Treatment Development Targeting Positive Affect Function in Adolescent Depression

针对青少年抑郁症积极情感功能的治疗开发

• 批准号: 8769167
• 负责人: DANA L MCMAKIN
• 金额: $ 7.66万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-12-10 至 2015-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8769167
• 关键词: Adherence; Adolescence; Adolescent; Affect; Affective; Age; Anhedonia; Area; Behavior assessment; Behavioral; Behavioral Mechanisms; Benchmarking; Brain; Child; Childhood; Chronic; Clinical; Clinical Psychology; Cognitive Therapy; Complement; Corpus striatum structure; Depressed mood; Development; Disease remission; Educational process of instructing; Emotions; Environment; Event; Exposure to; Feeling; Future; Goals; Grouping; Health; Impairment; Individual; Intervention; K-Series Research Career Programs; Learning Module; Manuals; Measures; Mental Depression; Mentors; Methods; Mood Disorders; Morbidity - disease rate; Motivation; Neuronal Plasticity; Participant; Pathway interactions; Patient Self-Report; Play; Positioning Attribute; Positive Reinforcements; Productivity; Protocols documentation; Psychological reinforcement; Puberty; Randomized; Randomized Controlled Trials; Recording of previous events; Recurrence; Relative (related person); Research; Research Personnel; Research Support; Research Training; Rewards; Role; Scientific Advances and Accomplishments; Signal Transduction; Suicide attempt; Symptoms; System; Testing; Time; Training; Translating; Universities; Work; Youth; accomplished suicide; affective neuroscience; base; brain behavior; career; child depression; clinical practice; cognitive control; comparison group; depressive symptoms; design; developmental plasticity; disability; early onset; effective therapy; experience; improved; indexing; innovation; insight; mortality; neural circuit; neuroimaging; novel; novel strategies; patient oriented; positive emotional state; psychosocial; relating to nervous system; satisfaction; skills; statistics; targeted treatment; theories; therapy development; treatment response; treatment trial; university student

DESCRIPTION (provided by applicant): Rates of depression rise sharply during adolescence, becoming a leading cause of lifetime disability with high rates of recurrence and chronic impairment. Despite progress in efficacious treatments, only 50% of treated adolescents attain sustained remission. Recent insights from developmental affective neuroscience suggest that there may be windows of brain plasticity during adolescence when certain skills for effectively managing affect (emotions and motivations) may best be acquired. To this end, the candidate's long term career objective is to develop more effective treatments for affective disorders among youth by utilizing a developmental affective neuroscience framework to guide this effort. The candidate's immediate focus is to target positive affective functioning among adolescents with depression, and to investigate growing evidence that adolescence may be an opportune maturational period for intervention. Normative remodeling of key neural substrates of positive affect and reward systems at puberty plays a role in the development of depression during adolescence. These changes may signal a relatively sensitive period (surrounding pubertal maturation) when practicing key skills for managing positive affect may have an enduring impact on brain-behavior mechanisms of depression. The current Mentored Patient Oriented Career Development Award will uniquely position the candidate to advance this agenda. Her background includes specialized training in child clinical psychology, treatment development for adolescent depression, psychosocial approaches to affective functioning, basic multivariate statistics, and a broad exposure to the basics of developmental affective neuroscience. To most effectively bridge developmental affective neuroscience with treatment innovation she seeks to deepen and extend her training to include: 1) a more intricate understanding of brain-behavior theories of positive affective functioning, particularly as they relate to the development of depression, 2) advanced statistics and methods for examining brain-behavior mechanisms in the context of pediatric treatment trials, and 3) strategies for treatment development that translate these brain-behavior theories and methods to clinical practice. The University of Pittsburgh is an outstanding environment in which to engage in the interdisciplinary training required to achieve these training goals. The candidate's mentors-David Brent, Ronald Dahl and Greg Siegle-have combined expertise in adolescent depression and treatment development, neuro-developmental pathways to affective disorders, and multi-method approaches to measuring brain-behavior mechanisms of treatment response. In addition to their individual productivity and strong mentoring histories, this team of investigators has collaborated on large-scale, interdisciplinary projects to advance the scientific understanding and treatment of affective disorders among youth. The proposed project draws on this training and expertise to develop a treatment module (6 sessions) for improving features of positive affective functioning among adolescents with depression. The Positive Affect Stimulation and Sustainment [PASS] module teaches strategies for sustaining positive affective states, with the goal of strengthening key neural circuitry during this period of developmental plasticity. Relative deficits in features of positive affective functioning are central to the development and clinical course of depression; yet, few treatments target these deficits. Behavioral activation increases exposure and reinforcement related to pleasant events, but emerging evidence suggests that affective states quickly fade for depressed individuals following positive experiences. As such, PASS may augment behavioral activation by extending affective experiences. The candidate's prior research supports the feasibility of PASS, as well as changes in subjective positive emotion and depressive symptoms. The current study proposes to extend this work with a randomized controlled trial (RCT) in which adolescents with depression (n=60; ages 12-17) will be randomized to PASS or Cognitive Therapy (a comparison treatment that does not target positive affective functioning) for 6 weeks. Participants will complete self report and behavioral assessments of targeted mechanisms and symptoms, and 34 participants will complete neuroimaging tasks designed to elicit positive affect and activate underlying neural circuitry (e.g. fronto-mesolimbic circuits). The primary goals of the current trial include: 1) establish feasibility and acceptability of PASS, 2) employ a multi-method approach to measure PASS related change in targeted mechanisms, and 3) explore PASS-related changes in sustainability and connectivity in key circuits within the fronto-mesolimbic network. All of these goals will inform iterative refinements of the manual, and will generate more specific hypotheses and methods for a future, large-scale RCT. Based on the results of this work, future trials may, e.g., include an augmentation design to determine if PASS adds value above and beyond behavioral activation, and may test hypotheses regarding opportune developmental windows (e.g. early vs. mid puberty) for the treatment approach.

描述（由申请人提供）：青春期抑郁症率急剧上升，成为终身残疾的主要原因，复发率高和慢性障碍。尽管有效治疗方面取得了进展，但只有50％的经过治疗的青少年可以持续缓解。发育情感神经科学的最新见解表明，在某些有效管理情感（情感和动机）的技能上，可能会在青春期中有大脑可塑性的窗口。为此，候选人的长期职业目标是通过利用发展性情感神经科学框架来指导这项工作，以为青年人之间的情感障碍开发更有效的治疗方法。候选人的直接重点是针对抑郁症的青少年的积极情感功能，并调查日益证据表明青春期可能是干预的适当成熟时期。青春期积极影响和奖励系统的关键神经基质的规范重塑在青春期的抑郁发展中起作用。这些变化可能标志着相对敏感的时期（周围的青春期成熟），而练习关键技能来管理积极影响可能会对抑郁症的脑行为机制产生持久的影响。目前的以患者为导向的职业发展奖将独特地定位候选人提高这一议程。她的背景包括儿童临床心理学的专门培训，青少年抑郁症的治疗发展，情感功能的心理社会方法，基本的多元统计以及广泛的发展情感神经科学基础知识。最有效地将发展性情感神经科学桥接通过治疗创新，她试图加深并扩展培训以包括：1）对脑部行为的积极情感功能的更为复杂的理解，尤其是当它们与抑郁症的发展相关时，2）在小儿治疗试验背景下检查脑行为机制的统计和方法，以及3）将这些脑行为理论和方法转化为临床实践的治疗发展策略。匹兹堡大学是一个杰出的环境，可以在其中进行实现这些培训目标所需的跨学科培训。候选人的导师戴维·布伦特（David Brent），罗纳德·达尔（Ronald Dahl）和格雷格（Greg Siegle）在青少年抑郁症和治疗发展方面的联合专业知识，情感障碍的神经发展途径以及测量治疗反应的大脑行为机制的多方法方法。除了他们的个人生产力和强大的指导历史外，该研究人员还合作开展了大规模的跨学科项目，以促进对年轻人情感障碍的科学理解和治疗。拟议的项目借鉴了此培训和专业知识，以开发一个治疗模块（6个课程），以改善抑郁症青少年的积极情感功能的特征。积极的影响刺激和维持[PASS]模块教授维持积极情感状态的策略，目的是在这一发展可塑性期间加强关键的神经回路。积极情感功能的特征的相对缺陷对于抑郁症的发展和临床过程至关重要。但是，很少有治疗方法针对这些缺陷。行为激活增加了与愉快事件相关的暴露和加强，但是新出现的证据表明，在积极的经历下，情感状态迅速消失了沮丧的个体。因此，通行证可以通过扩展情感体验来增强行为激活。候选人的先前研究支持通过的可行性，以及主观积极情绪和抑郁症状的变化。当前的研究建议通过随机对照试验（RCT）扩展这项工作，其中抑郁症的青少年（n = 60; 12-17岁）将被随机通过或认知疗法（一种不能靶向阳性情感功能的比较治疗）持续6周。参与者将完成针对目标机制和症状的自我报告和行为评估，34位参与者将完成旨在引起积极影响并激活潜在神经回路的神经影像学任务（例如，额 - 塞罗梅比克电路）。当前试验的主要目标包括：1）确定通行证的可行性和可接受性，2）采用多方法方法来衡量目标机制的通过相关变化； 3）探索关键电路中可持续性和连通性的通行证相关变化在额叶 - 溶胶网络中。所有这些目标都将为手册的迭代改进提供信息，并为未来的大规模RCT产生更具体的假设和方法。根据这项工作的结果，例如，未来的试验可能包括增强设计，以确定Pass是否增加了超过行为激活的价值，并且可以测试有关适当发育窗口的假设（例如，早期与中期青春期） 。