Multi-level Mechanisms of Behavioral Activation Therapy for Adolescent Depression

青少年抑郁症行为激活疗法的多层次机制

• 批准号: 10453989
• 负责人: W. EDWARD CRAIGHEAD
• 金额: $ 78.22万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-03 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10453989
• 关键词: Address; Adolescence; Adolescent; Adolescent Development; Age; Amygdaloid structure; Anterior; Behavior Therapy; Behavioral; Behavioral Mechanisms; Behavioral Symptoms; Biological Markers; Chronic; Clinical; Comprehension; Corpus striatum structure; Cues; Data; Decision Making; Detection; Development; Disease; Dorsal; Ecological momentary assessment; Emotions; Functional Magnetic Resonance Imaging; Future; Goals; Grant; Image; Individual; Insula of Reil; Intervention; Investigational Therapies; Knowledge; Link; Major Depressive Disorder; Measures; Mediating; Mediation; Mental Depression; Modeling; Modification; Monitor; Motivation; Participant; Patients; Pattern; Population; Prefrontal Cortex; Protocols documentation; Psychotherapy; Public Health; Research Domain Criteria; Rest; Rewards; Risk; Sampling; Scanning; Schedule; Severities; Techniques; Testing; Therapeutic Effect; Therapeutic Human Experimentation; Therapeutic Intervention; Treatment Efficacy; Ventral Striatum; Waiting Lists; avoidance behavior; base; child depression; contrast imaging; depressive symptoms; design; disability; effective therapy; efficacious treatment; functional MRI scan; imaging study; insight; interest; negative emotional state; neural circuit; neurobiological mechanism; neuroimaging; neuromechanism; novel; positive emotional state; precision medicine; relating to nervous system; response; reward anticipation; social; targeted treatment; therapy development; treatment response

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.

项目摘要/摘要 重度抑郁症（MDD）是一种毁灭性的临床疾病，是残疾的主要原因 全世界。青少年是一个关键的发展时期，在此期间，抑郁症的发展风险是 最伟大。行为激活（BA）心理治疗已成为青少年的一线治疗 抑郁症，但是介导治疗效率的基本神经生物学机制尚不清楚。 了解这些目标机制对于开发新型BA的适应至关重要，增强 通过BA的其他治疗方法，并通过对神经目标的更大理解来设计新的干预措施 机制。在当前的应用中，我们试图确定介导治疗的神经机制 在BA治疗期间对青少年抑郁症的反应。至关重要的是，回避行为的减少和 成功的BA治疗可能是通过操纵在不同的多个神经靶标而发生的 个人之间和/或内部之间的时间表。在青少年的横断面神经影像研究中 抑郁症，最常见的标志物是响应性的，以奖励腹侧纹状体的提示（VS）和 腹前额叶皮层（VMPFC）和杏仁核中的负面信息过度响应 显着性网络 - 构成前岛（AI）和背扣带回（DACC）。这些模式 低反应区域可能会独立或共同促进行为避免行为。 RDOC分别减少了奖励和避免威胁的动机的概念。因此，更饱满 了解BA的目标参与需要进行多次评估，将行为轨迹链接起来 在治疗过程中，这些神经回路的变化轨迹变化，症状改变 仅预先/后比较。为了解决这些问题，我们建议获得生态瞬间 评估（EMA）和纵向神经影像学数据在96个抑郁症的青少年样本中 完成16周的BA治疗课程。基线和之后将进行三种基于任务的fMRI扫描 会议第7和16会议，并将包括一组专注于评估行为避免行为的范例 货币和社会奖励。此外，将在 第3和第9课，在此期间，患者和治疗师将参与BA治疗的组成部分 患者接受功能磁共振成像扫描。这个“行为扫描仪的行为仪”协议将使我们能够更好 确定心理治疗期间基于任务的目标参与度量的生态有效性。拍摄 这些数据将共同理解BA避免的神经机制 行为，从而治疗抑郁症，此外，这些数据将建立一个平台，以发展未来 基于可识别神经元靶标的BA技术和/或新型治疗方法的修改。