Neural Correlates of Reward and Symptom Expression in Anorexia Nervosa

项目摘要/摘要 这个K23应用程序旨在支持Ann Haynos博士成为一名独立人士的首要目标 研究人员的重点是：(A)确定饮食紊乱的生物和心理机制；(B) 利用这些信息为饮食失调的新的和有针对性的治疗方法的开发提供信息。这个 建议的应用程序将通过提供先进的 培训：(A)发展理论方面的专门知识，并评估参与交叉的奖励机制-- 诊断精神病理学，并将这一知识转化为饮食失调的研究；(B)获得 进行神经生物学独立研究所需的神经成像知识和技能 饮食紊乱的基础；和(C)获得纵向设计、方法和分析方面的专业知识 需要进行研究，检查饮食紊乱的维持情况。为了实现这些目标，一位专家 已经组建了导师团队，由主要导师Scott Crow博士(进行翻译培训)组成 进食障碍研究和纵向方法论)，共同导师，Jazmin Camcong博士(针对 交叉诊断奖励模型)、Kelvin Lim博士(神经成像培训)和James Hodges博士( 生物统计学和纵向分析方面的培训)以及顾问安格斯·麦克唐纳博士三世和安格斯·麦克唐纳博士。 乔安娜·斯坦格拉斯(用于特定奖励和决策任务的培训)。 作为这次培训的一部分，海诺斯博士将完成一个项目，该项目将识别中脑边缘奖赏的反应 通常奖励刺激(即，娱乐视频剪辑)和特定于紊乱的刺激(即，限制性的)的电路 在最近体重恢复的神经性厌食症(AN)患者中)。这项研究将确定 无论中脑边缘回路对典型和/或特定于障碍的奖赏是否有反应，都能预测限制进食 以及复发的风险。AN与极差的预后和高死亡率有关。虽然 强化治疗可以将体重恢复到健康范围，有一半的人在一年内复发 体重恢复。这些糟糕的结果在一定程度上是由于对限制饮食的过度驱使 描述了这种紊乱的特征。对维持限制性的心理生物学机制知之甚少 进食并促进复发。然而，有初步研究表明，赤字估值通常 奖励线索和对特定于障碍的奖励的增强评估可能会影响症状。因此， 除了帮助实现候选人的培训目标外，该项目还将通过确定 奖励机制预测限制进食和复发。这一知识最终将促进 开发更有效的靶向治疗，促进AN的长期康复。

PROJECT SUMMARY/ABSTRACT This K23 application aims to support Dr. Ann Haynos her overarching goal of becoming an independent researcher focused on: (a) identifying biological and psychological mechanisms of disordered eating and (b) using this information to inform the development of novel and targeted treatments for eating disorders. The proposed application will strengthen the candidate's abilities to meet these goals by providing advanced training to: (a) develop expertise in theory and assessment of reward mechanisms involved in the cross- diagnostic psychopathology, and to translate this knowledge to research for eating disorders; (b) gain knowledge and skills in neuroimaging necessary to conduct independent research investigating neurobiological underpinnings of disordered eating; and (c) obtain expertise in longitudinal design, methodology, and analysis needed to conduct research examining maintenance of disordered eating. To achieve these goals, an expert team of mentors has been assembled, consisting of primary mentor, Dr. Scott Crow (for training in translational eating disorder research and longitudinal methodology), co-mentors, Dr. Jazmin Camcong (for training in cross-diagnostic reward models), Dr. Kelvin Lim (for training in neuroimaging) and Dr. James Hodges (for training in biostatistics and longitudinal analyses), as well as consultants Dr. Angus MacDonald, III, and Dr. Joanna Steinglass (for training in specific reward and decision-making tasks). As part of this training, Dr. Haynos will complete a project that will identify responses in mesolimbic reward circuitry to typically rewarding stimuli (i.e., entertaining video clips) and disorder-specific stimuli (i.e., restrictive eating cues) among recently weight restored individuals with anorexia nervosa (AN). This study will determine whether responding in mesolimbic circuitry to typical and/or disorder-specific rewards predicts restrictive eating and risk of relapse. AN is associated with extremely poor outcomes and high mortality rates. Although intensive treatment can restore weight to a healthy range, half of individuals with AN relapse within one year of weight restoration. These poor outcomes are due, in part, to the excessive drive towards restrictive eating characterizing this disorder. Little is known regarding the psychobiological mechanisms that maintain restrictive eating and promote relapse. However, there is initial research suggesting that deficit valuation of typically rewarding cues and enhanced valuation of disorder-specific rewards may influence AN symptoms. Therefore, in addition to assisting towards the candidate's training goals, this project will meet a critical need by identifying reward mechanisms predicting restrictive eating and relapse in AN. This knowledge will ultimately promote the development of more effectively targeted treatments promoting long-term recovery from AN.