Brain-Gut biomarkers of anxiety and depressive symptoms in youth with inflammatory bowel disease

项目总结/摘要 此K23职业发展奖申请旨在为PI的长期职业目标做好准备， 成为一名独立的临床科学家，专注于脑肠轴的研究，因为它涉及到 诊断为炎症性肠病的儿科患者的疾病、情绪和行为功能 （IBD）。根据这一目标，拟议的研究和职业发展计划将以试点数据为基础 在申请人的KL 2奖期间收集，证明了高 青年人对标准化实验室应激源的应激反应和更大的心理健康症状 新诊断为IBD。这些初步数据表明，应激反应（通过皮肤测量） 电导，自主神经系统（ANS）活动的可靠指标）响应压力挑战， 可以作为心理社会功能的生物标志物，然后可以用来对那些 受益于应对技能干预。因此，本研究的目标是进行纵向研究， 观察性研究（1）比较压力反应和心理健康症状之间的关系， IBD患者和健康对照组，（2）检查应激反应指数作为精神疾病的新预测因子。 和身体健康的结果。为此，我们建议招募一个观察性、纵向 新诊断IBD的青年队列（N=60），与年龄和性别匹配的健康对照组进行比较 （N=60），然后在24个月内的6个评估点进行随访。应力处理指数 评估包括皮肤电导和心率变异性，这两个验证的心理生理措施 压力处理。此外，本项目还将开发生物反馈增强应对技能培训计划 使用治疗组（n=20）和等待列表对照组（n=20），其中筛选阳性的IBD患者 焦虑和/或抑郁症状的患者将被随机分组。我们会评估治疗的可行性， 可接受性和心理症状、自主神经反应和IBD症状的初步结果。 职业发展活动将在一个跨学科指导小组的指导下进行， 在1）临床和转化研究，2）纵向数据分析和RCT方面提供高级培训 支持干预开发的方法，3）与以下方面相关的脑肠过程和临床管理 儿科IBD，和4）学术生产力和赠款写作。从K23提案中得出的结论将是有益的 在展示新诊断的青年人的疾病和心理社会功能的纵向轨迹， IBD和确定压力处理指数是否可以作为风险的客观生物标志物。结果 将被用来通知我们的生物反馈增强应对技能治疗方案的改进迭代， 关于确定治疗效果的机制，实施以尽量减少家庭负担，以及未来 随机临床试验。

Project Summary/Abstract This K23 Career Development Award application is designed to prepare the PI for her long-term career goal of becoming an independent clinical scientist with lines of research focused on the brain-gut axis as it relates to disease, emotional, and behavioral functioning in pediatric patients diagnosed with inflammatory bowel disease (IBD). Consistent with this goal, the proposed research and career development plan will build upon pilot data collected during the applicant's KL2 Award demonstrating a positive and significant relationship between high stress reactivity in response to a standardized laboratory stressor and greater mental health symptoms in youth newly diagnosed with IBD. These preliminary data suggest that stress reactivity (as measured via skin conductance, a reliable indicator of autonomic nervous system (ANS) activity) in response to a stress challenge, may serve as a biomarker of psychosocial functioning that could then be used to risk stratify youth who would benefit from coping skills interventions. Thus, the goals of the current study are to conduct a longitudinal observational study to (1) compare relationships between stress reactivity and mental health symptoms in patients with IBD and healthy controls and (2) examine indices of stress reactivity as novel predictors of mental and physical health outcomes in youth with IBD. To this end, we propose to recruit an observational, longitudinal cohort of youth newly diagnosed with IBD (N=60) to be compared to age and sex-matched healthy controls (N=60) at baseline and then followed at six assessment points across 24-months. Indices of stress processing to be assessed include skin conductance and heart rate variability, both validated psychophysiological measures of stress processing. Further, this project will develop a biofeedback enhanced coping skills training program using a treatment group (n=20) and wait-list control group (n=20) to which patients with IBD who screen positive for symptoms of anxiety and/or depression will be randomized. We will evaluate the treatment's feasibility, acceptability, and preliminary outcomes on psychological symptoms, autonomic reactivity, and IBD symptoms. Career development activities will take place under the mentorship of an interdisciplinary mentoring team to provide advanced training in 1) clinical and translational research, 2) longitudinal data analysis and RCT methodology to support intervention development, 3) brain-gut processes and clinical management relevant to pediatric IBD, and 4) scholarly productivity and grant writing. Findings from this K23 proposal will be instrumental in demonstrating longitudinal trajectories of disease and psychosocial functioning in newly diagnosed youth with IBD and determining whether indices of stress processing can serve as objective biomarkers of risk. Findings will be used to inform refined iterations of our biofeedback enhanced coping skills treatment protocol with focus on determining mechanisms of treatment effect, implementation to minimize burden on families, and a future randomized clinical trial.