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Longitudinal associations between depressive symptoms and clinical factors in ankylosing spondylitis patients: analysis from an observational cohort



Although cross-sectional studies have shown that ankylosing spondylitis-specific factors correlate with depressive symptom severity, the association of these factors over time is unresolved. We examined the demographic and clinical factors associated with longitudinal depressive symptom severity in AS patients.


We analyzed sociodemographic, clinical, behavioral and medication data from 991 patients from the Prospective Study of Outcomes in Ankylosing spondylitis cohort, and measured depression severity with the Center for Epidemiological Studies Depression (CES-D) Scale administered at approximately 6-month visit intervals. Multivariable longitudinal negative binomial regression models were conducted using generalized estimating equation modeling to assess the demographic, clinical, and medication-related factors associated with depression severity by CES-D scores over time.


The median baseline CES-D score (possible range 0–60) was 10.0 (interquartile range = 5, 17). In longitudinal multivariable analyses, higher CES-D scores were associated with longitudinal smoking, greater functional impairment, greater disease activity, self-reported depression, and poor global health scores. Marital status (e.g., being married) was associated with lower CES-D. Adjusted mean CES-D scores in our model decreased over time, with a significant interaction between time and gender observed.


This study identified longitudinal clinical factors such as greater disease activity, greater functional impairment, and poor global health to be associated with longitudinal depression severity. These factors are potentially modifiable and may help manage depressive symptoms in AS.

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The authors would like to thank the staff and participants of the Prospective Study of Ankylosing spondylitis PSOAS cohort. The PSOAS cohort is supported by grants from the United States Department of Health and Human Services, National Institutes of Health (NIH), National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), P01-052915-06 and from the Spondylitis Association of America (SAA). We acknowledge the support provided by the Biostatistics/ Epidemiology/Research Design (BERD) component of the UTHealth Center for Clinical and Translational Sciences (CCTS) for this project. CCTS is mainly funded by the NIH Centers for Translational Science Award (UL1TR000371) by the National Center for Advancing Translational Sciences (NCATS). Also, we acknowledge that management of data for this study was done using REDCap, which was partly supported by a Grant UL1 TR000445 from NCATS/NIH, awarded to Vanderbilt University. Dr. Mark Hwang is supported by the CCTS KL2 program (1KL2-TR-003168-01). Dr. Michael Ward is supported by the Intramural Research Program, NIAMS, NIH.

Author information




All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by MB, LG, MH, MI, JR, MW, and MW. The first draft of the manuscript was written by MH and all authors commented on previous versions of the manuscript. All the authors agreed to take full responsibility for all aspects of the study and the final manuscript.

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Correspondence to Mark C. Hwang.

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Conflict of interest

All authors declare they have do not have any conflicts of interest relative to the content of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, SAA, or NCATS.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by each participants Institutional Review board (Protocol, Date): Princess Alexandria Hospital (2005/221 March 6th 2009) Cedars Sinai Medical Center (CR00004630 October 1t, 2010) National Institute of Health (03-AR-0131 March 3rd 2003), University of California San Francisco (H63075-35456-01 March 12th 2010), and University of Texas Health Science Center at Houston (HSC-MS-07-0022 Feb 8th, 2007).

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Informed consent was obtained from all individual participants included in the study.

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Hwang, M.C., Lee, M.J., Gensler, L.S. et al. Longitudinal associations between depressive symptoms and clinical factors in ankylosing spondylitis patients: analysis from an observational cohort. Rheumatol Int 40, 1053–1061 (2020).

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  • Depression
  • Pharmacologic therapy
  • Comorbidities
  • Ankylosing spondylitis