The prevalence and severity of depression among people with autoimmune diseases like rheumatoid arthritis, psoriasis, Crohn’s disease, and systemic lupus erythematosus (SLE) appears to be high, according to data from recent studies. “Researchers have theorized that the increased immune activation associated with depression is a plausible biological pathway that could trigger autoimmune diseases,” explains Andrea L. Roberts, PhD. “Despite this possible connection, few analyses have looked at temporal associations between depression and subsequent development of autoimmune disease.”

Previous studies have suggested that depression and SLE were strongly related, but this research was based on the high prevalence of depression among existing patients with SLE. “To determine if depression is associated with the risk of developing SLE, we need to consider alternative possible causal structures, such as depression being an early symptom of SLE, the influence of pre-diagnostic SLE symptoms, and the potential for initial misdiagnoses,” Dr. Roberts says. A higher prevalence of health risk factors among people with depression may also account for higher risks of SLE.

For a study published in JAMA Psychiatry, Dr. Roberts and colleagues evaluated whether there was an association between depression and risk of incident SLE. A 20-year prospective analysis was conducted using data collected from two cohorts of women participating in the Nurses’ Health Study (1996-2012) and the Nurses’ Health Study II (1993-2013). In addition, the study examined the potential role of health risk factors on risks for developing SLE, including cigarette smoking, BMI, oral contraceptive use, menopause or postmenopausal hormone use, alcohol use, exercise, or diet.


Correlations Detected

Of the nearly 195,000 women assessed in the 20-year follow-up study, 145 SLE cases occurred. “We found that depression was associated with an over 2-fold increased risk of incident SLE in a proportional hazards regression model adjusted for race and age,” says Dr. Roberts (Table).

SLE risk was higher with each of the depression indicators modeled separately, including a clinician’s diagnosis of depression (hazard ratios [HRs], 2.19), antidepressant use (HR, 2.80), and scores on the 5-item Mental Health Inventory indicating the presence of depressed mood (HR, 1.70). The median time from depression to incident SLE was 4.5 years. In a study model using the date of first symptoms to indicate the onset of SLE, the association of depression and SLE symptom onset was nearly identical to risk estimates from the main analysis.

The study also used models to examine the link between individual health risk factors and risk for SLE. Diet, exercise, and alcohol use did not alter the link between depression and SLE, but depression remained strongly associated with the risk of incident SLE in models that further adjusted for BMI, cigarette smoking, and oral contraceptive and postmenopausal hormone use, whether at baseline only or using time-updated covariates. When compared with women who had no depression history, those with a history of it were more likely to be current cigarette smokers and to have used oral contraceptives and postmenopausal hormones but were less likely to exercise regularly.


Analyzing Implications

Results of the study further support for the hypothesis that depression may be a causal risk factor for developing SLE. “We see our study as a first step toward determining why depression increases risks for SLE, but more research is still needed to further establish this connection,” Dr. Roberts says. “In the meantime, clinicians should recognize that depression puts people at risk for many health conditions, including autoimmune disorders like SLE, because of its various disease processes,” Dr. Roberts says.

A key problem with studying SLE, according to Dr. Roberts, is that its symptoms could be mistaken with depression. “In some cases, early SLE may be initially misdiagnosed as depression,” she says. “Screening patients with SLE for a family history and symptoms of depression may lead to earlier detection of SLE. In addition, lifestyle interventions should be considered to reduce inflammation in patients with depression. This may decrease risks for autoimmune diseases as well as other negative health consequences associated with depression.”


Roberts AL, Kubzansky LD, Malspeis S, Feldman CH, Costenbader KH. Association of depression with risk of incident systemic lupus erythematosus in women assessed across 2 decades. JAMA Psychiatry. 2018;75(12):1225-1233. Available at:

Palagini L, Mosca M, Tani C, Gemignani A, Mauri M, Bombardieri S. Depression and systemic lupus erythematosus: a systematic review. Lupus. 2013;22(5):409-416.

Zhang J, Wei W, Wang CM. Effects of psychological interventions for patients with systemic lupus erythematosus: a systematic review and meta-analysis. Lupus. 2012;21(10):1077-1087.

Irwin MR, Davis M, Zautra A. Behavioral comorbidities in rheumatoid arthritis: a psychoneuroimmunological perspective. Psychiatr Times. 2008;25(9):1-9.