Depression May Increase Risk of Developing Lupus, Long-term Study Shows

Women with a history of depression have more than twice the risk of developing systemic lupus erythematosus (SLE), according to a two-decade prospective study from Harvard.

The study, “Association of Depression With Risk of Incident Systemic Lupus Erythematosus in Women Assessed Across 2 Decades,” was published in the journal JAMA Psychiatry.

Increasing evidence suggests that depression is associated with the subsequent development of any autoimmune disease.

Depression was shown to be frequent, and associated with more severe disease, among those with autoimmune diseases. Also, people with depression have increased immune activation and systemic inflammation, which could potentially trigger autoimmune disease.

But definitive data showing an association between depression and autoimmune disease is scarce.

Harvard researchers in Boston evaluated whether depression was associated with an increased risk of developing lupus in women participating in the Nurses’ Health Study (1996-2012) and the Nurses’ Health Study II (1993-2013). These are two of the largest prospective studies assessing potential risk factors for more than 30 diseases in women.

Researchers analyzed the data of 194,483 women (93% white), who were ages 28-93, over 20 years.

The presence of depression was assessed through clinical diagnosis, regular antidepressant use, or a score under 60 on the 5-item Mental Health Inventory (MHI-5) — a reliable method of evaluating mental health issues.

The results showed that 46,787 women (24%) had a history of depression, and that they were more likely to be smokers, and to have used oral contraceptives and postmenopausal hormones, while being less likely to do regular exercise, compared with those without a history of depression.

Over the two decades of follow-up, 145 women developed lupus, and the median time between depression and lupus diagnosis was 4.5 years. Women with a history of depression had a significantly greater risk of developing lupus — two times as high.

This association remained strong when researchers looked at the depression indicators (clinical diagnosis, antidepressant use, and MHI-5 scores) individually, and considered only women who had depression at least four years before lupus, depression status only at the beginning of the study, or lupus onset as the date of the first symptoms rather than date of diagnosis.

When the researchers analyzed the data taking into account health risk factors previously associated with lupus, they found that diet, exercise, or alcohol intake did not change the association between depression and lupus, while body mass index, smoking, and oral contraceptives and postmenopausal hormone use only slightly affected it.

These results suggest that the association between depression and lupus cannot be fully explained by the measured health risk factors, and that “depression is a causal risk factor for developing SLE, perhaps via altered immune function,” the researchers wrote.

They proposed that screening for lupus symptoms or family history of the disease in people with depression may help detect the disease in an early stage, and that reducing inflammation in these people through the adoption of lifestyle habits may potentially reduce the risk of autoimmune disease.

The team noted, however, that since nurses may be healthier than the general population of women, further studies are necessary to understand the general association between depression and lupus.