A nested case-control study from the Veteran Health Administration has found that post-traumatic stress disorder (PTSD) is significantly associated with increased rheumatoid arthritis (RA) risk—particularly among individuals who have never smoked. These findings, presented at ACR Convergence and published in Arthritis & Rheumatology, reveal that cigarette smoking modifies, rather than confounds, the PTSD–RA relationship and suggest a stronger link between PTSD and seronegative RA.

“Post-traumatic stress disorder (PTSD) is associated with increased systemic inflammation that may increase the risk of developing autoimmune disorders such as rheumatoid arthritis (RA),” the researchers noted. “We aimed to quantify the association between PTSD and the risk of developing RA in U.S. veterans, examining whether this association is confounded or modified by smoking.”

Researchers identified incident RA cases within the VA health system from 2006 to 2019 using a validated algorithm based on diagnostic codes, rheumatologist-confirmed diagnosis, positive autoantibodies or DMARD use, and ≥365 days of VA care. Each RA case was matched with up to 10 controls on age, sex, and year of enrollment. PTSD and other mental health disorders (OMH: depression, anxiety, bipolar disorder, substance use) were identified using ≥2 ICD-9/10 codes.

Multivariable conditional logistic regression examined associations between PTSD, OMH, and RA, adjusting for smoking, BMI, race, ethnicity, and urban/rural residence. Interaction models were used to assess whether smoking modified the effect of PTSD on RA risk, followed by stratified models based on smoking history and RA serostatus.

Key Findings:

• Cohort size: 357,361 veterans; 32,884 had RA

• Demographics: Mean age 53; 87% male; 70% had ever smoked

• RA cases: 76% were seropositive (RF and/or anti-CCP)

• PTSD & smoking: Both were significantly more common in RA patients than controls

• PTSD-RA interaction: A strong statistical interaction between PTSD and smoking was identified (p<0.001)

• Stratified analyses:

  • Never smokers with PTSD had a 54% increased risk of RA (aOR 1.54; 95% CI: 1.41–1.69)

  • Ever smokers with PTSD had a more modest increased risk (aOR 1.20; 95% CI: 1.16–1.25)

  • OMH (without PTSD) also increased RA risk but to a lesser degree

• Subtype association: PTSD was more strongly linked to seronegative RA than seropositive RA, across both sexes

“In addition to validating prior reports demonstrating an increased risk of RA attributable to both PTSD and cigarette smoking,” the authors concluded, “these results suggest that the relationship of PTSD with RA disease susceptibility is modified, rather than being confounded, by smoking status with a greater contribution to RA risk in never smokers.”

The findings add complexity to the understanding of autoimmune risk factors, suggesting that psychological trauma may be a stronger independent driver of RA in the absence of traditional inflammatory exposures like smoking. The differential association with seronegative RA also points to possible phenotype-specific pathways influenced by mental health.

These results underscore the need for further research into how stress and psychiatric disorders may shape autoimmune disease development, and how tailored prevention strategies could be deployed in vulnerable populations such as veterans.

Reference
Coziahr K, Sayles H, Johnson T, et al. Effect modification of cigarette smoking on the relationship between post traumatic stress disorder and rheumatoid arthritis risk [abstract]. Arthritis Rheumatol. 2025; 77 (suppl 9). https://acrabstracts.org/abstract/effect-modification-of-cigarette-smoking-on-the-relationship-between-post-traumatic-stress-disorder-and-rheumatoid-arthritis-risk.  Accessed October 15, 2025. ACR Convergence 2025