Genetic and neurophysiological correlates of the age of onset of alcohol use disorders in adolescents and young adults.

Discrete time survival analysis was used to assess the age-specific association of event-related oscillations (EROs) and CHRM2 gene variants on the onset of regular alcohol use and alcohol dependence. The subjects were 2,938 adolescents and young adults ages 12-25. Results showed that the CHRM2 gene variants and ERO risk factors had hazards which varied considerably with age. The bulk of the significant age-specific associations occurred in those whose age of onset was under 16. These associations were concentrated in those subjects who at some time took an illicit drug. These results are consistent with studies which associate greater rates of alcohol dependence among those who begin drinking at an early age. The age specificity of the genetic and neurophysiological factors is consistent with recent studies of adolescent brain development, which locate an interval of heightened vulnerability to substance use disorders in the early to mid teens

Examining associations between genetic and neural risk for externalizing behaviors in adolescence and early adulthood

Background: Researchers have identified genetic and neural risk factors for externalizing behaviors. However, it has not yet been determined if genetic risk is conferred in part through associations with more proximal neurophysiological risk markers. Methods: Participants from the Collaborative Study on the Genetics of Alcoholism, a large, family-based study of alcohol use disorders were genotyped and polygenic risk scores for externalizing (EXT PRS) were calculated, based on a recent large-scale GWAS. Associations with target P3 amplitude from a visual oddball task (P3) and broad endorsement of externalizing behaviors (indexed via self-report of alcohol, and cannabis use, and antisocial behavior) were assessed in participants of European (N = 2,885) and African ancestry (N = 1,408). Analyses were also stratified by age (adolescents, age 12-17.9 and young adults, age 18-32). Results: The EXT PRS was significantly associated with higher levels of externalizing behaviors among adolescents and young adults of European ancestry (EA) as well as among young adults of African ancestry (AA). P3 was inversely correlated with externalizing behaviors among young adults and EA adolescents. EXT PRS was not associated with P3 amplitude and therefore, there was no evidence that P3 amplitude indirectly accounted for the association between EXT PRS and externalizing behaviors. Conclusions: The EXT PRS and P3 amplitude were each significantly associated with externalizing behaviors with the most consistent effects seen in young adults. However, these associations with externalizing behaviors appear to be independent of each other, suggesting that they may index different facets of externalizing

Genetic and neurophysiological correlates of the age of onset of alcohol use disorders in adolescents and young adults.

Discrete time survival analysis was used to assess the age-specific association of event-related oscillations (EROs) and CHRM2 gene variants on the onset of regular alcohol use and alcohol dependence. The subjects were 2,938 adolescents and young adults ages 12-25. Results showed that the CHRM2 gene variants and ERO risk factors had hazards which varied considerably with age. The bulk of the significant age-specific associations occurred in those whose age of onset was under 16. These associations were concentrated in those subjects who at some time took an illicit drug. These results are consistent with studies which associate greater rates of alcohol dependence among those who begin drinking at an early age. The age specificity of the genetic and neurophysiological factors is consistent with recent studies of adolescent brain development, which locate an interval of heightened vulnerability to substance use disorders in the early to mid teens