Study Examines How Depression Subtypes May Stem from Osteoarthritis

Prostock-studio / shutterstock.com

People with or at risk for sympto­matic knee osteoarthritis (OA) may be assigned to four depression subtypes with distinct clusters of depressive symptoms that may affect pain and disability over time, according to a new study in Arthritis Care & Research.¹

Four depression subtypes were identified in the study using the Center for Epidemiologic Studies Depression scale—catatonic, anhedonic, melancholic and asymptomatic—that could one day drive treatment optimization for patients, says co-author Alan M. Rathbun, PhD, MPH, a research associate at the University of Maryland School of Medicine, Baltimore. The study was supported by the Rheumatology Research Foundation’s Scientist Development Award.

“Knee OA is clinically heterogeneous, like depression, and is characterized by ‘the disease’ and the ‘illness,’ corresponding to the structural pathology of the joint and patients’ experience of symptomology, respectively,” says Dr. Rathbun, whose research was inspired by his chronic perseverative stuttering and associated social anxiety. “Knee OA progression may cumulatively contribute to psychosocial impairment over time. Prior studies have not recognized the potential contributions of structural pathology to the development of depression, or that this process aggregates and isn’t confined to a finite period of time.”

Dr. Rathbun

As many as 20% of people with osteo­arthritis experience depression and anxiety symptoms, according to a 2016 meta-analysis, and research also shows that knee pain, impaired function and depressive symptoms are all associated.^2,3 Dr. Rathbun co-authored a 2017 study that showed depressive symptoms are significantly associated with disease progression.⁴

Pain severity significantly increases with the persistence of depression in patients with knee OA, according to his recent research.⁵ However, Dr. Rathbun feels these connections are not well understood. The new study examined how depression subtypes may stem from OA disease severity.

Study Highlights

The study’s 4,486 participants were part of the Osteoarthritis Initiative, a multi-center observational cohort study of both men and women sponsored by the National Institutes of Health (NIH). All had baseline symptomatic knee OA data and baseline radiographs read by certified technicians at Boston University.

The researchers applied latent class analy­sis (LCA) to the 20-item Center for Epidemiological Studies Depression Scale measured at baseline to identify groups with similar patterns of depressive symptoms, and then assigned subtypes to each participant using poster probability estimates. Relationships between depression subtypes and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain and disability subscales were modeled over four years and stratified by baseline knee OA status; 1,626 patients had symptomatic knee OA, and 2,860 patients were at risk.

When grouped into the four subtypes, 80.6% of participants were asymptomatic, 5.3% were catatonic, 10.6% were anhedonic and 3.5% were melancholic. Patients in the catatonic subtype expressed symptoms of psychomotor agitation. Those in the anhedonic subtype had symptoms associated with the inability to experience pleasure. Those in the melancholic subtype expressed symptoms related to reduced energy and movement, anhedonia and other somatic complaints. Some overlap exists, a consequence of the subtypes also correlating to differences in depression severity (a potential way to discern groups), in which a greater number and spectrum of symptoms equates to greater burden.

When researchers compared subtype characteristics, the catatonic and melancholic group members were more likely to be female, nonwhite, not married and of lower socioeconomic status compared with those in the asymptomatic group.

Associations were generally greater in those with symptomatic knee OA compared to at-risk participants. Among those with symptomatic knee OA, only the melancholic group had persistently greater pain and disability during the follow-up. When compared to the asymptomatic group, both the catatonic and anhedonic groups had small differences in pain and disability from baseline (≤1 rescaled WOMAC unit).

The results showed greater differences in pain between the melancholic and asymptomatic groups. These increased from 0.47 (95% confidence interval [CI]: -3.86, 4.62) at baseline to 4.79 (95% CI: -1.77, 11.35) at the fourth annual follow-up visit. Participants in the melancholic group also had increases in disability over four years, rising from 2.80 (95% CI: -1.84,7.44) at baseline to as much as 6.56 (95% CI: 1.72, 11.40) rescaled WOMAC units during the follow-up period.

Recognition of, and treatment for, specific depression subtypes remain a ways off, according to Dr. Rathbun. He says, “Nonetheless, our results highlight the potential spectrum of depressive symptomology in patients with musculoskeletal disorders, and interventions could be designed in such a way that they target both knee OA and depression—all potential phenotypes—simultaneously, rather than considering each condition in isolation as a uniform collection of symptomologies.”

Patients with certain depression subtypes may respond differently to various treatments, Dr. Rathbun says. “For example, antidepressants could have high efficacy for treating symptoms related to anhedonia, but not be particularly effective with respect to psychomotor agitation, which is perhaps more aptly addressed with exercise training.”