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

项目摘要/摘要 本研究旨在探讨肥胖症患者治疗反应的机制。 和暴饮暴食障碍(Bed)，这是一组患有OB的个体，对现有的治疗方法和 与急剧的体重增加轨迹和严重的发病率相关。具体地说，我们的目标是增加神经， 最近资助的分期随机临床试验(RCT)的认知和行为测量 单独和联合使用来司非他明(LDX-唯一具有FDA BED适应症的药物)和 认知行为疗法(CBT)-已证明的最好的床上行为疗法 在减少暴饮暴食方面的有效性，但在产生减肥方面没有效果)。拟议的研究受益于利用数据 即将在由NIH资助的RCT中收集，并将提供对神经、认知和行为的洞察 与OB和BED相关的机制和建议的治疗方法。这些数据也提供了检查的可能性 并探索概念上和经验上支持的结果的预测者、调节者和调解者。 其目的是使用功能磁共振成像来识别治疗前几个领域的大脑激活(关注 食物、认知控制、奖励处理和负面情绪)以及这些激活的变化 在三种12周的治疗条件(CBT、LDX、CBT/LDX)期间，随着时间的推移，与 结果是急性的(即治疗后)和较长期的(即6、12和18个月的后续评估)。 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是如何 将与治疗结果相关。这项研究将提供有关可能的新信息 这些不同的药理学和行为干预实现的“机械性”因素 结果。 这项拟议的研究将检查N=120名患有BED的OB患者，这些患者来自LDX和CBT的随机对照试验。功能磁共振成像 将在治疗前和治疗后进行，以确定食物线索反应性背后的大脑激活 (全神贯注阶段)、认知控制(控制受损阶段)、奖赏处理(狂欢剧集 情绪调节(负性情绪阶段)。这些领域的前处理水平和变化 他们在治疗过程中出现的神经关联将被前瞻性地检查与急性和长期- 期限结果。探索性测量将评估其他大脑测量(白质、灰质、休息状态、 电路)与治疗结果有关。评估冲动、强迫症和多巴胺的指标- 将获得依赖和多巴胺非依赖的认知和行为过程，以探索 CBT和LDX治疗反应的预测指标，确定与LDX和CBT相关的随时间的变化 并探索缓和和调解模式，以确定谁对特定治疗的反应最好 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.