Skip to main content

Jeffrey Sparks, MD, on Depression and RA Risk

Jeffrey Sparks, MD, on Depression and RA Risk

Thu, 10/15/2020 - 19:33

Findings of a new study show that women who have indicators of depression may be at subsequent increased risk for seronegative rheumatoid arthritis (RA).1

Regular antidepressant use was the depression indicator that was particularly associated with seronegative RA risk.

In reaching this conclusion, the researchers found that, among 195,358 women from the Nurses’ Health Study (NHS) and NHSII, there were 858 incident RA cases over 3,087,556 person‐years (median 17.9 years/participant). Of those RA cases, 65% were seropositive.

Compared with women without depression, women with depression had multivariable hazard ratios (95% confidence intervals) of 1.28 (1.10‐1.48) for subsequent development of all RA, 1.12 (0.93‐1.35) for seropositive RA, and 1.63 (1.27‐2.09) for seronegative RA. 

Jeffrey A. Sparks, MD, MMSc, was the study’s first author. Dr Sparks is an assistant professor of medicine at Harvard Medical School and the director of Immuno-Oncology and Autoimmunity in the Division of Rheumatology, Inflammation, and Immunity at Brigham and Women’s Hospital.

We asked Dr Sparks about his findings and how they may influence your approaches to screening and management.

AUTOIMMUNE LEARNING NETWORK: In what ways do your findings highlight the importance of screening for depression among all patients? What about the importance of screening for RA among women with depression? 

Jeffrey Sparks: Screening for depression is important due to its high prevalence and health ramifications. Our study identified RA as another possible consequence of depression. Future studies are needed to establish the utility of screening for RA among patients with depression.

ALN: Knowing that women with depression are at an increased risk for subsequent seronegative RA, what can clinicians do to reduce these patients’ RA risk or to delay the onset of RA? 

JS: There are relatively few established risk factors for seronegative RA, and we identified depression as a potentially novel association. Future work is needed to investigate whether treating depression may also modify RA risk. There is growing literature on how mental health conditions such as depression may influence systemic inflammation which, in turn, could increase RA risk.

ALN: Does receiving a diagnosis of depression before vs after the onset of RA present any different clinical challenges or considerations?

JS: Diagnosing and managing RA is more difficult when other chronic conditions are present. Depression can be particularly challenging in patients with RA since it may be difficult to ascribe underlying symptoms such as fatigue, low mood, and pain due to either RA disease activity or due to depression or both. Since depression onset may precede a clinical RA diagnosis, we performed our study with a time separation to ensure that depression was not a feature of untreated RA.

ALN: What clinical complications may arise if depression is left untreated among patients with RA?

JS: While our study only examined depression before RA, many of the bothersome symptoms of RA are also features of depression. It is possible that untreated depression may manifest as pain, fatigue, or stiffness that may make assessment of RA disease activity and treatment response more difficult. Conversely, symptoms ascribed to depression but actually due to RA may contribute to ongoing joint damage and systemic inflammation. Therefore, optimizing treatments for both depression and RA are necessary to improve symptoms and assess for RA disease activity.

ALN: What special treatment/management considerations should clinicians keep in mind when managing patients with both depression and RA?

JS: Providers and patients should be encouraged to seek mental health providers to appropriately diagnose and manage depression. There should be a multidisciplinary approach to depression and RA since both conditions typically require chronic medications and periodic evaluation. Clinicians should be aware that patients with depression may be at increased risk for developing RA, particularly the seronegative form without autoantibodies.


  1. Sparks JA, Malspeis S, Hahn J, et al. Depression and subsequent risk for incident rheumatoid arthritis among women. Arthritis Care Res (Hoboken). Published online September 16, 2020.
6 + 11 =
Solve this simple math problem and enter the result. E.g. for 1+3, enter 4.
Back to Top