Women with a history of depression had an increased risk of developing systemic lupus erythematosus (SLE) over a 20-year period compared with women without depression. These findings, reported in JAMA Psychiatry, suggest a history of depression is a strong predictor of SLE.1
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Adjustments made for health-related behaviors, including cigarette smoking, body mass index, oral contraceptive use, menopause or postmenopausal hormone use, alcohol use, exercise and diet only slightly attenuated these findings.
“Our study contributes to evidence that depression increases the risk for SLE and other autoimmune diseases,” says lead investigator Andrea Roberts, PhD, research scientist in the department of Environmental Health at Harvard T.H. Chan School of Public Health, Boston. “We found many health-related behaviors, such as exercise, diet and smoking, did not explain most of the increased risk. We take this as evidence there may be direct biological effects of depression that increase the risk of autoimmune disease, for example, via inflammation.”
Study Results at a Glance
The study’s data were collected from two cohorts of women participating in the Nurses’ Health Study (1996–2012) and the Nurses’ Health Study II (1993–2013) and were analyzed from August 2017 to May 2018.
SLE was classified as patients meeting four or more of the 11 ACR criteria, which were confirmed by medical record review, according to senior investigator Karen Costenbader, MD, MPH, rheumatologist and Lupus Program director at Brigham and Women’s Hospital, Boston. Depression was assessed according to three indicators: a clinician’s diagnosis of depression, regular antidepressant use or a score of less than 60 on the five-item Mental Health Inventory.
Cox proportional hazards regression models were used to estimate risk of SLE among study data for 194,483 women (age 28–93; 93% white) during 20 years of follow-up. SLE occurred in 145 women. Compared with women with no depression, women with a depression history displayed a subsequently higher risk of developing SLE.
Depression as a Sign of SLE
It’s not uncommon for patients living with chronic conditions, such as SLE and other rheumatic diseases, to experience depressive symptoms, including sadness, loneliness or despair. Separate research suggests that 25% of lupus patients experience major depression and 37% experience major anxiety.2
“We suggest clinicians be aware that depression is linked to an increased risk of autoimmune disease. So in women with depression, screening for family history of autoimmune disease and symptoms of autoimmune disease may be warranted,” Dr. Roberts says.
She also recommends rheumatologists make time to speak with SLE patients about possible symptoms of depression so these patients can be connected with mental health providers if needed.
Less understanding exists around pre-SLE depression and the underlying physiologic changes happening to patients experiencing depression that may make them more likely to develop SLE. Dr. Roberts, Dr. Costenbader and colleagues are exploring findings from this study to further understand whether women who develop SLE have different biological markers of immune function than women without SLE, and whether these markers are also related to depression.
“The more we understand about the risk factors for SLE, the better we will be at identifying those at risk and predicting onset of the disease,” Dr. Costenbader says.
Dr. Costenbader also notes several ways in which depression may be tied to a future elevated risk of SLE that remain to be determined. “Certainly people living with lupus experience higher rates of depression than do those without lupus, and perhaps this SLE-related depression can have onset even before more specific SLE signs and symptoms. Non-specific early symptoms of SLE, such as pain and fatigue, can also be misdiagnosed as depression. These two possibilities are important for physicians to note and remember in clinical encounters,” she says.
Additionally, Dr. Costenbader notes shared genetic or environmental exposures may exist that lead to the occurrence of the two disease states. Lastly, and perhaps most interestingly, depression is known to cause upregulation of inflammatory cytokine pathways that could fan the flames of brewing autoimmunity. “There is still much to study about this relationship,” she says.
Carina Stanton is a freelance science journalist based in Denver.
- Roberts AL, Kubzansky KD, Malspeis S, et al. Association of depression with risk of incident systemic lupus erythematosus in women assessed across two decades. JAMA Psychiatry. 2018 Dec;75(12):1225–1233.
- Zhang L, Fu T, Yin R, Zhang Q, Shen B. Prevalence of depression and anxiety in systemic lupus erythematosus: A systematic review and meta-analysis. BMC Psychiatry. 2017 Feb 14;17(1):70.