The Causal Role of Alcohol Use in Adolescent Externalizing and Internalizing Problems: A Mendelian Randomization Study

Background: The co-occurrence of alcohol use and externalizing/internalizing problems threatens adolescents’ mental health. Research on whether alcohol use and these problems are causal and the direction of the potential causal relationships is needed to understand the mechanisms of the co-occurrence. Methods: A Mendelian randomization analysis was conducted in which the aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as an instrumental variable for alcohol use phenotypes. In total, 1,608 Chinese adolescents (mean age 14.11 ± 1.83 years) were genotyped for the ALDH2 rs671 polymorphism. Three externalizing problems (aggression, delinquency, and attention problems) were measured with the Youth Self-Report inventory, and 2 internalizing problems (depression and anxiety) were measured with the self-reported Children's Depression Inventory and the Trait subscale of the State-Trait Anxiety Inventory. Results: Alcohol use was positively associated with all 3 externalizing and 2 internalizing problems, and the ALDH2 polymorphism had a significant effect on alcohol use. Aggression and attention problems were also significantly affected by the ALDH2 polymorphism, whereas no significant association was observed between the ALDH2 polymorphism and delinquency, anxiety, or depression. Conclusions: The results suggest that alcohol use is a cause of adolescent aggression and attention problems but not adolescent delinquency, anxiety, or depression.