Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Kano M

PROVIDER: S-EPMC5622133 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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

Kano Michiko M Muratsubaki Tomohiko T Van Oudenhove Lukas L Morishita Joe J Yoshizawa Makoto M Kohno Keiji K Yagihashi Mao M Tanaka Yukari Y Mugikura Shunji S Dupont Patrick P Ly Huynh Giao HG Takase Kei K Kanazawa Motoyori M Fukudo Shin S

Scientific reports 20170929 1

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 great ...[more]

PMID: 28963545

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Project description:Corticotropin-releasing hormone (CRH) plays an important role in the pathophysiology of irritable bowel syndrome (IBS) and regulates the stress response through two CRH receptors (R1 and R2). Previously, we reported that a CRHR1 gene polymorphism (rs110402, rs242924, and rs7209436) and haplotypes were associated with IBS. However, the association between the CRHR2 gene and IBS was not investigated. We tested the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are associated with IBS pathophysiology and negative emotion in IBS patients.A total of 142 IBS patients and 142 healthy controls participated in this study. Seven single nucleotide polymorphisms (SNPs) of the CRHR2 gene (rs4722999, rs3779250, rs2240403, rs2267710, rs2190242, rs2284217, and rs2284220) were genotyped. Subjects' psychological states were evaluated using the Perceived-Stress Scale, the State-Trait Anxiety Inventory, and the Self-Rating Depression Scale.We found that rs4722999 and rs3779250, located in intronic region, were associated with IBS in terms of genotype frequency (rs4722999: P = 0.037; rs3779250: P = 0.017) and that the distribution of the major allele was significantly different between patients and controls. There was a significant group effect (controls vs. IBS), and a CRHR2 genotype effect was observed for three psychological scores, but the interaction was not significant. We found a haplotype of four SNPs (rs4722999, rs3779250, rs2240403, and rs2267710) and two SNPs (rs2284217 and rs2284220) in strong linkage disequilibrium (D' > 0.90). We also found that haplotypes of the CRHR2 gene were significantly different between IBS patients and controls and that they were associated with negative emotion.Our findings support the hypothesis that genetic polymorphisms and haplotypes of CRHR2 are related to IBS. In addition, we found associations between CRHR2 genotypes and haplotypes and negative emotion in IBS patients and controls. Further studies on IBS and the CRH system are warranted.

Dataset Information

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

Publications

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

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