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）：抑郁症的发病率在青春期急剧上升，成为终身残疾的主要原因，复发率高，慢性损伤。尽管在有效治疗方面取得了进展，但只有50%的治疗青少年获得持续缓解。发展情感神经科学的最新见解表明，在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通过利用发展情感神经科学框架来指导这一努力，开发更有效的青少年情感障碍治疗方法。 候选人的直接重点是针对青少年抑郁症的积极情感功能，并调查越来越多的证据表明，青春期可能是一个适当的成熟期进行干预。青春期积极情感和奖励系统的关键神经基质的规范重塑在青春期抑郁症的发展中起着重要作用。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），练习管理积极情绪的关键技能可能对抑郁症的大脑行为机制产生持久的影响。 目前指导病人导向的职业发展奖将独特的定位候选人推进这一议程。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，特别是当它们与抑郁症的发展有关时，2）在儿科治疗试验的背景下检查大脑行为机制的先进统计和方法，以及3）将这些脑行为理论和方法转化为临床实践的治疗开发策略。匹兹堡大学是从事实现这些培训目标所需的跨学科培训的优秀环境。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的专业知识。除了他们的个人生产力和强大的指导历史，这支调查团队还合作开展了大规模的跨学科项目，以促进对青年情感障碍的科学理解和治疗。 拟议的项目利用这一培训和专门知识，开发一个治疗模块（6次会议），以改善青少年抑郁症患者的积极情感功能。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，目标是在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是抑郁症发展和临床过程的核心;然而，很少有治疗针对这些缺陷。行为激活增加了与愉快事件相关的暴露和强化，但新出现的证据表明，抑郁症患者在经历积极的经历后，情感状态会迅速消退。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随机对照试验（RCT）扩展这项工作，其中患有抑郁症的青少年（n=60;年龄12-17）将被随机分配到PASS或认知疗法（一种不针对积极情感功能的比较治疗）6周。参与者将完成自我报告和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和激活潜在神经回路（例如额叶-中脑边缘回路）的神经成像任务。本试验的主要目标包括：1）确定PASS的可行性和可接受性，2）采用多方法方法测量PASS相关的靶向机制变化，3）探索PASS相关的额-中边缘网络关键回路的可持续性和连通性变化。所有这些目标将为手册的迭代改进提供信息，并将为未来的大规模RCT产生更具体的假设和方法。根据这项工作的结果，未来的试验可能，例如，包括增强设计，以确定PASS是否在行为激活之上和之外增加价值，并且可以测试关于治疗方法的适当发育窗口（例如，青春期早期与青春期中期）的假设。 公共卫生相关性：抑郁症的发病率在青春期急剧上升，成为终身残疾的主要原因，复发率和慢性损伤率很高。尽管在有效治疗方面取得了进展，但只有50%的治疗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缓解即时症状，而且还可以降低死亡率，并改变一生中的发病率和健康状况。