Effect of Schizotypy on Cognitive Performance and Its Tuning by COMT val158 Met Genotype Variations in a Large Population of Young Men

Nikolaos Smyrnis, Dimitrios Avramopoulos, Ioannis Evdokimidis, Costas N. Stefanis, Hara Tsekou, Nicholas C. Stefanis

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


Background: Mirroring schizophrenia, specific dimensions of schizotypy are related to cognitive dysfunction. The relation of schizotypy and state psychopathology to cognitive performance and its link to catechol-O-methyltransferase (COMT) val158 met genotype variations was studied in a large sample of young men. Methods: State psychopathology and schizotypy were assessed with self-rated questionnaires. Cognitive performance was assessed with tests of reasoning ability, sustained attention, and verbal and spatial working memory. Subjects were genotyped for the val158 met polymorphism of the gene for COMT (low enzymatic activity met/met, intermediate met/val, and high val/val). Results: The val/val group had higher scores in measures of state psychopathology as well as negative and disorganized schizotypy dimensions, whereas there was no effect of COMT genotype on cognitive performance measures. Structural equation modeling showed that cognitive performance accuracy but not speed decreased with increasing negative schizotypy, increased with increasing paranoid schizotypy, and was not affected by state psychopathology. Increasing val loading resulted in a dose-dependent increase in the factor loading for the relation between negative schizotypy and cognitive performance accuracy. Conclusions: Different schizotypal phenotypes had opposing relations to cognitive performance in the population. COMT genotype modulated the relation between the negative schizotypal phenotype and cognitive performance.

Original languageEnglish (US)
Pages (from-to)845-853
Number of pages9
JournalBiological psychiatry
Issue number7
StatePublished - Apr 1 2007
Externally publishedYes


  • COMT
  • Catechol-O-methyltransferase
  • dopamine
  • executive function
  • prefrontal cortex
  • schizophrenia
  • schizotypy factors
  • sustained attention
  • working memory

ASJC Scopus subject areas

  • Biological Psychiatry


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