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， 的死亡率，以及慢性和复发性疾病的过程是难治性的，目前的治疗方法。 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， 精确治疗的发展依赖于对机械途径的识别， 支持症状表现。这个指导病人为导向的研究职业发展奖 (K23)将为斯图尔特·默里博士提供有针对性的培训和指导， 独立的研究，以描绘支持AN的关键机制途径为导向 医学。这反过来又将使随后的治疗开发工作能够针对 精确的致病机制，以改变其驱动AN免疫学的途径。的项目 本建议中概述的具体涉及恐惧条件反射和恐惧消退，因为（i） 恐惧在介绍AN，（ii）AN和疾病之间的实质性重叠，其特征在于 恐惧条件反射的扰动，以及（iii）缺乏与恐惧获得相关的经验证据 恐于灭，拥有一个专家导师和顾问团队，他们共同连接各个领域， 在AN、转化精神病学、神经影像学、恐惧消退和生物统计学的基础上，Murray博士旨在（i）索引 恐惧条件反射期间恐惧获得和恐惧消除的心理和生理标记 范例利用中性线索，和疾病特异性线索，和（ii）映射两者的神经生物标志物 恐惧获得和恐惧消退的神经影像学研究。预计这项研究的结果将 为AN治疗的精确目标的发展做出了重大贡献， 本文将把默里博士定位为精密领域的独立研究人员。 治疗AN。

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.