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

Acta Neuropsychiatr. 2018 Aug;30(4):218-225. doi: 10.1017/neu.2018.4. Epub 2018 Mar 21.

Abstract

Objective: Recent 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.

Methods: Schizophrenia 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).

Results: The reduction in auditory hallucination sub-scale score was significantly affected by COMT-GG genotype [Time×COMT interaction: F(1,28)=10.55, p=0.003, ɳ2=0.27]. Further, COMT-GG effect was epistatically influenced by the co-occurrence of NRG1-AA genotype [Time×COMT×NRG1 interaction: F(1,28)=8.09, p=0.008, ɳ2=0.22]. Irrespective of genotype, females showed better tDCS response than males [Time×Sex interaction: F(1,21)=4.67, p=0.04, ɳ2=0.18].

Conclusion: COMT-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.

Keywords: genes; hallucinations; schizophrenia; tDCS.

MeSH terms

  • Adult
  • Catechol O-Methyltransferase / genetics*
  • Female
  • Gene-Environment Interaction
  • Genotype
  • Hallucinations / complications
  • Hallucinations / genetics
  • Hallucinations / therapy*
  • Humans
  • Male
  • Middle Aged
  • Neuregulin-1 / genetics*
  • Polymorphism, Single Nucleotide*
  • Schizophrenia / complications
  • Schizophrenia / genetics
  • Schizophrenia / therapy*
  • Transcranial Direct Current Stimulation*
  • Young Adult

Substances

  • NRG1 protein, human
  • Neuregulin-1
  • Catechol O-Methyltransferase