New research published recently in Clinical Gastroenterology and Hepatology provides strong evidence that psychological factors need to be brought back into the clinical picture of peptic ulcer disease.
Once considered the main driver of this common disorder, psychosocial stress was practically pushed out of the etiological equation when researchers discovered the role of Helicobacter pylori and the influence of NSAIDs in causing gastric erosion.
Since the 1980s, these two factors have dominated medical thinking about how to diagnose and treat ulcers.
The new longitudinal study of 3,379 Danish adults by Susan Levenstein, MD, and colleagues found that stress significantly increased the incidence of peptic ulcer, regardless of subjects' H. pylori or NSAID status.
The study's participants were all enrolled in the World Health Organization's larger MONICA study of cardiovascular disease. To be eligible for the ulcer research, subjects had to be ulcer-free at baseline.
Internal & External Stress
All study subjects completed a 12-item questionnaire at enrollment in 1982-1983. Surviving participants were then re-interviewed using the same questionnaire at 5 years (n = 2809) and at 10 years (n = 2410) after enrollment. Questions covered a range of social and economic factors including housing and employment status, tranquilizer use, and family and personal issues.
Taking into account perceived distress as well as concrete life stressors, the investigators used a 0-10 stress index scale to measure participants' overall stress levels.
During follow-up interviews, subjects were asked whether or not they had undergone gastroscopy, barium swallow, or received an ulcer diagnosis. Rather than relying on patient self-reporting alone, the research team also reviewed participants' medical records from endoscopy and radiology examinations whenever this was possible.
They were able to obtain diagnostic reports from 170 of the 209 new ulcer cases reported in 1987, as well as from all new ulcers reported in 1993.
Stress Doubles the Odds
The investigators were able to confirm the development of ulcers—defined as a distinct breach in the gastric or duodenal mucosa based on endoscopic and radiological exam—in 76 of the study's participants.
In analyzing risk factors, they found that high stress more than doubled a patient's risk of developing gastric or duodenal ulcers. Ulcer incidence was significantly higher among subjects in the highest tertile of stress scores (3.5%) than those in the lowest tertile (1.6%) (adjusted odds ratio, 2.2; 95% confidence interval, 1.2-3.9; P<0.01) (Levenstein, et al. Clin Gastrol Hepatol. 2015;13(3): 498-506).
The important point is that the impact of stress on ulcer incidence was similar among those who were H. pylori seropositive and those who were seronegative. Likewise, the connection between stress and ulcers was independent of NSAID use.
The authors report that the odds ratio for incident ulcer per point of the stress index (1.19; 95% CI, 1.09–1.31; P<0.001) was unaffected after adjusting for H. pylori, inadequate sleep, and alcohol consumption. The ratio was slightly lower after adjustments for smoking, NSAID use, and lack of exercise (1.11; 95% CI, 1.01–1.23; P = .04), but the stress factor was a robust predictor.
On multivariable analysis, the investigators found that stress, socioeconomic status, smoking, H. pylori infection, and NSAIDs were all independent predictors of ulcer.
These findings encourage a critical rethinking of the role that stress plays in ulcer development.
The authors point out that only a minority of H. pylori or NSAID-exposed individuals develop ulcers. Additionally, they argue, because neither H. pylori nor NSAIDs can be implicated in 16%–31% of ulcer cases, other co-factors or alternative pathways must be involved.
Because of the intense focus on the NSAID and H. pylori theories of ulcer development, "authoritative sources now commonly discount or ignore a role for psychosocial factors," they write. This tendency has certainly extended out to the clinical setting.
Dr. Levenstein and colleagues urge medical practitioners to investigate all potential psychosocial stressors alongside other factors like H. pylori or NSAID exposure when treating ulcer patients.
Despite a variety of known adverse effects, including gastrointestinal ulceration and bleeding, NSAIDs remain among the most widely prescribed drugs worldwide (Syer, et al. J. Gastroent. 2015: 50(4):387-393), another clinical tendency that warrants a serious re-thinking.