Author(s): Gelernter J, Kranzler H, Coccaro EF, Siever LJ, New AS
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Abstract OBJECTIVE: The SLC6A4 locus encodes the serotonin transporter, which in turn mediates the synaptic inactivation of the neurotransmitter serotonin. A polymorphism located in the 5' promoter region of the gene is associated with altered transcriptional activity of SLC6A4; an earlier study reported an association of the polymorphism with anxiety- and depression-related traits, including harm avoidance and neuroticism. The authors attempted to replicate this finding. METHOD: They assessed genotype at the SLC6A4 promoter polymorphism, and an additional polymorphism in intron 2, in 322 American subjects of European and African ancestry, some with diagnoses of a personality disorder or substance dependence and some normal comparison subjects. Harm avoidance was measured by the Tridimensional Personality Questionnaire in all subjects, and neuroticism was measured by the NEO Five-Factor Inventory in 185 subjects. Allele frequencies in the groups were compared, and hierarchical multiple regression was used to examine the correlation of demographic features, psychiatric diagnostic group, and genotype with harm avoidance and neuroticism scores. RESULTS: Although the demographic factors and psychiatric diagnoses had effects on harm avoidance and neuroticism scores, there was no main effect of genotype on these personality measures. In the context of these overall negative findings, interactions were observed between sex and promoter system genotype and between race and promoter system genotype which suggest that the present findings are not wholly inconsistent with those of the earlier study. CONCLUSIONS: The authors were unable to replicate the association finding. The specific phenotypic composition of the groups studied with respect to other behaviors could have influenced ability to detect association of SLC6A4 polymorphisms with personality measures; population stratification for this locus is also of potential importance.
This article was published in Am J Psychiatry
and referenced in Journal of Psychiatry