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: 7504050
• 负责人: STEPHEN MATTHEW MALONE
• 金额: $ 45.69万
• 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 2011-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7504050
• 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(申请人提供)：青春期已被确定为对酒精的影响高度敏感的时期，多个证据汇聚在一起，包括：1)研究成人长期大量饮酒与神经心理和神经学的相关性，2)研究青春期典型的大脑发育，记录大脑在这一生命阶段的持续可塑性，以及3)对青春期大鼠的研究，表明它们因酒精暴露而出现功能和结构缺陷。尽管如此，现有的关于青少年酒精暴露的研究文献在规模和范围上都是有限的，青少年酒精使用在多大程度上代表了酒精暴露之前的真正因果影响或缺陷仍不清楚。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，我们提议对48对青少年同卵双胞胎进行纵向研究。16对14岁、15岁和16岁的双胞胎将完成一套补充的神经心理学、心理生理学和核磁共振测量，旨在提供对大脑结构的全面评估，这些结构被认为对酒精的影响最敏感(例如前额叶皮质和海马体)，并与奖励敏感性、执行控制和记忆有关。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。这对双胞胎将在最初测试一年后再次接受评估，以记录各种结构和功能措施的变化以及饮酒习惯的变化。对结果数据的分析将集中于确定：1)终生摄入与结构和功能缺陷有关；2)饮酒行为的变化预测缺陷增加；以及3)可测量的(例如，外化精神病理学)和未测量的(例如，通过MZ双胞胎对照设计考虑的遗传风险)混杂因素是否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被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。青春期是通常开始饮酒的时候。尽管越来越多的证据表明，这一时期更容易受到酒精的神经毒性影响，但现有的关于青少年酒精暴露的研究文献在规模和范围上都有限，这使得青少年饮酒对公共健康的影响变得不确定。这项针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，使用同卵双胞胎设计来控制对早期开始和问题饮酒的未测量影响。