Neural Mechanisms of CBT for Anxiety in Children with Autism Spectrum Disorder

CBT 治疗自闭症谱系障碍儿童焦虑的神经机制

• 批准号: 9897549
• 负责人: Kevin A Pelphrey
• 金额: $ 52.95万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-06-17 至 2022-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9897549
• 关键词: 12 year old; Adaptive Behaviors; Address; Affective; Aftercare; Amygdaloid structure; Anger; Anxiety; Anxiety Disorders; Behavioral; Biological; Biological Assay; Biological Markers; Brain; Child; Clinical; Clinical Trials; Cognitive Therapy; Data; Development; Diagnosis; Down-Regulation; Emotional; Emotions; Evidence based treatment; Exhibits; Exposure to; Face; Facial Expression; Failure; Family; Fright; Functional Magnetic Resonance Imaging; Functional disorder; Fusiform gyrus; Goals; Image; Impairment; Manuals; Measures; Mental Health Services; Methodology; Motion; Motion Perception; Neurobiology; Outcome; Pathological anxiety; Pathway Analysis; Patients; Perception; Prefrontal Cortex; Psychopathology; Public Health; Quality of life; Randomized; Randomized Controlled Trials; Regulation; Research; Rest; Role; Scanning; School-Age Population; Shapes; Social Functioning; Social Perception; Strategic Planning; Stress; Structure; Structure of superior temporal sulcus; Supportive care; Symptoms; System; Testing; active control; anxiety reduction; anxiety treatment; autism spectrum disorder; autistic children; base; blind; childhood anxiety; clinical efficacy; clinically significant; cognitive benefits; cognitive reappraisal; comorbidity; disability; efficacy testing; emotion regulation; emotional functioning; experience; face perception; impression; improved; indexing; magnetic resonance imaging biomarker; negative affect; neural circuit; neural network; neuromechanism; personalized care; personalized medicine; psychoeducation; public health relevance; relating to nervous system; response; skills; social; social deficits; treatment response

 DESCRIPTION (provided by applicant): Anxiety is among the most common concerns in children with autism spectrum disorder (ASD) who seek mental health services, causing suffering and family stress and exacerbating social disability. Cognitive- Behavioral Therapy (CBT) is a promising treatment for anxiety in children with high-functioning ASD, but the neural mechanisms supporting response to this treatment have not been studied. We will investigate the neural-systems-level targets of CBT for anxiety in children with ASD by evaluating brain indices of socio- emotional functioning with functional magnetic resonance imaging (fMRI) before and after treatment. CBT teaches emotion regulation skills, such as cognitive reappraisal, followed by behavioral exposure to anxiety- provoking situations. Because the goal of CBT is to replace automatic emotional reactivity with more controlled processing, we hypothesize that CBT aimed at the reduction of anxiety will enhance the neural circuitry that subserves the experience and regulation of emotions. This is a randomized controlled trial of CBT vs. Psychoeducation and Supportive Therapy (PST) in 100 school-age children with high-functioning ASD and moderate to severe anxiety. In addition, 50 matched typically-developing (TD) children will be scanned twice with a 16-week interval to enable interpretation of change in brain function in children with ASD after CBT vs. PST relative to TD children. CBT for anxiety will be provided using a structured manual that has been modified for children with ASD by increasing parental participation and addressing the role of core ASD symptoms in the experience and expression of anxiety. Subjects will be comprehensively characterized with regard to ASD diagnosis, IQ, adaptive behavior, and comorbid psychopathology. Primary measures of clinical outcomes will include the clinician-rated Pediatric Anxiety Rating Scale and the Clinical Global Impression-Improvement scale completed by an independent evaluator who will be blind to treatment assignment. Functional MRI will be collected as the subjects perform tasks involving emotion regulation, emotional face perception, biological motion perception, and resting state. We hypothesize that a positive response to CBT vs. PST, will be associated with increased activation of ventromedial and ventrolateral prefrontal cortices and increased amygdala-prefrontal functional connectivity during emotion regulation, along with reduced amygdala activation during emotional face perception. We will also examine the moderating effects of fMRI biomarkers of social functioning in ASD on response to CBT, and explore the utility of resting state fMRI in developing biomarkers of treatment response. This study will contribute to the understanding of the neuro circuitry of anxiety in ASD by 1) comparing children with ASD and anxiety to typically developing controls and 2) examining the association of reduction in anxiety after CBT vs. PST with changes in brain activity. Consistent with the IACC Strategic Plan for ASD Research, understanding of neural mechanisms will inform treatment of anxiety in ASD and improve the ability to select patients who are likely to benefit from CBT toward the goal of personalized care.

 描述（由适用提供）：焦虑是自闭症谱系障碍儿童（ASD）寻求心理健康服务，造成痛苦和家庭压力并加剧社会残疾的最常见问题之一。认知行为疗法（CBT）是对高功能ASD的儿童的焦虑疗法，但是支持对这种治疗的反应的神经机制尚未研究。我们将通过在治疗前和治疗后用功能磁共振成像（fMRI）评估社会情感功能化的大脑脑指数，从而研究ASD儿童CBT的神经系统级目标。 CBT教授情感调节技能，例如认知重新评估，然后是行为暴露于焦虑的情况下。因为CBT的目的是用更受控的处理替换自动情绪反应性，所以我们假设旨在减少动画的CBT将增强神经电路，从而实现情绪的体验和调节。这是CBT与心理教育和支持疗法（PST）的随机对照试验（在100名具有高功能ASD且中度至严重焦虑症的学龄儿童中）。此外，将有50个匹配的通常开发（TD）儿童两次扫描，间隔为16周，以解释CBT与TD儿童相对于PST后ASD儿童的脑功能变化。通过增加父母参与并解决核心ASD症状在焦虑体验和表达中的作用，将使用已针对ASD儿童进行修改的结构化手册来提供焦虑的CBT。关于ASD诊断，智商，适应性行为和合并症的心理病理学，受试者将得到全面的特征。临床结果的主要度量将包括临床评级的小儿焦虑评级量表和由独立评估者完成的临床全球印象改进量表，他们将对治疗分配视而不见。当受试者执行任务涉及情绪调节，情感面部感知，生物运动感知和静止状态时，将收集功能性MRI。我们假设对CBT与PST的积极反应将与情绪调节期间的腹侧和腹侧前额叶皮层的激活增加，并增加情绪调节过程中的杏仁核-prefrontal功能连接性，以及在情感面部感受期间杏仁核的激活降低。我们还将研究ASD中社会功能的fMRI生物标志物对CBT响应的调节作用，并探讨静止状态fMRI在开发治疗反应的生物标志物中的实用性。这项研究将有助于理解ASD中ASD焦虑的神经回路1）将ASD和焦虑与通常发展控制的儿童进行比较，以及2）检查CBT与PST后焦虑与脑活动变化的焦虑减少的关联。与ASD研究的IACC战略计划一致，对神经机制的理解将为ASD的焦虑治疗提供信息，并提高选择可能从CBT中受益于个性化护理目标的患者的能力。