Share this article on:

The Relationship Between Mental Health, Disease Severity, and Genetic Risk for Depression in Early Rheumatoid Arthritis

Euesden, Jack PhD; Matcham, Faith MSc; Hotopf, Matthew PhD; Steer, Sophia PhD; Cope, Andrew P. PhD; Lewis, Cathryn M. PhD; Scott, Ian C. PhD

doi: 10.1097/PSY.0000000000000462
Original Articles

Objective Reduced mental health (MH) is prevalent in rheumatoid arthritis (RA). Although longitudinal studies are limited, there is evidence that depression is associated with worse disease outcomes. We evaluated reciprocal relationships between MH, RA severity, and genetic risks for depression for 2 years in a well-characterized cohort of RA patients.

Methods We evaluated 520 early RA patients previously enrolled to two clinical trials. MH was measured using the short form-36 MH domain and mental component summary scores (MCS). MCS/MH associations over 2 years with disease activity (disease activity score on a 28-joint count), disability (health assessment questionnaire), pain visual analog scale scores, and a weighted genetic risk score for depression were tested using linear mixed-effects and regression models.

Results Poorer MH was associated with worse RA outcomes. Lower MCS scores (indicating worse MH) were seen in patients with a greater genetic risk for depression (weighted genetic risk score: coefficient = −1.21, p = .013). Lower baseline MCS was associated with lower 2-year improvements in disease activity score on a 28-joint count (coefficient = −0.02, p < .001), pain (coefficient = −0.33, p < .001), and health assessment questionnaire (coefficient = −0.01, p = .006). Baseline MCS was associated with changes in the swollen joint count (coefficient = −0.09, p < .001) and patient global assessment (coefficient = −0.28, p < .001) but not the tender joint count (p = .983) and erythrocyte sedimentation rate (p = .973). Only baseline pain visual analog scale (coefficient = −0.07, p = .002) was associated with 2-year changes in MCS.

Conclusions Reduced baseline MH was associated with lower improvements in disease activity, disability, and pain for 2 years, supporting current national guidelines recommending screening for depression in RA. Pain had a bidirectional relationship with MH. Depression genetic risk had a significant association with MH.

Supplemental digital content is available in the text.

From the SGDP Centre (Euesden, Lewis), and Department of Psychological Medicine (Matcham, Hotopf), Institute of Psychiatry, Psychology & Neuroscience, King's College London; Department of Rheumatology (Steer), Weston Education Centre, King's College Hospital; Academic Department of Rheumatology (Cope, Scott), Centre for Molecular and Cellular Biology of Inflammation, and Department of Medical and Molecular Genetics (Lewis, Scott), King's College London, London; MRC Integrative Epidemiology Unit (Euesden), School of Social and Community Medicine, University of Bristol, Bristol; and Research Institute for Primary Care & Health Sciences (Scott), Primary Care Sciences, Keele University, Staffordshire, United Kingdom.

Supplemental Content

Address correspondence and reprint requests to Jack Euesden, PhD, MRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Oakfield House, Oakfield Grove, Bristol, BS8 2BN, UK. E-mail:

Received for publication February 4, 2016; revision received January 26, 2017.

This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Copyright © 2017 by American Psychosomatic Society