No significant association between BDNF genotypes and remission in major depressive disorder patients treated with antidepressants

Photo by National Cancer Institute / Unsplash

Psychiatry research Published June 1, 2026 Medically reviewed June 1, 2026 Study authors: Cassam Sulliman Nora, Verstuyft Céline, Chappell Kenneth, Becquemont Laurent, Corruble Emmanuelle, C… PubMed ↗ DOI ↗ By Dr. Ji-eun Park, MD · Brain, Mind & Pain

Key Takeaway

Note no significant association between BDNF genotypes and remission in major depressive disorder.

This meta-analysis review synthesized data from studies involving 599 Caucasian patients with a major depressive episode treated with SSRIs, SNRIs, or TCAs. The primary outcome assessed was remission, defined as a MADRS score of 12 or less or a HAMD score of 7 or less. Secondary outcomes included changes from baseline HAMD or MADRS scores and response, defined as a 50% or greater reduction in scores.

The analysis compared Val/Val homozygotes against Met-allele carriers. Results showed no significant association between optimal response genotypes and remission. The relative risk was 1.02 with a 95% confidence interval of 0.89 to 1.18 and a p-value of 0.78. Specifically, 190 patients (56.4%) achieved remission in the optimal genotype group versus 146 patients (54.3%) in the non-optimal genotype response group.

The review did not report adverse events, serious adverse events, discontinuations, or tolerability. Follow-up duration was not reported. The authors did not identify specific limitations beyond the lack of reported safety data. The findings suggest that BDNF genotype status may not predict treatment response in this population.

Study Details

Study typeMeta analysis

Sample sizen = 599

EvidenceLevel 1

PublishedJun 2026

PMID41812474

View Original Abstract ↓

INTRODUCTION: Major depressive disorder (MDD) is a leading global health concern. Personalized medicine could enable a better response to antidepressants. Findings suggested optimal response genotypes of Val66Met genetic polymorphism of brain-derived neurotrophic factor (BDNF) (rs6265) in Caucasian depressed patients: selective serotonin reuptake inhibitors (SSRIs) associated with better clinical improvement in Val/Val homozygotes and selective norepinephrine reuptake inhibitors (SNRIs) or tricyclic antidepressants (TCAs) with better clinical improvement in Met-allele carriers. We aim to replicate these findings with a meta-analysis. METHODS: A systematic search of PubMed was performed. All included studies assessed the efficacy of one antidepressant class (SSRIs, SNRIs, or TCAs) in Caucasian patients with a major depressive episode (MDE) in the context of MDD according to BDNF Val66Met genotypes. The primary outcome was remission (MADRS ≤ 12 or HAMD ≤ 7); secondary outcomes were changes from baseline HAMD or MADRS scores and response (≥ 50% reduction). RESULTS: Seven studies were included. In total, 599 patients (357 Val/Val homozygotes and 242 Met-allele carriers) were analyzed. No significant association between optimal response genotypes and remission (190 (56.4%) in the optimal and 146 (54.3%) in the non-optimal genotype response group; fixed effects model: RR = 1.02, 95% CI [0.89; 1.18], p = 0.78) was observed. Similar results were observed for score changes and response. Sensitivity analyses confirmed these findings. Statistical power for primary outcome was 95%. CONCLUSION: We showed no significant association between the expected optimal response genotype of the BDNF Val66Met polymorphism and clinical improvement after antidepressant treatment in Caucasian depressed patients.