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

Published online by Cambridge University Press:  13 September 2011

E. Kattoulas ,
N. C. Stefanis ,
D. Avramopoulos ,
C. N. Stefanis ,
I. Evdokimidis  and
N. Smyrnis
E. Kattoulas
Affiliation:
University Mental Health Research Institute, National and Kapodistrian University of Athens, Athens, Greece 1st Psychiatry Department, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece
N. C. Stefanis
Affiliation:
University Mental Health Research Institute, National and Kapodistrian University of Athens, Athens, Greece 1st Psychiatry Department, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece
D. Avramopoulos
Affiliation:
McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD, USA
C. N. Stefanis
Affiliation:
University Mental Health Research Institute, National and Kapodistrian University of Athens, Athens, Greece
I. Evdokimidis
Affiliation:
Neurology Department, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece
N. Smyrnis*
Affiliation:
University Mental Health Research Institute, National and Kapodistrian University of Athens, Athens, Greece 1st Psychiatry Department, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, Athens, Greece
*
*Address for correspondence: N. Smyrnis, M.D., Ph.D., 1st Psychiatry Department, National and Kapodistrian University of Athens, Medical School, Eginition Hospital, 72 V. Sofias Avenue, Athens 11528, Greece. (Email: smyrnis@med.uoa.gr)
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Abstract

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.

Keywords

Antisaccadeendophenotypesoculomotorsaccadeschizophrenia candidate genessmooth eye pursuit
Type
Original Articles
Information
Psychological Medicine , Volume 42 , Issue 4 , April 2012 , pp. 757 - 767
Copyright
Copyright © Cambridge University Press 2011

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