Bidirectional Link Identified Between Depression, Inflammatory Joint Disease

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This analysis may require further research to determine whether other treatment-resistant depression or severe depression definitions are specifically associated with inflammatory joint disease.

There is a bidirectional association between inflammatory joint disease (IJD) and depression among patients, according to recent findings, although the link appears not to be likely impacted by patients’ treatment resistance or severity of their depression.1

These conclusions resulted from new research conducted to assess whether depression’s severity or a patient’s treatment depression impacts the link between the mental health condition and inflammatory joint diseases such as psoriatic arthritis (PsA), rheumatoid arthritis (RA), ankylosing spondylitis/spondyloarthropathies (AS), and juvenile idiopathic arthritis (JIA).

This research was led by Philip Brenner of the department of medicine solna’s clinical epidemiology division at Karolinska University Hospital Solna in Stockholm, Sweden. Brenner and colleagues noted that there is existing evidence that longer duration of depressive episode and increased exposure systemic inflammation can be correlated, adding that only 22% of those with TRD who are in remission a year following being diagnosed with TRD.2

“Therefore, the aim of this study was to investigate the bidirectional association between IJDs on one hand, and depression, severe depression and TRD on the other,” Brenner and colleagues wrote. “In order to accomplish this, we utilized data from nation-wide Swedish governmental registers including information on psychiatric and non-psychiatric diagnoses, filled drug prescriptions, sociodemographic characteristics and migration.”

Background and Methods

The investigators utilized data drawn from various Swedish governmental health care and population registers, 1 of which was the Swedish National Patient Register (NPR). The NPR provided the research team with access to data regarding clinician-registered diagnoses as well as medical procedures, covering inpatients fully since the year 1987 and specialized healthcare outpatients since the year 2001.

The team also accessed the Total Population Register (TPR), which records residence and migration data for all Swedish residents since 1968. The team additionally accessed prescription drug information through the Prescribed Drug Register (PDR), which gives information on all prescribed and filled drugs within Swedish pharmacies from July 2006 to the present, as well as the Longitudinal Integrated Database for Health Insurance and Labour Market Studies (LISA) containing sociodemographic information for all residents since 1990.

The investigators established 3 matched patient-comparator cohorts, the first of which (a) was made up of those diagnosed and treated for an episode of depression and these were matched with general population comparators. The second cohort (b) had reported a severe depressive episode and were matched with individuals from the main cohort with non-severe depression.

The third cohort (c) included subjects within the main cohort who had TRD and these subjects matched with non-TRD individuals from the main cohort. Both subjects and their comparators were noted as not being mutually exclusive across all of the cohorts.

The research team highlighted the retrospective and prospective IJD risk among subjects that had depression, and their analyses were adjusted to account for comorbidities as well as sociodemographic factors. This allowed the team to make a comprehensive assessment of the connections observed between depression and IJD.


Overall, the investigators looked at 180,218 subjects that had depression and no prior history of IJD, with 19% of their subjects meeting the established severe depression criteria and 12% meeting the criteria for having TRD. Those who had depression were found to have a greater risk for later IJD versus their population comparators (adjusted hazard ratio (aHR) for IJD 1.34 [95% CI 1.30–1.39]; for PsA, 1.45 [1.29–1.63]; RA, 1.27 [1.15–1.41]; AS, 1.32 [1.15–1.52]).

The research team noted that subjects in case-control research with reported depression were found to have a more frequent history of IJD versus the population controls (adjusted odds ratio (aOR) for any IJD 1.43 [1.37–1.50]; PsA 1.59 [1.46–1.73]; RA 1.39 [1.29–1.49]; JIA 1.52 [1.35–1.71]; AS 1.49 [1.36–1.64]). They added that these links were not shown to be substantially distinct for those with severe depression or with TRD.

“Limitations include the algorithm-based definitions of severe depression and TRD, lack of direct clinical data such as ratings of depression, IJD disease activity and pain, and the moderate follow-up time,” they wrote. “…(Some) patients may have had depression before the onset of IJD in the case-control studies, potentially overestimating risks. Inclusion in our study populations was based on recorded health care data, thus excluding those with depression that were not medically attended.”


  1. Brenner P, Askling J, Reutfors J, et al. Association between inflammatory joint disease and severe or treatment-resistant depression: population-based cohort and case-control studies in Sweden. Gen Hosp Psychiatry. 2024 Apr 27;89:23-31. doi: 10.1016/j.genhosppsych.2024.04.007. Epub ahead of print. PMID: 38714100.
  2. K Heerlein, G Perugi, W Hagedoorn, et al. Real-world evidence from a European cohort study of patients with treatment resistant depression: treatment patterns and clinical outcomes. J Affect Disord, 290 (2021), pp. 334-344.