Response to lithium prophylaxis: interaction between serotonin transporter and BDNF genes

Am J Med Genet B Neuropsychiatr Genet. 2007 Sep 5;144B(6):820-3. doi: 10.1002/ajmg.b.30420.


Both serotonin transporter and brain-derived neurotrophic factor (BDNF) genes have been previously implicated in the efficacy of lithium prophylaxis. The aim of the present study was to assess a possible interaction between serotonin transporter genotype (5HTTLPR) and BDNF Val66Met polymorphism, and the prophylactic response to lithium. The study was performed on 111 patients with bipolar mood disorders (43 male, 68 female), aged 30-77 (mean 54 years) who have been treated with lithium carbonate for at least 5 years (5-27 years, mean 15 years). In the group studied, 31 patients (28%) were classified as excellent responders (ER), 54 (49%) as partial responders (PR), and 26 (23%) as non-responders (NR) to lithium prophylaxis. Age at onset of the illness, duration of illness before treatment introduction and on lithium as well as number of affective episodes before lithium treatment did not differ between these three subgroups of patients. A significant interaction between BDNF and 5HTTLPR polymorphism and lithium response was found. S individuals (patients with s/s or s/l genotype) having Val/Val genotype were significantly more frequent in NR compared with ER or/and PR. Also, S individuals showed extreme differences in response to lithium prophylaxis depending on having either Val/Val or (Val/Met + Met/Met) genotypes of BDNF polymorphism: 9/48 (19%) of ER and 18/48 (37%) of NR in the first group, and 12/30 (40%) and 1/30 (3%) in the second group, respectively. The results obtained may show a significant epistatic interaction between 5-HTTLPR and BDNF polymorphism, and response to lithium prophylaxis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antimanic Agents / therapeutic use*
  • Bipolar Disorder / drug therapy*
  • Bipolar Disorder / genetics*
  • Bipolar Disorder / psychology
  • Brain-Derived Neurotrophic Factor / genetics*
  • Female
  • Genotype
  • Humans
  • Lithium Carbonate / therapeutic use*
  • Male
  • Middle Aged
  • Polymorphism, Genetic
  • Serotonin Plasma Membrane Transport Proteins / genetics*


  • Antimanic Agents
  • Brain-Derived Neurotrophic Factor
  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • Lithium Carbonate