Timing Effects of Heavy Alcohol Initiation on Adolescent Neurodevelopment

描述（由申请人提供）：青春期是一个发育期，在此期间，个人从事冒险行为，并可能开始使用酒精或其他药物。过去的研究表明，早期开始使用酒精与以后生活中更容易上瘾之间存在很强的相关性。青春期也是一个相当大的神经成熟的时期，特别是在被认为有助于更高层次认知的额叶脑区域，如决策和抑制。在大脑发育的这些关键时期使用大量酒精可能会永久性地破坏成熟过程，导致这些功能的长期缺陷，从而增加后续物质使用行为的风险。拟议的R 01项目的目的是前瞻性和纵向研究酒精对青少年认知，脑功能和脑结构的影响，使用神经影像学和神经心理学测试技术的发展阶段的影响。该项目将在250名处于风险中的非使用性12-14岁青年（基于酗酒家族史）中检查执行功能测试期间的神经心理学表现、执行和冒险fMRI任务期间的脑功能、前额叶和边缘系统区域的脑结构以及额纹状体白色物质完整性。我们假设，与发育匹配的非饮酒青年相比，在青春期饮酒的青年在这些指标上会出现异常，并且在青春期早期开始大量饮酒的青年比在发育后期开始大量饮酒的青少年表现出更大的异常。这项前瞻性研究将回答关于青少年开始大量饮酒的发育时间如何影响发育中的大脑的关键问题。公共卫生相关性：研究表明，青少年的大脑可能特别容易受到酒精的神经毒性作用的影响，并且早期使用与随后更大的成瘾行为风险有关。尽管如此，酒精使用在青少年中非常普遍。了解早期饮酒对青少年大脑发育的影响将有助于制定针对特定年龄和风险群体的干预措施，以减少饮酒行为。

DESCRIPTION (provided by applicant): Adolescence is a developmental period during which individuals engage in risk-taking behavior and are likely to initiate use of alcohol or other drugs. Past research suggests a strong correlation between early age of onset of alcohol use and a heightened vulnerability to addiction later in life. Adolescence is also a time of considerable neuromaturation, particularly in frontal brain regions thought to subserve higher level cognition, such as decision making and inhibition. Heavy alcohol use during these critical periods of brain development may permanently disrupt the course of maturation, resulting in long-term deficits in these functions and thereby increasing the risk of subsequent substance use behavior. The proposed R01 project is designed to prospectively and longitudinally examine the influence of developmental stage on the effects of alcohol on adolescent cognition, brain functioning, and brain structure, using neuroimaging and neuropsychological testing techniques. This project will examine neuropsychological performance during tests of executive functioning, brain functioning during executive and risk taking fMRI tasks, brain structure in prefrontal and limbic regions, and frontostriatal white matter integrity in 250 at-risk, non-using 12-14-year-old youth (based on family history of alcoholism). We hypothesize that youth who drink in adolescence will show abnormalities on these measures compared to developmentally-matched non-drinking youth, and that youth who initiate heavy drinking earlier in puberty will show greater abnormalities than teens that initiate heavy drinking later in development. This prospective study will answer critical questions about how developmental timing of adolescent heavy alcohol use initiation affects the developing brain. PUBLIC HEALTH RELEVANCE: Studies show that the adolescent brain may be particularly vulnerable to alcohol's neurotoxic effects, and that earlier use is associated with greater subsequent risk of addictive behaviors. Despite this, alcohol use is very common among adolescence. Understanding the impact of early alcohol use on the developing adolescent brain will facilitate the creation of interventions aimed at reducing alcohol drinking behaviors that are targeted at specific age and risk groups.