Multi-level Mechanisms of Behavioral Activation Therapy for Adolescent Depression

项目概要/摘要 重性抑郁症（MDD）是一种严重的临床疾病，是导致残疾的主要原因 国际吧青春期是一个关键的发展时期，在此期间，抑郁症的发展风险是 最棒的行为激活（BA）心理治疗已成为青少年的一线治疗方法 抑郁症，但介导治疗效果的潜在神经生物学机制仍不清楚。 理解这些靶机制是开发BA新适应的基础， 与BA的其他治疗，并设计新的干预措施，通过更好地理解神经靶点 机制等在当前的应用中，我们寻求识别介导治疗的神经机制 在BA治疗青少年抑郁症期间的反应。重要的是，避免行为的减少， 成功的BA治疗可以通过操作多个神经靶点来实现， 个体之间和/或个体内部的时间尺度。在青少年的横断面神经影像学研究中， 抑郁症，最常见的标志是腹侧纹状体（VS）对奖励线索的低反应， 腹内侧前额叶皮层（vmPFC）和杏仁核和大脑皮层对负面信息的过度反应。 显著性网络--包括前扣带回和背侧前扣带回。这些模式 低反应区和高反应区可以独立地或共同地通过神经元促进行为回避。 RDoC的概念，减少奖励和威胁避免的动机分别。因此，更全面的 要理解BA的目标参与，需要多项评估，将行为轨迹 在治疗过程中，症状随着这些神经回路的变化轨迹而变化， to just pre前/post后comparisons比较.为了解决这些问题，我们建议获得生态瞬间 在96名抑郁青少年的样本中， 完成16周的BA治疗三个基于任务的功能磁共振成像扫描将在基线和之后进行。 会议7和16，并将包括一套范式，重点是评估行为回避， 金钱和社会奖励。此外，两个简短的“行为调度扫描仪”会议将在 疗程3和9，在此期间，患者和治疗师将参与BA治疗的组成部分，而 患者接受功能磁共振成像扫描。这种“行为扫描仪”协议将使我们能够更好地 确定心理治疗期间目标参与的基于任务的测量的生态有效性。采取 总之，这些数据将有助于理解BA减少回避的神经机制 行为，从而治疗抑郁症，此外，这些数据将建立一个平台， BA技术的改进和/或基于可识别的神经靶点的新治疗。

Project Summary/Abstract Major Depressive Disorder (MDD) is a devastating clinical disorder and the leading cause of disability worldwide. Adolescence is a key developmental period during which risk for the development of depression is greatest. Behavioral Activation (BA) psychotherapy has emerged as a first-line treatment for adolescent depression, yet the underlying neurobiological mechanisms that mediate treatment efficacy remain unclear. Understanding these target mechanisms is fundamental to developing novel adaptations of BA, augmenting other treatments with BA, and designing new interventions informed by greater comprehension of neural target mechanisms. In the current application, we seek to identify the neural mechanisms that mediate treatment response during BA therapy for adolescent depression. Critically, reductions in avoidance behavior and successful BA treatment may occur through manipulation of multiple neural targets operating on different timescales between and/or within individuals. In cross-sectional neuroimaging studies of adolescent depression, the most common markers are hypo-responding to reward cues in the ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC) and hyper-responding to negative information in the amygdala and the salience network–comprising the anterior insula (aI) and dorsal anterior cingulate (dACC). These patterns of hypo- and hyper-responding regions may independently or jointly contribute to behavioral avoidance by the RDoC concepts of reduced motivation for rewards and threat avoidance, respectively. Consequently, a fuller understanding of target engagement for BA requires multiple assessments linking trajectories of behavioral and symptom change with trajectories of change in these neural circuits over the course of therapy as opposed to just pre/post comparisons. To address these concerns, we propose to acquire ecological momentary assessment (EMA) and longitudinal neuroimaging data in a sample of 96 depressed adolescents while they complete a 16-week course of BA therapy. Three task-based fMRI scans will occur at baseline and after sessions 7 and 16, and will include a set of paradigms focused on assessing behavioral avoidance for monetary and social rewards. In addition, two brief “behavioral-scheduling-in-scanner” sessions will occur at sessions 3 and 9 during which the patient and therapist will engage in a component of BA therapy while the patient undergoes an fMRI scan. This “behavioral-secheduling-in-scanner” protocol will allow us to better determine the ecological validity of task-based measures of target engagement during psychotherapy. Taken together, these data will enable understanding of the neural mechanisms through which BA reduces avoidance behavior and thereby treats depression, Further, these data will establish a platform for developing future modifications of BA techniques and/or novel treatments based on identifiable neural targets.