Fragmented early life environmental and emotional / cognitive vulnerabilities

破碎的早期生活环境和情感/认知脆弱性

基本信息

批准号：
8683240
负责人：
Tallie Z. Baram
金额：
$ 200万
依托单位：
UNIVERSITY OF CALIFORNIA-IRVINE
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-06-17 至 2018-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8683240
关键词：
Address Adolescence Adolescent Adolescent Behavior Affect American Animal Model Animals Behavior Behavioral Biological Markers Birth Brain Brain imaging Brain region Brain scan Caring Child Behavior Child Psychiatry Child health care Childhood Clinical Cognition Disorders Cognitive Complex Cross-Sectional Studies Data Data Set Defect Development Discipline Disease Ecology Emotional Emotional disorder Environment Event Female Functional Imaging Future Gene Expression Regulation Genes Genetic Goals Grant Human Image Individual Infant Behavior Informatics Intervention Investigation Knowledge Laboratories Laboratory Research Life Life Experience Literature Maternal Patterns of Care Mental disorders Methods Modeling Molecular Molecular Target Mothers Nature Neurology Neurons Neurosciences Outcome Pathology Pattern Public Health Research Research Personnel Resources Risk Rodent Rodent Model Role Scientist Signal Transduction Statistical Methods Structure Suggestion Synapses System Testing Time Translating Translations Validation analytical method base behavior influence clinical practice clinically significant cognitive function cohort design developmental psychology fetal improved infancy innovation male middle age multidisciplinary novel postnatal predictive modeling prenatal social statistics symposium tool

项目摘要

DESCRIPTION (provided by applicant): This is a revised application for a Conte Center addressing the complex developmental mechanisms contributing to adolescent vulnerabilities to mental illnesses. These are generally believed to arise from an interaction of genetic and environmental influences during sensitive developmental epochs, yet there are major gaps in our knowledge regarding the nature of these signals, and the mechanisms by which they promote disease. The innovative unifying hypothesis guiding this revised application is that disturbed patterns of maternal signals early in life, especially their fragmentation and unpredictability, contribute greatly to adolescent emotional and cognitive vulnerabilities. Guided by constructive suggestions of the original Reviewers, strong preliminary data now support this hypothesis. The overarching goal of the proposed Center is to execute a multi-dimensional and integrated plan that brings this exceedingly important clinical problem into both animal and human research laboratories. Capitalizing on their complementary strengths and employing cross-species platforms and sophisticated coordinated analytical methods, the Center aims to translate the resulting discoveries into clinically significant predictive models. The Centers approach benefits from a unique resource, a large well-characterized human cohort, to perform longitudinal and cross-sectional studies from fetal life to adolescence. Center research will focus on advanced structural and functional brain imaging in this cohort and in cognate animal models, combined with state-of-the-art molecular approaches to gene regulation in time and space. Center Aims will (1) characterize patterns of pre- and postnatal maternal signals that influence adolescent vulnerabilities across species, using conventional and innovative methods, and generate trajectories of altered behaviors in infancy, childhood and adolescence; (2) address the potential underlying mechanisms using common platforms in human and rodents, including structural and functional imaging, and mechanistic studies in rodents; 3) through a strong Statistics / Computational approach, combine behavioral and imaging outcomes along time to generate potentially predictive models for adolescent behaviors that augur pathology. The Center's significance derives from addressing crucial clinical questions via robust, cross-species multidisciplinary, state-of-the-art approaches. The Center tests a highly innovative hypothesis that builds on and provides a theoretical unifying framework for a large existing human and experimental literature. Major assets of the Center approach include a large longitudinal human cohort, predictive animal models, common methodological platforms across species, strong preliminary data, improved integration of Projects' design and data flow and rigorous and innovative analyses of the large and interdependent data sets and their integration into predictive models. Thus, the impact of the information generated by the Center will be substantial, aiming to transform our understanding of how early life environment contributes to disorders that affect 20% of adolescents. Emotional problems affect millions of Americans, and often start in adolescence. While we know that early-life events might contribute to the emergence of these problems, we know little about the mechanisms. A group of Scientists with diverse expertise combine to ask if signals from the mother before and after birth are important in creating vulnerabilities to emotional and cognitive problems, using animal models and brain scans to uncover the mechanisms.

描述（由申请人提供）：这是 Conte 中心的修订申请，旨在解决导致青少年易患精神疾病的复杂发展机制。人们普遍认为这些信号是由敏感发育时期遗传和环境影响的相互作用引起的，但我们对这些信号的性质及其促进疾病的机制的认识存在重大差距。指导这一修订后的应用的创新统一假设是，生命早期母亲信号的紊乱模式，尤其是它们的碎片化和不可预测性，极大地导致了青少年的情感和认知脆弱性。在最初审稿人的建设性建议的指导下，强有力的初步数据现在支持了这一假设。拟议中心的总体目标是执行一项多维综合计划，将这一极其重要的临床问题带入动物和人类研究实验室。该中心利用双方的互补优势，采用跨物种平台和复杂的协调分析方法，旨在将所得发现转化为具有临床意义的预测模型。该中心的方法受益于独特的资源，即大量特征明确的人类队列，可以进行从胎儿生命到青春期的纵向和横断面研究。中心研究将重点在该队列和同源动物模型中进行先进的结构和功能脑成像，并结合最先进的时间和空间基因调控分子方法。中心目标将（1）利用传统和创新方法，描述影响跨物种青少年脆弱性的产前和产后母体信号模式，并产生婴儿期、儿童期和青春期行为改变的轨迹； (2) 使用人类和啮齿动物的共同平台解决潜在的潜在机制，包括啮齿动物的结构和功能成像以及机制研究； 3）通过强大的统计/计算方法，将行为和成像结果结合起来，为预示病理的青少年行为生成潜在的预测模型。该中心的重要性源于通过强大的、跨物种的、多学科的、最先进的方法解决关键的临床问题。该中心测试了一个高度创新的假设，该假设建立在大量现有的人类和实验文献的基础上，并为其提供了理论统一框架。该中心方法的主要资产包括大型纵向人类队列、预测性动物模型、跨物种的通用方法平台、强大的初步数据、项目设计和数据流的改进整合以及对大型且相互依赖的数据集及其数据的严格和创新分析。集成到预测模型中。因此，该中心产生的信息的影响将是巨大的，旨在改变我们对早期生活环境如何导致影响 20% 青少年的疾病的理解。情绪问题影响着数百万美国人，并且通常从青春期开始。虽然我们知道生命早期的事件可能会导致这些问题的出现，但我们对其机制知之甚少。一群拥有不同专业知识的科学家联合起来，利用动物模型和脑部扫描来揭示其中的机制，以探究母亲在出生前后发出的信号是否对造成情绪和认知问题的脆弱性很重要。