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: 10261581
• 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/10261581
• 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; Psychoses; Reproducibility; Research; Research Personnel; Resources; Risk; Risk Factors; Sampling; Schizophrenia; Scoring Method; Site; Socioeconomic Status; Specificity; Structure; 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; 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.

破译精神疾病的生物学特征的努力现在越来越多地集中在青春期，一个时期