BDNF Val66Met polymorphism and resilience in major depressive disorder: the impact of cognitive psychotherapy

Objective: Clinical and biological correlates of resilience in major depressive disorder are scarce. We aimed to investigate the effect of the Val66Met polymorphism in the BDNF gene on resilience scores in major depressive disorder patients and evaluate the polymorphism's moderation effect on resilience scores in response to cognitive therapy. Method: A total of 106 major depressive disorder patients were enrolled in this clinical randomized study. The Resilience Scale and the Hamilton Rating Scale for Depression were applied at baseline, post-treatment, and at six months of follow-up. Blood samples were obtained at baseline for molecular analysis. Results: The baseline resilience scores were higher in patients with the Met allele (114.6±17.6) than in those with the Val/Val genotype (104.04±21.05; p = 0.037). Cognitive therapy treatment increased resilience scores (p ≤ 0.001) and decreased depressive symptoms (p ≤ 0.001). In the mixed-effect model, the Val/Val genotype represented a decrease in resilience scores (t218 = -1.98; p = 0.048), and the Val66Met polymorphism interacted with sex to predict an increase in total resilience scores during cognitive treatment (t218 = 2.69; p = 0.008). Conclusion: Our results indicate that cognitive therapy intervention could improve resilience in follow-up, considering that gender and genetic susceptibility are predicted by the Val66Met polymorphism.

Association Study Between Brain-Derived Neurotrophic Factor Genetic Polymorphism and Treatment Responses of Selective Serotonin Reuptake Inhibitor in Major Depressive Disorder

OBJECTIVES: Recent studies suggest that brain-derived neurotrophic factor (BDNF) may play a critical role in both mechanism of antidepressant action and the pathophysiology of major depressive disorder (MDD). The aim of this study is to evaluate whether the BDNF-gene Val66Met polymorphism is associated with susceptibility of MDD, and antidepressant response in a Korean population. METHODS: To explain genetic susceptibility of MDD, we genotyped the BDNF-gene Val66Met polymorphism in 137 patients with MDD and 91 age- and sex-similar control subjects. we also examined the association of the BDNF-gene Val66Met polymorphism and therapeutic response in 137 MDD patients who received a 6-week Selective Serotonin Reuptake Inhibitor (SSRI) treatment. RESULTS: There were no significant differences in the genotype or allele frequency of the BDNF polymorphism, between the MDD and control subjects. Furthermore, no significant differences were noted in the three-genotype groups (Val/Val, Val/Met, Met/Met) between responders and non-responders. However, heterozygous patients (Val/Met) in comparison to homozygous analogs (Val/Val or Met/Met) in BDNF polymorphism tended to have more improved 6-week antidepressant response (p=0.053). In addition, higher total HAM-D-score percentage change after 6 weeks of antidepressant medication was demonstrated for the heterozygote patients in comparison to homozygous analogs (p=0.006). CONCLUSION: This finding suggests the BDNF polymorphism is associated with improved therapeutic SSRI response for patients bearing the BDNF Val/Met heterozygote in comparison to the homozygous analogs.