Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety

到青春期，33%的人会受到焦虑症的影响，并可能成为慢性焦虑症，导致 抑郁、滥用药物、辍学，甚至自杀。为了减少焦虑并防止其后遗症， 患者必须及早得到有效治疗；然而，一线干预，认知行为疗法(CBT)，已经 异质反应，40%-60%的接受治疗的患者继续遭受残留物的损害 症状。CBT结果变化的原因仍不清楚，但个别(包括 发育)CBT的大脑行为目标的差异可能起到了作用。这项提案涉及两个问题 基本和开放的问题：1)CBT相关脑行为功能的个体差异是否会导致 与CBT结果的差异有关？2)发展对这种差异有贡献吗？通过定义维度 构建在多个分析层次上，NIMH的RDoC提供了一个框架来识别特定于患者的 CBT结果的机制，跨越传统的、绝对的焦虑症。的RDoC结构 认知控制(CC)、急性威胁(AT)和它们之间的相互作用(CC-AT)塑造了假设的大脑- 建议研究的CBT的行为目标。鉴于CBT有助于控制严重威胁，以实现 有效的调控，我们假设AT-、CC-和AT-CC定义的标记将预测和表征 CBT效应的机制。此外，根据新出现的证据(包括我们自己的试点数据)显示 认知控制的神经底物的后期发展与早期大脑反应性的增加相比 根据患者的不同，我们假设AT、CC、CC-AT标志物与CBT效应有不同的关系 年龄。这些假设将通过在多个分析层面上的测量数据来检验：大脑功能-结构 (fMRI，DTI)和行为性能指标在AT、CC和CC-AT结构中的应用，以及临床测量 280名青年的焦虑症。在这些人中，210名患有焦虑症的青少年将被随机分配接受CBT或 放松控制疗法和多水平数据将在治疗后再次收集。该项目将连接 发展神经科学和临床试验研究，以使机械理解如何不同 不同年龄的患者受益于CBT。

Impairing anxiety affects 33% of the population by adolescence and can become chronic, leading to depression, substance abuse, school-drop out and even suicide. To reduce anxiety and prevent its sequelae, patients must be effectively treated early; yet, the first line intervention, cognitive behavioral therapy (CBT), has a heterogeneous response with 40-60% of treated patients continuing to experience impairment from residual symptoms. The reasons for variability in CBT outcomes remain poorly understood, but individual (including developmental) differences in brain-behavioral targets of CBT may contribute. This proposal addresses two fundamental and open questions: 1) Do individual differences in CBT-relevant brain-behavioral functions lead to variation in CBT outcomes? and 2) Does development contribute to this variation? By defining dimensional constructs at multiple levels of analysis, NIMH's RDoC provides a framework for identifying patient-specific mechanisms of CBT outcomes, across traditional, categorical anxiety disorders. The RDoC constructs of Cognitive Control (CC), Acute Threat (AT) and their interactions (CC-AT) shape the selection of putative brain- behavior targets of CBT for the proposed study. Given that CBT facilitates control over acute threat to enable effective regulation, we hypothesize that AT-, CC- and AT-CC-defined markers will predict and characterize mechanisms of CBT effect. In addition, based on emerging evidence (including our own pilot data) showing later development of neural substrate for cognitive control compared to earlier increase in brain reactivity to threat, we hypothesize that AT, CC, CC-AT markers will differentially relate to CBT effect, depending on patient age. These hypotheses will be tested by measuring data at multiple levels of analysis: brain function-structure (fMRI, DTI) and behavioral performance to index in AT, CC and CC-AT constructs, and clinical measures of anxiety in 280 youths. Of these, 210 youths with impairing anxiety will be randomized to receive CBT or a relaxation control therapy and multilevel data will be collected again after treatment. The project will connect developmental neuroscience and clinical trial research to enable a mechanistic understanding of how different patients at different ages benefit from CBT.