Building a multi-factor etiological model of the emergence of general psychopathology (the "P factor") in adolescence with multi-modal neuroimaging in ABCD

利用 ABCD 多模态神经影像建立青春期一般精神病理学（“P 因素”）出现的多因素病因模型

• 批准号: 10415234
• 负责人: Chandra Sekhar Sripada
• 金额: $ 39万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-06-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10415234
• 关键词: Address; Adolescence; Adolescent; Age; Architecture; Brain; Brain imaging; Cognition; Complex; Data; Data Analytics; Data Collection; Data Set; Development; Dimensions; Early identification; Emotions; Environment; Etiology; Event; Exhibits; Family; Fractionation; Funding; Generations; Genetic; Genomics; Genotype; Grant; Growth; Household; Income; Individual; Intervention; Joints; Knowledge; Lead; Life; Link; Longitudinal Studies; Maps; Measures; Mediating; Methods; Modeling; Neighborhoods; Neurocognitive; Outcome; Parents; Parietal; Participant; Pattern; Phenotype; Properdin; Psychological Factors; Psychopathology; Reporting; Research; Residual state; Rest; Rewards; Risk; Seminal; Social Environment; Structure; System; Work; Youth; analytical method; brain shape; clinical translation; clinically relevant; cognitive development; cohesion; executive function; high risk; imaging modality; insight; longitudinal design; multimodal neuroimaging; neurodevelopment; neuroimaging; programs; psychiatric symptom; psychologic; relating to nervous system; secondary analysis; social; teacher

Abstract There is substantial evidence that psychopathology is structured hierarchically. In addition to two major specific factors, internalizing and externalizing, there is a single overarching general factor, the “P factor”, that explains a sizable share of variance in psychiatric symptoms. The P factor model represents a major recent advance in our understanding of the architecture of psychopathology. However, there is a critical gap in our current knowledge: We have little understanding of the neurodevelopmental etiological factors that produce the P factor during youth. We have an ideal opportunity to address this gap with the Adolescent Brain Cognitive Development (ABCD) longitudinal study (n=11,875; 4 biennial waves of data over the course of this five-year grant). We have formulated a Dual Dysmaturation Model in which the P factor arises from altered maturation during adolescence in two systems: executive control systems (leading to globally reduced higher-order cognition and inhibitory control) and impulse generation systems (leading to globally elevated impulse generation). We have also undertaken a comprehensive analysis of psychopathology data in ABCD to derive and validate a superordinate general psychopathology factor (“P factor”). Our overarching aim in this project is to build on these results and delineate the multi-factor etiology of the P factor in youth in ABCD, integrating knowledge across socio-environmental, psychological, neural, and genetic levels of analysis. More specifically we seek to achieve four aims. Aim 1 uses a latent growth modeling approach to quantify co- development of psychological variables (including executive functions, negative emotions, and aggressive impulses) with the emergence of the P factor over adolescence. In Aim 2, we use advanced methods to fractionate brain imaging maps into a small number of cohesive components. We then use latent growth modeling to identify brain components that co-develop with the P factor. For Aim 3, we delineate genetic factors that contribute to the P factor. For this aim, we identify brain components that mediate the relationship between polygenic risk for the P factor and the emergence of the P factor in late adolescence. For the Aim 4, we integrate the preceding factors (psychological, neural, and genetic) with additional socio-environmental variables to build an overall nomological network for the emergence of the P factor, and we distinguish this network from analogous networks for the emergence of internalizing and externalizing specific factors. By bringing together the seminal ABCD dataset and advanced multivariate multi-modal neuroimaging methods, this project will give us important new mechanistic insights into the multi-factor neurodevelopmental etiology of the P factor. This knowledge is a key input to downstream research programs, such as programs that seek to identify high-risk youth or to develop interventions that mitigate or block the emergence of psychopathology.

摘要 有大量的证据表明，精神病理学是分层结构的。除了两个具体的 因素，内化和外化，有一个单一的总体因素，“P因素”，解释了 在精神症状上有很大的差异P因子模型代表了最近的一个重大进展， 我们对精神病理学架构的理解然而，我们目前的工作中存在着一个关键的差距， 知识：我们对产生P的神经发育病因学因素知之甚少 青年时期的因素。 我们有一个理想的机会来解决这个差距与青少年大脑认知发展（ABCD） 纵向研究（n= 11，875;在本五年资助期间，每两年进行一次数据浪潮）。我们有 制定了一个双重不成熟模型，其中P因子来自于成熟过程中的改变。 青少年在两个系统：执行控制系统（导致全球减少高阶认知， 抑制控制）和脉冲生成系统（导致全局提升的脉冲生成）。我们有 还对ABCD中的精神病理学数据进行了全面分析，以得出并验证 高级一般精神病理学因素（“P因素”）。我们在这个项目中的首要目标是建立在 这些结果和描绘的多因素病因的P因子在青年ABCD，整合知识 在社会环境、心理、神经和遗传层面的分析。 具体而言，我们力求实现四个目标。目标1使用潜在增长模型方法来量化共同增长， 心理变量的发展（包括执行功能，负面情绪和攻击性） 冲动）随着青春期P因素的出现。在目标2中，我们使用先进的方法， 碎脑成像映射成少量的内聚成分。然后我们利用潜在增长 建模以识别与P因子共同发展的大脑成分。对于目标3，我们描述了遗传学 影响P因子的因素。为此，我们确定了调节这种关系的大脑成分， P因子的多基因风险与青春期后期P因子的出现之间的关系。对于Aim 4， 我们将上述因素（心理、神经和遗传）与其他社会环境因素相结合， 变量来建立一个P因素出现的整体法则网络，我们区分这一点， 网络从类似的网络出现的内部化和外部化的具体因素。 通过将开创性的ABCD数据集和先进的多变量多模态神经成像方法结合在一起， 该项目将为我们提供重要的新机制的见解，多因素的神经发育病因学， P因素。这些知识是下游研究计划的关键投入，例如寻求 确定高危青年或制定干预措施，减轻或阻止精神病理学的出现。