Jarcho J M, Chang L, Berman M, Suyenobu B, Naliboff B D, Lieberman M D, Ameen V Z, Mandelkern M A, Mayer E A
UCLA Center for Neurovisceral Sciences and Women's Health, Los Angeles, CA 90073, USA.
Aliment Pharmacol Ther. 2008 Aug 1;28(3):344-52. doi: 10.1111/j.1365-2036.2008.03721.x.
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.
To determine whether neural activity during rectal discomfort or psychological distress predicts symptom improvement following treatment with alosetron.
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.
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.
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.
肠易激综合征（IBS）治疗试验中的症状改善差异很大，只有50%-70%的患者可被视为有反应者。尽管我们已经证明5-HT3R拮抗剂阿洛司琼治疗后症状改善与杏仁核活性降低相关，但预测治疗反应性的因素尚不清楚。
确定直肠不适或心理困扰期间的神经活动是否可预测阿洛司琼治疗后的症状改善。
对17名无便秘的IBS患者在直肠不适刺激期间的基础心理困扰和神经活动（15O PET）进行测量，这些患者随后接受3周的阿洛司琼治疗。
治疗前扫描时双侧眶额皮质（OFC）和内侧颞回活动较少预示着症状改善更明显。人际敏感性较低预示着症状改善更明显，且与左侧OFC的活动呈正相关。连通性分析显示左侧OFC和右侧杏仁核的活动之间存在正相关。
5-HT3R拮抗剂阿洛司琼治疗肠易激病症状改善与治疗前左侧OFC的反应性有关，人际敏感性的主观测量可能部分反映了这一点。左侧OFC可能无法调节杏仁核对内脏刺激的反应，从而降低治疗效果。心理因素及其神经生物学相关性可能是IBS治疗结果的合理预测指标。
