The effect of tryptophan on the cortisol response to social stress is modulated by the 5-HTTLPR genotype

Psychoneuroendocrinology. 2013 Feb;38(2):201-8. doi: 10.1016/j.psyneuen.2012.05.016. Epub 2012 Jun 18.


Objective: The S'/S' (S/S, S/Lg and Lg/Lg) variant of the serotonin (5-HT) transporter gene linked polymorphic region (5-HTTLPR) is associated with less efficient neurotransmission and may be more reactive to 5-HT manipulations. We tested the effects of l-tryptophan supplements on the cortisol response induced by a social stressor in S'/S' and L'/L' (La/La) carriers.

Methods: In a double-blind parallel design, 25 S'/S' carriers and 21 L'/L' carriers were randomised to take l-tryptophan (2.8g/d) or placebo supplements for six days. At day 7 participants were exposed to the Trier Social Stress Test. Salivary cortisol and subjective mood states were monitored before, during and after the stress procedure.

Results: S'/S' carriers who took l-tryptophan supplements had a significantly lower cortisol response to stress than S'/S' carriers who took placebo. Tryptophan had no effect on cortisol in L'/L' carriers and no effect on subjective mood states in either genotype group.

Conclusion: Tryptophan attenuates the cortisol response to acute social stress depending on 5-HTTLPR genotype. S'/S' carriers may indeed be more reactive to 5-HT manipulations.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Affect / drug effects
  • Double-Blind Method
  • Female
  • Genotype
  • Humans
  • Hydrocortisone / metabolism*
  • Male
  • Patient Compliance
  • Polymorphism, Genetic / genetics
  • Saliva / metabolism
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Stress, Psychological / genetics
  • Stress, Psychological / metabolism*
  • Tryptophan / pharmacology*


  • Serotonin Plasma Membrane Transport Proteins
  • Tryptophan
  • Hydrocortisone