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: 8641726
• 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/8641726
• 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 Domain Criteria; 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（由适用提供）：重度抑郁症（MDD）的患病率在青春期期间增加了5倍，到18岁，大约20％的年轻人将经历抑郁发作。大约15岁的MDD性别差异开始出现，与男孩相比，女孩报告的抑郁发作是两倍 - 整个成年期的差异持续存在。这些发作与深远的短期和长期负面后果有关，并希望这些令人震惊的流​​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。通过为期五年的K23指导患者的研究职业发展奖，适用的研究将进行创新的研究线，研究奖励学习在青少年MDD中的作用，同时，将获得基本的培训，该培训将在循证治疗和神经科学领域中大大扩展专业知识。具体而言，该项目将检查女性青少年抑郁症的奖励功能障碍的基础的社会心理，行为和神经科学，以及这些机制的改善是否有助于心理治疗后症状衰减。嵌入在这个小说项目中的是明确的培训目标，该目标将在迭戈·皮萨加利（Diego Pizzagalli）博士（主要导师）和约翰·魏斯（John Weisz）博士（Co-Incortor）的指导下实施。首先，在研究的最初阶段，沮丧和健康的女性青少年将参加脑电图（EEG）实验，同时完成一项问题，这些任务是学习刺激性奖励意外事件的问题。 Pizzagalli博士和Greg Hajcak博士（顾问）将为收集，处理和分析的与事件相关的潜力（ERP）数据提供重要的培训，这将使候选人能够开发与基于实验室，基于实验室的奖励处理功能障碍评估的新研究技能。这种培训将通过心理生理研究协会组织的与事件相关的潜力（ERP）训练营的出席完成。其次，人际压力在潜在的抑郁症状，尤其是在女性青少年中起着重要作用，因此，参与者将完成同行评估任务，同时收集功能性磁共振成像（fMRI）数据。丹尼尔·派恩（Daniel Pine）博士（顾问）将提供有关对与奖励电路相关的数据的获取和分析的关键心态，以更好地了解同行拒绝和接受，奖励功能障碍和MDD之间的关系。为了补充这项培训，我还将参加Athinoula A. Martinos中心功能性MRI访问奖学金，这是对MR Research先生进行的为期5天的密集介绍。此外，为了更好地准备fMRI数据的分析，我也将 在基本和临床研究人员的SPM8开创性中注册，这是MIT提供的为期5天的密集研讨会。此外，我将完成通过哈佛医学院提供的神经生物学课程，以奠定有关神经解剖学和认知神经科学的牢固基础。最后，沮丧的女性青少年将完成16周的个人认知行为疗法，以研究对奖励处理的行为和神经元机制的治疗效果。为了实现这一目标，适用的将分别从Hajcak博士和Pizzagalli博士那里学习ERP数据和最先进的分布式来源本地化技术的时频分解。此外，尽管Weisz博士和Throod Bj rgvinsson（顾问）将提供专家心态以实施治疗研究，但Garrett Fitzmaurice博士（顾问）将培训该应用程序在使用高级回归方法进行分析中。补充Drs。 Weisz，Bj¿rgvinsson和Pizzagalli，我将参加临床试验原则，这是通过Harvar公共卫生学院提供的。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。总而言之，要解构有关MDD的发作和复发的更多中心问题，必须使用跨学科方法。特别是临床心理学和情感方面的综合培训 预计神经科学将大大提高我们对MDD病因和治疗的理解。根据五年的K23奖，将在四个完整领域发展能力：（1）临床研究设计； （2）社会心理，行为和神经舞的统计建模； （3）与MDD相关的神经解剖学和认知神经科学； （4）神经影像技术，特别是高密度的脑电图和fMRI。重要的是，麦克莱恩医院是与儿童和青少年进行研究的理想环境。临床和行为数据将在位于麦克莱恩校园的抑郁症，焦虑和压力研究中心（CDASR）中收集，其中包括配备2向对讲机系统的临床访谈室和行为测试室，以及用于行为观察的摄像机。神经影像学扫描将在神经影像中心完成，该中心距离麦克莱恩校园的CDASR短途步行路程。扫描设施非常适合与儿童进行研究（例如，为喜欢参加会议的父母提供“模拟” MRI扫描仪，等待区）。如果发生急性危机，麦克莱恩（McLean）通过临床评估中心提供24小时的临床支持，该中心专门稳定困境。总的来说，提出的研究和培训将为该应用提供神经科学和临床试验的牢固基础，同时还可以显着促进我们对青少年MDD实施的神经认知机制的理解。