Fragmented early life environmental and emotional / cognitive vulnerabilities

描述（由申请人提供）：这是一个修订后的应用程序的康特中心解决复杂的发展机制，有助于青少年的脆弱性，精神疾病。这些通常被认为是在敏感的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以及它们促进疾病的机制的认识存在重大空白。指导这项修订申请的创新统一假设是，在生命早期，母亲信号的干扰模式，特别是它们的碎片化和不可预测性，大大有助于青少年的情感和认知脆弱性。在最初的评论者的建设性建议的指导下，强有力的初步数据现在支持这一假设。该中心的总体目标是执行一个多维度的综合计划，将这一极其重要的临床问题带入动物和人类研究实验室。利用他们的互补优势，并采用跨物种平台和复杂的协调分析方法，该中心的目标是将由此产生的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一个独特的资源，一个大型的特征良好的人类队列，从胎儿到青春期进行纵向和横断面研究。研究中心将重点 先进的结构和功能脑成像在这个队列和同源动物模型，结合国家的最先进的分子方法，基因调控的时间和空间。中心的目标是：（1）使用传统和创新方法，描述影响不同物种青少年脆弱性的产前和产后母体信号的模式，并生成婴儿期、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，包括啮齿动物的结构和功能成像以及机制研究，解决潜在的潜在机制; 3）通过强大的统计/计算方法，联合收割机结合行为和成像结果沿着时间，以生成预示病理的青少年行为的潜在预测模型。该中心的重要性来自于通过强大的，跨物种的多学科，最先进的方法来解决关键的临床问题。该中心测试了一个高度创新的假设，该假设建立在现有的大量人类和实验文献的基础上，并为这些文献提供了一个理论统一的框架。该中心方法的主要资产包括大型纵向人类队列、预测动物模型、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集成以及对大型且相互依存的数据集及其集成的严格和创新分析。预测模型。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，而且往往始于青春期。虽然我们知道早期生活事件可能导致这些问题的出现，但我们对机制知之甚少。一群拥有不同专业知识的科学家联合收割机，利用动物模型和大脑扫描来揭示机制，询问母亲在出生前后发出的信号是否对情绪和认知问题产生重要影响。

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.