Severity of self-reported depressive symptoms in a healthy sample is modulated by trait Harm Avoidance, not by 5-HTTLPR polymorphism

Psychiatry Res. 2020 Sep;291:113029. doi: 10.1016/j.psychres.2020.113029. Epub 2020 May 16.


Background: The length of the serotonin transporter polymorphic region (5-HTTLPR) has been suggested to be associated with risk for developing depression, though with inconsistent evidence. Likewise, the personality trait Harm Avoidance (HA) has been linked to vulnerability for developing depression. However, no study has investigated whether there is an interaction effect between 5-HTTLPR and trait HA on depressive symptoms in healthy individuals.

Methods: A total of 319 healthy individuals were included in this cross-sectional study. All participants were genotyped for the 5-HTTLPR polymorphism and completed self-reported measures of personality trait HA with the Temperament and Character Inventory (TCI), and of depression with the Major Depression Inventory (MDI). Linear regression analyses were used to test interaction effects between 5-HTTLPR and HA on MDI. Post hoc analyses were further performed to investigate main effects of HA and possible interaction effects between 5-HTTLPR and HA sub-scales on MDI.

Results: No significant interaction effect between 5-HTTLPR and HA on MDI was found. A significant main effect of trait HA on MDI was found, indicating that personality trait HA is a viable vulnerability factor for even sub-clinical depressive symptoms.

Conclusion: This study finds a strong significant relationship between HA and MDI. Moreover, the present study supports the line of research indicating that candidate gene-by-interactions does not increase vulnerability for developing depression even at a sub-clinical level.

Keywords: 5-HTTLPR; Harm Avoidance; Serotonin transporter polymorphism; depression; vulnerability.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Avoidance Learning / physiology
  • Character
  • Cross-Sectional Studies
  • Depressive Disorder / diagnosis
  • Depressive Disorder / genetics*
  • Depressive Disorder / psychology
  • Female
  • Harm Reduction / physiology*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Self Report*
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Severity of Illness Index
  • Temperament / physiology*
  • Young Adult


  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins