Timing Effects of Heavy Alcohol Initiation on Adolescent Neurodevelopment

描述(申请人提供)：青春期是一个发展时期，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，开始饮酒的早期年龄与晚年更容易上瘾之间存在很强的相关性。青春期也是相当大的神经成熟期，特别是在被认为有助于更高水平认知的额叶脑区，如决策和抑制。在大脑发育的这些关键时期大量饮酒可能会永久性地扰乱大脑成熟的过程，导致这些功能的长期缺陷，从而增加随后的物质使用行为的风险。建议的R01项目旨在利用神经成像和神经心理测试技术，前瞻性和纵向地研究发育阶段对酒精对青少年认知、脑功能和脑结构的影响。该项目将测试250名高危、未使用的12-14岁青少年(基于酗酒家族史)的执行功能、执行和冒险过程中的大脑功能、前额叶和边缘区域的大脑结构以及额纹状体白质完整性的测试中的神经心理表现。我们假设，与发育匹配的不饮酒青少年相比，在青春期饮酒的青少年在这些指标上会表现出异常，而且在青春期较早开始大量饮酒的青少年将比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有关青少年开始使用重酒的发育时机如何影响发育中的大脑的关键问题。与公共健康相关：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影响，早期饮酒与随后发生成瘾行为的风险更大相关。尽管如此，饮酒在青春期非常普遍。了解早期饮酒对发育中的青少年大脑的影响将有助于制定针对特定年龄和风险群体的旨在减少饮酒行为的干预措施。

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.