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Schizophr Res. 2014 Apr;154(1-3):42-7. doi: 10.1016/j.schres.2014.02.017. Epub 2014 Mar 11.

The CSMD1 genome-wide associated schizophrenia risk variant rs10503253 affects general cognitive ability and executive function in healthy males.

Author information

1
Department of Psychiatry, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece.
2
Department of Psychiatry, Mount Sinai, New York, NY, USA; Department of Genetics and Genomic Science, Institute for Multiscale Biology, Mount Sinai, New York, NY, USA; Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center, Bronx, NY, USA.
3
Division of Psychiatry Research, The Zucker Hillside Hospital, Glen Oaks, NY, USA; Feinstein Institute for Medical Research, Manhasset, NY, USA.
4
Department of Psychiatry, Mount Sinai, New York, NY, USA; Mental Illness Research, Education, and Clinical Center (VISN 3), James J. Peters VA Medical Center, Bronx, NY, USA.
5
Department of Psychology, University of Crete, Rethymno, Crete, Greece.
6
Department of Psychiatry, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece. Electronic address: pbitsios@med.uoc.gr.

Abstract

BACKGROUND:

The single-nucleotide polymorphism (SNP) rs10503253, located within the CUB and Sushi multiple domains-1 (CSMD1) gene on 8p23.2, has reached genome-wide support as a risk factor for schizophrenia. There is initial but inconclusive evidence for a role of this variant in aspects of cognition.

METHODS:

We investigated the neurocognitive effects of the CSMD1 rs10503253 (C/A) polymorphism in a large, demographically homogeneous sample of young, healthy Greek Caucasian males (n=1149) phenotyped for a wide range of neuropsychological measures, most of which have been shown to be reliable endophenotypes for schizophrenia.

RESULTS:

The risk 'A' allele was associated with poorer performance on measures of general cognitive ability, strategy formation, spatial and visual working memory, set shifting, target detection and planning for problem solving but not for emotional decision making. Most of these effects were dependent on risk "A" allele dose, with AA and CC homozygotes being the worse and the best respectively, while CA individuals were intermediate. Potential genotype effects in Stroop and verbal memory performance were also suggested by our dataset.

DISCUSSION:

These results underline the relevance of the risk "A" allele to neurocognitive functioning and suggest that its detrimental effects on cognition, may be part of the mechanism by which the CSMD1 mediates risk for schizophrenia.

KEYWORDS:

CSMD1 gene; Cognition; Endophenotypes; Executive function; Schizophrenia

PMID:
24630139
DOI:
10.1016/j.schres.2014.02.017
[Indexed for MEDLINE]

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