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）：重度抑郁症（MDD）的患病率在青春期增加5倍，到18岁时，约20%的青少年将经历抑郁发作。在15岁左右，MDD的性别差异开始出现，女孩报告的抑郁发作次数是男孩的两倍--这种差异在整个成年期都存在。这些事件与深刻的短期和长期的负面后果，尽管这些令人震惊的流行病学数据，在青少年MDD的基础病理生理过程在很大程度上是未知的。在为期五年的K23导师以患者为导向的研究职业发展奖中，申请人将从事一项创新的研究，研究奖励学习在青少年MDD中的作用，同时接受必要的培训，这将大大扩展循证治疗和神经科学领域的专业知识。具体而言，该项目将研究心理，行为和神经机制支持奖励功能障碍抑郁症的女性青少年，以及这些机制的改善是否有助于心理治疗后的症状减轻。嵌入在这个新的项目是明确的培训目标，这将与Diego Pizzagalli博士（主要导师）和John Weisz博士（共同导师）的指导下实施。首先，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，同时完成一项任务，探索刺激奖励意外事件的学习。Pizzagalli博士和Greg Hajcak博士（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。这种培训将通过参加由心理生理研究学会组织的事件相关电位（ERP）靴子营来补充。其次，人际压力在增强抑郁症状中起着深刻的作用，特别是在女性青少年中，因此，参与者将完成一项同伴评价任务，同时收集功能性磁共振成像（fMRI）数据。丹尼尔派恩博士（顾问）将提供关于奖励电路相关数据的获取和分析的关键指导，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。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，这是一个为期5天的MR研究密集介绍。此外，为了更好地为fMRI数据的分析做准备，我还将 注册参加SPM 8基础和临床研究者研讨会，这是一个为期5天的密集研讨会，由麻省理工学院提供。此外，我将完成哈佛医学院提供的神经生物学课程，以发展神经解剖学和认知神经科学的坚实基础。最后，抑郁的女性青少年将完成16周的个体认知行为治疗，以研究治疗对奖励处理的行为和神经机制的影响。为了实现这一目标，申请人将分别从Hajcak博士和Pizzagalli博士那里学习ERP数据的时频分解和最先进的分布式源定位技术。此外，Weisz博士和Thr <$stur Bj <$rgvinsson博士（顾问）将为实施治疗研究提供专家指导，加勒特Fitzmaurice博士（顾问）将培训申请人使用高级回归方法进行分析。为了补充Weisz博士，Bj rgvinsson和Pizzagalli，我将参加临床试验的原则，这是通过公共卫生哈瓦尔学院提供的。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学应用。 总之，为了解构关于MDD发作和复发的更多核心问题，必须利用跨学科方法。特别是临床心理学和情感方面的综合培训， 神经科学有望极大地提高我们对MDD病因和治疗的理解。因此，为期五年的K23奖将在四个互补领域发展能力：（1）临床研究设计;（2）心理社会，行为和神经数据的统计建模;（3）与MDD相关的神经解剖学和认知神经科学;（4）神经成像技术，特别是高密度EEG和fMRI。重要的是，姆克林医院是一个理想的环境进行研究与儿童和青少年。临床和行为数据将在位于姆克林校区的抑郁、焦虑和压力研究中心（CDASR）收集，该中心包括配备双向对讲系统和用于行为观察的摄像机的临床访谈室和行为测试室。神经影像学扫描将在距离姆克林Campus的CDASR仅几步之遥的神经影像学中心完成。扫描设备非常适合儿童研究（例如，提供“模拟”MRI扫描仪，为喜欢参加会议的父母提供等候区）。在紧急危机的情况下，姆克林通过临床评估中心提供24小时临床支持，该中心专门负责稳定处于困境中的个人。总的来说，拟议的研究和培训将为申请人提供神经科学和临床试验的坚实基础，同时也大大提高了我们对青少年MDD中涉及的神经认知机制的理解。