Published online by Cambridge University Press: 23 May 2017
The current study used data from two longitudinal samples to test whether self-regulation, depressive symptoms, and aggression/antisociality were mediators in the relation between a polygenic score indexing serotonin (5-HT) functioning and alcohol use in adolescence. The results from an independent genome-wide association study of 5-hydroxyindoleacetic acid in the cerebrospinal fluid were used to create 5-HT polygenic risk scores. Adolescents and/or parents reported on adolescents’ self-regulation (Time 1), depressive symptoms (Time 2), aggression/antisociality (Time 2), and alcohol use (Time 3). The results showed that 5-HT polygenic risk did not predict self-regulation. However, adolescents with higher levels of 5-HT polygenic risk showed greater depression and aggression/antisociality. Adolescents’ aggression/antisociality mediated the relation between 5-HT polygenic risk and later alcohol use. Deficits in self-regulation also predicted depression and aggression/antisociality, and indirectly predicted alcohol use through aggression/antisociality. Pathways to alcohol use were especially salient for males from families with low parental education in one of the two samples. The results provide insights into the longitudinal mechanisms underlying the relation between 5-HT functioning and alcohol use (i.e., earlier aggression/antisociality). There was no evidence that genetically based variation in 5-HT functioning predisposed individuals to deficits in self-regulation. Genetically based variation in 5-HT functioning and self-regulation might be separate, transdiagnostic risk factors for several types of psychopathology.
This work was supported by Grants AA016213 and AA022097 (to L.C.) and AA023128 (to F.L.W.) from the National Institute on Alcohol Abuse and Alcoholism. Genotyping was supported by the Midwest Alcohol Research Center (P50 AA011998). The Child Development Project has been funded by Grants MH56961, MH57024 (including supplemental funds in response to NOT-RM-05-007 for collection of DNA), and MH57095 from the National Institute of Mental Health, HD30572 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, and DA016903 from the National Institute on Drug Abuse.