SLC6A4 methylation modifies the effect of the number of traumatic events on risk for posttraumatic stress disorder

Depress Anxiety. 2011 Aug;28(8):639-47. doi: 10.1002/da.20825. Epub 2011 May 23.


Background: Posttraumatic stress disorder (PTSD) is a common and debilitating mental disorder that occurs following exposure to a traumatic event. However, most individuals do not develop PTSD following even a severe trauma, leading to a search for new variables, such as genetic and other molecular variation, associated with vulnerability and resilience in the face of trauma exposure.

Method: We examined whether serotonin transporter (SLC6A4) promoter genotype and methylation status modified the association between number of traumatic events experienced and PTSD in a subset of 100 individuals from the Detroit Neighborhood Health Study.

Results: Number of traumatic events was strongly associated with risk of PTSD. Neither SLC6A4 genotype nor methylation status was associated with PTSD in main effects models. However, SLC6A4 methylation levels modified the effect of the number of traumatic events on PTSD after controlling for SLC6A4 genotype. Persons with more traumatic events were at increased risk for PTSD, but only at lower methylation levels. At higher methylation levels, individuals with more traumatic events were protected from this disorder. This interaction was observed whether the outcome was PTSD diagnosis, symptom severity, or number of symptoms.

Conclusions: Gene-specific methylation patterns may offer potential molecular signatures of increased risk for and resilience to PTSD.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • DNA Methylation / physiology*
  • Depression / diagnosis
  • Depression / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Health Surveys
  • Humans
  • Interview, Psychological
  • Life Change Events*
  • Male
  • Middle Aged
  • Prevalence
  • Promoter Regions, Genetic
  • Risk Factors
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Stress Disorders, Post-Traumatic / diagnosis*
  • Stress Disorders, Post-Traumatic / genetics*
  • Stress Disorders, Post-Traumatic / metabolism
  • Young Adult


  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins