P M Maloley1, B R England1, H Sayles2, G M Thiele1, K Michaud3, J Sokolove4, G W Cannon5, A M Reimold6, G S Kerr7, J F Baker8, L Caplan9, A J Case2, T R Mikuls10. 1. Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, NE, United States; University of Nebraska Medical Center, Omaha, NE, United States. 2. University of Nebraska Medical Center, Omaha, NE, United States. 3. University of Nebraska Medical Center, Omaha, NE, United States; National Data Bank for Rheumatic Diseases, Wichita, KS, United States. 4. AbbVie, Redwood City, CA, United States; VA Palo Alto Health Care System and Stanford University School of Medicine, Palo Alto, CA, United States. 5. Salt Lake City VA and the University of Utah, Salt Lake City, UT, United States. 6. Dallas VA and the University of Texas Southwestern, Dallas, TX, United States. 7. Washington, DC VA, Georgetown and Howard Universities, Washington, DC, United States. 8. Philadelphia VA and the University of Pennsylvania, Philadelphia, PA, United States. 9. Denver VA and the University of Colorado at Denver, Denver, CO, United States. 10. Veterans Affairs (VA) Nebraska-Western Iowa Health Care System, Omaha, NE, United States; University of Nebraska Medical Center, Omaha, NE, United States. Electronic address: tmikuls@unmc.edu.
Abstract
OBJECTIVE: Although post-traumatic stress disorder (PTSD) is identified as a risk factor in the development of rheumatoid arthritis (RA), associations of PTSD with disease progression are less clear. To explore whether PTSD might influence disease-related measures of systemic inflammation in RA, we compared serum cytokine/chemokine (cytokine) concentrations in RA patients with and without PTSD. METHODS: Participants were U.S. Veterans with RA and were categorized as having PTSD, other forms of depression/anxiety, or neither based on administrative diagnostic codes. Multiplex cytokines were measured using banked serum. Associations of PTSD with cytokine parameters (including a weighted cytokine score) were assessed using multivariable regression, stratified by anti-CCP status and adjusted for age, sex, race, and smoking status. RESULTS: Among 1,460 RA subjects with mean (SD) age of 64 (11) years and disease duration of 11 (11) years, 91% were male, 77% anti-CCP positive, and 80% ever smokers. Of these, 11.6% had PTSD, 23.7% other depression/anxiety, and 64.7% had neither. PTSD, but not depression/anxiety, was associated with a higher cytokine score and number of high-concentration analytes in adjusted models, though this was limited to anti-CCP positive subjects. PTSD was associated with heightened expression of several individual cytokines including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-17, IFN-γ, GM-CSF, MCP-1, and TNF-α. CONCLUSION: Anti-CCP positive RA patients with PTSD have higher serum cytokine concentrations than those without PTSD, demonstrating that systemic inflammation characteristic of RA is heightened in the context of this relatively common psychiatric comorbidity.
OBJECTIVE: Although post-traumatic stress disorder (PTSD) is identified as a risk factor in the development of rheumatoid arthritis (RA), associations of PTSD with disease progression are less clear. To explore whether PTSD might influence disease-related measures of systemic inflammation in RA, we compared serum cytokine/chemokine (cytokine) concentrations in RApatients with and without PTSD. METHODS:Participants were U.S. Veterans with RA and were categorized as having PTSD, other forms of depression/anxiety, or neither based on administrative diagnostic codes. Multiplex cytokines were measured using banked serum. Associations of PTSD with cytokine parameters (including a weighted cytokine score) were assessed using multivariable regression, stratified by anti-CCP status and adjusted for age, sex, race, and smoking status. RESULTS: Among 1,460 RA subjects with mean (SD) age of 64 (11) years and disease duration of 11 (11) years, 91% were male, 77% anti-CCP positive, and 80% ever smokers. Of these, 11.6% had PTSD, 23.7% other depression/anxiety, and 64.7% had neither. PTSD, but not depression/anxiety, was associated with a higher cytokine score and number of high-concentration analytes in adjusted models, though this was limited to anti-CCP positive subjects. PTSD was associated with heightened expression of several individual cytokines including IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-17, IFN-γ, GM-CSF, MCP-1, and TNF-α. CONCLUSION: Anti-CCP positive RApatients with PTSD have higher serum cytokine concentrations than those without PTSD, demonstrating that systemic inflammation characteristic of RA is heightened in the context of this relatively common psychiatric comorbidity.
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