Cognitive and neural mechanisms of cognitive-behavioral therapy for avoidant/restrictive food intake disorder

回避/限制性食物摄入障碍的认知行为疗法的认知和神经机制

• 批准号: 10570372
• 负责人: Kamryn T Eddy
• 金额: $ 108.3万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-07 至 2025-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10570372
• 关键词: Adolescent; Adult; Advocate; Affect; Aftercare; Age; Amygdaloid structure; Anterior; Brain region; Central Nervous System; Child; Chronic; Clinical; Clinical Trials; Cognitive; Cognitive Therapy; Counseling; Cues; Data; Dependence; Development; Disease remission; Dose; Eating; Eating Disorders; Evidence based treatment; Exhibits; Food; Fright; Functional Magnetic Resonance Imaging; Hyperactivity; Impairment; Individual; Intervention; Interview; Investigational Therapies; Learning; Malnutrition; Manuals; Measures; Mediating; Medical; Motivation; National Institute of Mental Health; Occupational Therapy; Outcome; Patients; Persons; Phase; Pica Disease; Prevention; Randomized; Randomized, Controlled Trials; Recommendation; Risk; Rumination Disorders; Standardization; Statistical Data Interpretation; Testing; Therapeutic Intervention; Thinking; Validation; Work; Youth; active control; arm; avoidant restrictive food intake disorder; behavior change; cingulate cortex; clinical trial analysis; dietary supplements; effectiveness trial; efficacy trial; food avoidance; multidisciplinary; neuromechanism; novel; nutrition; pressure; prevent; psychologic; psychosocial; response; severe mental illness; telehealth; treatment of anxiety disorders; trend

ABSTRACT Avoidant/restrictive food intake disorder (ARFID) affects 3% of children and adolescents and results in nutritional deficiencies, supplement dependence, and psychosocial impairment. ARFID follows a chronic course, and has no evidence-based treatment. The hallmark feature of ARFID is food avoidance, which may be maintained by extreme levels of food neophobia and/or hyperactivation of fear circuitry in response to food cues. Our team has developed a manualized cognitive-behavioral therapy (CBT-AR) that directly targets both food neophobia (cognitive mechanism) and fear circuitry (neural mechanism) to reduce food avoidance (clinical outcome). In line with NIMH’s experimental therapeutics approach, in this exploratory/developmental phased R61/R33, we will leverage a multidisciplinary team of experts in the treatment of ARFID, neural mechanisms of food motivation, and statistical analysis of clinical trials to conduct a mechanistic randomized controlled trial of CBT-AR. First, to establish target engagement, we will randomize 50 youth (ages 10-18yo) with ARFID in a 1:1 ratio to 15 weekly sessions (via telehealth) of CBT-AR vs. nutrition counseling to establish target engagement. We chose nutrition counseling as our active control because it does not include the crucial CBT-AR intervention of exposure, and is therefore unlikely to engage our target mechanisms. We hypothesize that, compared to nutrition counseling, patients randomized to CBT-AR will show significantly greater decreases in food neophobia (cognitive mechanism) and fear circuitry (neural mechanism) in response to food cues during a standardized fMRI food cue paradigm (primary ROI: anterior cingulate cortex [ACC]; secondary ROIs: amygdala, orbitofrontal cortex [OFC]). We will also examine weekly change in food neophobia (cognitive mechanism) to identify the number of sessions at which further benefit ceases, and use this optimized dose of CBT-AR for the R33. We will move on to the R33 if we are able to demonstrate a reduction of at least d=.40 in the CBT-AR group from pre- to post-treatment AND a post-treatment between- group difference of at least d=.40 in CBT-AR vs. nutrition counseling in either food neophobia (cognitive mechanism) OR fear circuitry (Go/No-Go ROI: ACC; neural mechanism). Next, we will randomize 70 youth (ages 10-18yo) with ARFID in a 1:1 fashion to the optimized dose of CBT-AR or the same number of sessions of nutrition counseling to replicate target engagement and establish target validation. We hypothesize that, compared to nutrition counseling, patients randomized to CBT-AR will exhibit significantly greater reductions in food avoidance, and that these reductions in food avoidance will be mediated by reductions in food neophobia (cognitive mechanism) and fear circuitry (neural mechanism) activation. If successful, the proposed intervention (CBT-AR) could fill an important unmet need for those living with ARFID and pave the way for larger-scale efficacy and effectiveness trials.

抽象的 回避/限制性食物摄入障碍 (ARFID) 影响 3% 的儿童和青少年及其结果 营养缺乏、补充剂依赖和心理社会障碍。 ARFID 遵循一个长期的 当然，并且没有循证治疗。 ARFID 的标志性特征是避免食物，这可能 通过极端水平的食物新恐惧症和/或恐惧电路的过度激活来应对 食物线索。我们的团队开发了一种手动认知行为疗法（CBT-AR），直接针对 食物恐惧症（认知机制）和恐惧回路（神经机制）都可以减少食物回避 （临床结果）。根据 NIMH 的实验治疗方法，在这个探索性/发展性的治疗中 分阶段 R61/R33，我们将利用多学科专家团队来治疗 ARFID、神经 食物动机的机制，以及临床试验的统计分析，以进行机制随机 CBT-AR 的对照试验。首先，为了建立目标参与度，我们将随机抽取 50 名青少年（10-18 岁） 以 1:1 的比例使用 ARFID 进行每周 15 次 CBT-AR 会议（通过远程医疗）与营养咨询，以建立 目标参与。我们选择营养咨询作为我们的主动控制，因为它不包括 暴露的关键 CBT-AR 干预，因此不太可能参与我们的目标机制。我们 假设与营养咨询相比，随机接受 CBT-AR 的患者将表现出显着的 食物恐惧症（认知机制）和恐惧回路（神经机制）显着减少 在标准化功能磁共振成像食物线索范式中对食物线索的反应（主要投资回报率：前扣带皮层 [ACC]；次要 ROI：杏仁核、眶额皮质 [OFC]）。我们还将检查每周的食物变化 Neophobia（认知机制）来确定进一步获益停止的会话次数，并使用 R33 的 CBT-AR 优化剂量。如果我们能够展示 R33，我们将转向 R33 CBT-AR 组从治疗前到治疗后至少减少 d=.40，并且治疗后- CBT-AR 与营养咨询在任一食物新恐惧症（认知 机制）或恐惧电路（Go/No-Go ROI：ACC；神经机制）。接下来，我们将随机抽取70名青少年 （10-18 岁）以 1:1 的方式使用 ARFID 与 CBT-AR 的优化剂量或相同次数的疗程 营养咨询，以复制目标参与并建立目标验证。我们假设， 与营养咨询相比，随机接受 CBT-AR 的患者将表现出显着更大的减少 避免食物的减少，并且这些避免食物的减少将通过减少食物来调节 新恐惧症（认知机制）和恐惧回路（神经机制）激活。如果成功的话， 拟议的干预措施（CBT-AR）可以满足 ARFID 生活者未满足的重要需求，并为 进行更大规模功效和有效性试验的方法。