Original Research

Behavior Genetics

, Volume 38, Issue 5, pp 476-483

Open Access This content is freely available online to anyone, anywhere at any time.

5-HTTLPR and Gender Moderate Changes in Negative Affect Responses to Tryptophan Infusion

  • Beverly H. BrummettAffiliated withDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center Email author 
  • , Christopher L. MullerAffiliated withCenter for Human Genetics, Duke University Medical Center
  • , Ann L. CollinsAffiliated withCenter for Human Genetics, Duke University Medical Center
  • , Stephen H. BoyleAffiliated withDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center
  • , Cynthia M. KuhnAffiliated withDepartment of Pharmacology and Cancer Biology, Duke University Medical Center
  • , Ilene C. SieglerAffiliated withDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center
  • , Redford B. WilliamsAffiliated withDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center
  • , Allison Ashley-KochAffiliated withCenter for Human Genetics, Duke University Medical Center

Abstract

Expression of the serotonin transporter is affected by the genotype of the 5-HTTLPR (short and long forms) as well as the genotype of the SNP rs25531 within this region. Based on the combined genotypes for these polymorphisms, we designated each allele as a high or low expressing allele according to established expression levels—resulting in HiHi, HiLo, & LoLo genotype groups for analysis. We evaluated effects of gender and the promoter genotype on induction of negative affect by intravenous infusion of l-tryptophan (TRP). The protocol consisted of a day-1 sham saline infusion and a day-2 active TRP infusion. Models assessed 5-HTTLPR composite genotype and gender as predictors of change in ratings of negative emotion during TRP infusion. During sham infusion there were no significant changes from baseline in mood ratings. During TRP infusion all negative affect ratings increased significantly from baseline (P’s < .02). The genotype × gender interaction was a significant predictor of depression-dejection (P = .013), and trended towards predicting anger−hostility (P = .084). Males in the HiHi group had greater increases in negative affect during infusion, compared to all groups except LoLo females, who also showed increased negative affect.

Keywords

5-HTTLPR Gender l-tryptophan Mood Serotonin SNP rs25531