Neural outcomes of moderating alcohol use in early adulthood

成年早期适度饮酒的神经后果

• 批准号: 10084576
• 负责人: STEPHEN MATTHEW MALONE
• 金额: $ 0.71万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-14 至 2021-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10084576
• 关键词: Abstinence; Address; Adolescence; Adult; Adverse effects; Affect; Age; Alcohol abuse; Alcohol consumption; Alcohol or Other Drugs use; Animals; Area; Brain; Brain region; Characteristics; Data; Data Analyses; Development; Drug usage; Etiology; Exposure to; Family Research; Female; Functional Magnetic Resonance Imaging; Gender; Genetic; Hippocampus (Brain); Individual; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Measures; Methods; Minnesota; Natural experiment; Neurons; Observation in research; Observational Study; Outcome; Pattern; Pharmaceutical Preparations; Preventive Intervention; Property; Recovery; Relapse; Research; Research Design; Residual state; Rest; Sampling; Shapes; Smoking; Statistical Methods; Structure; Surface; Synapses; Testing; Thick; Time; Twin Multiple Birth; Validation; adolescent brain development; alcohol and other drug; alcohol effect; alcohol exposure; alcohol measurement; alcohol use initiation; base; biobank; design; drinking; early adolescence; emerging adult; experience; genetics of alcoholism; guided inquiry; information processing; innovation; preadolescence; problem drinker; prospective; relating to nervous system; sobriety; sound; stem; white matter; young adult

Project Abstract Adolescence and early adulthood is a period of significant brain development, when different experiences shape the synaptic connections between neurons and information processing is increasingly integrated across various brain regions. It is also when substance use is at its greatest, on average. Research with animals indicates that the brain is particularly vulnerable to damaging effects of alcohol and other drugs during adolescence. However, most individuals moderate their drinking and it is arguably as important to understand the degree to which brain structural and functional effects of alcohol and other drug use tend to be reversed when individuals moderate their use as to understand effects of exposure to alcohol in the first place. However, several factors have slowed progress in this area. Samples have been small, especially in early studies, and the number of potential measures large, which, if properly controlled for, limits statistical power and, if not, increases the likelihood of chance findings. The lack of specific replicated associations suggests a need for studies that use discovery-based methods in large samples in addition to those that test specific hypotheses, and to replicate findings in independent samples. An additional obstacle to progress stems from the difficulty drawing inferences about causality in observational research. Associations between substance use or moderation and brain outcomes may reflect a causal effect of substance use or moderation or they may be spurious, reflecting the effect of a third, unobserved factor, such as a genetic liability, on both. For instance, individuals who stop abusing alcohol or other drugs may have less of a genetic liability toward excessive use than those who persist in problematic drinking, and any observed differences between the two groups of subjects may reflect this difference rather than any result of having desisted from problematic use. The present data analysis project is designed to address these challenges. We propose to study effects of cumulative alcohol use, the timing of exposure to alcohol and effects of moderating use on measures of brain structure and function in three large independent samples, which allows us to replicate findings and thereby increase confidence in them. We will use a combination of hypothesis-driven and discovery-based analyses. In addition, because two samples consist of twins, we will use an innovative co-twin differences research design, which takes advantage of differences in overall alcohol use, age of initiation and moderation of use that naturally occur within twin pairs to separate the effects of patterns of use and moderation from the genetic and other factors that influence them. This will permit us to make stronger inferences than is typically possible about which effects of alcohol use and moderation of use on measures of brain structure and function are likely to indicate a truly causal influence of exposure to alcohol and of reducing one’s exposure, which can inform prevention and intervention efforts as well as ongoing longitudinal studies.

项目摘要 青春期和成年早期是大脑发育的重要时期， 塑造神经元之间的突触连接，信息处理越来越多地整合在 不同的大脑区域平均而言，这也是物质使用最多的时候。动物研究 表明大脑特别容易受到酒精和其他药物的破坏性影响， 青春期然而，大多数人都会节制饮酒，这一点也很重要， 酒精和其他药物使用对大脑结构和功能的影响倾向于逆转的程度 当个人节制他们的使用，以了解暴露于酒精的影响摆在首位。然而，在这方面， 若干因素减缓了这方面的进展。样本一直很小，特别是在早期的研究中， 潜在测量的数量很大，如果适当控制，则限制统计功效，如果不适当控制， 增加了偶然发现的可能性缺乏特定的复制关联表明需要 除了那些检验特定假设的研究外，还使用大样本中基于发现的方法进行研究， 并在独立样本中重复研究结果。另一个阻碍进展的障碍是， 在观察研究中对因果关系进行推论。物质使用或 适度和大脑的结果可能反映了物质使用或适度的因果关系，或者它们可能是 虚假的，反映了第三个未观察到的因素的影响，如遗传责任，对两者的影响。比如说， 停止滥用酒精或其他药物的人可能对过度使用的遗传倾向较小 而那些坚持有问题饮酒的人，以及两组之间的任何观察到的差异， 受试者可能反映了这种差异，而不是停止有问题的使用的任何结果。本 数据分析项目旨在应对这些挑战。我们建议研究累积的 饮酒、饮酒时间以及适度饮酒对大脑结构测量的影响 并在三个大的独立样本中发挥作用，这使我们能够复制发现，从而增加 信任他们。我们将使用假设驱动和基于发现的分析相结合。此外，本发明还提供了一种方法， 由于两个样本都是双胞胎，我们将采用创新的双胞胎差异研究设计， 利用了整体酒精使用的差异，开始和适度使用的年龄， 发生在双胞胎对分离的影响模式的使用和节制从遗传和其他 影响他们的因素。这将使我们能够做出比通常可能的更强的推论， 酒精使用和适度使用对大脑结构和功能的影响可能会 表明接触酒精和减少接触酒精的真正因果关系，这可以告知 预防和干预工作以及正在进行的纵向研究。