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: 10208288
• 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/10208288
• 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; multimodality; 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 有大量证据表明，精神病理学是有层级结构的。除了两个主要具体内容 因素，内化和外化，有一个压倒一切的一般因素，“P因素”，它解释了 在精神症状上有相当大的差异。P因子模型代表了最近在 我们对精神病理学体系结构的理解。然而，我们目前存在着一个严重的差距 知识：我们对导致P的神经发育病因知之甚少 年轻时的因素。 我们有一个理想的机会来解决这个与青少年大脑认知发展(ABCD)的差距 纵向研究(n=11,875；在这项五年赠款过程中进行了4次两年一次的数据波动)。我们有 建立了双重不成熟模型，在该模型中，P因子产生于 两个系统中的青春期：执行控制系统(导致全球更高阶认知的减少和 抑制控制)和脉冲产生系统(导致全局提升的脉冲产生)。我们有 还对ABCD的精神病理学数据进行了全面的分析，以得出和验证 上位的一般精神病理因素(“P因素”)。我们在这个项目中的首要目标是在 这些结果并结合知识描述了ABCD中青年P因子的多因素病因 跨越社会环境、心理、神经和基因层面的分析。 更具体地说，我们寻求实现四个目标。目标1使用潜在增长建模方法来量化联合 发展心理变量(包括执行功能、负面情绪和攻击性 冲动)与青春期P因素的出现有关。在目标2中，我们使用先进的方法 分割的大脑成像映射成一小部分凝聚的成分。然后，我们使用潜在增长 建模以确定与P因子共同发育的大脑成分。对于目标3，我们描述了基因 影响P因子的因素。为此，我们确定了调节这种关系的大脑组件 P因子的多基因风险与青春期晚期P因子的出现之间的关系。对于目的4， 我们将前面的因素(心理、神经和遗传)与额外的社会环境相结合 变量为P因子的出现建立了一个整体的法理网络，我们区分了这一点 网络从类比网络中出现内化和外化的具体因素。 通过将开创性的ABCD数据集和先进的多变量多模式神经成像方法结合在一起， 该项目将给我们提供重要的新的机制洞察多因素神经发育病因学。 P因子。这一知识是下游研究项目的关键输入，例如寻求 确定高危青年或制定干预措施，以减轻或阻止精神病的出现。