Neurobiological mechanisms underlying effectiveness of CBT in IBS patients

描述（由申请人提供）：肠易激综合征（IBS）是一种普遍存在的，通常致残的胃肠道（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。NIH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CBT的标准和最小接触版本以及主动控制（AC）条件。人们普遍认为：a）改变的脑-肠相互作用（CBT的主要靶点）在IBS症状中起着重要作用，以及B）目前定义的IBS可能代表一种异质性疾病，这意味着任何治疗仅对一部分患者最有效。为了制定有效的IBS疾病管理计划，了解作用机制和预测治疗反应的因素至关重要。拟议的研究是两个NIDDK资助项目之间的协同互动，为应对这一挑战提供了独特的机会：IBSOS父母补助金的招募、评估和治疗部分与UCLA的脑成像基础设施相结合（PAIN@loni.org）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志物。使用治疗前后IBSOS参与者的多模态功能和结构MRI成像，结合心理社会和症状测量，该辅助建议将测试a）前额叶作为IBS症状中涉及的情绪唤醒、认知以及奖励网络的“枢纽”的一般假设; B）CBT将导致治疗前后这些网络的显著变化，更大的变化与更好的结果相关; c）治疗后这些网络的活性、连接性和结构完整性的变化在介导长期CBT结果方面发挥重要作用;以及d）这些网络的预处理完整性将预测CBT响应。 公共卫生相关性：认知行为疗法（CBT）已被证明是治疗肠易激综合征的有效方法。这项拟议的研究将有助于通过检查大脑结构和活动来确定CBT治疗的工作原理，因此可以改善治疗方法，并决定哪些患者可能受益最大。

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. PUBLIC HEALTH RELEVANCE: Cognitive Behavioral Therapy (CBT) has been shown to be an effective treatment for irritable bowel syndrome. The proposed study will help determine how CBT treatment works by examining brain structure and activity and therefore can lead to improvements in the treatment approach and decisions regarding which patients may benefit most.