Alcohol Use Disorders: Tracts, Twins, and Trajectories

Abstract

gray matter reduction in the cortical lateral frontal and temporal lobes and attenuated white matter growth of the corpus callosum and pons relative to nondrinking control subjects. In a study by Ruggeri et al. (2), alcohol use disorders were associated with hypermethylation in the 3:-protein-phosphatase-1G (PPM1G )g ene locus; more specifically, PPM1G hypermethylation was associated with the escalation of alcohol use, increased impulsiveness, and increased activity in the right subthalamic nucleus. How are thesetwoobservations—oneonneurocircuitryimagingchanges in adolescents and one on protein phosphatase methylation in adolescents—related? Theadolescentbrainundergoeswidespreadchangesinform and function, both within individual regions and in the connections betweenthem. Studies have shown that a reduction of cortical gray matter begins in preadolescence and continues into the mid-20s, possibly reflecting a normal pruning process(3,4).Equallycompellingaredatashowingthatwhite matter volume increases over the course of adolescence, presumably reflecting connectivity changes, including axonal extension and myelination (4). Mounting evidence suggests that the complex changes underlying neurodevelopment render the adolescent brain particularly vulnerable to the deleterious effects of alcohol. Heavy alcohol use during adolescence is associated with a range of neurobehavioral sequelae, including impairments in visuospatial processing, attention, and memory (5,6)andanincreased riskfor future alcoholuse disorders.