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

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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.