The Impact of Brain-Derived Neurotrophic Factor Polymorphism and Stimulation Parameters on the Response to Repetitive Transcranial Magnetic Stimulation: A Systematic Review

Abstract

Repetitive transcranial magnetic stimulation (rTMS) has been a common technique used to stimulate neuromodulatory changes, which can induce therapeutic benefits. However, the effects are variable, possibly resulting from personal factors such as genetic contribution and heterogeneous methodologies. The brain-derived neurotrophic factor (BDNF) plays a crucial role in rTMS-dependent neuroplasticity, but it is unclear how BDNF genotypes interact with the stimulation parameters of rTMS and contribute to the variable responses to neuromodulation. This systematic review aimed to (1) examine how BDNF polymorphisms are related to the after-effects of rTMS in humans and (2) investigate the association between BDNF polymorphism and rTMS stimulation parameters as contributing factors to the response to rTMS. Of the 36 studies included in this systematic review, 35 studies had at least one domain of high or unclear risk of bias; 53% of the studies in healthy individuals showed differences in TMS-derived or behavioral measures between Val/Val homozygotes and Met allele carriers. In stroke, neuromodulatory effects on corticospinal excitability and motor deficits were more evident in Val/Val homozygotes than Met allele carriers. Similarly, in depression, Val/Val homozygotes demonstrated more symptom improvement compared with Met allele carriers following rTMS. We discuss methodological considerations and provide suggestions for future research.