Document Detail


Evidence for Alterations in Central Noradrenergic Signaling in Irritable Bowel Syndrome.
MedLine Citation:
PMID:  22917679     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND/AIMS: Alterations in noradrenergic (NE) signaling have been implicated in the pathophysiology of irritable bowel syndrome (IBS), and adrenergic receptors are potential treatment targets. METHODS: To characterize central NE signaling in IBS, 11 patients and 11 healthy controls (HCs) were studied 3 times during an auditory oddball vigilance task after double-blind ingestion of the α2-adrenoreceptor (α2AR) antagonist yohimbine (YOH), the α2AR agonist clonidine (CLO), or placebo (PLA). Regional cerebral glucose metabolism was measured with [18F] fluorodeoxyglucose (FDG) positron emission tomography (PET). Measures of anxiety, early-life trauma, plasma NE and blood pressure were acquired. RESULTS: Patients had higher plasma NE levels than HCs before and after ingestion of all drugs (all p<0.05). YOH increased plasma NE and anxiety more in patients than HCs. After YOH, NE levels directly correlated with drug-induced increases in anxiety in IBS patients (r=0.61), but not HCs. IBS patients showed less YOH-mediated reduction of activity in a central arousal circuit, consistent with fewer functional presynaptic α2AR. In HCs, but not patients, activation of amygdala and subgenual anterior cingulate cortex (sgACC) were inversely correlated with activation of anterior mid cingulate cortex (aMCC), and state anxiety covaried directly with activity in limbic and right frontotemporal cortices, but indirectly with activity in left frontotemporal cortex. YOH-mediated reduction of activity in brainstem and amygdala inversely correlated with early life trauma. CONCLUSIONS: IBS patients showed evidence for increased noradrenergic activity consistent with downregulation of presynaptic inhibitory α2ARs. Activity within central arousal circuits was biased towards greater excitability and reduced corticolimbic inhibition in IBS. Early life trauma may be one mediator of these abnormalities.
Authors:
Steven Berman; Brandall Suyenobu; Bruce D Naliboff; Joshua Bueller; Jean Stains; Heng Wong; Mark Mandelkern; Leah Fitzgerald; Gordon Ohning; Arpana Gupta; Jennifer S Labus; Kirsten Tillisch; Emeran A Mayer
Related Documents :
301729 - Histiocytosis x; follow-up of 43 cases.
18640019 - Anca-associated lung fibrosis: analysis of 17 patients.
19222759 - Structural and functional abnormalities in lungs in patients with achalasia.
18822619 - Prevalence and predictors of pulmonary artery hypertension in systemic sclerosis.
3707629 - Pulmonary hypertension in the crest syndrome variant of systemic sclerosis.
9785159 - British thoracic society guidelines for the management of spontaneous pneumothorax: do ...
11801969 - The occurrence of sleep-disordered breathing among patients with head and neck cancer.
20950999 - Annular tilt as a screening test for right ventricular enlargement in patients with tet...
16531959 - The use of tips in chronic liver disease.
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-8-20
Journal Detail:
Title:  NeuroImage     Volume:  -     ISSN:  1095-9572     ISO Abbreviation:  Neuroimage     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-8-24     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9215515     Medline TA:  Neuroimage     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier Inc.
Affiliation:
Oppenheimer Family Center for Neurobiology of Stress, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Spin echo functional MRI in bilateral auditory cortices at 7 T: an application of B? shimming.
Next Document:  HTLV-1 infection: what determines the risk of inflammatory disease?