Brain-derived Neurotrophic Factors Val66Met and C270T Polymorphisms Influence Citalopram/Escitalopram Response in Chinese Patients with Major Depressive Disorder
Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 1Diabetes Research Institute, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, 3Clinical Research Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China, E-mail: [email protected]
The aim of this study was to investigate the association between two brain-derived neurotrophic factor polymorphisms (Val66Met and C270T) and response to citalopram/escitalopram treatment. Chinese patients who met diagnostic and Statistical Manual of Mental Disorders criteria for major depressive disorder (n=180) were prescribed citalopram/escitalopram for 6 weeks. Depression severity was evaluated using the 17-item Hamilton rating scale for depression at baseline and week 2, 4, and 6 of treatment. The expression quantitative trait loci analysis was performed to investigate the functional effect of Val66Met and C270T on brain-derived neurotrophic factor expression in the brain and blood. A significant difference was found in genotype (χ2=6.979, p=0.031, correction p=0.062) but not allele (p>0.05) frequencies of Val66Met between responders and non-responders. Homozygous GG showed a higher response than other two genotypes (χ2=5.218, p=0.022, correction p=0.044). In addition, the C allele and CC genotype of C270T were significantly related to higher remission over 6 weeks among females (C/T, p=0.027, correction p=0.054; CC/TT, p=0.023, correction p=0.046) and first-episode major depressive disorder patients (C/T, p=0.023, correction p=0.046; CC/TT, χ2= 6.870, p=0.009, correction p=0.018). Further expression quantitative trait loci analysis showed that Val66Met and C270T have functional effect on brain-derived neurotrophic factor expression in the brain. Brain-derived neurotrophic factor Val66Met and C270T polymorphisms were associated with therapeutic response to citalopram/escitalopram in Chinese major depressive disorder patients.