The BDNF Val(66)Met x 5-HTTLPR x child adversity interaction and depressive symptoms: An attempt at replication

Am J Med Genet B Neuropsychiatr Genet. 2008 Jan 5;147B(1):120-3. doi: 10.1002/ajmg.b.30576.


Kaufman et al. [2006] reported a higher order interaction effect between specific genetic and environmental factors in a model of depressive symptoms, requiring independent replication. BDNF Val(66)Met and 5-HTTLPR genotypes were determined in female participants pertaining to a large ongoing twin study. Participants also filled in questionnaires on childhood adversity and depressive symptoms. Two- and three-way interactions between genetic polymorphisms and early adversity were examined in models of depressive symptoms. BDNF Met allele(s) moderated the effect of early adversity on depressive symptoms (two-way interaction), and this BDNF Met x childhood adversity interaction in turn was moderated by 5-HTTLPR genotype (three-way interaction). However, a main effect of BDNF Met on childhood adversity was also observed, possibly indicating confounding by gene-environment correlation. Higher order interaction effects involving BDNF Val(66)Met, 5-HTTLPR and childhood adversity may contribute to the etiology of depressive illness.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Alleles*
  • Brain-Derived Neurotrophic Factor / genetics*
  • DNA Mutational Analysis
  • Depression / etiology
  • Depression / genetics*
  • Environment
  • Female
  • Genetic Variation
  • Genotype
  • Humans
  • Male
  • Methionine / genetics*
  • Middle Aged
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Surveys and Questionnaires
  • Valine / genetics*


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