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，但很少有调查研究这些变化在经历已知最早形式的抑郁症，学龄前抑郁症（PD）的儿童中的发育时间。这个以患者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，以开始填补这一知识空白。为申请人提供的独特指导和培训机会补充了他在临床心理学和临床人群研究方面的强大背景。申请人的长期目标是发展一个独立的程序化研究线，调查抑郁症的发育神经生物学。为了实现这一目标，本文提出了以下方面的指导和指导：1)使用功能磁共振成像（fMRI）系统地研究PD中功能性脑网络的发展；2)研究PD中脑网络与行为之间的关系；3)研究PD中网络组织与基于任务的fMRI活动之间的收敛性。一个由导师和顾问组成的跨学科专家团队将支持拟议的研究和培训计划。由于有大量的可用性，所提议的奖励的可行性得到了提高

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).!