Sex related differences in the effect of cognitive behavioral therapy on emotional arousal and salience circuits and the role of the gut microbiome

认知行为疗法对情绪唤醒和显着回路的影响以及肠道微生物组的作用与性别相关的差异

• 批准号: 10688185
• 负责人: Emeran A Mayer
• 金额: $ 37.56万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-01 至 2025-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688185
• 关键词: Aftercare; Anatomy; Arousal; Bacteroides; Behavior; Behavioral; Biological; Biological Markers; Brain; Brain Stem; Cell Nucleus; Characteristics; Clinical; Cognitive; Cognitive Therapy; Data; Disease; Effectiveness; Emotional; Female; Functional disorder; Funding; Goals; High Prevalence; Irritable Bowel Syndrome; Longitudinal Studies; Maintenance; Measures; Mediator; Outcome; Pain; Pathway interactions; Patients; Perception; Plasma; Play; Prevalence; Public Health; Publications; Research; Rest; Role; Sensory; Sex Differences; Stimulus; Subgroup; Symptoms; System; Technology; Testing; Therapeutic Effect; Treatment outcome; Woman; cognitive benefits; comorbidity; effective therapy; expectation; gut microbiome; locus ceruleus structure; male; men; microbial; microbiome; multisensory; neuroimaging; noradrenergic; patient subsets; personalized intervention; response; sex; therapy outcome; treatment as usual; treatment responders

ABSTRACT Cognitive Behavioral Therapy (CBT) is the most well researched and most effective treatment for IBS that targets the brain-gut-microbiome (BGM) axis, and preliminary data show that this therapeutic effect is associated with a reduction of brainstem connectivity with other brain networks and a change in relative abundance of Bacteroides taxa. The increased prevalence of IBS in women, the higher rate of comorbid non- GI pain conditions, as well as the higher prevalence in female IBS of increased sensitivity to a variety of internal and external stimuli (multisensory sensitivity) suggest the presence of important sex differences in some of these BGM mechanisms. Research performed by the UCLA SCOR during previous funding has established an increased responsiveness of the CRF-Locus Coeruleus system in female IBS subjects, suggesting that this noradrenergic brainstem system plays an important role in IBS pathophysiology. In addition, our earlier research has begun to identify clinical, functional and cortical brain mechanisms that may underlie these sex effects. Based on these preliminary data, the overall goal of this Project is to use CBT as a probe to study the relationship between specific disease-related alterations of the brain, brainstem, the gut microbiome, and symptomatic outcome, and identify the role of sex differences in these relationships. We will study male and female IBS patients before and after CBT or usual care using the advanced neuroimaging and microbiome technologies of the overall SCOR to test the following: Aim A. will identify sex differences in the impact of CBT on the connectivity between brainstem nuclei and brain networks and between these networks at rest and after provocation. Aim B. will identify sex differences in the impact of CBT on gut microbiome parameters and Aim C will identify clinical, brain and gut microbiome predictors of CBT outcomes.

抽象的 认知行为疗法（CBT）是对IB的研究和最有效的治疗方法 靶向脑肠球菌（BGM）轴，初步数据表明这种治疗作用是 与脑干与其他大脑网络的连通性的降低以及相对变化有关 丰富的细菌分类群。女性IBS的患病率增加，合并非合并的率较高 胃肠道疼痛状况以及对各种敏感性提高的女性IB的较高患病率 内部和外部刺激（多感官敏感性）表明存在重要的性别差异 其中一些BGM机制。 UCLA SCOR在以前的资金中进行的研究 在女性IBS受试者中建立了CRF-Locus二核系统的响应性， 表明这种去甲肾上腺素能的脑干系统在IBS病理生理学中起着重要作用。在 此外，我们较早的研究已开始确定可能的临床，功能和皮质大脑机制 这些性别影响是基础。基于这些初步数据，该项目的总体目标是将CBT用作 探究以研究大脑，脑干，肠道特定疾病相关的变化之间的关系 微生物组和有症状的结果，并确定性别差异在这些关系中的作用。我们将 研究CBT前后的男性和女性IBS患者或使用高级神经影像学和通常的护理 整体SCOR的微生物组技术测试以下内容：AIM A.将确定性别差异 CBT对脑干核与大脑网络之间以及这些网络之间的连通性的影响 休息和挑衅后。 AIM B.将确定CBT对肠道微生物组的影响的性别差异 参数和目标C将确定CBT结果的临床，大脑和肠道微生物组预测指标。