FUNCTIONAL BRAIN NETWORK DEVELOPMENT IN EARLY CHILDHOOD DEPRESSION

儿童早期抑郁症的功能性大脑网络发育

• 批准号: 8443092
• 负责人: Michael S Gaffrey
• 金额: $ 13.1万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-11 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8443092
• 关键词: 6 year old; Address; Adult; Age; Amygdaloid structure; Area; Award; Behavior; Behavioral; Behavioral Sciences; Brain; Brain region; Child; Childhood; Clinical; Clinical Psychology; Clinical Research; Collection; Complement; Complex; Crying; Data; Data Analyses; Data Set; Depressed mood; Development; Disease; Doctor of Medicine; Doctor of Philosophy; Dorsal; Early identification; Educational Curriculum; Emotional; Emotions; Ethical Issues; Exposure to; Face; Fellowship; Functional Magnetic Resonance Imaging; Funding; Goals; Graph; Hydrocortisone; Impairment; Individual; Instruction; Investigation; K-Series Research Career Programs; Knowledge; Lead; Learning; Life; Machine Learning; Major Depressive Disorder; Measures; Mental Depression; Mentors; Mentorship; Methods; Moods; Movement; National Institute of Mental Health; Neural Network Simulation; Neurobiology; Neurosciences; Nursery Schools; Pathway Analysis; Pattern; Physiology; Population; Postdoctoral Fellow; Prefrontal Cortex; Preventive; Process; Psychopathology; Public Health; Recording of previous events; Research; Research Activity; Research Personnel; Research Priority; Research Training; Rest; Risk; Risk Marker; Sampling; Scanning; School-Age Population; Seeds; Severities; Specificity; Strategic Planning; Symptoms; Techniques; Time; Training; Training Activity; Training Programs; Universities; Variant; Washington; Work; base; brain behavior; career; case control; clinically significant; cognitive control; depressive symptoms; developmental neurobiology; early childhood; early experience; emotion regulation; experience; innovation; interest; neuroimaging; novel; patient oriented; peer; programs; skills; success; theories; tool

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.

描述（由申请人提供）：抑郁症的神经影像学研究表明，这种疾病中的脑网络关系异常。尽管有这些引人注目的发现，但很少有调查研究这些改变的儿童的发展时机，这些儿童经历了最早已知的抑郁症，学龄前抑郁症（PD）。这个受过指导的以患者为导向的职业发展奖（K23）的目的是为申请人提供开始填补这一知识差距所需的技能和经验。申请人可获得的独特指导和培训机会与临床人群相辅相成。申请人的长期目标是开发一个独立的计划研究线，研究抑郁症的发育神经生物学。为了促进这一目标，提出了指导和指导。1）使用功能磁共振成像（fMRI）使用系统的方法来研究PD功能性脑网络开发的方法2）研究用于研究PD和3）方法的方法，用于研究网络组织与基于pD的FMRI Active中基于网络组织和基于任务的FMRI活动之间的融合。专业的导师和顾问团队将支持拟议的研究和培训计划。拟议奖励的可行性可通过大型套件的可用性增强 来自正在进行的纵向神经影像学研究的fMRI数据对具有PD史的学龄儿童及其年龄相同的健康同龄人（NIMH MH090786），以及从健康和抑郁的学龄前儿童（4-6岁）中获取PILOT fMRI数据方面的高度成功。使用这些样品，一种系统的方法研究了各个大脑区域或区域对，有针对性的子网和整个大脑网络（使用图理论方法）的功能性脑网络。将被计划在第二个目标中。将被检查与AIM 1中确定的与群体差异相关的行为相关性。在情绪观看范式中，大脑网络组织中的群体差异与基于fMRI任务的活动之间的重叠模式（在同一个人中收集）将是计划的探索目标的重点。假设1）PD将与默认模式网络连通性中断相关联2）非典型网络组织将与PD的抑郁严重程度和情绪调节困难有关，以及3）将存在网络和基于任务的组差异之间的高水平重叠。对PD中大脑网络的研究可能会揭示出独特的和早期发生的神经生物学标志物，这是持续情绪困难和/或以后的抑郁症的风险；信息对于开发旨在最大程度减轻抑郁症的公共卫生负担的新型预防治疗至关重要。本申请中提出的免费培训和研究计划将有助于申请人过渡到独立的研究职业，该职业针对NIMH研究的重点，该研究重点强调了大脑和行为科学的发现（战略计划）和精神病理学中大脑网络（RDOC）的研究。 公共卫生相关性：当前应用程序中概述的培训和研究目标将使候选人能够成为转化发展神经科学领域的独立研究人员，具有独特的专业知识，可以显着提高我们对抑郁症中脑网络的发展理解，以及他们如何在这种受损障碍中出现问题。尽管人们对抑郁症作为“网络疾病”的认识越来越多，但很少有研究研究抑郁症的儿童功能性脑网络组织。这样的研究可能会导致对儿童的早期识别，这些儿童后来将开发MDD并为新的预防治疗工作提供旨在最大程度地减少这一重要公共卫生问题负担的新预防治疗工作。因此，拟议的奖项旨在解决旨在减少抑郁症对公共卫生影响的重要联邦研究重点。