Psychiatry Investig.  2014 Apr;11(2):192-199. 10.4306/pi.2014.11.2.192.

Genetic Role of BDNF Val66Met and 5-HTTLPR Polymorphisms on Depressive Disorder

  • 1Department of Neuropsychiatry, Eulji University School of Medicine, Daejeon, Republic of Korea.
  • 2Department of Psychiatry, Eulji General Hospital, Seoul, Republic of Korea.
  • 3Department of Psychiatry, Eulji University Hospital, Daejeon, Republic of Korea.
  • 4Institute of Human Behavioral Medicine, Medical Research Institute, Seoul National University, Seoul, Republic of Korea.
  • 5Department of Psychiatry and Behavioral Science, Seoul National University College of Medicine, Seoul, Republic of Korea.
  • 6Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Republic of Korea.
  • 7Biomedical Research Institute, Seoul National University Hospital, Seoul, Republic of Korea.
  • 8Department of Neuropsychiatry, Dongguk University International Hospital, Dongguk University Medical School, Goyang, Republic of Korea.
  • 9Department of Psychiatry, SMG-SNU Boramae Medical Center, Seoul, Republic of Korea.
  • 10Department of Psychiatry, Keyo Hospital, Uiwang, Republic of Korea.


We investigated possible association between depressive disorders and BDNF Val66Met and 5-HTTLPR. Brain derived neurotrophic factor (BDNF) gene and serotonin transporter (SLC6A4) gene are promising candidate genes for depressive disorders. It has been suggested that BDNF promotes the survival and differentiation of serotonergic neurons and that serotonergic transmission exerts powerful control over BDNF gene expression.
Final analyses were performed on 186 patients with depressive disorders and 1032 controls. Val66Met polymorphism of BDNF gene and 5-HTTLPR polymorphism of serotonin transporter gene were genotyped and allele and genotypic associations on the diagnosis of depression and age at onset of depression were analyzed.
The 5-HTTLPR was positively associated with depressive affected status in the total sample and in females (p=0.038 for allelewise, p=0.015 for genotype-wise associations), but, not in males. The BDNF Val66Met showed no association with depression. BDNF Val66Met and 5-HTTLPR alone were not associated with age at onset of depression. Additional analysis on the interaction between BDNF Val66Met and 5-HTTLPR found a significant association with age at onset of depression in the entire patient group. This association was also found in the female but not in the male patient group. None of the positive results survived Bonferroni correction for multiple testing.
This result suggested that BDNF Val66Met and 5-HTTLPR may contribute to depressive disorders in a complex way and that the genetic effect could differ by gender. Further studies with large number of patients will be necessary.


BDNF Val66Met; 5-HTTLPR; Depressive disorder; Genetic polymorphism; Onset; Serotonin transporter

MeSH Terms

Brain-Derived Neurotrophic Factor*
Depressive Disorder*
Gene Expression
Polymorphism, Genetic
Serotonergic Neurons
Serotonin Plasma Membrane Transport Proteins
Brain-Derived Neurotrophic Factor
Serotonin Plasma Membrane Transport Proteins
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