Neural and psychological predictors of treatment response in irritable bowel syndrome patients with a 5-HT3 receptor antagonist: a pilot study.
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-HT3R antagonist alosetron is correlated with reduced amygdala activity.


OBJECTIVE
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 (15O 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-HT3R 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.
Jarcho
J M
JM
UCLA Center for Neurovisceral Sciences and Women's Health, Los Angeles, CA 90073, USA.
Chang
L
L
Berman
M
M
Suyenobu
B
B
Naliboff
B D
BD
Lieberman
M D
MD
Ameen
V Z
VZ
Mandelkern
M A
MA
Mayer
E A
EA
D000328:Adult; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D002243:Carbolines / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D043183:Irritable Bowel Syndrome / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D010865:Pilot Projects; D049268:Positron-Emission Tomography; D012007:Rectum / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D012189:Retrospective Studies; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D013315:Stress, Psychological / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000503:physiopathology; D016896:Treatment Outcome
D002243:Carbolines; D017366:Serotonin Receptor Agonists; C090840:alosetron