Abstract
BackgroundAlthough 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 MethodsSeventy-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. ResultsThe 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. ConclusionsThis 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)
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