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

项目摘要 炎症性肠病（IBD），包括克罗恩病和溃疡性结肠炎，是免疫- 介导的胃肠道疾病与慢性医疗和心理社会功能障碍有关。IBD是 越来越多地被概念化为脑肠轴的产物，这是一个描述神经网络的模型。 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。与脑-肠轴模型一致， IBD表现出ANS功能障碍，表明慢性应激反应。ANS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患者的HRV表现出与ANS刚性以及心理学一致的改变， 痛苦和对压力的情绪反应增加。这些自主功能的改变也是 在患有焦虑和抑郁症的个体中观察到，并且众所周知，患有IBD的青年 患上慢性焦虑和抑郁的风险增加。生物反馈训练，以治疗 HRV已导致疾病症状的改善以及年轻人情绪困扰的减少， 其他慢性胃肠道疾病。这项工作的目的是测试心率变异性作为一种 IBD儿童患者临床症状以及焦虑和抑郁症状的生物标志物 参加了生物反馈治疗项目在这个R 03项目中，我将建立在我的K23的工作上 （K23 DK 122115）将HRV确立为临床相关和可改变的生物标志物，可可靠地用于 对具有IBD临床症状和相关压力、抑郁和焦虑的年轻患者的治疗研究。我 开发并正在测试远程HRV生物反馈增强认知行为疗法（CBT） 40名患有IBD和焦虑和抑郁症状的青年的治疗计划。在R 03的支持下， 能够处理在基线、生物反馈期间以及在 后测，以评估HRV的轨迹，在这些年轻人目前正在接受治疗。当前的总体目标 研究的目的是（1）确定基线HRV与IBD临床症状、焦虑和 40例IBD青少年的抑郁症和（2）确定HRV是否随着虚拟的生物反馈增强而变化 CBT治疗干预。这R 03提供了一个来源的支持，一个新的途径调查HRV作为一个 脑-肠轴机制驱动慢性精神疾病患者的心理困扰和临床症状 小儿IBD。结合K23研究的结果，研究结果将支持竞争性R 01进行测试 生物反馈增强CBT干预的有效性，使用HRV作为主要结局变量， 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.