Heart rate variability as a modifiable biomarker of clinical symptoms and psychological functioning in pediatric patients with inflammatory bowel disease

项目总结 炎症性肠病(IBD)，包括克罗恩病和溃疡性结肠炎，是免疫的- 与慢性医学和心理社会功能障碍相关的介导性胃肠道疾病。IBD是 越来越被概念化为大脑-肠轴的产物，这是一种描述 中枢神经系统(CNS)、自主神经系统(ANS)、 下丘脑-垂体-肾上腺(HPA)轴和肠道。符合脑-肠轴模型的患者 IBD显示ANS功能障碍，提示慢性应激反应。ANS的功能可以是 通过心率变异性(HRV)测量，这是一种适用于儿科的非侵入性测量方法。早期证据 提示IBD患者表现出与ANS僵硬和心理一致的心率变异性改变。 痛苦和对压力的情绪反应增加。这些自主神经功能的改变也是 在焦虑和抑郁障碍患者中观察到，众所周知，患有IBD的青年 患慢性焦虑和抑郁的风险增加。生物反馈训练用于治疗脑血管疾病的改变 HRV导致了疾病症状的改善，并减少了患有 其他慢性胃肠道疾病。拟议工作的目标是测试心率变异性作为一种 IBD患儿临床症状及焦虑、抑郁症状的生物标志物 他们参加了一个生物反馈治疗项目。在这个R03项目中，我将在K23的工作基础上再接再厉 (K23DK122115)建立HRV作为临床相关和可修改的生物标记物，可可靠地用于 对具有IBD临床症状及相关应激、抑郁和焦虑的年轻患者的治疗研究。我 开发并正在测试一种远程HRV生物反馈增强型认知行为疗法(CBT) 治疗方案治疗40例伴有焦虑、抑郁症状的青少年IBD患者。有了R03支持，我们将 能够处理在基线、生物反馈会议期间和在 后测以评估这些正在接受治疗的青年的HRV轨迹。当前的总体目标是 研究的目的是：(1)确定基线心率变异性与IBD临床症状、焦虑和 40名患有IBD的青少年的抑郁和(2)确定HRV是否随虚拟的、生物反馈增强的变化而变化 CBT治疗干预。本R03为研究HRV的新途径提供了支持 脑-肠轴机制对慢性心理障碍及临床症状的影响 儿科IBD。结合K23研究的结果，研究结果将支持竞争性R01进行测试 使用HRV作为主要结果变量的生物反馈增强型CBT干预的有效性 临床改善的生物标志物。

PROJECT SUMMARY Inflammatory bowel diseases (IBD), including Crohn’s disease and ulcerative colitis, are immune- mediated gastrointestinal disorders associated with chronic medical and psychosocial dysfunction. IBD is increasingly conceptualized as a product of the brain-gut axis, a model that describes the network of communication between the central nervous system (CNS), the autonomic nervous system (ANS), the hypothalamic-pituitary-adrenal (HPA) axis, and the gut. Consistent with a brain-gut axis model, patients with IBD demonstrate dysfunction of the ANS indicative of a chronic stress response. ANS functioning can be measured via heart rate variability (HRV), a non-invasive measure suitable for pediatrics. Early evidence suggests that patients with IBD exhibit alterations in HRV consistent with ANS rigidity as well as psychological distress and increased emotional reactivity to stress. These alterations in autonomic functioning are also observed in individuals with anxiety and depressive disorders, and it is well recognized that youth with IBD are at increased risk for developing chronic anxiety and depression. Biofeedback training to treat alterations in HRV has led to improvements in disease symptoms as well as reductions in emotional distress for youth with other chronic gastrointestinal illnesses. The goal of the proposed work is to test the utility of HRV as a biomarker of clinical symptoms as well as symptoms of anxiety and depression in pediatric patients with IBD who are enrolled in a biofeedback therapy program. In this R03 project, I will build on the work of my K23 (K23DK122115) to establish HRV as a clinically relevant and modifiable biomarker that can be reliably used in treatment studies of young patients with clinical symptoms of IBD and related stress, depression, and anxiety. I developed and am currently testing a remote HRV biofeedback-enhanced cognitive behavioral therapy (CBT) treatment program in 40 youth with IBD and symptoms of anxiety and depression. With R03 support we will be able to process the rich but complex raw HRV data obtained at baseline, during biofeedback sessions, and at posttest to evaluate the trajectory of HRV in these youth currently in treatment. The overall goals of the current study are to (1) determine the relationship between baseline HRV and clinical symptoms of IBD, anxiety, and depression in 40 adolescents with IBD and (2) determine if HRV changes with a virtual, biofeedback-enhanced CBT treatment intervention. This R03 offers a source of support for a new avenue of inquiry into HRV as a brain-gut axis mechanism driving chronic psychological distress and clinical symptoms in patients with pediatric IBD. Combined with the outcomes of the K23 research, findings will support a competitive R01 to test efficacy of a biofeedback-enhanced CBT intervention, using HRV as a primary outcome variable and biomarker of clinical improvement.