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Original Investigation |

Autoimmune Diseases and Severe Infections as Risk Factors for Mood Disorders:  A Nationwide Study

Michael E. Benros, MD1,2; Berit L. Waltoft, MSc1; Merete Nordentoft, DrMedSc2,4; Søren D. Østergaard, MD3; William W. Eaton, PhD5; Jesper Krogh, MD2; Preben B. Mortensen, DrMedSc1,4
[+] Author Affiliations
1National Centre for Register-Based Research, Aarhus University, Aarhus, Denmark
2Mental Health Centre Copenhagen, University of Copenhagen, Faculty of Health Sciences, Copenhagen, Denmark
3Unit for Psychiatric Research, Aalborg Psychiatric Hospital, Aarhus University Hospital
4The Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark
5Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
JAMA Psychiatry. 2013;70(8):812-820. doi:10.1001/jamapsychiatry.2013.1111.
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Importance  Mood disorders frequently co-occur with medical diseases that involve inflammatory pathophysiologic mechanisms. Immune responses can affect the brain and might increase the risk of mood disorders, but longitudinal studies of comorbidity are lacking.

Objective  To estimate the effect of autoimmune diseases and infections on the risk of developing mood disorders.

Design  Nationwide, population-based, prospective cohort study with 78 million person-years of follow-up. Data were analyzed with survival analysis techniques and adjusted for calendar year, age, and sex.

Setting  Individual data drawn from Danish longitudinal registers.

Participants  A total of 3.56 million people born between 1945 and 1996 were followed up from January 1, 1977, through December 31, 2010, with 91 637 people having hospital contacts for mood disorders.

Main Outcomes and Measures  The risk of a first lifetime diagnosis of mood disorder assigned by a psychiatrist in a hospital, outpatient clinic, or emergency department setting. Incidence rate ratios (IRRs) and accompanying 95% CIs are used as measures of relative risk.

Results  A prior hospital contact because of autoimmune disease increased the risk of a subsequent mood disorder diagnosis by 45% (IRR, 1.45; 95% CI, 1.39-1.52). Any history of hospitalization for infection increased the risk of later mood disorders by 62% (IRR, 1.62; 95% CI, 1.60-1.64). The 2 risk factors interacted in synergy and increased the risk of subsequent mood disorders even further (IRR, 2.35; 95% CI, 2.25-2.46). The number of infections and autoimmune diseases increased the risk of mood disorders in a dose-response relationship. Approximately one-third (32%) of the participants diagnosed as having a mood disorder had a previous hospital contact because of an infection, whereas 5% had a previous hospital contact because of an autoimmune disease.

Conclusions and Relevance  Autoimmune diseases and infections are risk factors for subsequent mood disorder diagnosis. These associations seem compatible with an immunologic hypothesis for the development of mood disorders in subgroups of patients.

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Incidence Rate Ratios

Incidence rate ratios, with 95% CIs (error bars), of subsequent mood disorders in persons with autoimmune diseases and infections in Denmark, 1977-2010.

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