Document Detail


The association of schizophrenia risk D-amino acid oxidase polymorphisms with sensorimotor gating, working memory and personality in healthy males.
MedLine Citation:
PMID:  21471957     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is evidence supporting a role for the D-amino acid oxidase (DAO) locus in schizophrenia. This study aimed to determine the relationship of five single-nucleotide polymorphisms (SNPs) within the DAO gene identified as promising schizophrenia risk genes (rs4623951, rs2111902, rs3918346, rs3741775, and rs3825251) to acoustic startle, prepulse inhibition (PPI), working memory, and personality dimensions. A highly homogeneous study entry cohort (n = 530) of healthy, young male army conscripts (n = 703) originating from the Greek LOGOS project (Learning On Genetics Of Schizophrenia Spectrum) underwent PPI of the acoustic startle reflex, working memory, and personality assessment. The QTPHASE from the UNPHASED package was used for the association analysis of each SNP or haplotype data, with p-values corrected for multiple testing by running 10,000 permutations of the data. The rs4623951_T-rs3741775_G and rs4623951_T-rs2111902_T diplotypes were associated with reduced PPI and worse performance in working memory tasks and a personality pattern characterized by attenuated anxiety. Median stratification analysis of the risk diplotype group (ie, those individuals homozygous for the T and G alleles (TG+)) showed reduced PPI and working memory performance only in TG+ individuals with high trait anxiety. The rs4623951_T allele, which is the DAO polymorphism most strongly associated with schizophrenia, might tag a haplotype that affects PPI, cognition, and personality traits in general population. Our findings suggest an influence of the gene in the neural substrate mediating sensorimotor gating and working memory, especially when combined with high anxiety and further validate DAO as a candidate gene for schizophrenia and spectrum disorders.
Authors:
Panos Roussos; Stella G Giakoumaki; Eva Adamaki; Anastasios Georgakopoulos; Georgakopoulos Anastasios; Nikos K Robakis; Robakis K Nikos; Panos Bitsios
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-04-06
Journal Detail:
Title:  Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology     Volume:  36     ISSN:  1740-634X     ISO Abbreviation:  Neuropsychopharmacology     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-15     Completed Date:  2012-03-22     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  8904907     Medline TA:  Neuropsychopharmacology     Country:  England    
Other Details:
Languages:  eng     Pagination:  1677-88     Citation Subset:  IM    
Affiliation:
Department of Psychiatry and Behavioral Sciences, Faculty of Medicine, University of Crete, Heraklion, Crete, Greece. roussosp@edu.med.uoc.gr
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MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Anxiety / enzymology,  genetics
Cohort Studies
D-Amino-Acid Oxidase / genetics*
Genome-Wide Association Study / methods
Humans
Male
Memory, Short-Term / physiology*
Neural Inhibition / genetics
Personality / genetics*
Polymorphism, Genetic / genetics*
Schizophrenia / enzymology,  genetics*
Sensory Gating / genetics*
Young Adult
Chemical
Reg. No./Substance:
EC 1.4.3.3/D-Amino-Acid Oxidase
Comments/Corrections
Erratum In:
Neuropsychopharmacology. 2011 Oct;36(11):2370
Note: Anastasios, Georgakopoulos [corrected to Georgakopoulos, Anastasios]; Nikos, Robakis K [corrected to Robakis, Nikos K]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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