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

描述（由申请人提供）：青春期已被确定为对酒精影响高度敏感的时期，这是由多条证据汇聚而成的，包括：1）对成年人长期大量饮酒的神经心理学和神经学相关性的研究，2）对青春期典型大脑发育的研究，记录了大脑在这个生命阶段的持续可塑性，以及3）对由于酒精暴露而表现出功能和结构缺陷的青春期大鼠的研究。尽管如此，现有的研究文献对人类青少年的酒精暴露是有限的规模和范围，在多大程度上的青少年酒精使用的相关性代表真正的因果关系的影响或赤字，酒精暴露之前仍然不清楚。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对青少年单卵（MZ）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），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。双胞胎将在初步测试后一年再次进行评估，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相关; 2）饮酒行为的变化是否预示着缺陷的增加;以及3）测量的两种（例如，外化精神病理学）和不可测量的（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。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。青春期是酒精使用通常开始的时候。尽管汇聚线的证据表明，这一时期的高度脆弱性酒精的神经毒性作用之一，现有的研究文献对人类青少年的酒精暴露是有限的规模和范围，使不确定的青少年饮酒的公共卫生影响。这项对青少年同卵双胞胎（MZ）的纵向研究将使用对大脑结构和功能的全面评估，这些结构和功能被认为对酒精的影响最敏感，使用双胞胎设计来控制对早期开始和问题饮酒的不可测量的影响。

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.