Cognitive endophenotypes in impulsivity : 5-HTTLPR influences inhibitory control in healthy subjects

Background: The serotonin transporter polymorphism (5-HTTLPR), related to serotonin transmission in the brain, has been associated with impulsive behavior. Impulsive behavior and lack of inhibitory control are components in various psychiatric disorders. Although several studies have associated 5-HTTLPR and impulsivity, the literature is ambiguous. By measuring impulsivity with objective behavioural measures, and applying the triallelic classification of genotypes, this study aimed to explore the association between impulsivity and 5-HTTLPR. A subordinate aim was to investigate a possible sex by 5-HTTLPR genotype interaction on impulsivity. Methods: The data were collected as part of the project “Cognitive control, mood, brain function and genetics in major depressive disorder and healthy people”. The authors participated in collection of the data. The principal investigator of this project is Nils Inge Landrø. Participants in this study were 87 healthy adults from 19 to 61 years. Blood samples were drawn from all participants for 5-HTTLPR genotyping. Inhibition and response style were assessed with the stop signal task and the continuous performance test. Results: Results showed a significant effect of genotype on stop signal reaction time. An unexpected age difference between groups moderated this effect. Assuming dominance of the low expressive alleles, SS and SL groups were collapsed. Reanalysis showed significant effects of genotype and age on stop signal reaction time. No significant effect of genotype was found on response style. No significant interaction between genotype and sex was found. The effect of the short allele on response style showed an opposite pattern in men and women, but this effect was not significant. Conclusion: The present study links the serotonin transporter polymorphism to inhibitory control. Inhibition is a central component of executive functions and impairment in these functions are associated with various psychological disorders. Through its effect on inhibition, the short allele may constitute a genetic vulnerability for impulse control disorders and depression