The involvement of sleep in the relationship between the serotonin transporter gene-linked polymorphic region (5-HTTLPR) and depression: A systematic review

Jens H van Dalfsen*, C Rob Markus

*Corresponding author for this work

Research output: Contribution to journal(Systematic) Review article peer-review


BACKGROUND: Recent meta-analyses stimulate an ongoing debate whether 5-HTTLPR modulates the risk for depression including a more pronounced association between stress and depression in the short (S) allele relative to the long (L) allele. Elucidating the pathways by which 5-HTTLPR contributes to depression could resolve this controversy. Insomnia independently contributes to the onset and course of negative affective symptoms and, hence, represents one of the primary risk factors for depression. To evaluate the relevance of this relationship for the interaction between 5-HTTLPR and stress in depression, the present review investigated the moderating influence of 5-HTTLPR on the relationship between stress and sleep quality as well as on the relationship between sleep and affective symptomatology.

METHODS: A systematic search was performed in the PubMed and PsycINFO databases to include a complete outline of studies investigating the relationships of interest.

RESULTS: Results of the included articles reveal that the 5-HTTLPR S-allele relative to the L-allele increases the risk for stress-related sleep quality reductions and promotes the negative affective consequences of inadequate sleep.

LIMITATIONS: The apparent involvement of sleep in the association between 5-HTTLPR and depression remains to be more directly (empirically) examined and studies exploring the influence of 5-HTTLPR on sleep quality produced inconsistent results.

CONCLUSIONS: The reviewed findings support the involvement of sleep in the interaction between 5-HTTLPR and stress in depression. This could have important implications for the inconsistent findings characterizing this field of research and may provide valuable insight into the pathophysiological mechanisms underlying genetic contributions to depression.

Original languageEnglish
Pages (from-to)205-212
Number of pages8
JournalJournal of Affective Disorders
Early online date27 May 2019
Publication statusPublished - 1 Sept 2019


  • 5-HTTLPR
  • Depression
  • Gene-environment interaction
  • RISK
  • Sleep
  • Stress

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