Timing Effects of Heavy Alcohol Initiation on Adolescent Neurodevelopment

摘要： 青春期是个体从事冒险行为的发育期，很可能 开始使用酒精或其他药物。过去的研究表明，早期发病年龄与 酗酒和在晚年更容易上瘾。青春期也是一个 相当大的神经成熟，特别是在被认为有助于更高水平认知的额叶脑区， 比如决策和抑制。在大脑发育的这些关键时期大量饮酒 可能会永久性地破坏成熟的过程，导致这些功能的长期缺陷，从而 增加了随后的药物使用行为的风险。拟议的R01项目旨在 前瞻性和纵向考察了发育阶段对酒精影响的影响。 使用神经成像和神经心理学研究青少年的认知、脑功能和脑结构 测试技术。这个项目将测试在执行测试中的神经心理表现 功能，执行和冒险fMRI任务时的脑功能，前额叶和大脑结构 250名高危、未使用的12-14岁青年的边缘区域和额纹状体白质完整性(基于 家族酗酒史)。我们假设，在青春期饮酒的年轻人会表现出畸形。 这些措施与发育相匹配的不饮酒青年相比， 青春期早期饮酒会比青少年在青春期后开始大量饮酒表现出更大的异常 发展。这项前瞻性研究将回答以下关键问题： 青少年开始大量饮酒会影响大脑的发育。

Abstract: 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.