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: 10487460
• 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/10487460
• 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; Genetic Risk; Genomics; Impulsivity; Individual; Intoxication; Investigation; Link; Machine Learning; Maintenance; Manuscripts; Mediating; Methods; Modeling; Neurobiology; Pathway interactions; Pattern; Phenotype; Plant Roots; Policies; Prevention; Risk; Risk Factors; Risk-Taking; Sampling; Siblings; Structure; Substance Use Disorder; Testing; Thick; Tobacco; Twin Multiple Birth; Variant; Withdrawal; Youth; addiction; association cortex; base; behavioral phenotyping; brain behavior; burden of illness; cognitive control; cognitive development; cognitive reappraisal; comorbidity; cost; disease classification; disorder risk; early adolescence; early onset substance use; emerging adult; emotion regulation; executive function; fetal substance exposure; improved; indexing; multimodality; negative affect; neural correlate; neurobehavioral; neurodevelopment; neuromechanism; novel; polygenic risk score; prenatal; relating to nervous system; risk sharing; social; socioeconomics; substance misuse; substance use; 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.

项目概要/摘要 有问题的物质使用与巨大的个人和社会经济成本相关（占 约占全球疾病负担和全球死亡人数的 5%）。物质使用开始，进展到 大量使用和早发性物质使用障碍 (SUD) 通常出现在青春期和青年时期 成年期。从理论上讲，这一风险发展期是由典型的区域模式造成的。 异步大脑成熟（即边缘区域快速且早期发育，同时相对不成熟） 前额叶和多模式联合皮层）导致抑制不当行为的能力下降 当显着的环境线索出现时的情绪、欲望和行动。在后来的青年时期 稳定、减少或停止大量使用通常伴随着成熟的认知控制和 情绪调节能力与皮质发育相一致。大脑和行为的成熟也可能是 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，了解潜在的行为和神经机制 这些发育背景下共同的风险因素将广泛提高我们对病因的理解 物质涉案责任并细化处理和预防。在这个5年R01（响应PAR-19- 162），我们建议测试阶段性成瘾的假定行为和神经机制是否可能存在联系 广谱 SUD 基因组责任和物质参与轨迹的环境风险 使用青少年大脑和认知发展的纵向数据分析童年至成年早期 (ABCD) 研究（N=11,875，从 9 岁到 16 岁）以及其他独特地延长时间的样本 ABCD 的范围全面检查与物质使用相关的大脑行为发育相互作用 第830章 12-32 岁的个人）。解开广谱背后的行为和神经机制 SUD 的遗传和环境责任将有助于我们对物质使用开始的病因学理解， 升级和停止可能最终有助于与物质相关的政策、教育、疾病分类学、 预防、治疗。该项目的主要交付成果将是评估行为是否 神经表型可能代表多基因和多环境风险的潜在机制 物质使用障碍。