Neurocognitive fMRI Mechanisms of CBT and Lisdexamfetamine Outcomes in Obesity and BED

CBT 和赖右苯丙胺治疗肥胖和暴食症结果的神经认知功能磁共振成像机制

• 批准号: 10001505
• 负责人: CARLOS M GRILO
• 金额: $ 57.87万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001505
• 关键词: Acute; Adult; Affective Symptoms; Aftercare; Anterior; Applications Grants; Behavior Therapy; Behavioral; Behavioral Mechanisms; Binge Eating; Binge eating disorder; Body Weight decreased; Brain; Clinical; Cognitive; Cognitive Therapy; Corpus striatum structure; Cues; Data; Dopamine; Effectiveness; Empirical Research; FDA approved; Feeling; Food; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Funding; Grant; Impairment; Impulsivity; Individual; Inferior frontal gyrus; Intervention; Link; Measures; Mediating; Mediation; Mediator of activation protein; Modeling; Morbidity - disease rate; Negative Valence; Neurocognitive; Obesity; Outcome; Parents; Patients; Persons; Pharmaceutical Preparations; Pharmacology; Phase; Positive Valence; Prediction of Response to Therapy; Prefrontal Cortex; Process; Public Health; Randomized Clinical Trials; Recurrence; Refractory; Research Design; Research Domain Criteria; Research Support; Rest; Rewards; System; Testing; Time; Treatment outcome; United States National Institutes of Health; Vyvanse; Weight Gain; Work; adult obesity; arm; behavior measurement; behavioral construct; cingulate cortex; cognitive control; cognitive testing; comparative efficacy; craving; cue reactivity; design; emotion regulation; executive function; financial incentive; follow up assessment; food craving; gray matter; insight; negative affect; neural correlate; neuroimaging; novel; obesity treatment; outcome prediction; parent grant; primary outcome; prospective; psychologic; recruit; relating to nervous system; relative effectiveness; response; reward processing; theories; therapy outcome; treatment response; white matter

Project Summary / Abstract This study seeks to investigate mechanisms underlying treatment responses in individuals with obesity (OB) and binge-eating disorder (BED), a group of individuals with OB particularly refractory to existing treatments and associated with steep weight gain trajectories and significant morbidity. Specifically, we aim to add neural, cognitive and behavioral measures to a recently funded staged randomized clinical trial (RCT) to investigate alone and in combination lisdexamfetamine (LDX -the only medication with an FDA indication for BED) and cognitive behavioral therapy (CBT – the best established behavioral therapy for BED that has demonstrated efficacy in reducing binges but not in generating weight loss). The proposed study benefits from leveraging data about to be collected in a RCT funded by NIH and will provide insight into neural, cognitive and behavioral mechanisms linked to OB and BED and the proposed treatments. The data also provide the potential to examine and explore conceptually and empirically supported predictors, moderators, and mediators of outcomes. The aim is to use fMRI to identify pre-treatment brain activations across several domains (preoccupation with food, cognitive control, reward processing, and negative affect) and changes in those activations during three 12-week treatment conditions (CBT, LDX, CBT/LDX) associated prospectively and over time with outcomes acutely (i.e., at post-treatment) and at longer terms (i.e., 6, 12 and 18 month follow-up assessments). A similar approach will assess cognitive and behavioral measures to examine and explore how these domains will relate to treatment outcomes. This study will provide new and novel information regarding possible “mechanistic” factors through which these distinct pharmacological and behavioral interventions achieve outcomes. The proposed study will examine N=120 OB patients with BED recruited from a RCT of LDX and CBT. fMRI will be performed pre- and post-treatment to identify brain activations underlying food-cue reactivity (Preoccupation Phase), cognitive control (Impaired Control Phase), reward processing (Binge Episode Phase), and emotion regulation (Negative Affect Phase). Pre-treatment levels and changes in these domains and their neural correlates that occur with treatment will be examined prospectively in relation to acute- and long- term outcomes. Exploratory measures will assess other brain measures (white matter, gray matter, resting state, circuitry) in relation to treatment outcomes. Measures assessing impulsivity, compulsivity and dopamine- dependent and dopamine-independent cognitive and behavioral processes will be obtained to explore “predictors” of treatment responses to CBT and LDX, identify changes over time associated with LDX and CBT treatments and probe moderation and mediation models to identify who might respond best to specific treatments and potential mechanisms of action for CBT and LDX.

项目摘要 /摘要 这项研究旨在研究肥胖个体（OB）中治疗反应的基础机制 和食肉动物（BED），一群具有OB的人，特别是对现有治疗的难治性和 与蒸汽重量增加轨迹和明显的发病率相关。具体来说，我们旨在增加神经， 对最近资助的上演随机临床试验（RCT）进行认知和行为措施，以研究 单独和组合Lisdexamfetamine（LDX-唯一具有FDA床适应症的药物）和 认知行为疗法（CBT - 已证明的床的最佳已建立行为疗法 降低缠绕的效率，但不会产生体重减轻）。拟议的研究受益于利用数据 即将收集在由NIH资助的RCT中，并将提供有关神经，认知和行为的见解 与OB和BED有关的机制以及拟议的治疗方法。数据还提供了检查的潜力 并在概念和经验上探索结果的预测因素，主持人和结果的中介。 目的是使用fMRI识别几个领域的预处理脑激活 食物，认知控制，奖励处理和负面影响）以及这些激活的变化 在三个12周的治疗条件（CBT，LDX，CBT/LDX）期间 结果（即在治疗后）和更长的期限（即6、12和18个月的随访评估）。 类似的方法将评估认知和行为措施，以检查和探索这些领域如何 将与治疗结果有关。这项研究将提供有关可能的新的新信息 这些独特的药理和行为干预措施实现的“机械”因素 结果。 拟议的研究将检查从LDX和CBT RCT募集的N = 120 OB患者。 fMRI 将进行治疗前后进行的，以识别食物-CUE反应性的脑部激活 （关注阶段），认知控制（控制阶段受损），奖励处理（狂欢发作 阶段）和情绪调节（负面影响阶段）。预处理水平和这些域的变化 与治疗发生的它们的神经相关性将与急性和长期有关 术语成果。探索性措施将评估其他大脑措施（白质，灰质，静止状态， 电路）与治疗结果有关。衡量冲动，强迫性和多巴胺的评估 将获得依赖和多巴胺独立的认知和行为过程以探索 对CBT和LDX的治疗反应的“预测指标”，确定与LDX和CBT相关的随着时间的变化 治疗和探测措施和调解模型，以确定谁可能对特定治疗做出反应最佳 以及CBT和LDX的潜在作用机理。