Association of Stress-Related Disorders With Subsequent Autoimmune Disease.
Level 3 - non-randomized controlled study
Retrospective population- and sibling-matched cohort study
PubMed 29922828 · doi:10.1001/jama.2018.7028
What was done
Population- and sibling-matched retrospective cohort study using Swedish health registries between 1981 and 2013. The study included 106,464 patients with stress-related disorders (posttraumatic stress disorder, acute stress reaction, adjustment disorder, and other stress reactions), 1,064,640 matched unexposed individuals, and 126,652 full siblings. Cox proportional hazards regression estimated hazard ratios for 41 autoimmune diseases occurring beyond 1 year after stress disorder diagnosis, adjusting for multiple covariates.
What was found
Over a mean follow-up of 10 years, autoimmune disease incidence was 9.1 per 1000 person-years in exposed individuals, 6.0 in unexposed controls, and 6.5 in siblings (absolute rate differences: 3.12 [95% CI, 2.99-3.25] and 2.49 [95% CI, 2.23-2.76] per 1000 person-years compared with unexposed and sibling cohorts, respectively). Stress-related disorders were associated with increased autoimmune disease risk (HR, 1.36 [95% CI, 1.33-1.40]), with consistent results in sibling comparisons. For posttraumatic stress disorder, HRs were 1.46 (95% CI, 1.32-1.61) for any autoimmune disease and 2.29 (95% CI, 1.72-3.04) for multiple (3 or more) autoimmune diseases. Relative risk was higher in younger patients (HR, 1.48 for age 33 or younger vs 1.23 for age 51 or older; P for interaction < .001). Persistent SSRI use for 320 days or more in the first year of PTSD diagnosis was associated with attenuated risk compared to 179 days or less (HR, 1.82 vs 3.64; P for trend = .03).
Why it matters
This study provides large-scale evidence linking stress-related disorders to an elevated risk of subsequent autoimmune disease, independent of shared familial and genetic factors.
Limits
The study is observational and cannot demonstrate direct causation. Registry data captured specialist diagnoses, potentially missing milder cases treated in primary care. Unmeasured lifestyle factors and residual confounding remain possible despite sibling matching.
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