2026 ECNP Congress

PS01-1198

BDNF DNA methylation as a potential predictive biomarker of treatment response in major depressive disorder: a mini-systematic review

Ecem Atil — E. van Assche · University of Münster, Department of Psychiatry, Muenster, Germany

2026 ECNP Congress

Background

Major depressive disorder (MDD) is a leading cause of disability worldwide, and approximately 30% of patients do not respond to conventional treatments. Current treatments present challenges such as inadequate response rates, and difficulty in predicting response. Recent studies suggest that epigenetic mechanisms, particularly the DNA methylation of Brain-Derived Neurotrophic Factor (BDNF), may play a role in treatment mechanisms; specifically, BDNF hypermethylation is associated with better treatment responses, and various treatment methods may reverse this hypermethylation. This study aims to evaluate the relationship between BDNF DNA methylation and treatment response in MDD and its predictive value as a biomarker for treatment response.

Methods

This review was conducted in accordance with PRISMA guidelines. A comprehensive literature search was performed in PubMed and Scopus databases for studies published between 2003 and 2026. The following search terms were used: (BDNF OR “brain-derived neurotrophic factor”) AND (methylation OR “DNA methylation” OR epigenetics*) AND (depression OR “major depressive disorder” OR MDD) AND (antidepressant response OR treatment response OR treatment outcome).

Studies were included if they met the following criteria: 1) included human subjects diagnosed with MDD, 2) evaluated BDNF DNA methylation, and 3) assessed treatment response or related clinical outcomes after antidepressant, ketamine, electroconvulsive therapy (ECT), or repetitive transcranial magnetic stimulation (rTMS). All records were reviewed based on titles and abstracts, followed by a full-text assessment for suitability. A total of 147 records were identified via database search. After removing duplicate records using Zotero (n = 20), 128 studies were reviewed. Finally, 6 studies were included in the qualitative synthesis.

Results

The studies included have shown mostly consistent associations between BDNF DNA methylation and treatment outcomes in depressive disorders. For example, in patients receiving ECT, BDNF promoter methylation, particularly in exon I, was significantly lower in responders compared to non-responders.[1] Similarly, in patients with treatment-resistant depression treated with TMS, methylation levels at specific CpG regions were lower in responders than in non-responders.[2] Supporting this, it was suggested that patients with hypermethylation at a CpG region of the BDNF exon IV promoter had significantly higher remission rates than those without hypermethylation.[3] Another study associated increased BDNF methylation levels with better escitalopram treatment response and symptom improvement.[4] Conversely, one study linked antidepressant treatment to significant changes, particularly an increase in methylation levels over time.[5] In parallel to this, one study associated higher BDNF methylation with poor treatment outcomes for suicidal ideation in depressed patients.

Conclusions

This mini-systematic review suggests that BDNF DNA methylation may be a promising epigenetic biomarker for treatment response in MDD. Studies have predominantly shown that higher BDNF methylation is associated with better treatment outcomes, and this hypermethylation is reversed in patients who respond to treatment. However, differences in sample characteristics, treatment methods, and methodological approaches in studies present challenges in reaching definitive conclusions, and larger-scale, longitudinal research is needed. Epigenetic markers may contribute to the development of personalized, biomarker-focused treatment strategies for depression and to avoiding complicated and prolonged treatment processes.

References

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