Multi-level Mechanisms of Behavioral Activation Therapy for Adolescent Depression

项目摘要/摘要 严重抑郁障碍(MDD)是一种破坏性的临床疾病，也是导致残疾的主要原因 全世界。青春期是一个关键的发育期，在这一时期，抑郁症的发展风险 太棒了。行为激活(BA)心理疗法已成为青少年的一线治疗方法 抑郁症，但调节治疗效果的潜在神经生物学机制仍不清楚。 了解这些靶向机制对于开发BA的新适应、增强 BA的其他治疗，并设计新的干预措施，以更好地理解神经靶点 机械装置。在目前的应用中，我们试图确定调节治疗的神经机制。 BA治疗青春期抑郁症的反应。至关重要的是，回避行为的减少和 成功的BA治疗可以通过操作不同的神经靶点来实现 个人之间和/或个人内部的时间尺度。在青少年的横断面神经影像研究中 抑郁，最常见的标志是腹侧纹状体(VS)和 杏仁核腹内侧前额叶皮质(VmPFC)和对负面信息的高反应 突起网络--由前岛(Ai)和背侧前扣带(DACC)组成。这些模式 低反应区和高反应区可能独立地或联合地通过 RDoC的概念分别是减少奖励和威胁规避的动机。因此，一个更饱满的 了解BA的目标参与度需要进行多项评估，将行为轨迹与 与治疗过程中这些神经回路的变化轨迹相对应的症状变化 只进行前/后比较。为了解决这些问题，我们建议获取生态瞬间 对96名抑郁青少年进行评估(EMA)和纵向神经影像检查 完成为期16周的BA治疗。三次基于任务的fMRI扫描将在基线及之后进行 会议7和16，并将包括一套范例，重点评估行为回避 金钱和社会回报。此外，还将在以下时间举行两次简短的“扫描仪中行为调度”会议 会议3和9，在此期间，患者和治疗师将参与BA治疗的一个组成部分，而 病人接受功能核磁共振扫描。这一“扫描中的行为安全”协议将使我们能够更好地 确定心理治疗期间基于任务的目标投入措施的生态有效性。已被占用 总而言之，这些数据将有助于理解BA减少回避的神经机制 从而治疗抑郁症，进一步，这些数据将为未来的发展建立一个平台 基于可识别的神经靶点的BA技术的修改和/或新的治疗。

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.