5-HTTLPR-brain-derived neurotrophic factor (BDNF) gene interactions and early adverse life events effect on impulsivity in suicide attempters

World J Biol Psychiatry. 2019 Feb;20(2):137-149. doi: 10.1080/15622975.2017.1376112. Epub 2017 Oct 6.


Objectives: An expanding body of research suggests that childhood adverse experiences can lead to different negative health outcomes, including attempted suicide. Serotonergic genes such as the promoter region of the serotonin transporter gene (5-HTTLPR) have been associated both with impulsivity in suicide attempts and reactivity to environmental stress exposure. BDNF gene may play an epigenetic role.

Methods: We studied the influence of childhood stressful events and 5-HTTLPR genotype on impulsivity measured by Barratt Impulsivity Scale (BIS-10) in a multicentre sample of 1,655 suicide attempters (69.4% women, 30.6% men; mean age 40.13 years). A co-dominant additive genetic model was used for the statistical analyses. Interaction between 5-HTTLPR genotype and early trauma exposure was tested using moderated and multiple regression techniques. Interaction plots were used to explore BDNF genotype modulation.

Results: Mildly higher impulsivity scores were found in men with SS compared with SL or LL genotypes, and men with childhood emotional and physical abuse. Interaction analyses showed that combination of 5-HTTLPR-SS genotype and early trauma exposure increase impulsivity scores independently. Impulsivity scores were not affected by the modulation of BDNF genes.

Conclusions: Childhood trauma and 5-HTTLPR genotype seem to be independently involved in suicide attempts, sharing a common pathway of increasing impulsivity.

Keywords: Impulsivity; child maltreatment; genetic interaction; serotonin; suicide.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Adult Survivors of Child Adverse Events*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Epistasis, Genetic / genetics*
  • Female
  • Humans
  • Impulsive Behavior / physiology*
  • Male
  • Middle Aged
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Sex Factors
  • Suicide, Attempted*


  • Brain-Derived Neurotrophic Factor
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • BDNF protein, human