Association of Depression With Risk of Incident Systemic Lupus Erythematosus in Women Assessed Across 2 Decades

Importance

It has long been hypothesized that depression may increase the risk of developing autoimmune disease; however, rigorous empirical evidence is sparse.

Objective

To evaluate whether an association exists between depression and risk of incident systemic lupus erythematosus (SLE), a paradigmatic, systemic autoimmune disease.

Design, Setting, and Participants

This 20-year prospective, longitudinal cohort study evaluated data collected from 2 cohorts of women participating in the Nurses’ Health Study (1996-2012) and the Nurses’ Health Study II (1993-2013). Data analyses were conducted from August 2017 to May 2018.

Main Outcomes and Measures

Incident SLE with 4 or more American College of Rheumatology criteria was ascertained by self-report and confirmed by medical record review. Depression was assessed repeatedly throughout follow-up according to whether women reported having received a clinician’s diagnosis of depression, regular antidepressant use, or a score of less than 60 on the 5-item Mental Health Inventory (MHI-5). Whether longitudinally assessed health risk factors (eg, cigarette smoking, body mass index, oral contraceptive use, menopause or postmenopausal hormone use, alcohol use, exercise, or diet) accounted for increased SLE risk among women with vs without depression was examined. Cox proportional hazards regression models were used to estimate risk of SLE. In addition, the association of depression lagged by 4 years, and depression status at baseline with incident SLE throughout follow-up was assessed.

Results

Data from 194 483 women (28-93 years of age; 93% white) were included. During 20 years of follow-up, 145 cases of SLE occurred. Compared with women with no depression, women with a history of depression had a subsequent increased risk of SLE (HR, 2.67; 95% CI, 1.91-3.75;P < .001). Adjustment for body mass index, cigarette smoking, and oral contraception and postmenopausal hormone use slightly attenuated associations (adjusted HR, 2.45; 95% CI, 1.74-3.45;P < .001). The SLE risk was elevated with each of the 3 following depression indicators modeled separately: clinician’s diagnosis of depression (HR, 2.19; 95% CI, 1.29-3.71), antidepressant use (HR, 2.80; 95% CI, 1.94-4.05), and MHI-5 scores indicating depressed mood (HR, 1.70; 95% CI, 1.18-2.44). Associations remained strong when depression status was lagged by 4 years with respect to the outcome (HR, 1.99; 95% CI, 1.32-3.00) and when depression status at baseline was used as the exposure (HR, 2.28; 95% CI, 1.54-3.37).

Conclusions and Relevance

This study contributes to increasing evidence that depression may be associated with increased risk of SLE and suggests that the association is not fully explained by measured health factors or behaviors.