodwin
N. W. Andersson
Affiliation:
Department of Organic Psychiatric Disorders and Emergency Ward, Aarhus University Hospital, Risskov, Denmark Psychiatric Research Unit, Psychiatric Centre North Zealand, University of Copenhagen, Denmark Department of Psychology, Queens College and The Graduate Center, City University of New York (CUNY), Queens, New York, USA
L. N. Gustafsson
Affiliation:
Department of Organic Psychiatric Disorders and Emergency Ward, Aarhus University Hospital, Risskov, Denmark
N. Okkels
Affiliation:
Department of Organic Psychiatric Disorders and Emergency Ward, Aarhus University Hospital, Risskov, Denmark Psychiatric Hospital Augustenborg, Hospital of Southern Jutland, Denmark
F. Taha
Affiliation:
Department of Psychology, Queens College and The Graduate Center, City University of New York (CUNY), Queens, New York, USA
S. W. Cole
Affiliation:
Division of Hematology-Oncology, Department of Medicine, UCLA, School of Medicine, Los Angeles, USA
P. Munk-Jørgensen
Affiliation:
Department of Organic Psychiatric Disorders and Emergency Ward, Aarhus University Hospital, Risskov, Denmark
R. D. Goodwin*
Affiliation:
Department of Psychology, Queens College and The Graduate Center, City University of New York (CUNY), Queens, New York, USA Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA
*
* Address for correspondence: R. D. Goodwin, PhD, MPH, Department of Psychology, Queens College and The Graduate Center, City University of New York, 65-30 Kissena Bvld, Queens, NY 11367, USA. (Email: renee.goodwin@qc.cuny.edu)
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Abstract

Background.

Autoimmune diseases are associated with substantial morbidity and mortality, yet the etiology remains unclear. Depression has been implicated as a risk factor for various immune-related disorders but little is known about the risk of autoimmune disease. This study examined the association between depression and the risk of autoimmune disease, and investigated the temporal and dose-response nature of these relationships.

Method.

A prospective population-based study including approximately 1.1 million people was conducted using linked Danish registries. Depression and autoimmune diseases were diagnosed by physicians and documented in medical records. In total, 145 217 individuals with depression were identified between 1995 and 2012. Survival analyses were used to estimate the relative risk of autoimmune disease among those with, compared to without, depression. Analyses were adjusted for gender, age, and co-morbid mental disorders.

Results.

Depression was associated with a significantly increased risk of autoimmune disease [incidence rate ratio (IRR) 1.25, 95% CI 1.19–1.31], compared to those without a history of depression. Results suggest a general increased risk of autoimmune diseases following the onset of depression during first year (IRR 1.29, 95% CI 1.05–1.58), which remained elevated for the ensuing 11 years and beyond (IRR 1.53, 95% CI 1.34–1.76). Findings did not support a dose-response relationship.

Conclusions.

Depression appears to be associated with an increased risk of a range of autoimmune diseases. Depression may play a role in the etiology of certain autoimmune conditions. If replicated, findings could highlight additional clinical implications in the treatment and management of depression. Future studies are needed to investigate the possible social, genetic, and neurobiological underpinnings of these relationships.

Keywords

Autoimmune diseasedepressionepidemiologyhumanslongitudinal studiesprospective studies

Information

Type
Original Articles
Information
Psychological Medicine , Volume 45 , Issue 16 , December 2015 , pp. 3559 - 3569
Copyright
Copyright © Cambridge University Press 2015 

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References

Alonso, J, Angermeyer, MC, Bernert, S, Bruffaerts, R, Brugha, TS, Bryson, H, de Girolamo, G, Graaf, R, Demyttenaere, K, Gasquet, I, Haro, JM, Katz, SJ, Kessler, RC, Kovess, V, Lepine, JP, Ormel, J, Polidori, G, Russo, LJ, Vilagut, G, Almansa, J, Arbabzadeh-Bouchez, S, Autonell, J, Bernal, M, Buist-Bouwman, MA, Codony, M, Domingo-Salvany, A, Ferrer, M, Joo, SS, Martinez-Alonso, M, Matschinger, H, Mazzi, F, Morgan, Z, Morosini, P, Palacin, C, Romera, B, Taub, N, Vollebergh, WA, EsemeD/Mhedea Investigators ESotEoMDP (2004). Prevalence of mental disorders in Europe: results from the European Study of the Epidemiology of Mental Disorders (ESEMeD) project. Acta Psychiatrica Scandinavica 109 (Suppl. 420), 21–27.Google Scholar
Ananthakrishnan, AN, Khalili, H, Pan, A, Higuchi, LM, de Silva, P, Richter, JM, Fuchs, CS, Chan, AT (2013). Association between depressive symptoms and incidence of Crohn's disease and ulcerative colitis: results from the Nurses’ Health Study. Clinical Gastroenterology and Hepatology 11, 57–62.Google ScholarPubMed
Anaya, JM (2012). Common mechanisms of autoimmune diseases (the autoimmune tautology). Autoimmunity Reviews 11, 781–784.CrossRefGoogle ScholarPubMed
Andersen, TF, Madsen, M, Jorgensen, J, Mellemkjoer, L, Olsen, JH (1999). The Danish National Hospital Register. A valuable source of data for modern health sciences. Danish Medical Bulletin 46, 263–268.Google Scholar
Autoimmune Diseases Coordinating Committee (2005). Progress in Autoimmune Diseases Research: Report to Congress. US Department of Health and Human Services, Rockville, MD.Google Scholar
Bachen, EA, Chesney, MA, Criswell, LA (2009). Prevalence of mood and anxiety disorders in women with systemic lupus erythematosus. Arthritis and Rheumatism 61, 822–829.Google Scholar
Bakhshaie, J, Zvolensky, MJ, Goodwin, RD (2015). Cigarette smoking and the onset and persistence of depression among adults in the United States: 1994–2005. Comprehensive Psychiatry 60, 142–148.Google Scholar
Baysal, O, Durmus, B, Ersoy, Y, Altay, Z, Senel, K, Nas, K, Ugur, M, Kaya, A, Gur, A, Erdal, A, Ardicoglu, O, Tekeoglu, I, Cevik, R, Yildirim, K, Kamanli, A, Sarac, AJ, Karatay, S, Ozgocmen, S (2011). Relationship between psychological status and disease activity and quality of life in ankylosing spondylitis. Rheumatology International 31, 795–800.Google Scholar
Benros, ME, Pedersen, MG, Rasmussen, H, Eaton, WW, Nordentoft, M, Mortensen, PB (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.Google Scholar
Benros, ME, Waltoft, BL, Nordentoft, M, Ostergaard, SD, Eaton, WW, Krogh, J, Mortensen, PB (2013). Autoimmune diseases and severe infections as risk factors for mood disorders: a nationwide study. JAMA Psychiatry 70, 812–820.Google Scholar
Bock, C, Bukh, J, Vinberg, M, Gether, U, Kessing, L (2009). Validity of the diagnosis of a single depressive episode in a case register. Clinical Practice and Epidemiology in Mental Health 5, 4.Google Scholar
Boden, JM, Fergusson, DM, Horwood, LJ (2010). Cigarette smoking and depression: tests of causal linkages using a longitudinal birth cohort. British Journal of Psychiatry 196, 440–446.Google Scholar
Byrne, N, Regan, C, Howard, L (2005). Administrative registers in psychiatric research: a systematic review of validity studies. Acta Psychiatrica Scandinavica 112, 409–414.Google Scholar
Carta, MG, Hardoy, MC, Boi, MF, Mariotti, S, Carpiniello, B, Usai, P (2002). Association between panic disorder, major depressive disorder and celiac disease: a possible role of thyroid autoimmunity. Journal of Psychosomatic Research 53, 789–793.CrossRefGoogle ScholarPubMed
Carta, MG, Loviselli, A, Hardoy, MC, Massa, S, Cadeddu, M, Sardu, C, Carpiniello, B, Dell'Osso, L, Mariotti, S (2004). The link between thyroid autoimmunity (antithyroid peroxidase autoantibodies) with anxiety and mood disorders in the community: a field of interest for public health in the future. BMC Psychiatry 4, 25.Google Scholar
Degner, D, Meller, J, Bleich, S, Schlautmann, V, Ruther, E (2001). Affective disorders associated with autoimmune thyroiditis. Journal of Neuropsychiatry and Clinical Neurosciences 13, 532–533.Google Scholar
Dominguez, PL, Han, J, Li, T, Ascherio, A, Qureshi, AA (2013). Depression and the risk of psoriasis in US women. Journal of the European Academy of Dermatology and Venereology 27, 1163–1167.Google Scholar
Dowlatshahi, EA, Wakkee, M, Arends, LR, Nijsten, T (2014). The prevalence and odds of depressive symptoms and clinical depression in psoriasis patients: a systematic review and meta-analysis. Journal of Investigative Dermatology 134, 1542–1551.Google Scholar
Dube, SR, Fairweather, D, Pearson, WS, Felitti, VJ, Anda, RF, Croft, JB (2009). Cumulative childhood stress and autoimmune diseases in adults. Psychosomatic Medicine 71, 243–250.CrossRefGoogle ScholarPubMed
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. American Journal of Psychiatry 163, 521–528.CrossRefGoogle ScholarPubMed
Eaton, WW, Pedersen, MG, Nielsen, PR, Mortensen, PB (2010). Autoimmune diseases, bipolar disorder, and non-affective psychosis. Bipolar Disorders 12, 638–646.Google Scholar
Eaton, WW, Rose, NR, Kalaydjian, A, Pedersen, MG, Mortensen, PB (2007). Epidemiology of autoimmune diseases in Denmark. Journal of Autoimmunity 29, 1–9.Google Scholar
Engum, A (2007). The role of depression and anxiety in onset of diabetes in a large population-based study. Journal of Psychosomatic Research 62, 31–38.CrossRefGoogle Scholar
Fergusson, DM, Goodwin, RD, Horwood, LJ (2003). Major depression and cigarette smoking: results of a 21-year longitudinal study. Psychological Medicine 33, 1357–1367.Google ScholarPubMed
Giynas Ayhan, M, Uguz, F, Askin, R, Gonen, MS (2014). The prevalence of depression and anxiety disorders in patients with euthyroid Hashimoto's thyroiditis: a comparative study. General Hospital Psychiatry 36, 95–98.Google Scholar
Glaser, R, Kiecolt-Glaser, JK (2005). Stress-induced immune dysfunction: implications for health. Nature Reviews: Immunology 5, 243–251.Google Scholar
Gold, SM, Irwin, MR (2009). Depression and immunity: inflammation and depressive symptoms in multiple sclerosis. Immunology and Allergy Clinics of North America 29, 309–320.Google Scholar
Inal, V, Kitapcioglu, G, Karabulut, G, Keser, G, Kabasakal, Y (2010). Evaluation of quality of life in relation to anxiety and depression in primary Sjogren's syndrome. Modern Rheumatology 20, 588–597.Google Scholar
Irwin, MR, Cole, SW (2011). Reciprocal regulation of the neural and innate immune systems. Nature Reviews:Immunology 11, 625–632.Google ScholarPubMed
Irwin, MR, Miller, AH (2007). Depressive disorders and immunity: 20 years of progress and discovery. Brain, Behavior, and Immunity 21, 374–383.Google Scholar
Kiecolt-Glaser, JK, Glaser, R (2002). Depression and immune function: central pathways to morbidity and mortality. Journal of Psychosomatic Research 53, 873–876.Google Scholar
Kirim, S, Keskek, SO, Koksal, F, Haydardedeoglu, FE, Bozkirli, E, Toledano, Y (2012). Depression in patients with euthyroid chronic autoimmune thyroiditis. Endocrine Journal 59, 705–708.Google Scholar
Köhler, O, Benros, ME, Nordentoft, M, Farkouh, ME, Iyengar, RL, Mors, O, Krogh, J (2014). Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry 71, 1381–1391.Google Scholar
Korczak, DJ, Pereira, S, Koulajian, K, Matejcek, A, Giacca, A (2011). Type 1 diabetes mellitus and major depressive disorder: evidence for a biological link. Diabetologia 54, 2483–2493.Google Scholar
Kudielka, BM, Buske-Kirschbaum, A, Hellhammer, DH, Kirschbaum, C (2004). HPA axis responses to laboratory psychosocial stress in healthy elderly adults, younger adults, and children: impact of age and gender. Psychoneuroendocrinology 29, 83–98.Google Scholar
Lundberg, AS, Okkels, N, Gustafsson, LN, Larsen, JT, Sørensen, LU, Munk-Jørgensen, P (2013). A nationwide study on delirium in psychiatric patients from 1995 to 2011. Acta Neuropsychiatrica 26, 234–239.Google Scholar
Marcus, SC, Olfson, M (2010). National trends in the treatment for depression from 1998 to 2007. Archives of General Psychiatry 67, 1265–1273.Google Scholar
Matcham, F, Rayner, L, Steer, S, Hotopf, M (2013). The prevalence of depression in rheumatoid arthritis: a systematic review and meta-analysis. Rheumatology 52, 2136–2148.Google ScholarPubMed
Maunder, RG, Levenstein, S (2008). The role of stress in the development and clinical course of inflammatory bowel disease: epidemiological evidence. Current Molecular Medicine 8, 247–252.Google Scholar
McEwen, BS (2007). Physiology and neurobiology of stress and adaptation: central role of the brain. Physiological Reviews 87, 873–904.Google Scholar
Miller, AH, Maletic, V, Raison, CL (2009). Inflammation and its discontents: the role of cytokines in the pathophysiology of major depression. Biological Psychiatry 65, 732–741.Google Scholar
Miller, FW, Alfredsson, L, Costenbader, KH, Kamen, DL, Nelson, LM, Norris, JM, De Roos, AJ (2012). Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop. Journal of Autoimmunity 39, 259–271.Google Scholar
Mitsonis, CI, Potagas, C, Zervas, I, Sfagos, K (2009). The effects of stressful life events on the course of multiple sclerosis: a review. International Journal of Neuroscience 119, 315–335.Google Scholar
Mors, O, Perto, GP, Mortensen, PB (2011). The Danish Psychiatric Central Research Register. Scandanavian Journal of Public Health 39, 54–57.Google ScholarPubMed
Munk-Jorgensen, P, Mortensen, PB (1997). The Danish Psychiatric Central Register. Danish Medical Bulletin 44, 82–84.Google Scholar
Munk-Jørgensen, P, Okkels, N, Golberg, D, Ruggeri, M, Thornicroft, G (2014). Fifty years’ development and future perspectives of psychiatric register research. Acta Psychiatrica Scandinavica 130, 87–98.Google Scholar
Munk-Jorgensen, P, Ostergaard, SD (2011). Register-based studies of mental disorders. Scandanavian Journal of Public Health 39, 170–174.Google Scholar
Nery, FG, Borba, EF, Hatch, JP, Soares, JC, Bonfa, E, Neto, FL (2007). Major depressive disorder and disease activity in systemic lupus erythematosus. Comprehensive Psychiatry 48, 14–19.Google Scholar
Nguyen-Nielsen, M, Svensson, E, Vogel, I, Ehrenstein, V, Sunde, L (2013). Existing data sources for clinical epidemiology: Danish registries for studies of medical genetic diseases. Clinical Epidemiology 5, 249–262.Google Scholar
Pace, T, Mletzko, T, Alagbe, O, Musselman, D, Nemeroff, C, Miller, A, Heim, C (2006). Increased stress-induced inflammatory responses in male patients with major depression and increased early life stress. American Journal of Psychiatry 163, 1630–1633.CrossRefGoogle ScholarPubMed
Palagini, L, Mosca, M, Tani, C, Gemignani, A, Mauri, M, Bombardieri, S (2013). Depression and systemic lupus erythematosus: a systematic review. Lupus 22, 409–416.Google Scholar
Parker, G (2005). Register now: validity later. Acta Psychiatrica Scandinavica 112, 407–418.Google Scholar
Pedersen, CB, Gotzsche, H, Moller, JO, Mortensen, PB (2006). The Danish Civil Registration System. A cohort of eight million persons. Danish Medical Bulletin 53, 441–449.Google Scholar
Pedersen, CB, Mors, O, Bertelsen, A, Waltoft, BL, Agerbo, E, McGrath, JJ, Mortensen, PB, Eaton, WW (2014). A comprehensive nationwide study of the incidence rate and lifetime risk for treated mental disorders. JAMA Psychiatry 71, 573–581.CrossRefGoogle ScholarPubMed
Penninx, BW, Milaneschi, Y, Lamers, F, Vogelzangs, N (2013). Understanding the somatic consequences of depression: biological mechanisms and the role of depression symptom profile. BMC Medicine 11, 129.Google Scholar
Pop, VJ, Maartens, LH, Leusink, G, van Son, MJ, Knottnerus, AA, Ward, AM, Metcalfe, R, Weetman, AP (1998). Are autoimmune thyroid dysfunction and depression related? Journal of Clinical Endocrinology and Metabolism 83, 3194–3197.Google Scholar
Raevuori, A, Haukka, J, Vaarala, O, Suvisaari, JM, Gissler, M, Grainger, M, Linna, MS, Suokas, JT (2014). The increased risk for autoimmune diseases in patients with eating disorders. PloS ONE 9, e104845.Google Scholar
Raison, CL, Miller, AH (2012). The evolutionary significance of depression in Pathogen Host Defense (PATHOS-D). Molecular Psychiatry 18, 15–37.Google Scholar
Rotella, F, Mannucci, E (2013). Depression as a risk factor for diabetes: a meta-analysis of longitudinal studies. Journal of Clinical Psychiatry 74, 31–37.Google Scholar
Roy, T, Lloyd, CE (2012). Epidemiology of depression and diabetes: a systematic review. Journal of Affective Disorders 142(Suppl), S8–S21.Google Scholar
Schramm, C, Wahl, I, Weiler-Normann, C, Voigt, K, Wiegard, C, Glaubke, C, Brahler, E, Lowe, B, Lohse, AW, Rose, M (2014). Health-related quality of life, depression, and anxiety in patients with autoimmune hepatitis. Journal of Hepatology 60, 618–624.Google Scholar
Sharma, TR, Kline, DB, Shreeve, DF, Hartman, DW (2011). Psychiatric comorbidities in patients with celiac disease: is there any concrete biological association? Asian Journal of Psychiatry 4, 150–151.Google Scholar
Smith, DF, Gerdes, LU (2012). Meta-analysis on anxiety and depression in adult celiac disease. Acta Psychiatrica Scandinavica 125, 189–193.Google Scholar
StataCorp (2013). Stata Statistical Software: Release 13. StataCorp LP: College Station, TX.Google Scholar
Valtysdottir, ST, Gudbjornsson, B, Lindqvist, U, Hallgren, R, Hetta, J (2000). Anxiety and depression in patients with primary Sjogren's syndrome. Journal of Rheumatology 27, 165–169.Google Scholar
van de Ven, AC, Muntjewerff, JW, Netea-Maier, RT, de Vegt, F, Ross, HA, Sweep, FC, Kiemeney, LA, Vos, PE, Buitelaar, JK, Hermus, AR, den Heijer, M, Janzing, JG (2012). Association between thyroid function, thyroid autoimmunity, and state and trait factors of depression. Acta Psychiatrica Scandinavica 126, 377–384.Google Scholar
van der Heide, F, Wassenaar, M, van der Linde, K, Spoelstra, P, Kleibeuker, JH, Dijkstra, G (2011). Effects of active and passive smoking on Crohn's disease and ulcerative colitis in a cohort from a regional hospital. European Journal of Gastroenterology and Hepatology 23, 255–261.Google Scholar
van Gool, CH, Kempen, GI, Bosma, H, van Boxtel, MP, Jolles, J, van Eijk, JT (2007). Associations between lifestyle and depressed mood: longitudinal results from the Maastricht Aging Study. American Journal of Public Health 97, 887–894.Google Scholar
Vattakatuchery, JJ, Rickards, H, Cavanna, AE (2011). Pathogenic mechanisms of depression in multiple sclerosis. Journal of Neuropsychiatry and Clinical Neurosciences 23, 261–276.Google Scholar
Voinov, B, Richie, WD, Bailey, RK (2013). Depression and chronic diseases: it is time for a synergistic mental health and primary care approach. The Primary Care Companion for CNS Disorders 15, PCC.12r01468.Google Scholar
Zyrianova, Y, Kelly, BD, Gallagher, C, McCarthy, C, Molloy, MG, Sheehan, J, Dinan, TG (2006). Depression and anxiety in rheumatoid arthritis: the role of perceived social support. Irish Journal of Medical Science 175, 32–36.Google Scholar
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