Modeling poly-genomic risk in the relationship between brain structure and alcohol involvement from adolescence through adulthood

对从青春期到成年期大脑结构与酒精参与之间关系的多基因组风险进行建模

• 批准号: 9806726
• 负责人: RYAN H BOGDAN
• 金额: $ 26.49万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-09 至 2021-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9806726
• 关键词: Accounting; Address; Adolescence; Adolescent; Adolescent and Young Adult; Adult; Affect; Age; Alcohol Phenotype; Alcohol abuse; Alcohol consumption; Alcohol dependence; Alcohols; Atrophic; Attenuated; Autopsy; Behavior; Biosensor; Brain; Cessation of life; Cognition; Communities; Cues; Data; Development; Education; Emotional; Emotions; Esthesia; Etiology; European; Future; Gene Expression; Genomics; Heavy Drinking; Impulsivity; Individual; Individual Differences; Longitudinal Studies; Maintenance; Manuscripts; Mediating; Memory; Modeling; Not Hispanic or Latino; Pattern; Phenotype; Policies; Predisposing Factor; Predisposition; Prevention; Research; Rewards; Risk; Risk Factors; Risk-Taking; Sample Size; Series; Sleep; Structure; Testing; Time; Trauma; Youth; addiction; alcohol consequences; alcohol effect; alcohol exposure; alcohol involvement; alcohol risk; alcohol use disorder; alcohol use initiation; association cortex; base; binge drinking; burden of illness; cognitive control; cognitive reappraisal; cohort; cost; data sharing; database of Genotypes and Phenotypes; disease classification; drinking; drinking onset; early alcohol use; emerging adult; emotion regulation; gene discovery; genome wide association study; gray matter; indexing; innovation; interest; multimodality; negative affect; neurodevelopment; neuroimaging; neurotoxic; preventable death; prospective; relating to nervous system; social; socioeconomics; theories; underage drinking; young adult

PROJECT SUMMARY/ABSTRACT Alcohol use is associated with significant personal and socioeconomic costs (accounting for more than 5% of global disease burden as well as worldwide deaths). Alcohol use initiation, progression to heavy episodic drinking, and early onset alcohol use disorder 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 maturation may also be influenced by alcohol use. However, whether alcohol use alters brain maturation and/or results from individual differences in neural development attributable to predipsositional genomic background is unclear and can only be addressed by genomically-informed longitudinal research with extensive alcohol phenotyping. In this 2-year R21, we propose to add genome-wide association study (GWAS) content to 2 longitudinal neuroimaging studies of adolescents and young adults (n=696; spanning ages 12-33 with annual neuroimaging and biannual alcohol characterization) to examine whether brain changes during adolescence and young adulthood associated with alcohol use may represent polygenic risk factors and/or represent consequences of heavy alcohol exposure. Disentangling the contributions of predisposing factors from consequences of alcohol on structural brain trajectories will inform our etiologic understanding of alcohol use during adolescence and young adulthood that could contribute to alcohol- related policy, education, nosology, prevention, and treatment. Primary deliverables from this project will be manuscripts examining whether polygenic propensity to alcohol use, as well as risk for impulsivity and negative affect and deficits in cognition, modify trajectories of brain maturation and further alter the course of youth alcohol engagement. Further, due to the extensive scope of longitudinal data available in these studies (e.g., other neural phenotypes, psychiatric, sleep, trauma, biosensor assessments), the addition of GWAS data will provide benefits to the broader research community through data sharing (e.g., dbGaP) and contribute to consortia-based gene discovery efforts (e.g., ENIGMA, PGC).

项目摘要/摘要 饮酒与巨大的个人和社会经济成本有关（占超过5％ 全球疾病负担以及全球死亡）。饮酒的启动，向沉重发作的发展 在青春期和成年期间通常会出现饮酒和早期饮酒障碍。这 理论上认为，风险的发展期是由区域异步大脑的典型模式产生的 成熟（即，边缘区域的快速和早期发展以及相对不成熟的前额叶和 多模式关联皮层）导致抑制不适当的情绪，欲望， 当存在显着的环境提示时。在成年后期的稳定期间， 减少或不再使用大量使用通常与成熟的认知控制和情感一起发生 调节能力与皮质发展一致。大脑成熟也可能受酒精的影响 使用。但是，酒精使用是否改变了脑的成熟和/或来自神经个体差异的结果 归因于预性基因组背景的发展尚不清楚，只能通过 具有广泛酒精表型的基因组知觉的纵向研究。在这2年的R21中，我们建议 将全基因组关联研究（GWAS）含量添加到2个青少年的纵向神经影像学研究 和年轻人（n = 696；年龄在12-33岁之间，每年神经影像学和双年一次的酒精表征） 检查青春期和与饮酒相关的青春期和成年期间的大脑变化是否可能 表示多基因风险因素和/或表示大量酒精暴露的后果。解开 酒精对结构脑轨迹的后果的易感性因素的贡献将为我们的 对青春期和成年期饮酒的病因学了解可能有助于酒精 相关政策，教育，性科，预防和治疗。该项目的主要可交付成果将是 手稿检查了饮酒的多基因倾向以及冲动和负面的风险 影响和缺陷认知，修改大脑成熟的轨迹并进一步改变青年酒精的进程 订婚。此外，由于这些研究可用的纵向数据范围广泛（例如，其他神经 表型，精神病，睡眠，创伤，生物传感器评估），GWAS数据的添加将提供好处 通过数据共享（例如DBGAP）向更广泛的研究社区致力于基于财团的基因 发现工作（例如，谜，PGC）。