The contribution of BDNF and 5-HTT polymorphisms and early life stress to the heterogeneity of major depressive disorder: a preliminary study

Aust N Z J Psychiatry. 2012 Jan;46(1):55-63. doi: 10.1177/0004867411430878.


Objective: Two reported genetic polymorphisms related to the production of brain-derived neurotrophic factor (BNDF) and reuptake by the serotonin transporter (5-HTT) appear to contribute to depression in combination with stressful life events. The aim of the current study was to investigate the contribution of early life stress (ELS), BDNF (Val versus Met alleles) and 5-HTT polymorphisms (L versus S alleles) to melancholic (n = 65) and non-melancholic depression (n = 59).

Methods: A mediation approach ((G × G) × E mediation model) was employed to confirm the indirect effects of ELS on the relationship between 5-HTTPLR × BDNF polymorphism combinations and depression subtype. A series of binary logistic regressions were then conducted to determine whether genotype, ELS, and their interaction were able to predict depression subtype.

Results: Key findings indicated that BDNF and 5-HTT polymorphisms in combination with ELS contributed to the development of non-melancholic depression. An interaction between BDNF and ELS increased the risk of non-melancholia by 3.327, whereas the interaction between 5-HTT and ELS increased risk by 2.406.

Conclusion: The results support a role for genetic factors in the development of non-melancholia. The lack of findings in melancholia indicates that other mechanisms may underlie the subtype. Alternatively, null findings may reflect a Type II error associated with a small sample size. Future studies should consider further examination of differential gene-environment interactions for melancholia versus non-melancholia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Brain-Derived Neurotrophic Factor / genetics*
  • Depressive Disorder, Major / complications
  • Depressive Disorder, Major / diagnosis
  • Depressive Disorder, Major / genetics*
  • Depressive Disorder, Major / psychology*
  • Female
  • Genetic Predisposition to Disease / genetics*
  • Genotype
  • Humans
  • Life Change Events*
  • Male
  • Middle Aged
  • Psychiatric Status Rating Scales / statistics & numerical data
  • Risk Factors
  • Serotonin Plasma Membrane Transport Proteins / genetics*
  • Stress, Psychological / complications
  • Stress, Psychological / genetics
  • Stress, Psychological / psychology*


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