Fear Conditioning and Fear Extinction in Anorexia Nervosa

项目摘要 神经性厌食症(AN)是最有害的精神疾病之一，表现出较高的发病率。 死亡率高，慢性病病程复发，对目前的治疗方法难以奏效。 此外，AN的病因仍然难以捉摸。虽然迫切需要更有效的治疗方法，但 精确治疗的发展取决于对机械途径的识别 作为症状表现的基础。这项以患者为导向的研究事业发展奖 (K23)将为斯图尔特·默里博士开始职业生涯提供有针对性的培训和指导 独立研究，旨在勾勒出支撑 症状学。这反过来将使后续的治疗开发工作能够有针对性地进行 精确的致病机制来改变它们驱动症状的途径。这些项目 本提案中概述的具体涉及恐惧条件作用和恐惧消退，考虑到(I) 对AN的陈述中的恐惧，(Ii)AN和障碍之间的大量重叠，其特征为 恐惧条件作用中的扰动，以及(Iii)和缺乏与恐惧习得有关的经验证据 害怕在一场战争中灭绝。拥有一支由专家导师和顾问组成的团队，共同在各个领域架起桥梁 在翻译精神病学、神经成像、恐惧消退和生物统计学方面，默里博士的目标是(I)索引 恐惧条件反射中恐惧获得和恐惧消退的心理和生理标志 利用中性线索和特定于障碍的线索的范式，以及(Ii)映射两者的神经生物标记物 通过神经成像获得恐惧和消除恐惧。预计这项研究的结果将 为制定精确的治疗目标和培训做出重大贡献 本文将把默里博士定位为精密领域的独立研究员 安非他命的治疗。

PROJECT ABSTRACT Anorexia nervosa (AN) is among the most pernicious of psychiatric disorders, demonstrating elevated rates of mortality, and a chronic and relapsing illness course that is refractory to current treatment approaches. Further, the etiology of AN remain elusive. While more efficacious treatments are urgently needed, the development of precision treatments is dependent upon the identification of mechanistic pathways that underpin symptom presentations. This mentored patient-oriented research career development award (K23) will provide targeted training and mentorship for Dr. Stuart Murray to embark upon a career of independent research oriented towards the delineation of key mechanistic pathways underpinning AN symptomatology. This, in turn, will allow subsequent treatment development efforts to be targeted towards precise pathogenic mechanisms to alter the pathway by which they drive AN symptomatology. The projects outlined in this proposal relate specifically to fear conditioning and fear extinction, given (i) the centrality of fear in presentations of AN, (ii) the substantial overlap between AN and disorders characterized by perturbations in fear conditioning, and (iii) and the absence of empirical evidence relating to fear acquisition and fear extinction in AN. With a team of expert mentors and consultants that collectively bridge the fields of AN, translational psychiatry, neuroimaging, fear extinction, and biostatistics, Dr. Murray aims to (i) index psychological and physiological markers of fear acquisition and fear extinction during a fear conditioning paradigm utilizing both neutral cues, and disorder-specific cues, and (ii) map the neural biomarkers of both fear acquisition and fear extinction via neuroimaging. It is expected that the results of this study will contribute significantly to the development of precision targets for AN treatments, and the training encapsulated herein will position Dr. Murray as an independent researcher in the field of precision treatment for AN.