Impact of DRD2/ANKK1 and COMT Polymorphisms on Attention and Cognitive Functions in Schizophrenia

PLoS One. 2017 Jan 13;12(1):e0170147. doi: 10.1371/journal.pone.0170147. eCollection 2017.

Abstract

Background: Cognitive deficits such as poor selective attention and executive functions decline have been reported in patients with schizophrenia. Many studies have emphasized the role of dopamine in regulating cognitive functions in the general population as well as in schizophrenia. However, the relationship between cognitive processes, schizophrenia and dopaminergic candidate genes is an original approach given interesting results. The purpose of the current exploratory study was to examine the interaction of dopaminergic genes (coding for dopamine receptor D2, DRD2, and for Catecholamine-O-Methyl-Transferase, COMT) with the diagnostic of schizophrenia in (i) the executive control of attention, (ii) selective attention, and (iii) executive functions.

Methods and results: We recruited 52 patients with schizophrenia and 53 healthy controls who performed the Stroop Color-Word Test, the Attention Network Test and the Wisconsin Card Sorting test. Four single nucleotide polymorphisms (SNPs) in the DRD2 gene (rs6275, rs6277, rs2242592 and rs1800497) and two SNPs in the COMT gene (rs4680 and rs165599) have been genotyped. Patients with schizophrenia performed significantly worse than controls in all cognitive performance, taking into account demographic variables. A significant gene by disease interaction was found for the Stroop interference (p = 0.002) for rs6275 of the DRD2 gene. The COMT Val/Val genotype and schizophrenia were associated with increased number of perseverative errors (p = 0.01).

Conclusions: In our study, the DRD2 gene is involved in attention while the COMT gene is implicated in executive functions in patients with schizophrenia.

MeSH terms

  • Adult
  • Aged
  • Attention*
  • Catechol O-Methyltransferase / genetics*
  • Catechol O-Methyltransferase / physiology
  • Executive Function*
  • Female
  • Genotype
  • Humans
  • Linkage Disequilibrium
  • Male
  • Middle Aged
  • Neuropsychological Tests
  • Polymorphism, Genetic*
  • Protein Serine-Threonine Kinases / genetics*
  • Protein Serine-Threonine Kinases / physiology
  • Receptors, Dopamine D2 / genetics*
  • Receptors, Dopamine D2 / physiology
  • Schizophrenia / genetics*
  • Schizophrenia / physiopathology
  • Schizophrenic Psychology
  • Stroop Test

Substances

  • DRD2 protein, human
  • Receptors, Dopamine D2
  • COMT protein, human
  • Catechol O-Methyltransferase
  • ANKK1 protein, human
  • Protein Serine-Threonine Kinases

Grants and funding

All other authors declare no conflicts of interest that influence their work.The authors received no specific funding for this work. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.