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: 8028508
• 负责人: DANA L MCMAKIN
• 金额: $ 14.12万
• 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 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8028508
• 关键词: Adherence; Adolescence; Adolescent; Affect; Affective; Age; Anhedonia; Area; Behavior assessment; Behavioral; 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; Impairment; Individual; Intervention; K-Series Research Career Programs; 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; 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; 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. PUBLIC HEALTH RELEVANCE: 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. By developing novel approaches for intervening during key periods of development and brain maturation, the proposed research and training carries potential not only to alleviate immediate symptoms, but also to reduce mortality, and alter morbidity and well being across the lifetime.

描述（由申请人提供）：青春期抑郁症发病率急剧上升，成为导致终生残疾的主要原因，且复发率和慢性损伤率很高。尽管有效治疗取得了进展，但只有 50% 的接受治疗的青少年获得持续缓解。发展情感神经科学的最新见解表明，青春期可能存在大脑可塑性的窗口，此时可以最好地获得有效管理情感（情绪和动机）的某些技能。为此，候选人的长期职业目标是利用发展情感神经科学框架来指导这一工作，为青少年情感障碍开发更有效的治疗方法。 候选人的当前重点是针对患有抑郁症的青少年的积极情感功能，并调查越来越多的证据表明青春期可能是干预的合适成熟期。青春期积极情感和奖励系统的关键神经基质的规范性重塑在青春期抑郁症的发展中发挥着作用。这些变化可能标志着一个相对敏感的时期（青春期成熟前后），此时练习管理积极情绪的关键技能可能会对抑郁症的大脑行为机制产生持久影响。 当前的“以病人为导向的指导职业发展奖”将为候选人提供独特的优势来推进这一议程。她的背景包括儿童临床心理学的专业培训、青少年抑郁症的治疗开发、情感功能的心理社会方法、基本的多元统计以及广泛接触发展情感神经科学的基础知识。为了最有效地将发展情感神经科学与治疗创新联系起来，她寻求深化和扩展她的培训，包括：1）对积极情感功能的大脑行为理论有更复杂的理解，特别是与抑郁症发展相关的理论，2）高级在儿科治疗试验中检查大脑行为机制的统计数据和方法，以及3）将这些大脑行为理论和方法转化为临床实践的治疗开发策略。匹兹堡大学是进行实现这些培训目标所需的跨学科培训的绝佳环境。候选人的导师——大卫·布伦特、罗纳德·达尔和格雷格·西格尔——结合了青少年抑郁症和治疗开发、情感障碍的神经发育途径以及测量治疗反应的大脑行为机制的多方法方面的专业知识。除了个人生产力和强大的指导历史之外，该研究团队还合作开展了大规模的跨学科项目，以促进对青少年情感障碍的科学理解和治疗。 拟议的项目利用这种培训和专业知识来开发一个治疗模块（6 个疗程），以改善抑郁症青少年的积极情感功能特征。积极情感刺激和维持 [PASS] 模块教授维持积极情感状态的策略，其目标是在这一发育可塑性时期加强关键神经回路。积极情感功能特征的相对缺陷对于抑郁症的发展和临床过程至关重要。然而，很少有治疗方法能够针对这些缺陷。行为激活会增加与愉快事件相关的接触和强化，但新出现的证据表明，抑郁症患者在经历积极经历后，情感状态会迅速消失。因此，PASS 可以通过扩展情感体验来增强行为激活。候选人之前的研究支持 PASS 的可行性，以及主观积极情绪和抑郁症状的变化。目前的研究建议通过一项随机对照试验 (RCT) 来扩展这项工作，其中患有抑郁症的青少年（n=60；年龄 12-17 岁）将被随机分配接受 PASS 或认知疗法（一种不针对积极情感功能的比较治疗） ）持续 6 周。参与者将完成自我报告和针对目标机制和症状的行为评估，34 名参与者将完成旨在引发积极影响并激活潜在神经回路（例如额中脑边缘回路）的神经影像学任务。当前试验的主要目标包括：1）建立 PASS 的可行性和可接受性，2）采用多种方法来衡量目标机制中与 PASS 相关的变化，以及 3）探索关键电路中与 PASS 相关的可持续性和连通性变化在额中脑边缘网络内。所有这些目标都将为手册的迭代完善提供信息，并将为未来的大规模随机对照试验产生更具体的假设和方法。根据这项工作的结果，未来的试验可能包括增强设计，以确定 PASS 是否增加了行为激活之外的价值，并可能测试有关治疗方法的适当发育窗口（例如青春期早期与中期）的假设。 公共健康相关性：青春期抑郁症发病率急剧上升，成为导致终生残疾的主要原因，且复发率和慢性损伤率很高。尽管有效治疗取得了进展，但只有 50% 的接受治疗的青少年获得持续缓解。通过开发在发育和大脑成熟的关键时期进行干预的新方法，拟议的研究和培训不仅有可能减轻直接症状，而且有可能降低死亡率，并改变一生中的发病率和福祉。