Serotonin transporter and GABA(A) alpha 6 receptor variants are associated with neuroticism

Background. A tendency to experience negative affect, as measured by the neuroticism component of the Neuroticism, Extraversion, and Openness Personality Inventory (NEO-PI), is a trait marker for major depression. Epidemiologic studies indicate a strong genetic component, but to date few specific genetic variants have been definitively implicated. A serotonin transporter promoter polymorphism (5-HTTLPR) has been extensively studied in neuroticism and several psychiatric disorders, with inconclusive results. A GABA(A) receptor alpha6 subunit variant (Pro385Ser) has been associated with alcohol-related traits but has not been studied in neuroticism or depression. Methods. A total of 384 subjects who completed the NEO-PI were genotyped at 5-HTTLPR and Pro385Ser. Associations between polymorphisms and both alcohol use and personality domains were tested. Results: The 5-HTTLPR short allele (p = .008) and Pro385Ser Pro allele (p = .003) are associated with higher neuroticism scores. The 5-HTTLPR long allele (p = .006), but not Pro385Ser, is also associated with an increased presence of alcohol use. In addition, there is a nonsignificant suggestion of an interaction: the effect of 5-HTTLPR on neuroticism might be dependent on the Pro385Ser genotype. Conclusions: These findings support a role for the serotonin transporter and GABA(A) alpha6 subunit in depression-related traits.