Val66Met polymorphism in the BDNF gene and antidepressant response in depression: an updated meta-analysis

The Val66Met polymorphism in the brain-derived neurotrophic factor (BDNF) gene has been linked to antidepressant treatment response in patients with major depressive disorder (MDD), yet findings remain inconclusive. This updated meta-analysis aimed to clarify this association and explore subgroup effects based on antidepressant class and treatment duration.

A systematic search of PubMed, Web of Science, and Google Scholar was conducted through 27 December 2024. Studies were included if they assessed BDNF rs6265 genotypes and antidepressant response in MDD. Data were extracted and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using Review Manager 5.4 under four genotypic models. Study quality was assessed using the Clark-Baudouin scale, and sensitivity and subgroup analyses were performed.

Fourteen studies with 19 datasets were included in the meta-analysis. The overall outcomes indicated no association between the polymorphism and treatment response to antidepressants. Upon removal of outlier studies and studies that deviated from the Hardy-Weinberg equilibrium, significant and homogenous associations were noted with a strong relationship among East Asians treated with selective serotonin reuptake inhibitors (SSRIs).

The Met allele may predict favorable antidepressant response in SSRI-treated East Asian patients. Limitations include small sample sizes, moderate study quality, and limited ethnic diversity.