Although most patients exposed to Helicobacter pylori and nonsteroidal anti-inflammatory drugs (NSAIDs) do not develop ulcers, these two factors are often believed to be causes of ulcer development, while the role of psychological stress is often discounted. But does psychological stress increase ulcer risk independent of H. pylori and NSAID use?

In a population-based sample of 3,379 Danish adults who were born in 1922, 1932, 1942, or 1952 without a history of ulcer from the World Health Organization’s MONICA study, blood samples, along with psychological, social, behavioral, and medical data were collected from 1982–1983. As part of the assessment, a 0- to 10-point stress index scale measured stress based on concrete life stressors and perceived stress; the surviving participants were interviewed again in 1987–1988 and 1993–1994. Ulcer was diagnosed in patients with a distinct breach in the mucosa and all diagnoses were confirmed with a review of radiologic and endoscopic reports.

In the patients with a confirmed ulcer diagnosis, incidence was significantly greater among participants in the highest tertile of stress scores vs. the lowest tertile (3.5% vs. 1.6%, respectively). Even in a multivariate model including H pylori, NSAID use, socioeconomic status, and smoking, stress remained a significant predictor of ulcer. Stress increased the risk for both gastric and duodenal ulcers.

It is proposed that stress may promote peptic ulcer via increased acid load, effects of hypothalamic-pituitary-adrenal axis activation on healing, altered blood flow, or cytokine-mediated impairment of mucosal defense. Clinicians treating ulcer patients should be aware of psychological stress as a potential risk factor for ulcer, which may warrant lifestyle modifications to reduce stress.