Altered brain and gut responses to corticotropin-releasing hormone (CRH) in patients with irritable bowel syndrome

• Published in: Scientific reports Vol. 7; no. 1; pp. 12425 - 11
• Main Authors: Kano, Michiko, Muratsubaki, Tomohiko, Van Oudenhove, Lukas, Morishita, Joe, Yoshizawa, Makoto, Kohno, Keiji, Yagihashi, Mao, Tanaka, Yukari, Mugikura, Shunji, Dupont, Patrick, Ly, Huynh Giao, Takase, Kei, Kanazawa, Motoyori, Fukudo, Shin
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 29.09.2017; Nature Publishing Group
• Subjects: 59/36; 631/378/1831; 692/4020/1503/1502/2071; Adrenal glands; Adrenocorticotropic hormone; Adrenocorticotropic Hormone - metabolism; Adult; Autonomic nervous system; Brain mapping; Colon; Colon - drug effects; Cortex (cingulate); Corticotropin-releasing hormone; Corticotropin-Releasing Hormone - pharmacology; Female; Functional magnetic resonance imaging; Gastrointestinal Motility - drug effects; Gyrus Cinguli - drug effects; Humanities and Social Sciences; Humans; Hypothalamic-pituitary-adrenal axis; Hypothalamo-Hypophyseal System - drug effects; Hypothalamus; Intestine; Irritable bowel syndrome; Irritable Bowel Syndrome - physiopathology; Magnetic Resonance Imaging - methods; Male; Motility; multidisciplinary; Neuroimaging; Parasympathetic nervous system; Pituitary; Pituitary-Adrenal System - drug effects; Rectum; Science; Science (multidisciplinary); Stress, Physiological
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-09635-x

Stress is a known trigger of irritable bowel syndrome (IBS) and exacerbates its gastrointestinal symptoms. However, underlying the physiological mechanism remains unknown. Here, we investigated hypothalamic–pituitary–adrenal (HPA) axis, colonic motility, and autonomic responses to corticotropin-releasing hormone (CRH) administration as well as brain activity alterations in IBS. The study included 28 IBS patients and 34 age and sex-matched healthy control subjects. IBS patients demonstrated greater adrenocorticotropic hormone (ACTH) responses to CRH than control subjects. Male IBS patients had greater increases in colonic motility than male HCs after CRH. Female IBS patients showed altered sympathovagal balance and lower basal parasympathetic tone relative to female control subjects. Brain responses to rectal distention were measured in the same subjects using functional magnetic resonance imaging, and their associations with individual ACTH responses to CRH were tested. A negative association between ACTH response to CRH and activity in the pregenual anterior cingulate cortex (pACC) during rectal distention was identified in controls but not in IBS patients. Impaired top-down inhibitory input from the pregenual ACC to the HPA axis may lead to altered neuroendocrine and gastrointestinal responses to CRH. Centrally acting treatments may dampen the stress induced physical symptoms in IBS.