Association of a triallelic serotonin transporter gene promoter region (5-HTTLPR) polymorphism with stressful life events and severity of depression

Am J Psychiatry. 2006 Sep;163(9):1588-93. doi: 10.1176/ajp.2006.163.9.1588.


Objective: The lower expressing allele of the serotonin transporter gene 5' promoter region (5-HTTLPR) polymorphism is reported to be associated with susceptibility to depression and suicidality in response to stressful life events. The authors examined the relationship of a triallelic 5-HTTLPR polymorphism to stressful life events, severity of major depression, and suicidality.

Method: Mood disorder subjects (N=191) and healthy volunteers (N=125), all Caucasian subjects of European origin, were genotyped for the triallelic 5-HTTLPR polymorphism (higher expressing allele: L(A); lower expressing alleles: L(G), S). All subjects underwent structured clinical interviews to determine DSM-IV diagnoses, ratings of psychopathology, stressful life events, developmental history, and suicidal behavior. CSF 5-HIAA was assayed in a subgroup of subjects.

Results: Lower expressing alleles independently predicted greater depression severity and predicted greater severity of major depression with moderate to severe life events compared with the higher expressing L(A) allele. No associations with suicidal behavior and CSF 5-HIAA were found.

Conclusions: Lower expressing transporter alleles, directly and by increasing the impact of stressful life events on severity, explain 31% of the variance in major depression severity. The biological phenotype responsible for these effects remains to be elucidated.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Alleles
  • Depressive Disorder, Major / diagnosis*
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / psychology
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Gene Expression / genetics
  • Gene Frequency / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Hydroxyindoleacetic Acid / cerebrospinal fluid
  • Hydroxyindoleacetic Acid / metabolism
  • Life Change Events*
  • Male
  • Phenotype
  • Polymorphism, Genetic*
  • Promoter Regions, Genetic / genetics*
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Serotonin Plasma Membrane Transport Proteins / metabolism
  • Severity of Illness Index
  • Suicide / psychology
  • Suicide / statistics & numerical data


  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Hydroxyindoleacetic Acid