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）：通过多项汇聚的证据，青春期已被确定为对酒精影响高度敏感的时期，包括：1）对成人长期大量饮酒的神经心理学和神经学相关性的研究，2）对酒精影响的研究青春期典型的大脑发育记录了大脑在此生命阶段的持续可塑性，3) 对青春期大鼠的研究表明，由于酒精暴露而出现功能和结构缺陷。尽管如此，现有关于人类青少年酒精暴露的研究文献在规模和范围上都有限，并且青少年饮酒的相关性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发育大脑影响的性质和范围的理解，我们提出了一项针对 48 对青少年同卵双胞胎 (MZ) 的纵向研究。十六对 14、15 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，旨在对被认为对酒精影响最敏感的大脑结构（例如前额皮质和海马体）进行全面评估）并与奖励敏感性、执行控制和记忆力有关。他们还将完成对酒精使用、其他药物使用和相关精神病理学的全面评估。初步测试一年后，这对双胞胎将再次接受评估，以记录各种结构和功能措施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是否：1）终生摄入时的暴露与结构和功能缺陷相关； 2）饮酒行为的改变预示着赤字的增加； 3）可测量的（例如，外化精神病理学）和未测量的（例如，通过 MZ 双胞胎对照设计解释的遗传风险）混杂因素可以解释青少年饮酒的结构和功能相关性。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、全面地研究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神经毒性作用最脆弱的时期，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有限，因此不确定青少年饮酒对公共健康的影响。这项针对青少年同卵双胞胎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，并使用双胞胎设计来控制对早期饮酒和问题饮酒的不可测量的影响。