Characterizing pubertal and age mechanisms of neurodevelopment and association with rising internalizing symptoms

表征青春期和年龄神经发育机制以及与内化症状上升的关系

• 批准号: 10586147
• 负责人: Deanna Barch
• 金额: $ 80.78万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-03-07 至 2025-12-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10586147
• 关键词: Acceleration; Address; Adolescence; Adolescent; Age; Anxiety; Attention; Behavioral; Biological Assay; Brain; Brain imaging; Child; Childhood; Clinical; Coupling; Data; Data Set; Development; Ensure; Ethnic Origin; Evaluation; Foundations; Funding; Goals; Hormonal; Hormones; Human; Individual; Investigation; Link; Literature; Longitudinal Studies; Longitudinal cohort; Measures; Mediating; Mental Depression; Mental Health; Mental disorders; Methods; Modality; Modeling; Pathway interactions; Patient Self-Report; Process; Psychopathology; Puberty; Race; Research; Risk; Sampling; Socioeconomic Status; Structure; Symptoms; System; Testing; Time; United States National Institutes of Health; Variant; Work; Youth; boys; brain pathway; cognitive development; cohort; connectome; data analysis pipeline; emerging adult; girls; human data; informant; multimodality; neurodevelopment; novel; pubertal timing; puberty transition

PROJECT SUMMARY Building comprehensive accounts of human brain development from childhood to early adulthood is crucial to our understanding of both healthy neurodevelopment and the mechanisms underlying threats to youths’ mental health. Brain development unfolds on multiple levels, but the field lacks a comprehensive understanding of whether the trajectories of development are fundamentally similar or different across modalities (e.g., structure and function), and how they reflect developmental mechanisms associated with puberty or age (or both). The proposed research aims to generate a systematic and comprehensive multimodal account of typical neurodevelopment from ages 5 to 21, with a particular focus on a) identifying age versus pubertal- and hormonal-based mechanisms that undergird development in childhood and adolescence; b) systematic analyses across brain structure, function, and connectivity using state-of-the-art acquisition and analysis approaches; and c) evaluation of maturational variation in multimodal coupling across brain systems/ modalities as a function of development. Once established, this multimodal model of typical neurodevelopment will be used to test a conceptual model proposing that early pubertal timing leads to intensification of internalizing symptoms due to disruptions in brain development, including alterations in multimodal coupling. Specifically, models of the impact of early pubertal timing predict either further enhanced coupling with early puberty (neurodevelopmental acceleration) or disruptions in coupling due to neurodevelopmental delays. To compare these competing models and advance our understanding of the neurodevelopmental pathways by which early pubertal timing contributes to the rise of internalizing symptoms during adolescence, the research will use both hypothesis-driven methods and novel validated analysis pipelines for data-driven exploration of developmental changes in coupling, with careful attention to robustness and replication. The primary dataset will be the Human Connectome Project in Development (HCPD), a large, NIH funded, multimodal brain imaging dataset that includes a comprehensive assessment of brain structure, function, and connectivity paired with pubertal and hormonal measures and extensive behavioral and clinical measures in both a cross-sectional cohort of N=1300+ youth ages 5 to 21, and a longitudinal cohort (N=252) spanning ages 9 to 17 capturing the pubertal transition. This sample is purposefully strong diversity in race, ethnicity, and socioeconomic status. Key findings will be replicated to ensure robustness and generalizability in the Adolescent Brain and Cognitive Development (ABCD) longitudinal study. Our Specific Aims are to: A1) Establish a comprehensive, systematic account of age-and pubertal-linked pathways of brain development across multiple modalities of brain structure and function; A2) Test hypotheses about the relations of age and pubertal development to coupling across brain modalities; and A3) Test hypotheses about the neurodevelopmental mechanisms contributing to the rise in internalizing symptoms during the pubertal transition.

项目摘要 建立从童年到成年初期人类脑发育的全面说明对 我们对健康的神经发育以及对年轻人心理威胁的机制的理解 健康。大脑发展在多个层面上展开，但该领域缺乏对 发展轨迹在根本上是相似的还是不同的，例如结构 和功能），以及它们如何反映与青春期或年龄相关的发展机制（或两者兼而有之）。 拟议的研究旨在产生典型的系统和全面的多模式帐户 从5到21岁的神经发育，特别关注A）识别年龄与青春期和青春期 基于荷尔蒙的机制，这些机制是童年和青少年发展的基于激素的发展； b）系统 使用最先进的获取和分析跨大脑结构，功能和连通性进行分析 方法； c）评估跨大脑系统的多模式耦合的成熟变化/ 模式与发展的函数。建立后，这种典型神经发育的多模式模型 将用于测试早期青春期时间的概念模型提案，导致对 由于大脑发育的破坏而导致的内部症状，包括多模式耦合的改变。 具体而言，青春期早期时机影响的模型预测了与早期的进一步增强的耦合 青春期（神经发育加速度）或由于神经发育延迟而导致的耦合中断。到 比较这些竞争模型，并通过 早期的青春期时序有助于青少年期间内在症状的兴起，研究 将同时使用假设驱动的方法和新的经过验证的分析管道来进行数据驱动的探索 耦合的发展变化，仔细注意鲁棒性和复制。主要数据集 将是人类开发中的连接组项目（HCPD），这是一个大型的，由NIH资助的多模式的大脑 成像数据集包括对大脑结构，功能和连接配对的全面评估 两种横截面的青春期和荷尔蒙测量以及广泛的行为和临床测量 n = 1300+ 5至21岁的青年队的队列和一个9至17岁的纵向队列（n = 252）捕获 青春期过渡。该样本在种族，种族和社会经济地位方面有目的地强大的多样性。 将重复关键发现以确保青少年大脑和认知的鲁棒性和概括性 发展（ABCD）纵向研究。我们的具体目的是：A1）建立一个全面的，系统的 大脑结构多种方式跨多种方式的年龄和青春期关联途径的描述 和功能； A2）测试假设关于年龄和青春期发展与耦合的关系的假设 脑形态； A3）测试假设关于导致上升的神经发育机制的假设 在青春期过渡期间内化症状。