Neurobehavioral pathways of polygenic and polyenvironmental effects on the onset and maintenance of substance involvement

多基因和多环境影响的神经行为途径对物质参与的发生和维持

• 批准号: 10656534
• 负责人: ARPANA AGRAWAL
• 金额: $ 39.38万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-15 至 2026-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10656534
• 关键词: Accounting; Adolescence; Adolescent; Adolescent and Young Adult; Adult; Age; Alcohols; Architecture; Attenuated; Behavior; Behavioral; Behavioral Mechanisms; Brain; Cessation of life; Childhood; Corpus striatum structure; Cues; Data; Data Analyses; Development; Disease; Education; Emotional; Emotions; Environment; Environmental Exposure; Environmental Risk Factor; Etiology; Genetic; Genomics; Impulsivity; Individual; Intoxication; Investigation; Link; Machine Learning; Maintenance; Manuscripts; Mediating; Methods; Modeling; Neurobiology; Occupations; Pathway interactions; Pattern; Phenotype; Policies; Prevention; Risk; Risk Factors; Risk Taking; Sampling; Shapes; Siblings; Structure; Substance Use Disorder; Testing; Thick; Tobacco; Twin Multiple Birth; Variant; Withdrawal; Youth; addiction; association cortex; behavior prediction; behavioral phenotyping; brain behavior; burden of illness; cognitive control; cognitive development; cognitive reappraisal; comorbidity; coping; disease classification; disorder risk; early adolescence; early onset substance use; economic cost; emerging adult; emotion regulation; executive function; fetal substance exposure; genetic risk factor; improved; indexing; multimodality; negative affect; neural; neural correlate; neurobehavioral; neurodevelopment; neuromechanism; novel; polygenic risk score; prenatal; risk sharing; social; socioeconomics; substance misuse; substance use; theories; young adult

PROJECT SUMMARY/ABSTRACT Problematic substance use is associated with significant personal and socioeconomic costs (accounting for approximately 5% of global disease burden and worldwide deaths). Substance use initiation, progression to heavy use, and early onset substance use disorders (SUDs) commonly emerge during adolescence and young adulthood. This developmental period of risk is theorized to result from typical patterns of regionally asynchronous brain maturation (i.e., rapid and early development of limbic regions alongside relatively immature prefrontal and multimodal association cortices) resulting in a diminished ability to suppress inappropriate emotions, desires, and actions when salient environmental cues are present. During later young adulthood the stabilization, reduction, or desistance of heavy use typically occurs alongside maturing cognitive control and emotional regulation abilities coinciding with cortical development. Brain and behavioral maturation may also be influenced by substance use. As genetic and environmental risk factors for substance involvement are predominantly shared across substances, understanding the behavioral and neural mechanisms underlying these shared risk factors in a developmental context will broadly improve our etiologic understanding of substance involvement liability and refine treatment and prevention. In this 5-year R01 (responding to PAR-19- 162), we propose to test whether putative behavioral and neural mechanisms of stage-based addiction may link broad spectrum SUD genomic liability and environmental risk to substance involvement trajectories from childhood – young adulthood using longitudinal data from the Adolescent Brain and Cognitive Development (ABCD) Study (N=11,875 followed from ages 9-16) along with other samples that uniquely extend the temporal scope of ABCD to comprehensively examine brain-behavior developmental interplay related to substance use and misuse (e.g., National Consortium on Alcohol and Neurodevelopment in Adolescence followed 830 individuals from ages 12-32). Disentangling the behavioral and neural mechanisms underlying broad spectrum genetic and environmental liability to SUD will inform our etiologic understanding of substance use initiation, escalation, and desistence that may ultimately contribute to substance-related policy, education, nosology, prevention, and treatment. Primary deliverables from this project will be manuscripts evaluating whether behavior and neural phenotypes may represent mechanisms underlying polygenic and polyenvironmental risk for substance use disorders.

项目摘要/摘要 有问题的物质使用与重大的个人和社会经济成本有关（考虑到 大约5％的全球疾病伯恩和全球死亡）。药物使用启动，发展 大量使用和早期发作药物使用障碍（SUD）通常在青少年和年轻人期间出现 成年。理论上认为，这种风险的发展时期是由区域性的典型模式产生的 异步脑成熟（即，边缘区域的快速和早期发展与相对不成熟 前额叶和多模式关联皮层），导致抑制不适当的能力降低 当存在显着的环境线索时，情绪，欲望和行动。在成年后期 稳定，减少或重度使用的目的地通常与成熟的认知控制和 情绪调节能力与皮质发展一致。大脑和行为成熟也可能是 受物质使用的影响。由于物质参与的遗传和环境风险因素是 主要跨物质共享，了解行为和神经机制 在发展环境中这些共同的风险因素将广泛提高我们对 物质参与责任以及完善的治疗和预防。在这5年的R01中（响应Par-19-- 162），我们建议测试基于阶段成瘾的推定行为和神经机制是否可以联系起来 从 童年 - 青少年使用青少年大脑和认知发展的纵向数据 （ABCD）研究（n = 11,875，随后是9-16岁）以及其他延伸临时的样本 ABCD的范围全面检查与药物使用相关的脑行为发展相互作用 和小姐（例如，Adoledcente的全国酒精和神经发育联盟随后830 来自12-32岁的个人。解散广泛的行为和神经机制 对SUD的遗传和环境责任将为我们对物质使用开始的病因理解， 升级和抵抗最终可能有助于与物质相关的政策，教育，肿瘤学， 预防和治疗。该项目的主要可交付成果将是评估行为的手稿 神经表型可能代表多基因和多基环境风险的机制 物质使用障碍。