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

项目总结/摘要 本研究旨在探讨肥胖（OB）患者治疗反应的机制 和暴食症（BED），一组患有OB的个体对现有治疗特别难治， 与急剧的体重增加轨迹和显著的发病率相关。具体来说，我们的目标是增加神经， 认知和行为的措施，以最近资助的分期随机临床试验（RCT），以调查 单独和联合使用利右苯丙胺（LDX -唯一一种FDA指示用于BED的药物）， 认知行为疗法（CBT）-最好的建立行为疗法的床，已证明 减少暴食但不产生体重减轻的功效）。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，认知和行为的深入了解。 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查 并探讨概念和经验支持的预测因子，主持人，结果和调解人。 目的是使用功能磁共振成像来识别治疗前大脑激活的几个领域（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 在三种12周治疗条件（CBT、LDX、CBT/LDX）期间，前瞻性地和随着时间的推移， 急性结果（即，在治疗后）和在更长的期限（即，6、12和18个月随访评估）。 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 与治疗结果有关。这项研究将提供新的和新颖的信息， 这些不同的药理学和行为干预通过“机械”因素实现 结果。 拟议的研究将检查从LDX和CBT的RCT中招募的N=120名患有BED的OB患者。fMRI 将在治疗前和治疗后进行，以确定食物提示反应性背后的大脑激活 （专注阶段），认知控制（控制受损阶段），奖励处理（狂欢发作 情绪调节（negative Affect Phase）。治疗前水平和这些领域的变化 和他们的神经相关性，发生与治疗将前瞻性地检查有关的急性和长期- 长期成果。探索性测量将评估其他大脑测量（白色物质、灰质、静息状态， 电路）与治疗结果的关系。评估冲动，强迫和多巴胺的措施- 将获得依赖性和多巴胺非依赖性的认知和行为过程，以探索 CBT和LDX治疗反应的“预测因子”，确定与LDX和CBT相关的随时间推移的变化 治疗和探测适度和调解模型，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.