Schizophrenia-related RGS4 gene variations specifically disrupt prefrontal control of saccadic eye movements

E. Kattoulas, N. C. Stefanis, D. Avramopoulos, C. N. Stefanis, I. Evdokimidis, N. Smyrnis

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Background The gene encoding the regulator of G-protein signaling subtype 4 (RGS4), located on chromosome 1q23-3, has been proposed as a possible susceptibility gene for schizophrenia and has been specifically linked to prefrontal cortical structural and functional integrity.Method The effects of four core single nucleotide polymorphisms (SNPs) within the RGS4 gene on oculomotor parameters in a battery of oculomotor tasks (saccade, antisaccade, smooth eye pursuit, fixation) were investigated in a sample of 2243 young male military conscripts. Results The risk allele of RGS4SNP18 was found to be associated with two variables of antisaccade performance, increased error rate and variation in the correct antisaccade latency. By contrast, the same allele and also the risk allele of RGS4SNP4 led to an improvement in smooth eye pursuit performance (increased gain). Structural equation modeling confirmed that the combined gene variation of RGS4SNP4 and RGS4SNP18 was a significant predictor of antisaccade but not smooth eye pursuit performance. Conclusions These Results provide evidence for a specific effect of schizophrenia-related RGS4 genotype variations to prefrontal dysfunction measured by oculomotor indices of performance in normal individuals, further validating the hypothesis that RGS4 is related to prefrontal dysfunction in schizophrenia.

Original languageEnglish (US)
Pages (from-to)757-767
Number of pages11
JournalPsychological medicine
Issue number4
StatePublished - Apr 2012


  • Antisaccade
  • endophenotypes
  • oculomotor
  • saccade
  • schizophrenia candidate genes
  • smooth eye pursuit

ASJC Scopus subject areas

  • Applied Psychology
  • Psychiatry and Mental health


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