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（由适用提供）：重度抑郁症（MDD）的患病率相对较低（即1-3％），但在青少年期间大幅增加。由 18岁，大约15％的青少年将至少经历一集的MDD发作。越来越多的研究实现了奖励电路中的异常情况，因为在青少年的抑郁症状发展和维持中起着关键作用。重要的是，这些奖励循环异常已与阿尼奥尼亚（Anhedonia）联系在一起（即改善了愉悦或对奖励刺激的反应性钝化）。行为激活（BA）代表了青少年抑郁症的非药物干预措施的诺言，并且与认知行为疗法（CBT）至少与症状减轻和降低成人样本中继电器的风险有关。最近，Promise数据已从BA的应用到抑郁症的青少年出现。可以将BA概念化为直接针对Anhedonia的治疗方法。更具体地说，BA通过行为改变策略旨在逐渐增加患者接触并参与有益的刺激并积极加强经验，以旨在逐渐增加患者的接触和参与。鉴于这种治疗重点，BA可能对苦苦挣扎的伴鼻涕症状较高的青少年特别有益。根据演讲研究，将研究Anhedonia和奖励功能在预测BA中治疗反应中的作用。此外，将进行分析，以检查BA中反性症状症状的基础上与奖励相关的神经和行为机制。为了检验假设，本研究整合了来自三个分析单位的奖励功能的评估：1）神经回路（即，通过功能磁共振成像[fMRI]货币奖励任务探测神经奖励的奖励任务探测神经奖励函数），2）行为（即，具有概率的奖励任务[PRT] I. Snaith-Hamilton愉悦量表[塑造]和生态瞬时评估[EMA]）。除了拟议的研究外，四年制K23奖还将允许候选人在三个完整的领域发展能力。首先，参与者将在治疗前后进行fMRI，同时完成奖励任务探索奖励循环功能的货币奖励任务。 McLean Imaging Center的首席物理学家Blaise Frederick（顾问），使用fMRI研究抑郁症和Anhedonia的病理生理学的领导者Diego Pizzagalli博士将在获取，处理，处理和分析FMRI中提供关键的培训。 数据。这项培训将使候选人能够开发将功能神经影像整合到其抑郁症治疗研究计划中所需的技能，以更深入地探究症状改善的潜在神经力学。 fMRI方法论的课程工作将补充个人心态和动手培训，包括1）功能性MRI访问奖学金，这是通过哈佛大学 - 马萨诸塞州技术学院（MIT）健康科学科学与技术科（HST）的Athinoula A. Martinos中心提供的功能磁共振成像课程； 2）MATLAB通过MIT/HST提供的药物； 3）MIT的基本和临床研究人员的SPM8； 4）通过MARTINOS中心提供的MRI和FMRI结构和功能性大脑连通性。其次，为了获得症状变化的更细粒度和自然主义评估，以及青少年在多大程度上获得和利用BA中鼓励的技能的程度，适用的将接受Erika Forbes博士（Co-Mentor）的生态瞬时评估（EMA）培训，Erika Forbes博士（Co-Contoror），是EMA与沮丧且健康的青少年一起使用EMA的先驱。 Garret Fitzmaurice博士（顾问）将在该项目中提出的纵向心理社会（EMA）和神经（fMRI）假设进行统计咨询，以测试纵向社会心理（EMA）和神经（fMRI）假设。最后，拟议的培训计划将使候选人大大加深他对青少年抑郁症功能性神经解剖学的理解，并特别关注神经循环的奖励处理和Anhedonia（Pizzagalli＆Forbes博士）。临床咨询和监督将通过与DRS会议获得。 BA的领先当局Sona Dimidjian（顾问）和麦克莱恩医院行为健康部分计划主任ThrösturBjörgvinsson（顾问）。总的来说，拟议的研究和培训将为fMRI和EMA的应用提供牢固的基础，并可能对与奖励相关的预处理预测指标和症状改善的机制产生重要的发现。项目完成后，候选人将做好最佳准备，以努力进行创新的研究计划，整合神经，行为和社会心理研究方法，以回答这些重要问题。总而言之，该奖项将使候选人能够过渡到一个全面且独立的研究人员，并拥有一系列互补和尖端的评估和神经评估工具，以研究青年人的抑郁症。