Examination of Reward Processing in the Treatment of Adolescent Major Depression

奖励处理在青少年重度抑郁症治疗中的检验

• 批准号: 8509096
• 负责人: RANDY PATRICK AUERBACH
• 金额: $ 17.16万
• 依托单位: MCLEAN HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8509096
• 关键词: Acute; Address; Adolescence; Adolescent; Adolescent Development; Adult; Aftercare; Age; Amygdaloid structure; Anterior; Anxiety; Area; Behavior; Behavioral; Behavioral Mechanisms; Biological Markers; Camping; Characteristics; Child; Clinical; Clinical Investigator; Clinical Psychology; Clinical Research; Clinical Trials; Cognitive; Cognitive Therapy; Complement; Corpus striatum structure; Data; Data Analyses; Depressed mood; Distress; Dorsal; Educational workshop; Electroencephalography; Enrollment; Environment; Epidemiology; Etiology; Evaluation; Event-Related Potentials; Evidence based treatment; Exhibits; Feedback; Fellowship; Female Adolescents; Foundations; Frequencies; Functional Magnetic Resonance Imaging; Functional disorder; Goals; Hospitals; Hour; Individual; Insula of Reil; Interview; Laboratories; Learning; Link; Magnetic Resonance Imaging; Major Depressive Disorder; Measures; Mediating; Mental Depression; Mentored Patient-Oriented Research Career Development Award; Mentors; Mentorship; Methods; National Institute of Mental Health; Neuroanatomy; Neurobiology; Neurocognitive; Neurophysiology - biologic function; Neurosciences; Parents; Participant; Pathway interactions; Phase; Play; Prefrontal Cortex; Prevalence; Process; Psychological reinforcement; Psychophysiology; Psychosocial Factor; Psychotherapy; Public Health Schools; Quality Control; Recurrence; Relative (related person); Reporting; Research; Research Design; Research Technics; Research Training; Rewards; Role; Scanning; Sex Characteristics; Signal Detection Analysis; Social status; Societies; Source; Specific qualifier value; Statistical Models; Stimulus; Stress; Sum; Symptoms; System; Techniques; Time; Training; Training Technics; Translational Research; Treatment outcome; Visit; Walking; Youth; affective neuroscience; attenuation; base; behavior observation; behavior test; boys; cingulate cortex; cognitive neuroscience; data acquisition; density; depressive symptoms; experience; girls; improved; indexing; innovation; insight; interdisciplinary approach; medical schools; neurobiological mechanism; neuroimaging; neuromechanism; novel; peer; prospective; psychosocial; public health relevance; relating to nervous system; research clinical testing; research study; response; reward circuitry; reward processing; skills; social; treatment effect; treatment response

DESCRIPTION (provided by applicant): The prevalence of major depressive disorder (MDD) increases 5-fold during adolescence, and by the age of 18, approximately 20% of youth will experience a depressive episode. Around the age of 15, gender differences in MDD begin to emerge with girls reporting twice as many depressive episodes as compared to boys - a difference that persists throughout adulthood. These episodes are associated with profound short- and long-term negative consequences, and despite these alarming epidemiological data, the pathophysiological processes underlying MDD in adolescents are largely unknown. Throughout the five-year K23 Mentor Patient-Oriented Research Career Development Award, the applicant will pursue an innovative line of research examining the role of reward learning in adolescent MDD, and at the same time, receive essential training, which will significantly extend expertise in the domains of evidence-based treatments and neuroscience. Specifically, the project will examine psychosocial, behavioral, and neural mechanisms underpinning reward dysfunction in depressed female adolescents, and whether improvement in these mechanisms contributes to symptom attenuation following psychotherapy. Embedded within this novel project are clear training aims, which will be implemented with guidance from Dr. Diego Pizzagalli (primary mentor) and Dr. John Weisz (co-mentor). First, in the initial phase of the study, depressed and healthy female adolescents will participate in an electroencephalography (EEG) experiment while completing a task that probes learning of stimulus-reward contingencies. Dr. Pizzagalli and Dr. Greg Hajcak (consultant) will provide critical training for collecting, processing, and analyzing event-related potential (ERP) data, which will allow the candidate to develop new research skills linked to objective, laboratory-based assessments of reward processing dysfunction. Such training will be complemented by attendance of the Event-Related Potential (ERP) Boot Camp organized by the Society for Psychophysiological Research. Second, interpersonal stress plays a profound role in potentiating depressive symptoms, particularly among female adolescents, and thus, participants will complete a peer evaluation task while functional magnetic resonance imaging (fMRI) data are collected. Dr. Daniel Pine (consultant) will provide key mentorship regarding the acquisition and analysis of data associated with reward circuitry to better understand the relationship among peer rejection and acceptance, reward dysfunction, and MDD. To supplement this training I will also enroll in the Athinoula A. Martinos Center Functional MRI Visiting Fellowship, which is a 5-day intensive introduction to MR research. Moreover, to better prepare for the analysis of fMRI data, I will also register in the SPM8 seminar for Basic and Clinical Investigators, which is a 5-day intensive workshop offered through MIT. Further, I will complete a Neurobiology course offered through Harvard Medical School in order to develop a strong foundation regarding neuroanatomy and cognitive neuroscience. Last, depressed female adolescents will complete 16-weeks of individual cognitive behavioral therapy to investigate the treatment effects on behavioral and neural mechanisms that underlie reward processing. In pursuit of this goal, the applicant will learn time-frequency decomposition of ERP data and state-of-the-art distributed source localization techniques from Dr. Hajcak and Dr. Pizzagalli, respectively. Additionally, while Dr. Weisz and Dr. Thr¿stur Bj¿rgvinsson (consultant) will provide expert mentorship for implementing the treatment study, Dr. Garrett Fitzmaurice (consultant) will train the applicant in the use of advanced regression methods for analysis. To complement Drs. Weisz, Bj¿rgvinsson, and Pizzagalli, I will enroll in Principles of Clinical Trials, which is offered through the Harvar School of Public Health. The course addresses different aspects of clinical trials including study design, quality control, and biostatistical applications. In sum, to deconstruct more central questions regarding the onset and recurrence of MDD, it is essential to utilize an interdisciplinary approach. In particular, integrated training in clinical psychology and affective neuroscience is expected to dramatically improve our understanding of the etiology and treatment of MDD. Accordingly, the five-year K23 Award will develop competency in four complementary areas: (1) clinical research design; (2) statistical modeling of psychosocial, behavioral, and neural data; (3) neuroanatomy and cognitive neuroscience associated with MDD; and (4) neuroimaging techniques, specifically high-density EEG and fMRI. Importantly, McLean Hospital is an ideal environment to conduct research with children and adolescents. Clinical and behavioral data will be collected in the Center for Depression, Anxiety and Stress Research (CDASR), which is located on the McLean Campus, and includes clinical interview rooms and behavioral testing rooms that are equipped with a 2-way intercom system and a video camera for behavioral observations. Neuroimaging scans will be completed in the Neuroimaging Center located a brief walk from the CDASR on the McLean Campus. Scanning facilities are well suited to research with children (e.g., availability of a "mock" MRI scanner, waiting area for the parents who like to attend the session). In case of an acute crisis, McLean provides 24-hour clinical support through the Clinical Evaluation Center, which specializes in the stabilization of individuals in distress. Collectively, the research and training proposed will provide the applicant with a strong foundation in neuroscience and clinical trials, while also significantly advancing our understanding of neurocognitive mechanisms implicated in adolescent MDD.

描述（由申请人提供）：青春期期间重度抑郁症 (MDD) 的患病率增加了 5 倍，到 18 岁时，大约 20% 的青少年会在 15 岁左右经历抑郁发作，性别差异较大。重度抑郁症开始出现，女孩的抑郁发作次数是男孩的两倍——这种差异在整个成年期持续存在，尽管这些症状令人震惊，但这些发作与严重的短期和长期负面后果有关。根据流行病学数据，青少年 MDD 的病理生理过程在很大程度上是未知的。在为期五年的 K23 Mentor 以患者为导向的研究职业发展奖中，申请人将进行一项创新的研究，探讨奖励学习在青少年 MDD 中的作用。同时，接受必要的培训，这将显着扩展循证治疗和神经科学领域的专业知识，具体来说，该项目将检查抑郁女性青少年奖赏功能障碍的心理社会、行为和神经机制，以及是否有所改善。这些机制有助于心理治疗后症状的减轻。这个新颖的项目中包含了明确的培训目标，这些目标将在迭戈·皮萨加利博士（主要导师）和约翰·韦兹博士（联合导师）的指导下实施。在研究的初始阶段，抑郁和健康的女性青少年将参与脑电图（EEG）实验，同时完成一项探索学习刺激奖励意外事件的任务。 （顾问）将提供收集、处理和分析事件相关电位（ERP）数据的关键培训，这将使候选人能够开发与奖励处理功能障碍的客观、基于实验室的评估相关的新研究技能。其次，人际压力在加剧抑郁症状方面发挥着深远的作用，特别是在女性青少年中，因此参与者将完成同伴评估任务。同时功能磁共振成像Daniel Pine 博士（顾问）将收集有关奖励回路相关数据的关键指导，以更好地了解同伴拒绝和接受、奖励功能障碍和 MDD 之间的关系。我还将参加 Athinoula A. Martinos 中心功能 MRI 访问奖学金，这是为期 5 天的 MR 研究强化介绍。此外，为了更好地为 fMRI 数据分析做好准备，我还将参加。 注册参加面向基础和临床研究者的 SPM8 研讨会，这是麻省理工学院提供的为期 5 天的强化研讨会。此外，我将完成哈佛医学院提供的神经生物学课程，以便为神经解剖学和认知神经科学打下坚实的基础。抑郁症女性青少年将完成为期 16 周的个体认知行为治疗，以研究治疗对奖励处理背后的行为和神经机制的影响。为了实现这一目标，申请人将学习 ERP 数据的时频分解和。此外，还分别采用了 Hajcak 博士和 Pizzagalli 博士以及 Weisz 博士和 Thr¿ 博士的最先进的分布式源定位技术。 stur Bj¿ rgvinsson（顾问）将为实施治疗研究提供专家指导，Garrett Fitzmaurice 博士（顾问）将培训申请人使用高级回归方法进行分析。 rgvinsson 和 Pizzagalli，我将参加哈佛公共卫生学院提供的临床试验原理课程，该课程涉及临床试验的不同方面，包括研究设计、质量控制和生物统计应用。关于 MDD 的发病和复发的核心问题，必须采用跨学科方法，特别是临床心理学和情感的综合培训。 神经科学预计将极大地提高我们对 MDD 病因和治疗的理解。因此，为期五年的 K23 奖将培养四个互补领域的能力：(1) 临床研究设计；(2) 心理社会、行为和治疗的统计模型。神经数据；(3) 与 MDD 相关的神经解剖学和认知神经科学；以及 (4) 神经影像技术，特别是高密度脑电图和功能磁共振成像技术。青少年的临床和行为数据将在位于麦克莱恩校区的抑郁、焦虑和压力研究中心 (CDASR) 收集，包括配备双向对讲系统的临床访谈室和行为测试室。用于行为观察的摄像机将在神经影像中心完成，该中心距离麦克莱恩校区的 CDASR 不远，扫描设施非常适合儿童研究（例如，可以使用扫描设备）。如果发生严重危机，麦克莱恩通过临床评估中心提供 24 小时临床支持，该中心专门致力于稳定陷入困境的个人。 ，拟议的研究和培训将为申请人提供神经科学和临床试验方面的坚实基础，同时也显着增进我们对青少年 MDD 涉及的神经认知机制的理解。