Background/Purpose: Posttraumatic stress disorder (PTSD) is associated with autoimmune dysfunction, but the relationship between PTSD and the incidence of autoimmune disorders has not been studied prospectively. We examined the prospective association between PTSD and rheumatoid arthritis (RA) risk and tested markers of adverse health behaviors, cigarette smoking and body mass index (BMI), as possible mediators.

Methods: The Nurses’ Health Study II (NHSII) is a longitudinal cohort of 116,430 female nurses enrolled in 1989 at ages 25–42 years. A subset (N = 50,347) completed the Brief Trauma Questionnaire and the Lifetime PTSD screen, validated questionnaires that include date of worst trauma (proxy for date of PTSD onset). Participants were categorized into 5 groups based on trauma exposure and PTSD symptoms: 1) no trauma (referent), 2) trauma but no PTSD symptoms, 3) trauma and 1-3 PTSD symptoms, 4) trauma and 4-5 PTSD symptoms and 5) trauma and 6-7 PTSD symptoms. Incident RA (N = 185) after 1989 was confirmed by medical record review. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between PTSD and RA risk, adjusted for age, questionnaire year, race and parental education. We also examined the association between PTSD and seropositive and seronegative RA risk. To assess whether BMI and smoking mediated these associations, BMI and smoking measured after PTSD onset were added to the models. To assess whether BMI and smoking were confounders, we performed a subgroup analysis, including variables assessed before PTSD onset (BMI at age 18 and smoking before age 19) among women who experienced PTSD onset after age 20.

Results: Compared to women unexposed to trauma, women exposed to trauma and reporting more than 4 PTSD symptoms were at higher risk for incident RA. RA risk increased with increasing number of PTSD symptoms (4-5 PTSD symptoms: HR 1.78, 95% CI 1.03-3.09; 6-7 PTSD symptoms: HR 1.91, 95% CI 1.03-3.56) (Table). Results were similar for the association between PTSD and seropositive RA risk (4-7 PTSD symptoms: HR 1.90, 95% CI 1.09-3.33). This trend was also noted in a subanalysis predicting seronegative RA, but the HR was lower and did not reach statistical significance (1.68, 95% CI 0.69-4.08). Both BMI and smoking status attenuated the association between PTSD and incident RA. In secondary analyses among patients who developed PTSD at age > 20, the HR for association with PTSD was lower (HR 1.57, 95% CI 0.56-4.43), but neither BMI at age 18 nor smoking before age 19 changed the HR (HR 1.58, 95% CI 0.56-4.45).

Conclusion: These results suggest that PTSD may increase RA risk. Additional studies are needed to elucidate the pathways by which PTSD is associated with RA risk, specifically to assess whether this association is due to adverse health behaviors, increased reporting and healthcare utilization or alterations in immune pathways due to dysregulated stress response.