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

ABSTRACT Introduction TMS has been a common technique used to stimulate neuromodulatory changes, which can have therapeutic effects. The underlying mechanism is still unknown, however it is thought to cause neuroplastic changes via LTD or LTP. However, the effects are highly variable, with demographics and baseline physiology thought to be playing a role. Objectives The purposes of this systematic review were 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. Materials and Methods Studies identified from PubMed, The Cochrane Library, and Embase were screened for eligibility. Data were extracted from the selected studies by one reviewer and verified by another reviewer. Risk of Bias was assessed using the Cochrane Collaboration’s tool. Results were synthesized narratively. Results Of the 224 initial studies, 35 were included in this systematic review. 33 out of 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. The neuromodulatory effects were more reliable in Val/Val homozygotes than 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 improvement in depression symptoms compared with Met allele carriers following rTMS. The role of BDNF polymorphism in other disorders remained unclear. Conclusion It remains inconclusive whether and how BDNF genotype impacts the effects of rTMS. Methodological heterogeneity in the stimulation parameters, such as dosage and excitatory or inhibitory protocols, interact with BDNF polymorphism and contribute to the response to rTMS.