Alignment of cortical development trajectories with emergent dimensional psychopathology and related risk factors among early adolescents in the ABCD Study

ABCD 研究中青少年早期皮质发育轨迹与新兴维度精神病理学和相关危险因素的一致性

• 批准号: 10472710
• 负责人: Joshua Lawrence Roffman
• 金额: $ 42万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-15 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10472710
• 关键词: Adolescence; Adolescent; Adult; Age; Age of Onset; Artificial Intelligence; Biological; Biology; Brain; Cerebral cortex; Child; Child Behavior Checklist; Clinical; Clinical assessments; Conflict (Psychology); Data; Development; Dimensions; Disease; Early Diagnosis; Early Intervention; Enrollment; Environmental Risk Factor; Epidemiology; Etiology; Event; Family; Family dynamics; Foundations; Genomics; Heritability; Image; Individual; Intercept; Intervention; Knowledge; Life; Link; MRI Scans; Machine Learning; Magnetic Resonance Imaging; Maps; Measures; Mediating; Mediation; Mental Depression; Mental Health; Mental disorders; Methods; Mood Disorders; Onset of illness; Outcome; Participant; Pattern; Plant Roots; Predictive Factor; Prevention; Process; Prospective Studies; Psychopathology; Reproducibility; Research; Research Personnel; Resources; Risk; Risk Factors; Sampling; Schizophrenia; Scoring Method; Site; Socioeconomic Status; Specificity; Symptoms; Syndrome; Testing; Thick; Thinness; Time; Toxic effect; United States National Institutes of Health; Work; Youth; age related; base; cognitive development; critical period; effective intervention; experience; follow-up; genomic data; indexing; longitudinal design; machine learning method; neighborhood safety; neuroimaging; novel; nutrition; polygenic risk score; precision medicine; prenatal; preventive intervention; psychiatric genomics; psychosis risk; spatiotemporal; standardize measure; stressor; theories

Efforts to decipher biological signatures for mental illness now focus increasingly on adolescence, a period of rapid brain development that immediately precedes the peak age of onset for many disorders. Maturation of the cerebral cortex during this time has long been thought to mediate emergence of early symptoms. However, while specific cortical changes have been implicated in a small number of specific syndromes, for the most part, patterns in cortical development that underlie the differentiation of psychopathology remain uncertain. The ongoing Adolescent Brain Cognitive Development (ABCD) study provides an unprecedented opportunity to align emergence of specific patterns of psychopathology with specific changes in cortical maturation. Over the next 5 years, ABCD will obtain annual, standardized measures dimensional psychopathology, and biennial MRI scans, of 11,875 youths across 21 US-based sites, covering age 9 to 16. The proposed studies will leverage this longitudinal design to discover regionally- and temporally-specific features of cortical development that associate with emergence of dimensional psychopathology, and then to relate these patterns to specific profiles of underlying genomic and environmental risk. Analysis of baseline data from age 9-10, included in this application, indicates that psychopathology is in early stages of differentiation, although already strongly related to polygenic risk for child-onset disorders, and to well- established pre- and post-natal environmental insults. Aim 1 of the proposed studies will juxtapose clinical and imaging data from baseline through three follow-up time points, focusing primarily on whether departures from neurotypical age-related cortical thinning trajectories (assessed via intercept, slope, and quadratic indices) associate with emergence of specific dimensions of illness. The precise temporal alignment of clinical and cortical thinning trajectories will take an initial step towards inferring causal relationships, which will be further substantiated through triangulation with genomic (Aim 2) and environmental (Aim 3) risk profiles. Polygenic scoring methods developed by the Psychiatric Genomics Consortium will be used to determine whether cortical maturation trajectories developed in Aim 1 mediate relationships between genomic risk and emergent dimensional psychopathology. Then, using data from hundreds of environmental measures that canvass participants’ daily activities, nutrition, life stressors, socioeconomic status, family dynamics, neighborhood safety, and numerous other factors, we will use novel machine learning methods to develop profiles of exposomic risk factors that predict emergent dimensional psychopathology, and determine whether cortical maturation patterns mediate the relationship between environmental risk profiles and clinical course. By the conclusion of the proposed studies we hope to establish specific cortical signatures that bridge causal factors with emergent psychopathology in adolescence, and that can be leveraged to develop new preventative interventions.

现在，为精神疾病破译生物学特征的努力现在越来越重视青少年，这是一个时期 快速大脑的发育紧接在许多疾病的发作年龄之前。成熟 长期以来，人们一直认为这段时间的大脑皮层可以介导早期症状的出现。 但是，尽管已经在少数特定综合症中实施了特定的皮质变化，但 大多数情况下，皮质发展的模式是精神病理学分化的基础 不确定。正在进行的青少年脑认知发展（ABCD）研究提供了前所未有的 有机会使精神病理学特定模式与皮质的特定变化保持一致 成熟。在接下来的5年中，ABCD将获得年度标准化措施维度 精神病理学和双年展的MRI扫描，涵盖21个美国地点的11,875名年轻人，涵盖9至16岁。 拟议的研究将利用这种纵向设计来发现区域和暂时特定的 与维度心理病理学的出现相关的皮质发展的特征，然后 将这些模式与潜在基因组和环境风险的特定概况联系起来。基线分析 本应用程序中包括的9-10岁的数据表明，心理病理学处于早期阶段 差异化，尽管已经与儿童疾病的多基因风险密切相关，并且与 建立了产前和产后的环境侮辱。拟议的研究的目标1将与临床并置 从基线到三个随访时间点成像数据，主要集中于是否偏离 神经型与年龄相关的皮质变薄轨迹（通过截距，斜率和二次指数评估） 与疾病的特定维度的出现相关。临床和 皮质稀疏轨迹将朝着推断因果关系迈出第一步，这将是进一步的 通过基因组（AIM 2）和环境（AIM 3）风险特征来证实。多基因 精神科基因组学共同制定的评分方法将用于确定是否是否 AIM 1基因组风险与新兴的媒体关系中发展的皮质成熟轨迹 维度心理病理学。然后，使用来自数百种环境措施的数据 参与者的日常活动，营养，生活压力源，社会经济地位，家庭动态，社区 安全和许多其他因素，我们将使用新颖的机器学习方法来开发 预测新兴尺寸心理病理学的外胚体风险因素，并确定皮质是否是否 成熟模式介导环境风险概况与临床过程之间的关系。由 拟议研究的结论我们希望建立特定的皮质特征，以弥合因果因素 随着青少年的新兴心理病理学 干预措施。