No Way Around But Through: Mechanisms of Persistence and Remission of Habits in Anorexia Nervosa

别无选择，只能通过：神经性厌食症习惯的持续和缓解机制

• 批准号: 10585957
• 负责人: Karin Foerde
• 金额: $ 69.55万
• 依托单位: NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-02-01 至 2028-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10585957
• 关键词: Acute; Anorexia Nervosa; Behavior; Behavior Control; Behavior assessment; Behavioral; Behavioral Mechanisms; Body Weight decreased; Brain; Caloric Restriction; Calories; Characteristics; Chronic; Clinical; Corpus striatum structure; Cues; Dedications; Disease; Disease remission; Dorsal; Eating Behavior; Eating Disorders; Eligibility Determination; Energy Intake; Fatty acid glycerol esters; Food; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Habits; Hospitals; Individual; Inpatients; Life; Link; Measures; Mediating; Mental disorders; Morbidity - disease rate; Outcome; Participant; Patients; Pattern; Prefrontal Cortex; Registries; Relapse; Research; Resistance; Role; Sampling; Severity of illness; System; Time; Weight; Woman; cognitive neuroscience; experience; experimental study; follow-up; food restriction; high risk; improved; improved outcome; learned behavior; longitudinal course; maladaptive behavior; mortality; neural; neural circuit; neuroimaging; neuromechanism; patient registry; programs; prospective; recruit; relapse prevention; relapse risk; restrictive eating; treatment research; weight restoration

Anorexia nervosa (AN) is a serious disorder with a mortality rate among the highest of any psychiatric illness. Central to the morbidity and mortality of AN is a persistent tendency to restrict caloric intake below the body's needs, with a specific tendency to limit calories derived from fat. This perplexing behavior is highly resistant to change, even with a full course of inpatient treatment and weight restoration. Furthermore, restrictive eating patterns are linked to the high rates of relapse after hospital discharge. In order to improve outcomes and long-term remission rates, it is critical to better understand the pathophysiology of illness. This proposal specifically aims to elucidate mechanisms that contribute to the perpetuation of illness and, conversely, to sustained remission. One putative mechanism of persistent maladaptive behavior is habit formation, through which learned behaviors become relatively insensitive to goals. Habit behavior is associated with neural activity in dorsal frontostriatal systems. Here, we will assess habitual and goal-directed behavior across three experiments to provide an in-depth assessment of the behavioral and neural mechanisms that support persistence of illness, as well as remission from illness. This comprehensive battery includes an augmented Two-Step decision task to assess the preponderance of habitual vs goal-directed behavior (modified to improve habit sensitivity), the Avoidance Habit task to assess habit formation in the setting of aversive outcomes, and a Pavlovian Instrumental Transfer task to assess how strongly context cues exacerbate habitual behavior. The task battery will also measure general vs food-specific abnormalities. Our central hypothesis is that habits contribute to the persistence of illness, whereas goal-directed behavior contributes to remission. To examine brain and behavior characteristics associated with short and long-term remission, we leverage our longstanding research unit, which has a successful program for full weight restoration (acute remission), and has a Research Registry that has been in place for more than a decade. We will administer our task battery with fMRI to acutely weight restored inpatients with AN (n=80), individuals in longer-term remission from AN (n=40, recruited from the Research Registry), and healthy comparison women (HC, n=40). We will also invite all eligible patients in the Research Registry (n=397, currently) to complete our task battery online, in order to assess habitual vs goal-directed behavior across a large sample, spanning a range of experiences from relapse to long-term remission after acute weight restoration. In addition, the acutely weight restored AN sample will be followed for 6 months after hospital discharge, a time of high relapse risk, to examine longitudinally the association between behavioral and neural characteristics and outcome. Findings from this study will help determine whether the mechanisms that support persistence of illness also support remission, thereby clarifying targets for relapse prevention treatment.

神经性厌食症（AN）是一种严重的疾病，在任何精神病学中最高的死亡率 疾病。 AN的发病率和死亡率的核心是将热量摄入量限制在以下的持续趋势 人体的需求，特定的趋势限制了脂肪的卡路里。这种困惑的行为很高 即使经过全面的住院治疗和体重恢复，也可以抵抗变化。此外， 限制性饮食模式与住院后的高复发率有关。为了改善 结局和长期缓解率，更好地了解疾病的病理生理学至关重要。这 提案专门旨在阐明有助于疾病延续的机制 相反，要持续缓解。持续适应不良行为的一种推定的机制是习惯 形成，通过这种行为对目标变得相对不敏感。习惯行为与 在背额叶系统中具有神经活动。在这里，我们将评估习惯性和目标指导的行为 在三个实验中，对行为和神经机制进行了深入评估 支持疾病的持久性以及疾病缓解。这个全面的电池包括 增强两步决策任务，以评估习惯性与目标指导行为的优势 （修改以提高习惯敏感性），避免习惯任务，以评估习惯形成 厌恶结果和帕夫洛维亚工具转移任务，以评估背景线索的强烈情境提示 加剧习惯行为。任务电池还将测量一般与食物特异性异常。 我们的中心假设是习惯有助于疾病的持续性，而目标定向 行为有助于缓解。检查与短和相关的大脑和行为特征 长期缓解，我们利用了我们的长期研究部门，该单位成功了 重量恢复（急性缓解），并具有一项研究注册表，该注册表已不止于 十年。我们将使用fMRI管理我们的任务电池，以急性重量恢复（n = 80）， 从An（n = 40，从研究注册表招募）的长期缓解的个人，健康 比较女性（HC，n = 40）。我们还将邀请所有研究注册中的所有合格患者（n = 397， 目前）要在线完成我们的任务电池，以评估一个习惯性与目标指导的行为 大型样本，跨越急性重量后从复发到长期缓解的一系列经验 恢复。此外，急性恢复了样本，将在医院后6个月进行 出院，一个高复发风险的时间，纵向检查行为与神经之间的关联 特征和结果。这项研究的发现将有助于确定支持的机制是否支持 疾病的持久性也支持缓解，从而阐明了预防复发治疗的靶标。