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

项目摘要/摘要 在DSM-5中，回避性/限制性食物摄入障碍(ARFID)被确定为限制性饮食障碍，并且 与大量的医疗发病率、精神共病和高昂的治疗费用有关。维修 ARFID的机制尚不清楚。然而，ARFID的认知行为模型表明 通过减少负面影响的负面强化，可能是理解这些高度持久的关键 以及医学危害行为。这个为期5年的以患者为中心的K23研究职业发展 获奖申请使用一种创新的、多学科的方法来研究这一假设 成人ARFID患者与健康对照组神经回路和激素功能的差异(HC) 并探索实时情绪和行为与大脑响应性和 内分泌向食物刺激发出信号。具体地说，该建议利用了从基金资助的持续数据收集 R01(MH108595)研究青年ARFID的神经生物学，并通过关注 成人，包括一周的生态瞬时评估(EMA)。杏仁核的激活， 海马体、前脑岛、前扣带回皮质和内侧前额叶皮质(大脑边缘区域 和控制情绪处理的边缘旁回路)，以及 标准膳食(与情绪和焦虑相关的激素)将在患有ARIFD的成年人之间进行比较 和HC。EMA对负面情绪和饮食行为的评分将被用来测试负面情绪是否 减少了ARFID中常见的有问题的饮食行为(即拒绝进食)。作为最终目标，这项研究 将探索边缘/边缘旁环路的活动以及异常皮质醇和催产素是否与负性 在一周的EMA期间，影响水平以及关于回避性/限制性饮食的报告。这个项目 代表了成人ARFID的第一次探索，ARFID的第一次情绪功能检查，以及 这是对ARFID认知行为模型的第一次严格测试。与该项目对应的培训计划 将支持肯德拉·R·贝克尔博士成为一名独立的临床科学家，并制定一项研究计划 研究进食/进食中情感和奖赏维持机制的神经生物学基础 更好地了解疾病轨迹，并为个性化的病理公式提供信息。的每一个目标 这项研究对应着一个具体的培训目标，它将映射到博士能力的四个主要领域。 Becker：(1)可重复的功能磁共振方法，(2)内分泌数据的研究设计和分析/解释，(3)， EMA方法，包括集成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.Thomas博士(主要)的指导下实施 导师)、伊丽莎白·A·劳森博士和劳拉·M·霍尔森博士(共同导师)、斯蒂芬·A·旺德利希博士和罗斯博士 D.Crosby(合作者)，Kamryn T.Eddy博士和MadHusmita Misra博士(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).