FUNCTIONAL BRAIN NETWORK DEVELOPMENT IN EARLY CHILDHOOD DEPRESSION

描述（由申请人提供）：抑郁症的神经影像学研究表明，这种疾病中存在异常的脑网络关系。尽管有这些令人信服的发现，但很少有调查研究儿童经历最早已知形式的抑郁症，学龄前抑郁症（PD）的这些变化的发展时间。这个指导以病人为导向的职业发展奖（K23）的目的是为申请人提供必要的技能和经验，开始填补这一知识差距。独特的导师和培训机会提供给申请人补充了他在临床心理学和临床人群研究的强大背景。申请人的长期目标是开发一个独立的研究项目，调查抑郁症的发育神经生物学。为了促进这一目标，指导和指导提出了1）应用系统的方法来研究功能性脑网络的发展在PD使用功能性磁共振成像（fMRI）2）研究脑网络和行为之间的关系在PD和3）研究网络组织和任务之间的收敛的方法在PD基于功能性磁共振成像活动。一个由导师和顾问组成的跨学科专家小组将支持拟议的研究和培训计划。建议的奖励的可行性增强了可用性的一个大集合 来自一项正在进行的纵向神经影像学研究的fMRI数据，该研究针对有PD病史的学龄儿童及其同龄健康同龄人（NIMH MH 090786），以及从健康和抑郁的学龄前儿童（4-6岁）中获得试点fMRI数据的高水平成功。使用这些样本，在单个脑区域或区域对、目标子网络和全脑网络（使用图论方法）的水平上研究功能性脑网络的系统方法被计划用于目标1。作为第二个目标，将检查与目标1中确定的群体差异相关的行为。大脑网络组织和功能磁共振成像任务为基础的活动在情绪面部观察范式（收集在同一个人）的组之间的重叠模式将是一个计划的探索性目标的重点。假设1）PD将与破坏的默认模式网络连接相关2）非典型网络组织将与PD中的抑郁严重程度和情绪调节困难相关3）网络和基于任务的组差异之间的高度重叠将存在。对帕金森病患者大脑网络的研究可能揭示持续情绪困难和/或后期抑郁症风险的独特和早期发生的神经生物学标志物;信息对于开发旨在最大限度地减少抑郁症公共卫生负担的新型预防性治疗可能至关重要。本申请中提出的免费培训和研究计划将促进申请人过渡到独立的研究职业生涯，解决NIMH研究优先事项，强调大脑和行为科学（战略计划）的发现以及精神病理学（RDoC）的大脑网络研究。 公共卫生相关性：在当前应用程序中概述的培训和研究目标将使候选人成为翻译发育神经科学领域的独立研究人员，具有独特的专业知识，可以显着增加我们对抑郁症大脑网络的发展理解以及他们如何在这种损害性疾病中出错。尽管越来越多的人认识到抑郁症是一种“网络疾病”，但很少有研究对早期抑郁症儿童的功能性大脑网络组织进行研究。这些研究可能会导致早期识别儿童谁以后会发展MDD和通知新的预防性治疗工作，旨在尽量减少这一重要的公共卫生问题的重大负担。因此，拟议的奖项解决了重要的联邦研究重点，旨在减少抑郁症对公共卫生的影响。

DESCRIPTION (provided by applicant): Neuroimaging studies of depression have suggested aberrant brain network relationships in this disorder. Despite these compelling findings there have been very few investigations examining the developmental timing of these alterations in children experiencing the earliest known form of depression, Preschool Depression (PD). The purpose of this mentored Patient-Oriented Career Development Award (K23) is to provide the applicant with the skills and experience necessary to begin filling this knowledge gap. The unique mentorship and training opportunities available to the applicant complement his strong background in clinical psychology and research with clinical populations. The applicant's long-term goal is to develop an independent programmatic line of research investigating the developmental neurobiology of depression. To facilitate this goal, instruction and mentoring are proposed in 1) applying a systematic approach to the study of functional brain network development in PD using functional magnetic resonance imaging (fMRI) 2) methods for studying the relationships between brain networks and behavior in PD and 3) methods for studying the convergence between network organization and task based fMRI activity in PD. An expert interdisciplinary team of mentors and consultants will support the proposed research and training plan. The feasibility of the proposed award is enhanced by the availability of a large set of fMRI data from an ongoing longitudinal neuroimaging study of school age children with a history of PD and their same age healthy peers (NIMH MH090786) as well as a high level of success in obtaining pilot fMRI data from healthy and depressed preschoolers (4-6 years old). Using these samples, a systematic approach investigating functional brain networks at the level of individual brain regions or region pairs, targeted subnetworks, and whole brain networks (using graph theory methods) is planned for aim 1. As a second aim, the behavioral correlates associated with group differences identified in aim 1 will be examined. Patterns of overlap between group differences in brain network organization and fMRI task-based activity during an emotion face-viewing paradigm (collected in the same individuals) will be the focus of a planned exploratory aim. It is hypothesized that 1) PD will be associated with disrupted Default Mode Network connectivity 2) atypical network organization will be related to depression severity and emotion regulation difficulties in PD and 3) a high level of overlap between network and task based group differences will be present. The study of brain networks in PD may reveal unique and early occurring neurobiological markers of risk for continued mood difficulties and/or later depression; information potentially critical for developing novel preventative treatments aimed at minimizing depression's public health burden. The complimentary training and research plans proposed in this application will facilitate the applicant's transition into an independent researc career addressing NIMH research priorities that emphasize discoveries in the brain and behavioral sciences (Strategic Plan) and the study of brain networks in psychopathology (RDoC).! PUBLIC HEALTH RELEVANCE: The training and research goals outlined in the current application will enable the candidate to become an independent researcher in the field of translational developmental neuroscience, with unique expertise that could significantly increase our developmental understanding of brain networks in depression and how they go awry in this impairing disorder. Despite growing recognition of depression as a 'network illness', there have been very few studies examining functional brain network organization in children with very early occurring depression. Such studies could lead to the earlier identification of children who will later develop MDD and inform new preventive treatment efforts aimed at minimizing the significant burden of this important public health issue. Thus, the proposed award addresses important federal research priorities aimed at reducing the impact of depression on public health.