Dimensional Brain Behavior Predictors of CBT Outcomes in Pediatric Anxiety

到青春期，33%的人口受到损害性焦虑的影响，并且可能成为慢性病， 抑郁症，药物滥用，辍学，甚至自杀。为了减少焦虑并防止其后遗症， 患者必须得到有效的早期治疗;然而，一线干预，认知行为疗法（CBT）， 异质性反应，40-60%的治疗患者继续经历残留 症状CBT结果变异的原因仍然知之甚少，但个体（包括 CBT的大脑行为目标的差异可能起作用。该提案涉及两个 基本和开放性问题：1）CBT相关脑行为功能的个体差异是否导致 CBT结果的差异吗（2）发育是否对这种变异有贡献？通过定义维度 在多个层次的分析结构，NIMH的RDoC提供了一个框架，用于识别患者特异性 CBT结果的机制，在传统的，分类焦虑症。的RDoC结构 认知控制（CC），急性威胁（AT）及其相互作用（CC-AT）塑造了假定的大脑选择- CBT的行为目标为拟议的研究。鉴于CBT有助于控制急性威胁， 有效调控，我们假设AT-，CC-和AT-CC-定义的标志物将预测和表征 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， 与早期脑反应性增加相比，认知控制的神经基质发育较晚， 威胁，我们假设AT，CC，CC-AT标记物将与CBT效应差异相关，这取决于患者 年龄这些假设将通过测量多个层次的分析数据进行测试：大脑功能-结构 (fMRI，DTI）和行为表现指数在AT，CC和CC-AT结构，和临床措施， 280名年轻人的焦虑其中，210名患有损害性焦虑的青少年将随机接受CBT或 放松控制治疗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，使机械理解如何不同 不同年龄段的患者从CBT中受益。

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.