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（由申请人提供）：焦虑是自闭症谱系障碍（ASD）儿童最常见的问题之一，他们寻求心理健康服务，造成痛苦和家庭压力，并加剧社会残疾。认知-行为疗法（CBT）是治疗高功能ASD儿童焦虑的一种有前途的治疗方法，但支持这种治疗反应的神经机制尚未研究。我们将通过在治疗前后用功能性磁共振成像（fMRI）评估社交情绪功能的大脑指数，研究CBT治疗ASD儿童焦虑的神经系统水平目标。CBT教授情绪调节技能，如认知重新评估，然后是行为暴露于焦虑激发的情况。因为CBT的目标是用更可控的处理取代自动情绪反应，我们假设旨在减少焦虑的CBT将增强有助于情绪体验和调节的神经回路。这是一项在100名患有高功能ASD和中度至重度焦虑的学龄儿童中进行的CBT与心理教育和支持治疗（PST）的随机对照试验。此外，将对50名匹配的典型发育（TD）儿童进行两次扫描，间隔16周，以解释ASD儿童在CBT与PST后相对于TD儿童的脑功能变化。焦虑的CBT将使用结构化手册提供，该手册已通过增加父母参与和解决核心ASD症状在焦虑体验和表达中的作用为ASD儿童进行了修改。受试者将在ASD诊断、智商、适应行为和共病精神病理学方面进行全面表征。临床结局的主要指标将包括临床医生评定的儿科焦虑评定量表和临床总体印象改善量表，由对治疗分配不知情的独立评价者完成。当受试者执行涉及情绪调节、情绪面部感知、生物运动感知和静息状态的任务时，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，沿着情绪面孔感知过程中杏仁核激活的减少。我们还将研究ASD中社会功能的fMRI生物标志物对CBT反应的调节作用，并探索静息状态fMRI在开发治疗反应生物标志物中的实用性。这项研究将有助于理解ASD中焦虑的神经回路，方法是：1）将患有ASD和焦虑的儿童与典型的发育对照组进行比较，2）检查CBT与PST后焦虑减少与大脑活动变化的相关性。与IACC ASD研究战略计划一致，对神经机制的理解将为ASD焦虑的治疗提供信息，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。