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

 描述(申请人提供)：焦虑是自闭症谱系障碍(ASD)儿童最常见的担忧之一，他们寻求心理健康服务，导致痛苦和家庭压力，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景的治疗方法，但支持这种治疗反应的神经机制尚未被研究。我们将通过功能磁共振成像(FMRI)评估治疗前后社会情绪功能的脑指数，来研究CBT治疗ASD儿童焦虑的神经系统水平的目标。CBT教授情绪调节技能，如认知重新评估，然后是行为暴露在引发焦虑的情况下。由于CBT的目标是用更可控的处理取代自动的情绪反应，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。这是一项对100名患有高功能自闭症和中度至重度焦虑的学龄儿童进行的CBT与心理教育和支持疗法(PST)的随机对照试验。此外，50名匹配的典型发育(TD)儿童将接受两次扫描，每隔16周进行一次扫描，以解释与TD儿童相比，CBT与PST后ASD儿童脑功能的变化。焦虑症的CBT将使用结构化手册提供，该手册已针对ASD儿童进行了修改，增加了父母的参与，并解决了ASD核心症状在焦虑体验和表达中的作用。受试者将在自闭症的诊断、智商、适应行为和并存的精神病理学方面进行全面的特征描述。临床结果的主要衡量标准将包括临床医生评级的儿科焦虑量表和由独立评估者完成的临床总体印象改善量表，该评估者将对治疗分配视而不见。当受试者执行涉及情绪调节、情绪面孔知觉、生物运动知觉和休息状态的任务时，将收集功能磁共振。我们假设，与PST相比，CBT的积极反应将与情绪调节期间腹内侧额叶皮质和腹外侧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，而在情绪面孔感知期间杏仁核的激活减少。我们还将研究ASD社会功能的fMRI生物标记物对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记物方面的作用。这项研究将通过1)将患有ASD和焦虑的儿童与典型的对照组进行比较，以及2)检验CBT与PST后焦虑减轻与大脑活动变化的关系，从而有助于理解ASD焦虑的神经回路。与IACC ASD研究战略计划一致，对神经机制的了解将为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。

 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.