The serotonin transporter gene-linked polymorphic region (5-HTTLPR) and the sleep-promoting effects of tryptophan: A randomized placebo-controlled crossover study

Jens H van Dalfsen*, C Rob Markus

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


BACKGROUND: The low-expressive short (S) allele of a functional polymorphism (5-HTTLPR) within the serotonin (5-hydroxytriptamine; 5-HT) transporter gene (SLC6A4) has been associated with a reduced functioning of the brain 5-HT system relative to the long (L) allele. As a consequence, the S-allele is found to predispose individuals to a higher risk of sleep quality reduction and clinical insomnia.

AIMS: The present study investigated whether subchronic pre-sleep tryptophan administration could compensate for this predisposition by improving sleep in 5-HTTLPR S-allele carriers.

METHODS: In a double-blind placebo-controlled crossover design a sample of homozygous 5-HTTLPR S-allele (n = 47) and L-allele (n = 51) carriers were assessed for subjective (sleep diary) and objective (actigraphy) sleep during a treatment protocol consisting of 1 week of placebo (1000 mg/day) and 1 week of tryptophan administration (1000 mg/day).

RESULTS: The results support the sleep-promoting effects of tryptophan. Tryptophan improved objective sleep efficiency and objective wake after sleep onset irrespective of allelic variation. There was a marginally significant improvement of subjective sleep quality in the 5-HTTLPR S-allele group but not in the L-allele group following tryptophan relative to placebo intake. In contrast, a significantly poorer sleep quality in the S-allele as opposed to the L-allele group in the placebo condition was not observed in the tryptophan condition.

CONCLUSIONS: Tryptophan augmentation promises to be a valuable treatment strategy for sleep impairments related to genetic deficiencies in 5-HT functioning.

Original languageEnglish
Pages (from-to)948-954
Number of pages7
JournalJournal of Psychopharmacology
Issue number8
Early online date25 Jun 2019
Publication statusPublished - Aug 2019


  • 5-HTTLPR
  • Sleep
  • insomnia
  • serotonin
  • tryptophan

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