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，死亡率是所有精神疾病中最高的 疾病。 AN 发病率和死亡率的核心是持续将热量摄入限制在低于 身体的需要，特别倾向于限制来自脂肪的卡路里。这种令人费解的行为非常 即使接受了完整的住院治疗和体重恢复，也无法改变。此外， 限制性饮食模式与出院后的高复发率有关。为了改善 为了了解结果和长期缓解率，更好地了解疾病的病理生理学至关重要。这 该提案的具体目的是阐明导致疾病长期存在的机制， 反之，达到持续缓解。持续不良适应行为的一种假定机制是习惯 形成，通过这种形成，习得的行为变得对目标相对不敏感。习惯行为相关 与背侧额纹状​​体系统的神经活动有关。在这里，我们将评估习惯性和目标导向的行为 跨越三个实验，对行为和神经机制进行深入评估 支持疾病的持续存在以及疾病的缓解。这种综合电池包括一个 增强的两步决策任务来评估习惯行为与目标导向行为的优势 （经过修改以提高习惯敏感性），回避习惯任务用于评估在以下情况下的习惯形成 厌恶的结果，以及巴甫洛夫工具转移任务来评估上下文线索的强度 加剧习惯性行为。任务电池还将测量一般异常与食物特定异常。 我们的中心假设是，习惯会导致疾病的持续存在，而目标导向的行为会导致疾病的持续存在。 行为有助于缓解。检查与短期和长期相关的大脑和行为特征 为了长期缓解，我们利用我们长期的研究单位，该单位拥有一个成功的全面缓解计划 体重恢复（急性缓解），并拥有一个已经存在多年的研究登记处 十年。我们将使用功能磁共振成像来管理我们的任务组，以帮助体重急剧恢复的 AN 住院患者 (n=80)， AN 长期缓解的个体（n = 40，从研究登记处招募）和健康的 比较女性（HC，n=40）。我们还将邀请研究登记处的所有符合条件的患者（n=397， 目前）在线完成我们的任务电池，以便评估整个过程中的习惯行为与目标导向行为 大样本，涵盖急性体重后从复发到长期缓解的一系列经历 恢复。此外，体重急剧恢复的AN样本将在出院后跟踪6个月 出院时，复发风险很高，纵向检查行为和神经之间的关联 特点和结果。这项研究的结果将有助于确定支持机制是否 疾病的持续存在也支持缓解，从而明确了预防复发的治疗目标。