The short (S) allele of the serotonin transporter polymorphism and acute tryptophan depletion both increase impulsivity in men

Neurosci Lett. 2010 Apr 12;473(3):208-11. doi: 10.1016/j.neulet.2010.02.048. Epub 2010 Feb 25.


Reduced serotonergic neurotransmission is implicated in impulsive behavior. We studied the triallelic system of the serotonin transporter gene linked polymorphic region (5-HTTLPR) and acute manipulation of serotonin together to further delineate the mechanisms by which serotonergic neurotransmission affects impulsivity. Fifty-two healthy participants (38 men and 14 women) underwent acute tryptophan depletion (ATD) or placebo in a randomized, double-blind, parallel group experiment. Impulsive response style was measured on two versions of the Continuous Performance Task (CPT), and calculated using signal detection theory. We observed a dose-dependent effect for the short (S') allele of the 5-HTTLPR on impulsive response style. Individuals who had the S'/S' genotype were more impulsive than individuals with the L/S' genotype. Participants with the L/S' genotype were more impulsive than those with the L/L genotype. ATD increased impulsivity in men, and decreased impulsivity in women. These data demonstrate for the first time that reduced serotonergic tone as a result of either 5-HTTLPR genotype, or experimental ATD, are both independently and additively, associated with elevated impulsive response style in Caucasian men.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Double-Blind Method
  • Female
  • Genotype
  • Humans
  • Impulsive Behavior / genetics*
  • Male
  • Polymorphism, Genetic
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Sex Factors
  • Signal Detection, Psychological
  • Tryptophan / deficiency
  • Whites


  • Serotonin Plasma Membrane Transport Proteins
  • Tryptophan