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

项目概要/摘要 本研究旨在调查肥胖症 (OB) 患者治疗反应的潜在机制 暴食症 (BED)，这是一组对现有治疗特别难治的 OB 患者， 与急剧的体重增加轨迹和显着的发病率相关。具体来说，我们的目标是添加神经网络， 最近资助的一项分阶段随机临床试验 (RCT) 的认知和行为测量 单独或联合使用赖右安非他明（LDX - FDA 唯一批准用于 BED 的药物）和 认知行为疗法（CBT——针对暴食症最成熟的行为疗法，已证明 能有效减少暴饮暴食，但不能减轻体重）。拟议的研究受益于利用数据 即将在 NIH 资助的随机对照试验中收集，并将提供对神经、认知和行为的见解 与 OB 和 BED 相关的机制以及拟议的治疗方法。这些数据还提供了检验的潜力 并探索概念和经验支持的结果预测因素、调节因素和中介因素。 目的是使用功能磁共振成像来识别跨多个领域的治疗前大脑激活（专注 食物、认知控制、奖励处理和负面影响）以及这些激活的变化 在三个为期 12 周的治疗条件（CBT、LDX、CBT/LDX）期间，前瞻性地并随着时间的推移与 急性（即治疗后）和长期（即 6、12 和 18 个月的随访评估）结果。 类似的方法将评估认知和行为测量，以检查和探索这些领域如何 会与治疗结果相关。这项研究将提供有关可能的新的和新颖的信息 这些不同的药理学和行为干预措施通过“机械”因素实现 结果。 拟议的研究将检查从 LDX 和 CBT 的随机对照试验中招募的 N=120 名患有 BED 的 OB 患者。功能磁共振成像 将在治疗前和治疗后进行，以识别食物提示反应背后的大脑激活 （全神贯注阶段）、认知控制（控制受损阶段）、奖励处理（暴饮暴食阶段） 阶段）和情绪调节（负面影响阶段）。这些领域的治疗前水平和变化 以及治疗过程中发生的神经相关性将根据急性和长期症状进行前瞻性检查 期限结果。探索性测量将评估其他大脑测量（白质、灰质、静息状态、 电路）与治疗结果的关系。评估冲动、强迫性和多巴胺的措施 将获得依赖性和非多巴胺依赖性的认知和行为过程来探索 CBT 和 LDX 治疗反应的“预测因子”，识别与 LDX 和 CBT 相关的随时间的变化 治疗以及探索调节和中介模型，以确定谁可能对特定治疗反应最好 以及 CBT 和 LDX 的潜在作用机制。

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.