Re-examining the pain–depression vicious cycle in knee osteoarthritis: a random-intercept cross-lagged panel analysis
Year: 2026
Type: article
Abstract: BACKGROUND: Pain and depression frequently co-occur in knee osteoarthritis (OA), traditionally viewed as a vicious cycle in which each worsens the other over time. However, conventional cross-lagged models cannot separate stable differences between individuals from real year-to-year changes within a person. We therefore used a random-intercept cross-lagged panel model (RI-CLPM) in the Osteoarthritis Initiative (OAI). METHODS: Of 4,796 enrolled OAI participants with, or at risk of, knee OA, 4,638 contributed data across four annual waves from months 12 to 48. The RI-CLPM was applied to knee pain (WOMAC scale, worse knee) and depressive symptoms (CES-D scale), using full-information maximum likelihood. We contrasted it with a traditional model (CLPM), replicated it in a later six-wave window (months 36 to 96), and tested moderation by sex, arthritis severity, baseline pain and baseline depression, alongside covariate-adjusted and sensitivity analyses. Sensitivity analyses used a cognitive-affective CES-D subscale excluding somatic items, alternative model constraints and an alternative standardisation. RESULTS: The RI-CLPM fitted well and the between-person trait correlation was substantial (standardised r = 0.39, p < 0.001), whereas within-person cross-lagged paths were small and non-significant in both directions (pain to depression standardised beta = 0.019, 95% CI -0.010 to 0.048; depression to pain beta = 0.009, 95% CI -0.019 to 0.036). A classical CLPM on identical data showed significant reciprocal paths (both beta approximately 0.08) but fitted poorly; separating the random intercepts reduced the cross-lagged coefficients by roughly 77-89%. The pattern was reproduced in the second window, unchanged by covariates, and no moderator test survived correction for multiple testing. Using a cognitive-affective CES-D subscale reduced both cross-lagged paths further (0.014 and - 0.001) and the trait correlation to 0.34. CONCLUSIONS: In knee OA, the link between pain and depression was mainly explained by stable differences between individuals. At annual intervals we found limited evidence for reciprocal within-person effects, which is not evidence that none exist; shorter-term dynamics were not estimable. Depressive symptoms should still be assessed, but the findings do not support an automatic year-to-year feedback loop, and do not show whether treating one symptom improves the other.
Source: BMC Musculoskeletal Disorders
Authors: Yannick Bruns, Hendrik Fahlbusch
Institutions: Medizinische Hochschule Hannover, Regio Kliniken
Language: English
Subfield: Pharmacology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,090
OpenAlex ID: W7208780420