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Psychological factors have been associated with knee osteoarthritis pain severity
and treatment outcomes, yet their combined contribution to phenotypic heterogeneity
is poorly understood. In particular, empirically-derived psychological profiles must
be replicated before they can be targeted or considered for treatment studies. The
objectives of this study were to (1) confirm previously identified psychological profiles
using unsupervised clustering methods in persons with knee osteoarthritis pain, (2)
determine the replicability of profiles using supervised machine learning in a different
sample, and (3) examine associations with clinical pain. Participants with knee osteoarthritis
pain were recruited for two multi-site studies: Study1 (n=270, mean age=56.8 ± 7.6,
male=37%), and Study2 (n=164, mean age=57.73±7.8, male=36%). Similar psychological
constructs (e.g. optimism, coping, somatization, affect, depression, and anxiety),
sociodemographic and pain characteristics were assessed in both samples. Unsupervised
hierarchical clustering analysis was first conducted on Study1 data to derive clusters,
followed by a supervised linear discriminant analysis applied to Study2 data to assess
replicability of psychological clusters. Associations among cluster membership and
pain outcomes were examined using one-way analysis of covariance, controlling for
race, age, sex, education, and study site in both datasets. Based on the psychological
data in Study1, four distinct clusters emerged. These clusters showed strong associations
with psychological variables (p's<0.001), and clinical pain (p's=0.001–0.03), indicating
good internal and external validation of the cluster interpretability. Using Study1
as the training data, we predicted the clusters in Study2 using linear discriminative
analysis. The resulting four clusters also showed similar associations with psychological
variables (p's<0.001), and clinical pain (p's=0.001–0.005), demonstrating replicability
of profiles and their characteristics. This study demonstrates the critical role psychological
function plays in knee osteoarthritis pain and highlights the need to consider multiple
psychological factors when developing targeted interventions. Roger Fillingim: R37AG033906,
Yenisel Cruz-Almeida: R01AG059809, R01AG067757, Zhiguang Huo: R01AG059809, R01AG067757.
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© 2021 Published by Elsevier Inc.