Brain-derived neurotrophic factor gene polymorphism (Val66Met) and the early response to antidepressant in Chinese Han population

Abstract

Major depressive disorder (MDD) is a genetically complex and heterogeneous disorder. Accumulating evidence suggests that brain derived neurotrophic factor (BDNF) is involved in the pathophysiology of MDD. A functional nonsynonymous single nucleotide polymorphism that causes an amino-acid substitution of valine to methionine is located in the coding exon of BDNF gene at amino acid position 66 (Val66Met, rs6265) (Sen et al., 2003). The BDNF Val/Met polymorphism has become a main target for pharmacogenetic studies because of its role in the pathophysiology of MDD. In this study, we investigated the association between treatment outcome with different antidepressants [selective serotonin reuptake inhibitors (SSRIs) and venlafaxine] and BDNF Val/Met polymorphism in a prospective naturalistic setting in Chinese Han population.This prospective cohort study consisted of 159 MDD patients (78 men and 81 women with a mean age of 35.8 years, SD = 12.8 years), as assessed by two senior psychiatrists through clinical interview and confirmed with the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, 4th edition-text revision (First et al., 2002). All the patients were aged between 18 and 60 years and gave written informed consent. The project was approved by the Ethics Committee of the Guangzhou Psychiatric Hospital and administrated at China clinical trait (ChiCTR-TNRC-10001112, http://www.chictr.org/). Detailed information is available on request.The 17-item Hamilton rating scale for depression (HAM-D) (Hamilton, 1967) and the Clinical Global Impression were used to assess the severity of depression. Response was defined as an at least 50% decrease in HAM-D scores.The BDNF Val/Met polymorphism was in Hardy-Weinberg equilibrium. The change of HAM-D score at week 4 in the SSRI group [total n = 104, with fluoxetine (n = 6), fluvoxamine (n = 3), citalopram (n = 51), paroxetine (n = 17), sertraline (n = 27)] was significantly different between different genotype groups (genotype counts: ValVal/ValMet/MetMet) [mean (SD): 55% (33%) vs. 64.4% (27.1%) vs. 73.4% (29.2%); P = 0.019, JonckheereTerpstra test]. In addition, the rate of response in Met/ Met genotype carriers was marginally statistically significant higher than that in Val/Met carriers and Val/Val carriers (89.7 vs. 70.8% and 63%, x 2 = 5.659, P = 0.059). The analysis revealed that the adjusted odds ratio for response was 4.85 in Met allele carriers compared with Val/Val genotype carriers (adjusted for age at onset, number of previous depressive episodes, initial severity of the depression, and gender) (x 2 = 4.051, P = 0.044, 95% confidence interval = 1.04-22.58). However, no significant difference in improvement was found between BDNF genotype groups at week 6 [mean (SD): 70.9% (30.7%) vs. 71.6% (28.8%) vs. 77.2% (28.6%), P = 0.502, Kruskal-Wallis test].As for venlafaxine (n = 55), the changes of HAM-D scores after 4 weeks and 6 weeks of antidepressant treatment were not significantly different according to BDNF genotype [mean (SD), a...

Advances in Biomarkers of Major Depressive Disorder

“…Some studies found an association between rs6265 and antidepressant response. In Chinese, rs6265 was associated with early antidepressant response [99]. In elderly MDD, Met66 allele carriers were more likely to be remitted at 6 months [100].…”

Brain-derived neurotrophic factor Val66Met polymorphism and 6-month antidepressant remission in depressed Caucasian patients

“…Some studies suggest an association between the Val66Met polymorphism and response or remission with antidepressant drugs, either in Asian (Choi et al, 2006;Xu et al, 2012;Yoshida et al, 2007; or in Caucasian (Alexopoulos et al, 2010;El-Hage et al, 2015;Lanctôt et al, 2010) patients. However, several studies failed to replicate this association, both in Asian (Ji et al, 2013;Kang et al, 2010;Katsuki et al, 2012;Tsai et al, 2003) and in Caucasian (Brunoni et al, 2013;Domschke et al, 2010;Kocabas et al, 2011;Licinio et al, 2009;Musil et al, 2013;Taylor et al, 2011;Wilkie et al, 2007) patients, especially two 6-month studies (Bukh et al, 2010, Taylor et al, 2011 and the powerful study comprising the STAR-D results (Domschke et al, 2010).…”

Serotonin Transporter Gene: A New Polymorphism May Affect Response to Antidepressant Treatments in Major Depressive Disorder

“…Recent meta-analyses reported that the heterozygous genotype may be a predictor of better antidepressant response [38][39][40], but negative findings have also been reported [60][61][62][63][64][65][66][67][68][69][70][71]. The inconsistency in previous results may be at least partly due to different rs6265 allele and genotype distribution across populations.…”