The Role of Negative Affect in the Cognitive-Behavioral Model of Avoidant/Restrictive Food Intake Disorder: An Integrated Analysis of Neural Circuitry, Hormones, and Momentary Negative Emotions

项目总结/摘要 避免/限制性食物摄入障碍（ARFID）在DSM-5中被确定为限制性饮食障碍， 与大量的医学发病率、精神病合并症和高治疗费用相关。维护 ARFID的机制尚不清楚。然而，ARFID的认知行为模型表明， 负强化，通过减少负面影响，可能是理解这些高度持久性的关键， 以及医学上的危害行为这5年K23-以患者为导向的研究职业发展 奖项申请使用创新的多学科方法来研究这一假设 与健康对照组相比，ARFID成人的神经回路和激素功能存在差异（HC） 并探索实时情绪和行为与大脑反应之间的关系， 内分泌信号对食物刺激的反应。具体而言，该提案利用了从一个受资助的 R 01（MH 108595）研究了青年ARFID的神经生物学，并通过关注以下内容扩展了这些方法： 包括一周的生态瞬时评估（EMA）。杏仁核的激活， 海马、前额叶、前扣带皮层和内侧前额叶皮层（边缘系统中的脑区 和大脑边缘回路控制情绪处理），以及皮质醇和催产素水平， 将在患有ARIFD的成人之间比较标准化膳食（与情绪和焦虑相关的激素） 和HC。EMA对负面情绪和饮食行为的评级将被用来测试负面情绪是否是 减少以下常见的有问题的饮食行为（即，在ARFID中拒绝食物。作为最终目标，本研究 我将探索边缘系统/脑边缘系统回路的活动以及异常的皮质醇和催产素是否与负相关。 影响水平以及在一周EMA期间的回避/限制性饮食报告。这个项目 代表了ARFID在成人中的首次探索，ARFID中情绪功能的首次检查， 对ARFID的认知行为模型进行了严格的首次测试。本项目对应的培训计划 将支持肯德拉·R博士贝克尔成为一名独立的临床科学家， 研究进食中情感和奖赏维持机制的神经生物学基础 疾病，以更好地了解疾病的轨迹，并告知病理学的个性化配方。每一个目标 这项研究对应于一个具体的培训目标，这将映射到四个主要领域的能力博士。 Becker：（1）可重复的fMRI方法，（2）研究设计和内分泌数据的分析/解释，（3）， EMA方法，包括整合神经生物学变量的高级纵向数据分析，以及（4） 职业发展。培训目标将在Jennifer J.托马斯博士（初级）的指导下实施 导师），伊丽莎白·A.放大图片作者：Laura M. Holsen（共同导师），Drs. Stephen A. Wonderlich和Ross D.克罗斯比（合作者）和Kamryn T. Eddy和Madhusmita Misra（其他重要贡献者）。

PROJECT SUMMARY/ABSTRACT Avoidant/restrictive food intake disorder (ARFID) is identified as a restrictive eating disorder in DSM-5 and is associated with substantial medical morbidity, psychiatric comorbidity, and high treatment costs. Maintenance mechanisms for ARFID are unknown. However, the cognitive behavioral model of ARFID suggests that negative reinforcement, via reductions in negative affect, may be key in understanding these highly persistent and medically compromising behaviors. This 5-year K23-Patient-Oriented Research Career Development award application addresses this hypothesis using an innovative, multi-disciplinary approach to examine differences in neural circuitry and hormone functioning in adults with ARFID compared to healthy controls (HC) and to explore the relationships between real-time emotions and behaviors with brain responsivity and endocrine signaling to food stimuli. Specifically, this proposal leverages ongoing data collection from a funded R01 (MH108595) investigating the neurobiology of ARFID in youth and extends these methods by focusing on adults and including one week of ecological momentary assessment (EMA). Activation in the amygdala, hippocampus, anterior insula, anterior cingulate cortex, and medial prefrontal cortex (brain regions in the limbic and paralimbic circuits governing emotional processing) as well as cortisol and oxytocin levels around a standardized meal (hormones associated with mood and anxiety) will be compared between adults with ARIFD and HC. EMA ratings of negative emotions and eating behaviors will be used to test whether negative affect is reduced following common problematic eating behaviors (i.e., food refusal) in ARFID. As a final aim, this study will explore if activity in limbic/paralimbic circuitry and aberrant cortisol and oxytocin correlate with negative affect levels as well as reports of avoidant/restrictive eating during the one-week EMA period. This project represents the first exploration of ARFID in adults, the first examination of emotional functioning in ARFID, and a rigorous first test of the cognitive-behavioral model of ARFID. The training plan corresponding to this project will support Dr. Kendra R. Becker in becoming an independent clinical scientist with a program of research examining neurobiological underpinnings of affect and reward maintenance mechanisms in feeding/eating disorders to better understand illness trajectory and inform personalized formulations of pathology. Each aim of the study corresponds to a specific training goal, which will map onto four main areas of competency for Dr. Becker: (1) reproducible fMRI methodology, (2) study design and analysis/interpretation of endocrine data, (3), EMA methodology including advanced longitudinal data analysis integrating neurobiological variables, and (4) career development. Training goals will be implemented under the guidance of Dr. Jennifer J. Thomas (primary mentor), Drs. Elizabeth A. Lawson and Laura M. Holsen (co-mentors), Drs. Stephen A. Wonderlich and Ross D. Crosby (collaborators), and Drs. Kamryn T. Eddy and Madhusmita Misra (other significant contributors).