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European Archives of Psychiatry and Clinical Neuroscience

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Open Access 01-12-2012 | Original Paper

Genetic polymorphisms of 5-HTT and DAT but not COMT differentially affect verbal and visuospatial working memory functioning

Authors: David Zilles, Jobst Meyer, Thomas Schneider-Axmann, Savira Ekawardhani, Eva Gruber, Peter Falkai, Oliver Gruber

Published in: European Archives of Psychiatry and Clinical Neuroscience | Issue 8/2012

Abstract

Working memory deficits are found in different psychiatric populations and are most pronounced in schizophrenia. There is preliminary evidence from pharmacological studies that the verbal and visuospatial subcomponents of working memory are subject to differential neurotransmitter modulation. Here, we investigated the impact of well-known polymorphisms of the dopamine transporter gene (SLC6A3, DAT) and the catechol-O-methyl-transferase gene (COMT) as well as the serotonin transporter gene (SLC6A4, 5-HTT) on these specific working memory subcomponents in a mixed sample of patients and healthy individuals. Twenty healthy subjects and 80 patients diagnosed with schizophrenia, bipolar I disorder, or obsessive-compulsive disorder underwent genotyping for the DAT variable number of tandem repeats (VNTR), the COMT val/met-, and the 5-HTT promoter length polymorphism (5-HTTLPR) and neuropsychological testing using a battery of well-characterized, brain circuit–specific working memory tasks. DAT genotype revealed a significant and selective effect on visuospatial working memory, while there was no effect on verbal working memory functioning. 5-HTT genotype, by contrast, exerted a significant and selective effect on verbal working memory task performance. COMT genotype did not show any influence on either working memory domain. The results of the present study provide evidence for a differential impact of genetic polymorphisms of the dopaminergic and serotonergic systems on verbal and visuospatial working memory functioning. Together with prior evidence suggesting the existence of subgroups of schizophrenia patients exhibiting isolated deficits in only one working memory domain, this finding further supports the idea of endophenotypically and pathophysiologically distinct subgroups of schizophrenia with implications for personalized therapeutic approaches.

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Title: Genetic polymorphisms of 5-HTT and DAT but not COMT differentially affect verbal and visuospatial working memory functioning
Authors: David Zilles
Jobst Meyer
Thomas Schneider-Axmann
Savira Ekawardhani
Eva Gruber
Peter Falkai
Oliver Gruber
Publication date: 01-12-2012
Publisher: Springer-Verlag
Published in: European Archives of Psychiatry and Clinical Neuroscience / Issue 8/2012
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI: https://doi.org/10.1007/s00406-012-0312-0

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Genetic polymorphisms of 5-HTT and DAT but not COMT differentially affect verbal and visuospatial working memory functioning

Abstract

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Abstract

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