Neuroscience-informed treatment to remotely target reward mechanisms in post-acute anorexia nervosa

项目摘要/摘要 神经性厌食症是一种发病率和死亡率极高的严重疾病。显然 成人AN缺乏有效的治疗方法，尤其是在急性后阶段 级别护理(例如，住宿、部分医院计划[PHP])。大多数患者在以下情况下症状稳定 强化治疗，但高达50%的复发率和更多的残留或合并疾病(例如，情感性) 出院后的症状。在这一阶段，通常无法获得或无法获得适当的门诊治疗。 尽管关于促进AN的生物行为机制的知识迅速增长，但这一信息 很少被纳入到治疗中。一套机械性的目标越来越被公认为 与此相关的是奖励制度。奖励(也就是积极的情感或效价)系统一直是 牵涉到无数精神障碍的维持，包括常见的和共病(例如，情绪 和焦虑症)。包括我们的试点数据在内的大量证据表明，拥有一部剧的人 缺陷奖励对通常被认为是奖励的体验(例如，社交、饮食)的敏感度， 类似于那些有情感障碍的人。然而，与其他精神疾病不同的是，患有 对减肥经历和暗示(如锻炼、低卡路里食物)也表现出更高的奖励敏感度。 急性AN中的饥饿似乎加剧了这些过程。然而，同样的问题也会影响体重- 恢复了一个，这表明它们代表了核心的疾病机制。尽管奖励异常现象长期以来一直是 文献中指出，目前还没有将积极情绪作为主要干预目标的治疗方法。 为了弥补这一差距，我们将测试远程部署的针对阳性的心理社会治疗 情感，积极情感治疗(PAT)，可以改变奖励机制，提高治疗结果 急性期后AN。PAT是一种认知行为疗法，最初设计用于治疗情绪和焦虑症 并由我们的团队进行调整，以针对An(Pat-An)中的奖励异常。我们的试点数据显示，帕特-安， 亲自或通过远程治疗，有效地瞄准积极的情绪和奖励敏感性，以改善BMI 以及进食障碍、焦虑和抑郁症状。我们将把这项调查扩大到后急性时期 在此期间，我们预计将更有效地利用奖励系统，因为 饥饿的生物制约。具有广义AN(N=70)离开住宅或PHP的成年人将是 随机接受24周的PAT-AN或主动对照(心理教育和行为治疗)作为辅助 照常治疗。治疗将通过高度可访问和可扩展的远程治疗形式提供。 在整个治疗和随访过程中，受试者将完成一种新型的多模式电池(例如，移动递送电池 和神经认知测量)评估，测量奖励敏感性和临床症状。这个项目将 允许我们精确地测试枯萎一种由生物行为机制科学提供信息的创新疗法， 第一次，直接针对长期以来被认为导致急性AN后的奖励中断。

PROJECT SUMMARY/ABSTRACT Anorexia nervosa (AN) is a serious illness with extremely high morbidity and mortality rates. Clearly efficacious treatments are lacking for adults with AN, especially during the post-acute stage following higher- level care (e.g., residential, partial-hospital program [PHP]). Most patients achieve symptom stability in intensive treatment, but up to 50% relapse and more experience residual or co-morbid (e.g., affective) symptoms after discharge. Appropriate outpatient treatment is often unavailable or inaccessible in this stage. Despite a rapid growth in the knowledge on the biobehavioral mechanisms promoting AN, this information has rarely been incorporated into treatment. One set of mechanistic targets increasingly acknowledged as relevant to AN are those of the reward system. The reward (a.k.a., positive affect or valence) system has been implicated in maintenance of myriad psychiatric disorders, including common AN co-morbidities (e.g., mood and anxiety disorders). A wealth of evidence, including our pilot data, suggests that individuals with AN show deficit reward sensitivity to experiences generally considered rewarding (e.g., social interactions, eating), similar to those with affective disorders. However, distinct from other psychiatric illnesses, individuals with AN also show elevated reward sensitivity to weight-loss experiences and cues (e.g., exercise, low-calorie foods). Starvation in acute AN appears to exacerbate these processes. However, these same problems affect weight- restored AN, suggesting they represent core illness mechanisms. Although reward anomalies have long been noted in the literature, currently no treatments for AN designate positive affect as a primary intervention target. To remedy this gap, we will test whether a remotely-deployed psychosocial treatment targeting positive affect, Positive Affect Treatment (PAT), can alter reward mechanisms and enhance treatment outcomes in post-acute AN. PAT is a cognitive-behavioral therapy originally designed to treat mood and anxiety disorders and adapted by our team to target reward anomalies in AN (PAT-AN). Our pilot data suggest that PAT-AN, delivered in person or via teletherapy, effectively targets positive affect and reward sensitivity to improve BMI and eating disorder, anxiety, depressive symptoms. We will extend this investigation to the post-acute period of AN, during which we expect to even more effectively engage the reward system, due to the removal of the biological constraints of starvation. Adults with broadly-defined AN (N = 70) leaving residential or PHP will be randomized to 24 weeks of PAT-AN or active control (psychoeducation and behavior therapy) as adjunctive to treatment as usual. Treatment will be delivered via the highly accessible and scalable format of teletherapy. Throughout treatment and follow-up, subjects will complete a novel multimodal battery (e.g., mobile-delivered and neurocognitive measures) assessing measuring reward sensitivity and clinical symptoms. This project will allow us to precisely test wither an innovative therapy informed by biobehavioral mechanistic science can, for the first time, directly target the reward disruptions long believed to contribute to post-acute AN.