Volume 140, Issue 3, Pages 761-765.e5 (March 2011) The Role of Stress on Physiologic Responses and Clinical Symptoms in Irritable Bowel Syndrome  Lin Chang  Gastroenterology  Volume 140, Issue 3, Pages 761-765.e5 (March 2011) DOI: 10.1053/j.gastro.2011.01.032 Copyright © 2011 AGA Institute Terms and Conditions

Figure 1 Physiologic and pathologic responses to stress. An adult's resilience or vulnerability to stress can be determined by genetic inherence and early life experiences. Activation of the central stress response sets in motion the HPA axis, ANS, and other adaptive systems. Stress-induced changes in GI function occur and these can in turn result in perceived symptoms of IBS. (Adapted from Lightman, 2008.84) Gastroenterology 2011 140, 761-765.e5DOI: (10.1053/j.gastro.2011.01.032) Copyright © 2011 AGA Institute Terms and Conditions

Supplementary Figure 1 The role of stress in the development and modulation of IBS symptoms.5 Different types of stressors may play a role in the permanent biasing of stress responsiveness, the transient activation of the stress response, the increased vulnerability of developing IBS, and the persistence of symptoms (From Mayer EA et al,5 with permission). Gastroenterology 2011 140, 761-765.e5DOI: (10.1053/j.gastro.2011.01.032) Copyright © 2011 AGA Institute Terms and Conditions

Supplementary Figure 2 The stress system.85 The HPA axis has been studied extensively in the stress response. Neurons in the medial parvocellular region of the PVN of the hypothalamus release corticotropin releasing hormone (CRH) and arginine vasopressin (AVP). This then triggers the secretion of adrenocorticotropin hormone (ACTH) from the pituitary gland, subsequently leading to the production of glucocorticoids by the adrenal cortex. The stress-induced responsiveness of the HPA axis is in part modulated by the ability of glucocorticoids to regulate ACTH and CRF release by binding to 2 corticosteroid receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR), which are part of the feedback loop. Under normal physiologic conditions, after the HPA axis is activated and the stressor is perceived to have subsided, these feedback loops are triggered at various levels of the system to shut down the HPA axis and return to a set homeostatic point. However, the amygdala has a feed-forward mechanism to activate the HPA axis during stress to deal with the challenge. Reprinted by permission from Macmillan Publishers Ltd: Nature Reviews Neuroscience 2009;10:434–445, copyright 2009. Gastroenterology 2011 140, 761-765.e5DOI: (10.1053/j.gastro.2011.01.032) Copyright © 2011 AGA Institute Terms and Conditions