Autoimmune diseases can be associated with depression

ABSTRACT FROM: Andersson NW, Gustafsson LN, Okkels N, et al. Depression and the risk of autoimmune disease: a nationally representative, prospective longitudinal study. Psychol Med 2015;45:3559–69.

What is already known on this topic

Autoimmune diseases are, according to a previous nationwide Danish register study, associated with a 57% increased subsequent risk of depression (45% after excluding the effect of infections).¹ However, no large-scale study has previously investigated the longitudinal associations with autoimmune diseases after the depression diagnosis.

Methods of the study

Andersson et al investigated the longitudinal association between the date of a first-time hospital contact for depression and the subsequent risk of a first-time hospital contact for autoimmune diseases. The authors used the Danish nationwide registers with virtually complete follow-up of all hospital contacts with depression and autoimmune diseases. A total of 145 217 individuals with a hospital contact for depression were identified during the years 1995–2012, and each individual was match-controlled with six other individuals from the Danish population (resulting in a total study population of 1 016 519 individuals). During the study period, among the target population, a total of 2780 (1.9%) individuals had a subsequent hospital contact for autoimmune diseases. Depression and autoimmune diseases were diagnosed by physicians and documented in medical records and the registers. Survival analyses were used and analyses were adjusted for gender, age and comorbid mental disorders.

What this paper adds

• A hospital contact with depression was associated with an increased risk of subsequent hospital contacts for autoimmune diseases by 25% (incidence rate ratio (IRR) 1.25, 95% CI 1.19 to 1.31), when compared with individuals without a history of depression.

• The risk of autoimmune diseases did not increase in a dose–response association with the number of depressive episodes (1 depressive episode IRR 1.26, 95% CI 1.19 to 1.33 and ≥2 depressive episode IRR 1.20, 95% CI 1.05 to 1.38).

• The risk of hospital contacts with autoimmune diseases remained similarly elevated over time since the depression diagnosis.

• The specific autoimmune diseases with an increased risk were type 1 diabetes (IRR 1.47, 95% CI 1.33 to 1.63, n=723), multiple sclerosis (IRR 1.46, 95% CI 1.26 to 1.69, n=317), Crohn's disease (IRR 1.36, 95% CI 1.16 to 1.60, n=275), psoriasis (IRR 1.45, 95% CI 1.13 to 1.85, n=124), systemic lupus erythematosus (IRR 1.38, 95% CI 1.00 to 1.91, n=74), primary adrenocortical insufficiency (IRR 2.33, 95% CI 1.36 to 3.98, n=28) and idiopathic thrombocytopenic purpura (IRR 1.85, 95% CI 1.10 to 3.11, n=27).

• In individuals ≥50 years of age, the only significant association was observed for individuals with only one episode of depression and between 50 and 69 years of age (IRR 1.20, 95% CI 1.10 to 1.31, n=580), and non-existing in more elderly individuals.

Limitations

• The temporal order of the diagnosis might be affected by the fact that autoimmune diseases are known to have a long period of undetected illness before being diagnosed and might not require a hospital contact at diagnosis; hence, some of the autoimmune diseases might not be incident but pre-existing to the depression diagnosis with reverse causation than indicated by the study.

• There was no specific temporal association or dose–response association with the depression diagnosis questioning whether psychological stress associated with the hospital contact for depression is actually influencing the increased risk of autoimmune diseases, or whether it is other factors associated with depression, such as psychiatric medication, genetic factors, infections, smoking and altered diet.

What next in research

Based on the current evidence, there seems to be a bidirectional relationship between autoimmune diseases and mental disorders, such as depression, schizophrenia and eating disorders.^{1 2} Main risk factors for autoimmune diseases are interactions between genetics and environmental factors, such as infections.³ Previous studies on schizophrenia have shown that the subsequently increased risk of autoimmune diseases is partly explained by the increased occurrence of infections in individuals with schizophrenia,² which might also be the case for individuals with depression.¹ It is questionable whether the accumulated psychological stress associated with depression is causally associated with autoimmune diseases, since there were no dose–response or temporal relationships with the depression diagnosis in this study and animal studies have been inconsistent on this matter;⁴ however, psychological stress has been shown to cause flare-ups of symptoms from autoimmune diseases and cause increased vulnerability towards acquiring infections.^{3 4} Currently efforts are being made to investigate the possible genetic contribution to the bidirectional association between autoimmune diseases and other immune-related diseases with mental disorders. Moreover, immune-related factors are increasingly recognised as important risk factors for mental disorders and randomised studies have shown beneficial effects of anti-inflammatory treatment on depression symptoms, which could substantially improve the current treatment in immune-related subgroups with depression.⁵

Do these results change your practices and why?

Yes. This and other studies highlight that, even though autoimmune diseases are rather rare in absolute numbers, clinicians should pay attention to and check for autoimmune diseases and other important somatic comorbidity in patients with depression and other mental illnesses. This is particularly true in the diagnostic process, but also during subsequent treatment, where the excess occurrence of physical diseases is associated with increased mortality.