Of the brain-gut axis in the pathophysiology of Crohn's disease

Studies on the interaction between the central nervous system and the gastrointestinal system have shed light on the neurobiological response to stress via the hypothalamic-pituitaryadrenal and the hypothalamic-autonomic nervous system axes. These findings support a role of psychological and environmental factors in the course of gastrointestinal disorders and their influence on the neuroendocrine regulation of the immune system. Crohn's disease (CD) is a chronic inflammatory condition of the gastrointestinal tract, whose etiology involves genetic, psychological, immune and inflammatory factors. A higher prevalence of psychiatric diagnosis has been observed in CD patients. Both longitudinal and cross-sectional studies have explored the relationship between psychological stress and severity and/or clinical course of CD, with different, even conflicting, results. In several chronic diseases and stress-related psychological disorders, an alteration has been observed of the HPA response that through glucocorticoids modulate the immune/inflammatory reaction. In animal models of colitis, psychological or environmental stress may increase gastrointestinal permeability, allowing abnormal antigen presentation to the immune system and leading to the exacerbation and perpetuation of intestinal inflammation. The increased intestinal permeability under stress is mediated by corticotropin-releasing hormone stimulation through nicotinic, adrenergic and cholinergic receptors, suggesting a complex interplay between sympathetic and parasympathetic nervous systems. This review will examine and discuss the relationship between psychological stress and CD, investigating the role played by the hypothalamic-pituitary-adrenal and the hypothalamic-autonomic nervous system axes in stress-related psychological disorders, and the possible influence of chronic stress on the intestinal inflammation, in particular in CD. Copyright (c) 2008 S. Karger AG, Basel.