Background: Preclinical studies have shown that brain-derived neurotrophic factor (BDNF) may be involved in antidepressant action, and the BDNF gene has been suggested to be involved in the pharmacological treatment of major depressive disorder (MDD). In this study, the relationship between BDNF Val66Met polymorphism (Single Nucleotide Polymorphism Database ID: rs6265) and severity of depression, efficacy of fluoxetine and its side effects was tested in Chinese patients with MDD. Methods: Patients with MDD took the oral selective serotonin reuptake inhibitor (SSRI) fluoxetine (20 mg/day) for 6 weeks. Its clinical efficacy and side effects were measured by the 17-item Hamilton Rating Scale for Depression and the Treatment-Emergent Symptoms Scale (TESS), respectively. The patients were genotyped for Val66Met polymorphism of the BDNF gene. Results: In the multivariate regression analysis, there was no significant association between severity of depression and BDNF Val66Met polymorphism. There was no association between efficacy of fluoxetine and BDNF Val66Met polymorphism, but there was a marginal positive suggestion that heterozygous patients tended to have a better remission with fluoxetine in comparison with homozygous analogs. Insomnia and decreased sexual desire, side effects of fluoxetine, may have an association with the BDNF Val66Met polymorphism, and Met allele carriers showed a lower incidence of these side effects. Conclusions: These results indicate that there was a lack of association between severity of depression and BDNF Val66Met polymorphism in Chinese patients with MDD. The BDNF Val66Met polymorphism may play a major role in the efficacy and side effects of SSRI (fluoxetine) in Chinese patients with MDD.

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