Genetic polymorphisms and the adequacy of brain stimulation: state of the art

Heterogeneity of therapeutic response to brain stimulation techniques has inspired scientists to uncover the secrets to success or failure of these projects. Genetic polymorphisms are one of the major causes of this heterogeneity.

More than twenty genetic variants within more than ten genes (e.g. BDNF, COMT, DRD2, TRPV1, 5-HT1A, 5-HHT, P2RX7, VEGF, TPH1, TPH2, ACE, APOE, GNB3, NET, NMDA receptors, and RGS4) have been investigated, among which the BDNF gene and its polymorphism, Val66Met, is the best documented variant. We review the genotypic combinations, which are reported to interact with the work of brain stimulation, of which the DRD2 C957T polymorphism is the most prominent type. Finally, implications of transcranial magnetic stimulation in deciphering the interaction between genetic background (e.g. SCN1A and 5-HTT) and drugs (e.g. carbamazepine and citalopram) at the cortical excitability level is explained. Expert commentary: Studies are ongoing to find missing factors responsible for heterogeneity of response to brain stimulation techniques. Further knowledge about genetic factors affecting the therapeutic response to brain stimulation techniques might provide helpful guidelines for choosing ideal candidates for treatment.