Longitudinal Assessment of Eating-related Anxiety in Anorexia Nervosa

项目摘要。神经性厌食症是一种以自我饥饿和害怕体重为特征的行为障碍。 收获。体重恢复到BMI为19-21仍然是严重AN的主要治疗方法，尽管复发率很高 在第一年高达50%。这些高复发率背后的机制仍不清楚。用餐-- 伴发焦虑是AN患者的一个显著特征。随着疾病的发展，进食行为在- 不断增长的驱动力似乎是有条件地避免摄入高能量食物，即所谓的恐惧性食物， 这表明，以暴露为基础的治疗方法可能有助于推动缓解。然而，在许多密集的 在治疗方案中，管饲取代以膳食为基础的营养是越来越多的方法。因此，需要的是 对于确定成功治疗AN和AND的机制和方法非常有用 哪些神经行为因素使个体对治疗有反应或抵抗？研究：前- 实验将解决习得性厌恶饮食后恐惧食物的习惯性程度。 暴露在类似类型的食物中普遍存在(目标1)。基于任务的功能磁共振与此行为相结合 这种方法将能够确定习惯性焦虑反应的神经基础(目标2a)。最后， 将使用一种机器学习方法来预测基于基线神经激活和 确定对治疗有反应和耐药的个体(目标2b)。通过展示寻址的重要性 将与食物相关的焦虑作为主要的治疗目标，并检查由恐惧食物激活的神经回路，这 该项目有可能1)改变在多个级别的护理和社交饮食环境中对待AN的方式，以及 2)加强对维持治疗难治性的神经生物学的理解。职业发展： 培训计划将为PI提供a)临床相关的临床课程现象学培训， 以及用于评估饮食失调的有效工具，这些工具对制定临床相关假说很重要 和数据解释，b)关于功能磁共振数据的高级统计方法的实践培训，c)有机会 将她在影响食物选择的因素方面的培训与所获得的结果结合起来，以及d)在赠款编写方面的培训 和职业发展，开始独立的研究生涯。环境：约翰斯·霍普金斯大学是一个优秀的 为健康和疾病状态和IS的协作、跨学科和转化性研究提供环境 专注于指导初级教职员工。约翰霍普金斯医院在精神病学方面排名全国第一， 美国首屈一指的医学研究机构医学院与饮食失调 该计划被全国公认为治疗进食障碍的领先计划。职业目标：建议的 研究和培训计划的目标是满足PI成为独立人员的总体职业目标 一位在大学环境中研究饮食失调的生物学基础的学术研究人员提供了 更大的R01提案所需的技能和试点数据，以检查驱动的神经机制 饮食失调行为的本质，目的是改善现有的治疗方法和个性化护理。

Project Summary. Anorexia nervosa (AN) is a behavioral disorder marked by self-starvation and fear of weight gain. Weight restoration to a BMI of 19-21 remains the mainstay of treatment for severe AN despite relapse rates in the first year of up to 50%. The mechanisms underlying these high relapse rates remain unknown. Meal- associated anxiety is a striking feature in patients with AN. As the disorder develops, eating behaviors are in- creasingly driven by what appears to be a conditioned avoidance of energy dense foods, known as fear foods, suggesting that exposure-based approaches to treatment may help drive remission. However, in many intensive treatment programs, tube feeding over meal-based nutrition is increasingly the approach. Thus, the need is great for determining what mechanisms and approaches underly the successful treatment of AN and what neurobehavioral factors render individuals responsive versus resistant to treatment. Research: Ex- periments will address the extent to which habituation of learned aversions to fear foods following meal-based exposure generalizes across similar types of foods (Aim 1). Task-based fMRI combined with this behavioral approach will allow the determination of the neural substrates of habituated anxiety responses (Aim 2a). Finally, a machine-learning approach will be used to predict anxiety ratings based on baseline neural activation and identify individuals responsive vs resistant to treatment (Aim 2b). By demonstrating the significance of addressing food-related anxiety as a primary treatment target and examining the neural circuitry activated by fear foods, this project has potential to 1) alter how AN is treated across multiple levels of care and social eating settings, and 2) enhance understanding of the neurobiology that sustains treatment refractoriness. Career Development: The training plan will provide the PI with a) clinically relevant training in the phenomenology of AN, clinical course, and validated instruments used to assess eating disorders important to formulating clinically relevant hypotheses and data interpretation, b) hands-on training in advanced statistical methods for fMRI data, c) opportunity to integrate her training in factors that influence food choice with obtained results, and d) training in grant writing and career development to launch an independent research career. Environment: Johns Hopkins is an excellent environment for collaborative, interdisciplinary, and translational research in healthy and disease states and is focused on mentoring junior faculty. The Johns Hopkins Hospital is ranked #1 in the nation for Psychiatry, with the School of Medicine being the leading research medical institution in the United States and the Eating Disorder Program nationally recognized as a leading program for eating disorder treatment. Career Goal: The proposed research and training program is targeted to meet the PI's overall career goal of becoming an independent academic researcher investigating the biological basis of eating disorders at a university setting by providing the skills and pilot data necessary for larger R01 proposals to examine neural mechanisms underlying the driven nature of eating disorder behaviors with the goal of improving existing treatments and personalizing care.