Stress in the Etiology of Crohn's Disease

Research has demonstrated stress can be a contributing factor in Crohns disease. The mechanisms involved vary widely depending on the animal model studied, but it can be concluded stress and other environmental factors affect both the systemic and local immune status of the intestine. Stress signals are perceived by the central nervous system (CNS), triggering transmission of the signal to the intestine via neuroendocrine mediators. The hypothalamic-pituitary-adrenal axis and the sympathetic-adrenal-medullary axis can modulate secretory, absorption, and barrier functions in the gut.³⁹

Crohns Disease is characterized by increased intestinal permeability and extensive animal research has shown stress significantly influences intestinal permeability.⁴⁰ Factors involved in the effects of stress on gut permeability include corticotropinreleasing factor (CRF), the autonomic nervous system, and the enteric nervous system. CRF is produced and secreted by the hypothalamus, but has also been found to be secreted in the colonic crypts during times of stress, resulting in increased intestinal permeability.⁴¹ The CNS also influences the degree of intestinal inflammation via the autonomic⁴² and enteric nervous systems.⁴³

Stress can also contribute to exacerbations of already existing disease. Two prospective studies demonstrated psychological stress, anxiety, and depression are associated with increased Crohns Disease activity. In one study, 18 Crohns Disease patients were followed prospectively at 8- to 12-week intervals for two years. Disease activity was measured using the CDAI, Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI). The study revealed a strong association between BDI scores and current disease activity when measured simultaneously. Both BDI- and BAI-score increases were independently associated with increased CDAI scores in a subsequent visit 8-12 weeks later.⁴⁴

The second study involved 47 Crohns Disease patients in remission (after a documented flare) followed for 18 months and assessed using the same scoring inventories as the first study. These researchers also demonstrated psychological stress, anxiety, depression, and altered quality of life were likely to influence further Crohns disease activity following a relapse.⁴⁵

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