A genetic profile of refractory individuals with major depressive disorder and their responsiveness to transcranial magnetic stimulation.

BackgroundMajor depressive disorder (MDD) is a debilitating illness characterized by the persistence of negative thoughts and emotions. Although antidepressant medications are effective, less than half of patients achieve complete remission despite multiple treatment trials. Repetitive transcranial magnetic stimulation (rTMS) has proven effective in the treatment of depression, especially for patients resistant to antidepressant medications. Remission rates when using rTMS for treatment-resistant depression (TRD) patients are between 30% and 40%. The responsiveness to pharmacotherapy and rTMS therapy may be influenced by genetic factors.ObjectiveHere we aim to characterize the genetic profile of refractory individuals with MDD and their rTMS responsiveness.MethodsWe used an extreme-phenotype design (rTMS responders vs. non-responders) and conducted a genome wide association study on 48 participants and 593,260 SNPs.ResultsWe identified 53 significant SNP associations. Gene-set enrichment analysis showed that significantly associated genes loaded onto synaptic plasticity regulation pathways. Among the genes found differentially expressed in rTMS responders compared to non-responders were APP, GRID2 and SPPL2A genes.ConclusionsBased on these findings, we suggest that the identified genes may influence of rTMS responsiveness. Furthermore, the rTMS responsiveness may be associated with several pathways and not just to the influence of a single gene. To the best of our knowledge, this is the first report on the genetic profile of rTMS response using a GWAS approach. Nevertheless, further studies are necessary to enlight the molecular mechanism by which these genes affect response to rTMS treatment.