Examining Reward-Related Predictors and Mechanisms of Change in BA Treatment for Anhedonic Adolescents

检查快感缺失青少年 BA 治疗中与奖励相关的预测因子和变化机制

• 批准号: 9566296
• 负责人: Christian Anthony Webb
• 金额: $ 19.05万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-25 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9566296
• 关键词: Adolescence; Adolescent; Adult; Affect; Aftercare; Age; Anhedonia; Area; Award; Behavior; Behavioral; Behavioral Mechanisms; Brain; Childhood; Clinical; Clinical Investigator; Cognitive Therapy; Competence; Consultations; Corpus striatum structure; Data; Depressed mood; Development; Disease; Dorsal; Ecological momentary assessment; Exhibits; Exposure to; Fellowship; Foundations; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Grain; Growth; Guidelines; Health Sciences; Health Technology; Hospitals; Image; Individual; Institutes; Intervention; Intervention Studies; Investigational Therapies; Knowledge; Lead; Light; Link; Magnetic Resonance Imaging; Maintenance; Major Depressive Disorder; Massachusetts; Measures; Medial; Medicine; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methodology; Modeling; National Institute of Mental Health; Neural Pathways; Neuroanatomy; Nucleus Accumbens; Participant; Patient Recruitments; Patient Self-Report; Patients; Play; Positive Valence; Prediction of Response to Therapy; Prefrontal Cortex; Prevalence; Protocols documentation; Reporting; Research; Research Domain Criteria; Research Methodology; Research Personnel; Research Training; Rewards; Risk; Role; Sampling; Stimulus; Sum; Supervision; Symptoms; System; Targeted Research; Task Performances; Technology; Teenagers; Testing; Training; Treatment outcome; Visit; Youth; authority; base; behavior measurement; behavioral clinical trial; behavioral health; child depression; depressive symptoms; design; experience; improved; innovation; meetings; neural circuit; neuroimaging; neuromechanism; pleasure; programs; psychosocial; public health relevance; putamen; recruit; reduce symptoms; relapse risk; relating to nervous system; response; reward circuitry; reward processing; single episode major depressive disorder; skills; symptomatic improvement; tool

 DESCRIPTION (provided by applicant): The prevalence of major depressive disorder (MDD) is relatively low in childhood (i.e., 1-3%), but increases substantially during adolescence. By the age of 18, approximately 15% of adolescents will have experienced at least one episode of MDD. A growing body of research implicates abnormalities in reward circuitry as playing a critical role in the development and maintenance of depressive symptoms in adolescents. Importantly, these reward-circuitry abnormalities have been linked to anhedonia (i.e., decreased pleasure or blunted reactivity to rewarding stimuli). Behavioral Activation (BA) represents a promising - and relatively simple to deliver - nonpharmacologic intervention for adolescent depression, which has been shown to be at least as effective as Cognitive Behavioral Therapy (CBT) with regards to symptom reduction and lowering the risk of relapse in adult samples. More recently, promising data have emerged from the application of BA to depressed adolescents. BA can be conceptualized as a treatment directly targeting anhedonia. More specifically, BA targets anhedonia through behavioral change strategies aimed at gradually increasing patients' exposure to and engagement with rewarding stimuli and positively reinforcing experiences. Given this treatment focus, BA may be particularly beneficial for adolescents struggling with relatively elevated levels of anhedonic symptoms. Accordingly, the present study will examine the role of anhedonia and reward functioning in predicting treatment response in BA. In addition, analyses will be conducted examining the reward-related neural and behavioral mechanisms underlying anhedonic symptom improvement in BA. To test hypotheses, this study integrates assessments of reward functioning from three units of analysis: 1) neural circuits (i.e., via a functional magnetic resonance imaging [fMRI] monetary reward task probing neural reward- circuitry functioning), 2) behavioral (i.e., with a probabilisti reward task [PRT] designed to objectively probe anhedonic behavior) and 3) self-report (i.e., Snaith-Hamilton Pleasure Scale [SHAPS] and Ecological Momentary Assessment [EMA]). In addition to the proposed research, the four-year K23 Award will allow the candidate to develop competency in three complementary areas. First, participants will undergo fMRI at pre- and post-treatment while completing a monetary reward task probing reward-circuitry functioning. Dr. Diego Pizzagalli (mentor), a leader in the use of fMRI to investigate the pathophysiology of depression and anhedonia, and Dr. Blaise Frederick (consultant), lead physicist at the McLean Imaging Center, will provide critical training in the acquisition, processing, and analysis of fMRI data. This training will allow the candidate to develop the skills necessary to integrate functiona neuroimaging into his depression treatment research program to more deeply probe the underlying neural mechanisms of symptom improvement. Individual mentorship and hands-on training will be supplemented by coursework in fMRI methodology, including 1) the Functional MRI Visiting Fellowship, an fMRI course offered through the Athinoula A. Martinos Center at the Harvard-Massachusetts Institute of Technology (MIT) Division of Health Sciences & Technology (HST); 2) MATLAB for Medicine offered through MIT/HST; 3) SPM8 for Basic and Clinical Investigators at MIT; and 4) Structural and Functional Brain Connectivity via MRI and fMRI offered through the Martinos Center. Second, to obtain a more fine- grained and naturalistic assessment of symptom change and the extent to which adolescents acquire and utilize the skills encouraged in BA, the applicant will receive training in Ecological Momentary Assessment (EMA) from Dr. Erika Forbes (co-mentor), a pioneer in the use of EMA with depressed and healthy adolescents. Dr. Garret Fitzmaurice (consultant) will provide statistical consultation in Growth Curve Modeling to test the longitudinal psychosocial (EMA) and neural (fMRI) hypothesis proposed in the project. Finally, the proposed training plan would allow the candidate to substantially deepen his understanding of the functional neuroanatomy of adolescent depression, with a particular focus on the neural circuitry subserving reward processing and anhedonia (Drs. Pizzagalli & Forbes). Clinical consultation and supervision will be obtained through meetings with Drs. Sona Dimidjian (consultant), a leading authority in BA, and Thröstur Björgvinsson (consultant), Director of the Behavioral Health Partial Program at McLean Hospital. Collectively, the proposed research and training will provide the applicant with a strong foundation in fMRI and EMA, and may yield important findings regarding the reward-related pretreatment predictors and mechanisms of symptom improvement in anhedonic and depressed youth. Upon completion of the project, the candidate will be optimally prepared to pursue an innovative research program integrating neural, behavioral and psychosocial research methods to answer these important questions. In sum, this award would allow the candidate to transition into a well-rounded and independent researcher armed with an array of complementary and cutting-edge assessment and neuro-investigative tools for the study of depression in youth.

 描述（由申请人提供）： 重度抑郁症 (MDD) 的患病率在儿童期相对较低（即 1-3%），但在青春期显着增加。 18 岁时，大约 15% 的青少年至少经历过一次 MDD。越来越多的研究表明，奖赏回路异常在青少年抑郁症状的发展和维持中发挥着关键作用。神经回路异常与快感缺失（即，对奖励刺激的愉悦感降低或反应迟钝）有关，行为激活 (BA) 是一种很有前途且相对简单的非药物疗法。青少年抑郁症的干预措施已被证明在减轻症状和降低成人样本复发风险方面至少与认知行为疗法（CBT）一样有效。最近，从 BA 的应用中得出了有希望的数据。 BA 可以被概念化为一种直接针对快感缺失的治疗方法，更具体地说，BA 通过旨在逐渐增加患者接触和参与奖励性刺激和积极强化体验的策略来针对行为快感缺失。特别有益因此，本研究将研究快感缺失和奖励功能在预测 BA 治疗反应中的作用。此外，还将进行分析，检查快感缺失背后的奖励相关神经和行为机制。为了检验假设，本研究整合了三个分析单元的奖励功能评估：1）神经回路（即通过功能性磁共振成像 [fMRI] 金钱奖励任务探测神经奖励回路）功能），2）行为（即，旨在客观地探究快感缺乏行为的概率奖励任务 [PRT]）和 3）自我报告（即，斯奈斯-汉密尔顿快乐量表 [SHAPS] 和生态瞬时评估 [EMA]）。除了拟议的研究之外，为期四年的 K23 奖还将允许候选人发展三个互补领域的能力。首先，参与者将在术前和术后接受功能磁共振成像（fMRI）。治疗后，同时完成探索奖励电路功能的金钱奖励任务。Diego Pizzagalli 博士（导师）是使用功能磁共振成像研究抑郁症和快感缺失病理生理学的领导者，Blaise Frederick 博士（顾问）是首席物理学家。在麦克莱恩成像中心，将提供功能磁共振成像采集、处理和分析方面的关键培训 该培训将使候选人能够发展将功能性神经影像学整合到其抑郁症治疗研究计划中所需的技能，以更深入地探讨症状改善的潜在神经机制。 导师个人和实践培训将通过功能磁共振成像方法学课程进行补充。 ，包括 1) 功能 MRI 访问奖学金，这是由哈佛 - 麻省理工学院 (MIT) 健康科学与技术 (HST) 部门 Athinoula A. Martinos 中心提供的功能 MRI 课程； 2）通过 MIT/HST 提供的 MATLAB for Medicine；3）为 MIT 的基础和临床研究人员提供的 SPM8；以及 4）通过 Martinos 中心提供的通过 MRI 和 fMRI 实现的结构和功能性大脑连接。症状变化的自然评估以及青少年获得和利用 BA 鼓励的技能的程度，申请人将接受 Erika Forbes 博士的生态瞬时评估 (EMA) 培训Garret Fitzmaurice 博士（共同导师）是在抑郁和健康青少年中使用 EMA 的先驱，他将提供生长曲线建模方面的统计咨询，以测试纵向社会心理 (EMA) 和神经 (fMRI) 提出的假设。最后，拟议的培训计划将使候选人能够大大加深对青少年抑郁症功能神经解剖学的理解，特别关注支持奖励处理和快感缺失的神经回路（Drs. Pizzagalli & Forbes）将通过与 BA 权威 Sona Dimidjian 博士（顾问）和 McLean 医院行为健康部分项目主任 Thröstur Björgvinsson（顾问）的会面获得临床咨询和监督。拟议的研究和培训将为申请人提供 fMRI 和 EMA 方面的坚实基础，并可能在与奖励相关的治疗前预测因素和快感缺失和症状改善机制方面产生重要发现。项目完成后，候选人将做好充分准备，开展一项整合神经、行为和心理社会研究方法的创新研究项目，以回答这些重要问题。总之，该奖项将使候选人能够转变为一个良好的人。全面而独立的研究人员配备了一系列补充和尖端的评估和神经研究工具，用于研究青少年抑郁症。