Neurocognitive Risk For Alcoholism Into Adulthood

描述(申请人提供)：本项目的科学问题集中在18-23岁期间的四个核心发育现象：1)这一时期通常是生命过程中饮酒最高的时期；2)接近这一时期结束时，对大多数年轻人来说，饮酒开始减少；3)对于人口中风险较高的人群，高消费模式仍在继续；4)当这些关键的行为转变正在发生时，负责努力控制和奖励反应/激励反应的神经网络也在成熟，尽管速度不同。关于青少年饮酒和干预的社会政策，有三个尚未回答的问题需要解决：a)这些神经网络的成熟在多大程度上导致了饮酒行为在这一发育阶段发生的变化？b)大量饮酒是否影响了这些网络的成熟？c)社会环境增强者和先前的个体风险差异如何调节或缓和这两种结果？在过去的5年里，这个项目调查了后来问题酒精使用的神经认知和大脑功能指标，确定了问题使用的轨迹以及风险和弹性的神经指标。这一修订后的延续项目建立在先前工作的基础上，将调查扩展到成年早期，并确定大量饮酒对人格、神经认知和大脑功能的影响，以及整个青春期和成年期早期风险、大量饮酒和社会背景(社会支持、同伴饮酒、环境侮辱)之间的相互作用。受试者是密歇根纵向研究的参与者，这是一项酒精使用障碍的高风险家庭研究，从幼年开始就表征了气质、行为风险和社会背景，从青春期早期就开始研究神经认知风险。从青春期晚期开始，就对这些参与者中的一部分进行了相关脑功能的fMRI研究。在接下来的5年里，这项研究将探索努力控制和激励反应的两个领域，从大脑功能(额纹状体和额叶边缘回路和连接的调节/失调)、神经认知和个性水平进行评估。神经认知和个性评估将从12岁开始，每隔3年进行一次(N=1456)；从18岁开始，参与者中的一部分(N=225)将继续每年通过功能磁共振进行评估。成像工作的一个重要新焦点是额叶和皮质下突起之间的相互作用，将使用延迟折扣任务进行纵向探索，以及额纹状体和额缘功能连接分析。研究结果将描述饮酒行为、社会环境以及大脑功能和连接性变化之间的关系。一个特别的焦点是饮酒行为在多大程度上滞后于大脑变化或引领大脑变化，以及社会环境在调节这种变化中所起的作用。 与公共卫生相关：该项目可能会促进更深入地了解在大量饮酒和酒精使用障碍达到顶峰时，这两种现象的易感性背后的中间神经通路。研究结果将为性情、行为、大脑网络和社会环境风险如何相互作用提供新的知识，影响饮酒行为和大脑功能网络的稳定性和变化，可以说是一生中饮酒最关键的发育期。这一发现将对早期识别、预防和早期治疗高危个人以及那些处于酗酒生涯早期阶段的人产生影响。

DESCRIPTION (provided by applicant): The scientific issues of this project are focused around four core developmental phenomena of the 18-23 year old period: 1) this period is normatively the highest alcohol consumption interval in the life course; 2) toward the end of this interval, for the majority of young adults, a decrease in consumption begins to take place; 3) for a higher risk subset of the population, the high consumption pattern continues; and 4) while these critical behavioral shifts are occurring, the neural networks responsible for effortful control and reward response/incentive reactivity are also maturing, albeit at different rates. Three corollary, as yet unanswered questions critical to both social policy about youthful drinking and intervention, are to be addressed: A) To what degree are the changes in drinking behavior taking place over this developmental interval attributable to the maturation of these neural networks?; B) Does heavy alcohol consumption influence the maturation of these networks?; C) How do social environmental reinforcers and prior individual differences in risk mediate or moderate both of these outcomes? During the past 5 years, this project has investigated neurocognitive and functional brain indicators of later problem alcohol use, identifying trajectories of problem use and neural indicators of risk and resilience. This revised continuation project builds on this prior work by extending the investigation into early adulthood and identifying effects of heavy drinking on personality, neurocognition and brain function as well as the interactions between early risk, heavy drinking, and social context (social supports, peer drinking, environmental insults) throughout adolescence and early adulthood. Subjects are participants in the Michigan Longitudinal Study, a high risk for alcohol use disorder family study that has been characterizing temperament, behavioral risk and social context since early childhood and neurocognitive risk since early adolescence. Associated brain function has been studied using fMRI since late adolescence in a subset of these participants. Over the next 5 years, the study will probe the two domains of Effortful Control, and Incentive Reactivity, assessed at the levels of brain function (Regulation/dysregulation of frontostriatal and frontolimbic circuitry and connectivity), neurocognition, and personality. Neurocognitive and personality assessments will continue at 3 year intervals (N= 1456), starting at age 12; a subset of participants (N = 225) will continue to be assessed yearly via fMRI starting at age 18. An important new focus of the imaging work is the interaction between frontal and subcortical processes, to be explored longitudinally using a delayed discounting task, and frontostriatal and frontolimbic functional connectivity analyses. Results will developmentally characterize the relationship between drinking behavior, social environment, and brain function and connectivity change. A special focus is the extent to which drinking behavior lags brain change or leads it, and the role that social environment plays in moderating such change. PUBLIC HEALTH RELEVANCE: This project is likely to promote a more in-depth understanding about the intermediate neural pathways underlying susceptibility to heavy drinking and alcohol use disorder at an age interval when both of these phenomena reach their peak. Results will provide new knowledge of how temperament, behavior, brain networks and social environmental risk interact, influencing stability and change in drinking behavior and brain functional networks at arguably the most critical developmental period for alcohol use in the lifespan. Findings will have implications for early identification, prevention, and early treatment of at risk individuals, as well as those in the early stages of an alcohol abusing career.