Neurobiological mechanisms underlying effectiveness of CBT in IBS patients

描述（由申请人提供）：肠易激综合征（IBS）是一种普遍的，经常致残的胃肠道（GI）疾病，没有足够的药物治疗选择。非药物治疗，尤其是认知行为疗法（CBT）可能是许多IBS患者的有效治疗方法。美国国立卫生研究院资助的IBS结果研究（IBSOS）是迄今为止最全面的CBT疗效研究，包括标准和最小接触版本的CBT和主动控制（AC）条件。人们普遍认为，a)改变脑-肠相互作用（CBT的主要目标）在IBS症状中起重要作用，b)目前定义的IBS可能是一种异质性疾病，这意味着任何治疗方法都只对一部分患者最有效。因此，为了制定有效的肠易激综合征疾病管理方案，了解其作用机制和预测治疗反应的因素至关重要。拟议的研究是NIDDK资助的两个项目之间的协同互动，为解决这一挑战提供了一个独特的机会：IBSOS家长资助的招募、评估和治疗部分与加州大学洛杉矶分校（PAIN@loni.org）的脑成像基础设施相结合，将使该项目能够有效地测试有关IBS CBT治疗的神经生物学机制的特定假设，并开发患者可能从这些治疗中受益的预测标记物。利用IBSOS参与者在治疗前后的多模态功能和结构MRI成像，结合心理社会和症状测量，本辅助建议将验证a)一般假设，即前脑岛是参与IBS症状的情绪唤醒、认知和奖励网络的“枢纽”；b) CBT将导致这些网络在治疗前后发生显著变化，变化越大，结果越好；c)治疗后这些网络的活动、连通性和结构完整性的变化在调节CBT的长期结果中起重要作用；d)治疗前这些网络的完整性将预测CBT反应。

DESCRIPTION (provided by applicant): Irritable bowel syndrome (IBS) is a prevalent, often disabling gastrointestinal (GI) disorder without adequate pharmacologic treatment options. Non pharmacological treatment, most notably Cognitive Behavioral Therapy (CBT) may be an effective treatment for many IBS patients. The NIH funded IBS Outcome Study (IBSOS) is the most comprehensive CBT efficacy study to date, including standard and minimal contact versions of CBT and an active control (AC) condition. There is general agreement a) that altered brain-gut interactions, the primary target of CBT, play an important role in IBS symptoms, and b) that IBS as currently defined is likely to represent a heterogeneous disorder, implying any treatment will be most effective for only a subset of patients. In order to develop effective disease management programs for IBS, it is therefore critically important to understand mechanisms of action and factors predictive of treatment response. The proposed study, a synergistic interaction between two NIDDK funded programs, provides a unique opportunity to address this challenge: The recruitment, assessment and treatment components of the IBSOS parent grant combined with the brain imaging infrastructure at UCLA (PAIN@loni.org) will enable this project to efficiently test specific hypotheses regarding both the neurobiological mechanisms underlying CBT treatment for IBS, and to develop predictive markers for which patients may benefit from these treatments. Using multimodal functional and structural MRI imaging of IBSOS participants before and after treatment in combination with psychosocial and symptom measures, this ancillary proposal will test a) the general hypothesis that the anterior insula functions as a "hub" for emotional arousal, cognitive as well as reward networks involved in IBS symptoms; b) that CBT will result in significant changes in these networks pre to post treatment with greater changes associated with better outcomes; c) that changes in activity, connectivity and structural integrity of these networks following treatment play an important role in mediating long term CBT outcomes; and d) that pre-treatment integrity of these networks will predict CBT response.