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

Srijan Sen, Sandra Villafuerte, Randolph Nesse, Scott F. Stoltenberg, Jeffrey Hopcian, Lillian Gleiberman, Alan Weder, Margit Burmeister

Research output: Contribution to journalArticlepeer-review

114 Scopus citations


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 α6 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) α6 subunit in depression-related traits.

Original languageEnglish (US)
Pages (from-to)244-249
Number of pages6
JournalBiological Psychiatry
Issue number3
StatePublished - Feb 1 2004
Externally publishedYes


  • Anxiety
  • Association
  • Depression
  • Interaction
  • NEO-PI
  • Personality
  • Polymorphism
  • Serotonin
  • γ-aminobutyric acid

ASJC Scopus subject areas

  • Biological Psychiatry


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