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）是一种严重的精神疾病，其死亡率是所有精神疾病中最高的 病AN的发病率和死亡率的中心是持续倾向于将热量摄入限制在 这是一个特殊的趋势，限制来自脂肪的热量。这种令人困惑的行为是高度 即使经过一个完整的住院治疗和体重恢复过程，此外，委员会认为， 限制性饮食模式与出院后复发率高有关。为了提高 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 该提案特别旨在阐明导致疾病持续存在的机制， 相反，持续缓解。一个假定的机制，持续适应不良的行为是习惯 形成，通过这种形成，习得的行为变得对目标相对不敏感。习惯行为与 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 通过三个实验，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，以评估习惯行为与目标导向行为的优势 （修改以提高习惯敏感性），避免习惯任务，以评估在以下情况下的习惯形成： 厌恶的结果，和巴甫洛夫仪器转移任务，以评估如何强烈的背景线索， 加剧习惯性行为。任务组合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存在，而目标导向的 行为有助于缓解。为了检查与短和短相关的大脑和行为特征， 长期缓解，我们利用我们的长期研究单位，其中有一个成功的计划，充分 体重恢复（急性缓解），并有一个研究登记处，已经到位超过一个 十年我们将使用fMRI对急性体重恢复的AN住院患者（n=80）进行任务组合， AN长期缓解的个体（n=40，从研究登记处招募）和健康 比较女性（HC，n=40）。我们还将邀请研究登记处的所有合格患者（n=397， 目前）完成我们的任务电池在线，以评估习惯与目标导向的行为在一个 大样本，涵盖从急性加重后复发到长期缓解的一系列经历 修复此外，将在医院后对急性体重恢复的AN样本进行6个月的随访 出院后，复发风险高的时间，纵向检查行为和神经之间的联系， 特点和结果。这项研究的结果将有助于确定是否支持的机制， 疾病的持续存在也有助于缓解，从而明确了预防复发治疗的目标。