Gene polymorphisms and response to transcranial direct current stimulation for auditory verbal hallucinations in schizophrenia

ObjectiveRecent observations demonstrate a significant ameliorative effect of add-on transcranial direct current stimulation (tDCS) on auditory verbal hallucinations (AVHs) in schizophrenia. Of the many SNPs, NRG1 rs35753505 and catechol-o-methyl transferase (COMT) rs4680 polymorphisms have shown to have a strong association with neuroplasticity effect in schizophrenia.MethodsSchizophrenia patients (n=32) with treatment resistant auditory hallucinations were administered with an add-on tDCS. The COMT (rs4680) and NRG1 (rs35753505) genotypes were determined. The COMT genotypes were categorised into Val group (GG; n=15) and Met group (GG/AG; n=17) and NRG1 genotypes were categorised into AA group (n=12) and AG/GG group (n=20).ResultsThe reduction in auditory hallucination sub-scale score was significantly affected by COMT-GG genotype [TimexCOMT interaction: F(1,28)=10.55, p=0.003, ?(2)=0.27]. Further, COMT-GG effect was epistatically influenced by the co-occurrence of NRG1-AA genotype [TimexCOMTxNRG1 interaction: F(1,28)=8.09, p=0.008, ?(2)=0.22]. Irrespective of genotype, females showed better tDCS response than males [TimexSex interaction: F(1,21)=4.67, p=0.04, ?(2)=0.18].ConclusionCOMT-GG and NRG1-AA genotypes aid the tDCS-induced improvement in AVHs in schizophrenia patients. Our preliminary observations need replication and further systematic research to understand the neuroplastic gene determinants that modulate the effect of tDCS.