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Neural and psychological predictors of treatment response in irritable bowel syndrome patients with a 5‐HT 3 receptor antagonist: a pilot study
Author(s) -
JARCHO J. M.,
CHANG L.,
BERMAN S. M.,
SUYENOBU B.,
NALIBOFF B. D.,
LIEBERMAN M. D.,
AMEEN V. Z.,
MANDELKERN M. A.,
MAYER E. A.
Publication year - 2008
Publication title -
alimentary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.308
H-Index - 177
eISSN - 1365-2036
pISSN - 0269-2813
DOI - 10.1111/j.1365-2036.2008.03721.x
Subject(s) - medicine , irritable bowel syndrome , amygdala , orbitofrontal cortex , gastroenterology , prefrontal cortex , psychiatry , cognition
Aliment Pharmacol Ther 28 , 344–352 Summary Background Symptom improvement in irritable bowel syndrome (IBS) treatment trials varies widely, with only 50–70% of patients qualifying as responders. Factors predicting treatment responsiveness are not known, although we have demonstrated that symptom improvement with the 5‐HT 3 R antagonist alosetron is correlated with reduced amygdala activity. Aim To determine whether neural activity during rectal discomfort or psychological distress predicts symptom improvement following treatment with alosetron. Methods Basal psychological distress and neural activity ( 15 O PET) during uncomfortable rectal stimulation were measured in 17 nonconstipated IBS patients who then received 3 weeks of alosetron treatment. Results Greater symptom improvement was predicted by less activity in bilateral orbitofrontal cortex (OFC) and medial temporal gyrus during pre‐treatment scans. Lower levels of interpersonal sensitivity predicted greater symptom improvement and were positively related to activity in left OFC. Connectivity analysis revealed a positive relationship between activity in the left OFC and right amygdala. Conclusions Irritable bowel disease symptom improvement with 5‐HT 3 R antagonist alosetron is related to pre‐treatment reactivity of the left OFC, which may be partially captured by subjective measures of interpersonal sensitivity. The left OFC may fail to modulate amygdala response to visceral stimulation, thereby diminishing effectiveness of treatment. Psychological factors and their neurobiological correlates are plausible predictors of IBS treatment outcome.