The role of psychological stress in inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an idiopathic inflammatory condition of the gastrointestinal tract whose natural history is one of periods of remission and relapse. The aetiology is complex and reflects an interaction between genes and environment. Psychological stress has long been reported by both doctors and patients as worsening disease activity in IBD. Prospective studies of the relationship between disease relapse and adverse life events have produced conflicting results, in part due to the inherent difficulties of such studies. However, several more recent analyses have suggested that both adverse life events and chronic perceived stress can contribute to disease relapse. There is also an increasing body of evidence to suggest that experimental stress can increase mucosal inflammation both in patients with IBD and in animal models of colitis. Despite this increase in understanding the pro-inflammatory effects of stress in IBD, thus far only a few limited studies have examined stress reduction as a therapeutic modality.

Mawdsley JE ，Rampton DS 《NEUROIMMUNOMODULATION》

Psychological stress in IBD: new insights into pathogenic and therapeutic implications.

Mawdsley JE ，Rampton DS 《-》

Stress and animal models of inflammatory bowel disease--an update on the role of the hypothalamo-pituitary-adrenal axis.

Chronic psychosocial stress has been repeatedly shown in humans to be a risk factor for the development of several affective and somatic disorders, including inflammatory bowel diseases (IBD). There is also a large body of evidence from rodent studies indicating a link between stress and gastrointestinal dysfunction, resembling IBD in humans. Despite this knowledge, the detailed underlying neuroendocrine mechanisms are not sufficiently understood. This is due, in part, to a lack of appropriate animal models, as most commonly used rodent stress paradigms do not adequately resemble the human situation and/or do not cause the development of spontaneous colitis. Therefore, our knowledge regarding the link between stress and IBD is largely based on rodent models with low face and predictive validity, investigating the effects of unnatural stressors on chemically induced colitis. These studies have consistently reported that hypothalamo-pituitary-adrenal (HPA) axis activation during stressor exposure has an ameliorating effect on the severity of a chemically induced colitis. However, to show the biological importance of this finding, it needs to be replicated in animal models employing more clinically relevant stressors, themselves triggering the development of spontaneous colitis. Important in view of this, recent studies employing chronic/repeated psychosocial stressors were able to demonstrate that such stressors indeed cause the development of spontaneous colitis and, thus, represent promising tools to uncover the mechanisms underlying stress-induced development of IBD. Interestingly, in these models the development of spontaneous colitis was paralleled by decreased anti-inflammatory glucocorticoid (GC) signaling, whereas adrenalectomy (ADX) prior to stressor exposure prevented its development. These findings suggest a more complex role of the HPA axis in the development of spontaneous colitis. In the present review I summarize the available human and rodent data in order to provide a comprehensive understanding of the biphasic role of the HPA axis and/or the GC signaling during stressor exposure in terms of spontaneous colitis development.

Reber SO 《-》

Brain-gut interactions in inflammatory bowel disease.

Psycho-neuro-endocrine-immune modulation through the brain-gut axis likely has a key role in the pathogenesis of inflammatory bowel disease (IBD). The brain-gut axis involves interactions among the neural components, including (1) the autonomic nervous system, (2) the central nervous system, (3) the stress system (hypothalamic-pituitary-adrenal axis), (4) the (gastrointestinal) corticotropin-releasing factor system, and (5) the intestinal response (including the intestinal barrier, the luminal microbiota, and the intestinal immune response). Animal models suggest that the cholinergic anti-inflammatory pathway through an anti-tumor necrosis factor effect of the efferent vagus nerve could be a therapeutic target in IBD through a pharmacologic, nutritional, or neurostimulation approach. In addition, the psychophysiological vulnerability of patients with IBD, secondary to the potential presence of any mood disorders, distress, increased perceived stress, or maladaptive coping strategies, underscores the psychological needs of patients with IBD. Clinicians need to address these issues with patients because there is emerging evidence that stress or other negative psychological attributes may have an effect on the disease course. Future research may include exploration of markers of brain-gut interactions, including serum/salivary cortisol (as a marker of the hypothalamic-pituitary-adrenal axis), heart rate variability (as a marker of the sympathovagal balance), or brain imaging studies. The widespread use and potential impact of complementary and alternative medicine and the positive response to placebo (in clinical trials) is further evidence that exploring other psycho-interventions may be important therapeutic adjuncts to the conventional therapeutic approach in IBD.

Bonaz BL ，Bernstein CN 《-》

Role 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-pituitary-adrenal 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.

Stasi C ，Orlandelli E 《-》