Impaired recognition of fear facial expressions in 5-HTTLPR S-polymorphism carriers following tryptophan depletion

Psychopharmacology (Berl). 2006 Dec;189(3):387-94. doi: 10.1007/s00213-006-0581-2. Epub 2006 Sep 30.


Rationale: Genotype at the 5' promoter region (5-HTTLPR) of the serotonin transporter has been implicated in moderating the effects of acute tryptophan depletion on neurocognitive functioning. Acute tryptophan depletion has been associated with the processing of fear-relevant cues, such as emotional expressions, but the effect of genotype at the 5-HTTLPR has not been assessed.

Objective: The present study investigated the effects of acute tryptophan depletion on the recognition of standardized facial expressions of emotions in healthy volunteers classified as ll homozygotes or s carriers.

Materials and methods: A double-blind between-groups design was used with volunteers randomly selected to ingest capsules containing an amino acid mixture specifically lacking tryptophan, or placebo capsules containing lactose. 5 h after capsule ingestion, subjects were required to identify anger, disgust, fear, happiness, sadness, and surprise expressions that progressed from neutral to each full emotional expression in 5% steps.

Results: Tryptophan depletion significantly impaired the recognition of fearful facial expressions in s carriers but not ll homozygotes. This impairment was specific to fear expressions. No significant differences in the recognition of other expressions were found. Free tryptophan levels were correlated with fear recognition in s carriers but not ll homozygotes.

Conclusions: The effects of acute tryptophan depletion on the processing of emotional expressions varies as a function of genotype at the 5-HTTLPR. Depletion impairs the recognition of fear in s carriers but not ll homozygotes. This finding reinforces the importance of considering genotype when assessing the behavioral effects of pharmacologic modulation.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Cognition Disorders / psychology*
  • Double-Blind Method
  • Facial Expression*
  • Fear / physiology
  • Fear / psychology
  • Female
  • Humans
  • Male
  • Polymorphism, Genetic
  • Recognition, Psychology*
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Tryptophan / deficiency*


  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Tryptophan