Differential effects of the catechol-O-methyltransferase Val158Met genotype on the cognitive function of schizophrenia patients and healthy Japanese individuals

PLoS One. 2013 Nov 25;8(11):e76763. doi: 10.1371/journal.pone.0076763. eCollection 2013.

Abstract

Background: The functional polymorphism Val158Met in the catechol-O-methyltransferase (COMT) gene has been associated with differences in prefrontal cognitive functions in patients with schizophrenia and healthy individuals. Several studies have indicated that the Met allele is associated with better performance on measures of cognitive function. We investigated whether the COMT Val158Met genotype was associated with cognitive function in 149 healthy controls and 118 patients with schizophrenia.

Methods: Cognitive function, including verbal memory, working memory, motor speed, attention, executive function and verbal fluency, was assessed by the Brief Assessment of Cognition in Schizophrenia (BACS-J). We employed a one-way analysis of variance (ANOVA) and a multiple regression analysis to determine the associations between the COMT Val158Met genotype and the BACS-J measurements.

Results: The one-way ANOVA revealed a significant difference in the scores on the Tower of London, a measure of executive function, between the different Val158Met genotypes in the healthy controls (p = 0.023), and a post-hoc analysis showed significant differences between the scores on the Tower of London in the val/val genotype group (18.6 ± 2.4) compared to the other two groups (17.6 ± 2.7 for val/met and 17.1 ± 3.2 for met/met; p = 0.027 and p = 0.024, respectively). Multiple regression analyses revealed that executive function was significantly correlated with the Val158Met genotype (p = 0.003). However, no evidence was found for an effect of the COMT on any cognitive domains of the BACS-J in the patients with schizophrenia.

Conclusion: These data support the hypothesis that the COMT Val158Met genotype maintains an optimal level of dopamine activity. Further studies should be performed that include a larger sample size and include patients on and off medication, as these patients would help to confirm our findings.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Analysis of Variance
  • Attention
  • Catechol O-Methyltransferase / genetics*
  • Cognition
  • Dopamine / metabolism
  • Executive Function
  • Female
  • Genotype*
  • Humans
  • Male
  • Memory
  • Middle Aged
  • Neuropsychological Tests
  • Polymorphism, Genetic
  • Regression Analysis
  • Schizophrenia / genetics*

Substances

  • Catechol O-Methyltransferase
  • Dopamine

Grants and funding

This study was funded by a Grant-in-Aid for Scientific Research (KAKENHI) from the Japan Society for the Promotion of Research (JSPS, # 24590652), Mitsubishi Pharma Research Foundation. Asteras Schizophrenia Research Foundation and a grant from the Hirosaki Research Institute for Neurosciences. Norio Yasui-Furukori has received grant/research support or honoraria from, and been on the speakers of Astra, Dainippon, Eli Lilly, GSK, Janssen-Pharma, Meiji. Mochida, MSD, Otsuka, Pfizer, Takada and Yoshitomi. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.