Linking Depression and Anxiety With Higher 28-joint Disease Activity Score in RA

These results support the researchers' previous findings from clinical trial data showing a longitudinal relationship between baseline depression and anxiety, and patient global assessment as well as fo.llow-up tender joints

In a study recently published in Musculoskeletal Disorders, symptoms of depression and anxiety, because of their effect on both patient global assessments and tender joints, were found to be implicated in rheumatoid arthritis (RA) activity.1

“The relationship between mental and physical health is bidirectional. Experiencing psychological distress may inflate the subjective severity of patient-reported symptoms such as pain and tenderness,” wrote Faith Matcham, MSC, from King’s College London and colleagues. “Psychological distress may [also] impact health outcomes by influencing health behaviors such as medication adherence and smoking.”

An increase in psychological symptoms in RA is associated with poorer patient outcomes, including increased pain, fatigue, service usage, and enhanced risk of premature mortality. A recent systematic review showed that only 7 studies had examined the longitudinal relationships between depression and RA outcomes.Thus, researchers sought to investigate the relationship between baseline depression and anxiety, and patient global assessments of RA disease activity in a longitudinal study.

To examine the psychological factors associated with disease outcomes in RA, researchers conducted a 1 year prospective study, for which patients attending a rheumatology outpatient clinic at King’s College Hospital were approached. Forty six percent (109) of the 235 patients who completed the questionnaire reported having RA. Of those, only 56 had clinically verified RA and were included in the analysis (78.6% women, mean age 53.6 years, 64.8% white). The average time between baseline and follow-up was 1.1 years (SD = 0.4).

Results from this study indicated that 1) depression and anxiety scores at baseline were not significant predictors of the 28-joint Disease Activity Score (DAS28) at 1-year follow-up after full adjustment; 2) depression and anxiety were significantly associated with the subjective components of the DAS28, swollen joint count and Patient Global Assessment; and 3) depression and anxiety were not significantly associated with the odds of reaching clinical remission at 1-year follow-up after adjusting for covariates.

These results support the researchers’ previous findings from clinical trial data showing a longitudinal relationship between baseline depression and anxiety, and patient global assessment as well as follow-up tender joints.3

While the researchers did not replicate their previous finding of an association between depression and anxiety and poorer outcomes in RA, they argued that this might be due to “a lack of statistical power to predict a binary outcome.”

 “The current study uses a more robust, validated method of identifying depression and anxiety, in a more heterogeneous clinical sample, with longer and more variable disease duration. This strengthens the evidence indicating a prospective relationship between depression and anxiety and poorer subjective disease outcomes in RA,” the authors wrote.

The researchers noted that there are several possible explanations for the associations found between depression and anxiety and patient global assessment and tender joint counts. Psychological distress is associated with worsened health behaviors such as failing to take medications as prescribed, increased smoking, or reduced physical activity, which can contribute to worsened disease outcomes. “The association between depression and anxiety and the subjective elements of DAS28 would suggest that depression/anxiety impact perceptions and behaviors, rather than immune dysregulation,” the authors wrote.

Further investigation of mediators between depression/anxiety and RA are warranted. Potential targets for investigation include negative cognitions (eg, repetitive negative thinking), behavioral activity, and health behaviors. 

Summary & Clinical Applicability

As measured by the DAS28, symptoms of depression and anxiety have implications for disease activity, primarily due to their influence on patient global assessment and tender joints.

This finding has implications in treatment decisions, as inflated DAS28 may point to psychological comorbidities and non-inflammatory pain, rather than bona fide RA activity, even in the presence of low levels of inflammatory disease markers.

Limitations & Disclosures

  • Sample size was small, limiting statistical power and the ability to control for relevant covariates
  • Lack of clinician-verified diagnosis of RA in majority of patients
  • Lack of sociodemographic data available. Because low socioeconomic status is associated with increased susceptibility to depression and RA, these findings may not be generalizable to the general RA population. The researchers did note, however, that King’s College Hospital cares mostly for people in South East London, which has a higher level of deprivation than the London average.
  • Lack of data available for psychopharmacotherapy and medications for RA

The authors declare that they have no competing interests.


  1. Matcham F, Ali S, Irving K, Hotopf M, Chalder T. Are depression and anxiety associated with disease activity in rheumatoid arthritis? A prospective study. BMS Musculoskelet Disord. 2016;17(155).
  2. Rathbun AM, Reed GW, Harrold LR. The temporal relationship between depression and rheumatoid arthritis disease activity, treatment persistence and response: a systematic review. Rheumatology (Oxford). 2013;52:1785– 1794.
  3. Matcham F, Norton S, Scott DL, Steer S, Hotopf M. Symptoms of depression and anxiety predict treatment response and long-term physical health outcomes in rheumatoid arthritis: secondary analysis of a randomized controlled trial. Rheumatology (Oxford). 2016;55(2):268-278.

This article originally appeared on Rheumatology Advisor