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

基本信息

批准号：
9028985
负责人：
Kevin A Pelphrey
金额：
$ 56.53万
依托单位：
YALE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-17 至 2021-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9028985
关键词：
12 year old Adaptive Behaviors Address Affective Aftercare Amygdaloid structure Anger Anxiety Anxiety Disorders Behavioral Biological Biological Assay Biological Markers Biological Neural Networks Brain Child Clinical Clinical Trials Cognitive Cognitive Therapy Data Development Diagnosis Down-Regulation Educational process of instructing 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 Lead Manuals Measures Mental Health Services Motion Motion Perception Neurobiology Outcome Pathological anxiety Patients Perception Prefrontal Cortex Process 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 base blind childhood anxiety clinical efficacy clinically significant cognitive reappraisal disability efficacy testing emotion regulation experience face perception imaging biomarker impression improved indexing neural circuit neuromechanism personalized care personalized medicine psychoeducation public health relevance relating to nervous system response skills social treatment response

项目摘要

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（由申请人提供）：焦虑是寻求心理健康服务的自闭症谱系障碍 (ASD) 儿童最常见的问题之一，它会造成痛苦和家庭压力，并加剧社交障碍。认知行为疗法 (CBT) 是一种很有前途的治疗方法。对于高功能 ASD 儿童的焦虑，但尚未研究支持这种治疗反应的神经机制，我们将通过评估 ASD 儿童的大脑指数来研究 CBT 对 ASD 儿童焦虑的神经系统水平目标。治疗前后通过功能磁共振成像 (fMRI) 进行社会情绪功能训练，教授情绪调节技能，例如认知重新评估，然后进行引发焦虑的行为暴露，因为 CBT 的目标是用自动情绪反应代替。更受控的处理，我们追求旨在减少焦虑的 CBT 将增强有助于情绪体验和调节的神经回路。这是一项 CBT 与心理教育和支持治疗 (PST) 的随机对照试验。此外，还将对 100 名患有高功能 ASD 和中度至重度焦虑的学龄儿童进行两次扫描，间隔 16 周，以解释 ASD 儿童的大脑功能变化。在 CBT 与 PST 相对于 TD 儿童的焦虑的 CBT 治疗之后，将使用针对 ASD 儿童进行修改的结构化手册，通过增加家长参与并解决核心 ASD 症状在焦虑体验和表达中的作用。受试者将在自闭症谱系障碍 (ASD) 诊断、智商、适应性行为和共病精神病理学方面进行全面表征。临床结果的主要衡量标准将包括临床医生评定的儿科焦虑评定量表和由独立评估员完成的临床总体印象改善量表。当受试者执行情绪调节、情绪面部感知、生物运动感知和静息状态时，我们将收集功能性 MRI 数据。 PST 与情绪调节过程中腹内侧和腹外侧前额叶皮质的激活增加以及杏仁核-前额叶功能连接的增加有关，同时与情绪面部感知过程中杏仁核激活的减少有关。我们还将检查自闭症谱系障碍中社会功能的功能磁共振成像生物标志物的调节作用。这项研究将有助于了解自闭症谱系障碍 (ASD) 焦虑的神经回路。 1) 将患有 ASD 和焦虑的儿童与正常发育的对照儿童进行比较，2) 检查 CBT 与 PST 后焦虑减少与大脑活动变化的关系，与 IACC 自闭症谱系障碍研究战略计划一致，了解神经机制将为治疗提供信息。减少 ASD 患者的焦虑，并提高选择可能从 CBT 中受益的患者的能力，以实现个性化护理的目标。