Alcohol Effects on the Adolescent Brain: A Study of Monozygotic Twin Differences

酒精对青少年大脑的影响：同卵双胞胎差异的研究

• 批准号: 7391511
• 负责人: STEPHEN MATTHEW MALONE
• 金额: $ 46.93万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7391511
• 关键词: 16 year old; Abstinence; Accounting; Acute; Adaptive Behaviors; Address; Adolescence; Adolescent; Adult; Affect; Age; Alcohol abuse; Alcohol consumption; Alcoholic beverage heavy drinker; Alcohols; Animal Experimentation; Behavior; Brain; Characteristics; Chronic; Cognitive deficits; Competence; Coupled; Data; Deltastab; Development; Drug usage; Estrogen Receptors; Female Adolescents; Funding; Genetic Risk; Goals; Heavy Drinking; Hippocampus (Brain); Human; Image; Informal Social Control; Intake; Learning; Left; Life; Literature; Longitudinal Studies; Magnetic Resonance Imaging; Male Adolescents; Measures; Memory; Memory impairment; Monozygotic Twinning; Monozygotic twins; Nature; Neurologic; Pattern; Prefrontal Cortex; Problem behavior; Process; Prospective Studies; Psychopathology; Psychophysiology; Public Health; Range; Rattus; Research; Rewards; Risk Behaviors; Staging; Structure; System; Testing; Thinking; Tissues; Twin Multiple Birth; Week; Woman; alcohol effect; alcohol exposure; alcohol sensitivity; base; binge drinking; critical developmental period; design; drinking; drinking behavior; executive function; girls; male; memory recognition; men; neuropsychological; neurotoxic; neurotoxicity; problem drinker; relating to nervous system; size; underage drinking

DESCRIPTION (provided by applicant): Adolescence has been identified as a period of heightened sensitivity to alcohol's effects by multiple converging lines of evidence including: 1) research on the neuropsychological and neurological correlates of chronic heavy alcohol use in human adults, 2) research on typical brain development in adolescence documenting the brain's continued plasticity during this life stage, and 3) research on adolescent rats demonstrating functional and structural deficits due to alcohol exposure. Nonetheless, the existing research literature on alcohol exposure in human adolescents is limited in both size and scope, and the extent to which the correlates of adolescent alcohol use represent true causal effects or deficits that predated alcohol exposure remains unclear. To address limitations with existing research and expand our understanding of the nature and range of alcohol effects on the adolescent developing brain, we propose a longitudinal study of 48 pairs of adolescent monozygotic (MZ) twins. Sixteen pairs each of 14, 15, and 16-year old twins will complete a complementary set of neuropsychological, psychophysiological and MRI measures designed to provide a comprehensive assessment of brain structures thought to be most sensitive to alcohol's effects (e.g., prefrontal cortex and hippocampus) and related to reward sensitivity, executive control, and memory. They will also complete a comprehensive assessment of alcohol use, other drug use, and associated psychopathology. The twins will be assessed again one year after initial testing to document change in the various structural and functional measures as well as change in drinking practices. Analysis of the resulting data will focus on determining whether: 1) lifetime exposure at intake is associated with structural and functional deficits; 2) change in drinking behavior predicts increasing deficits; and 3) both measured (e.g., externalizing psychopathology) and unmeasured (e.g., genetic risk as accounted for through the MZ co-twin control design) confounders can account for the structural and functional correlates of adolescent drinking. The information obtained in this longitudinal study will be used to design a larger R01 application that systematically and comprehensively investigates the effects of alcohol on the adolescent brain. Adolescence is when alcohol use typically begins. Despite converging lines of evidence pointing to this period as one of heightened vulnerability to alcohol's neurotoxic effects, the existing research literature on alcohol exposure in human adolescents is limited in both size and scope, rendering uncertain the public health implications of adolescent drinking. This longitudinal study of adolescent monozygotic (MZ) twins will use a comprehensive assessment of brain structures and functions thought to be most sensitive to alcohol's effects, using a co-twin design to control for unmeasured influences on early initiation and problem drinking.

描述（由申请人提供）：通过多项证据，青春期已被确定为对酒精影响高度敏感的时期，包括：1)对成人慢性大量饮酒的神经心理学和神经学相关研究；2)对青春期典型大脑发育的研究，记录了大脑在这一生命阶段的持续可塑性；3)对青春期大鼠的研究，证明了酒精暴露导致的功能和结构缺陷。尽管如此，关于人类青少年酒精暴露的现有研究文献在规模和范围上都是有限的，青少年酒精使用的相关因素在多大程度上代表了酒精暴露之前的真正因果效应或缺陷仍不清楚。为了解决现有研究的局限性，并扩大我们对酒精对青少年大脑发育影响的性质和范围的理解，我们提出了一项对48对青少年同卵双胞胎的纵向研究。16对14岁、15岁和16岁的双胞胎将完成一套互补的神经心理学、心理生理学和MRI测量，旨在全面评估被认为对酒精影响最敏感的大脑结构（例如，前额叶皮层和海马体），以及与奖励敏感性、执行控制和记忆相关的大脑结构。他们还将完成对酒精使用、其他药物使用和相关精神病理的全面评估。在最初的测试一年后，这对双胞胎将再次接受评估，以记录各种结构和功能指标的变化，以及饮酒习惯的变化。对所得数据的分析将侧重于确定：1)摄入时的终生暴露是否与结构和功能缺陷有关；2)饮酒行为的改变预示着赤字的增加；3)可测量的混杂因素（如外化精神病理学）和不可测量的混杂因素（如通过MZ双胞对照设计计算的遗传风险）都可以解释青少年饮酒的结构和功能相关性。在这项纵向研究中获得的信息将用于设计一个更大的R01应用程序，系统和全面地调查酒精对青少年大脑的影响。青春期通常是开始饮酒的时期。尽管越来越多的证据表明，这一时期是酒精对神经毒性作用的高度脆弱性之一，但现有的关于人类青少年酒精暴露的研究文献在规模和范围上都是有限的，因此青少年饮酒对公共卫生的影响是不确定的。这项对青春期同卵双胞胎（MZ）的纵向研究将对被认为对酒精影响最敏感的大脑结构和功能进行全面评估，使用双胎设计来控制未测量的对早期开始饮酒和问题饮酒的影响。