Predictive roles of brain-derived neurotrophic factor Val66Met polymorphism on antidepressant efficacy of different forms of prefrontal brain stimulation monotherapy: A randomized, double-blind, sham-controlled study

Chih Ming Cheng, Chen Jee Hong, Hui Ching Lin, Po Jui Chu, Mu Hong Chen, Pei Chi Tu, Ya Mei Bai, Wen Han Chang, Chi Hung Juan, Wei Chen Lin, Shih Jen Tsai, Tung Ping Su, Cheng Ta Li*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Background: Although repetitive transcranial magnetic stimulation (rTMS) and prolonged intermittent theta-burst stimulation (piTBS) can induce changes in synaptic plasticity, the influence of brain-derived neurotrophic factor (BDNF) genotypes on their antidepressant effects remain unknown. Hence, we investigated the BDNF polymorphism contribution to the antidepressant effect of different forms left-sided prefrontal stimulations in a randomized, sham-controlled study Methods: Seventy-five patients with medication-resistant depression were randomly assigned into three monotherapy groups: piTBS, high-frequency(HF) rTMS, or sham. The acute treatment period was two weeks. 17-item Hamilton Depression Rating scale (HDRS-17) were applied at baseline, week-1, and week-2. The primary outcome was percentage changes of HDRS-17 (%HDRS-17 changes) analyzed by generalized estimating equation (GEE) model. Results: The GEE analysis revealed a significant interaction between group, time, and BDNF genotypes effects on %HDRS-17 changes over time. In patients carrying Val homozygotes, piTBS and HF-rTMS both exhibited significantly greater %HDRS reduction than sham at week-2. In Met carriers, only piTBS showed better efficacy than sham at week-2 (piTBS vs. sham, -41.1% vs.-18.9%, p=0.004). Regarding the influence of different BDNF genotypes on antidepressant efficacy in each intervention, only HF-rTMS exhibited significantly different degrees of %HDRS-17 changes between Val homozygotes and Met carriers (-68.5% vs. -26.4%, p=0.012, respectively), but piTBS delivered the consistent efficacy regardless of the BDNF polymorphism. Conclusions: This is the first study to confirm the different impacts of BDNF genotypes on the effect of different left-sided prefrontal brain stimulation. BDNF Val66Met polymorphism may play a role in the antidepressant response of piTBS and HF-rTMS. (Trial Registration Number UMIN-CTR:UMIN000020892: Registration date: Feb.4, 2016)

Original languageEnglish
Pages (from-to)353-359
Number of pages7
JournalJournal of Affective Disorders
Volume297
DOIs
StatePublished - 15 Jan 2022

Keywords

  • Antidepressant efficacy
  • BDNF polymorphism
  • Prolonged intermittent theta-burst stimulation
  • Repetitive transcranial magnetic stimulation
  • Val66Met

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