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Published in: European Archives of Psychiatry and Clinical Neuroscience 6/2018

Open Access 01-09-2018 | Original Paper

COMT and GAD1 gene polymorphisms are associated with impaired antisaccade task performance in schizophrenic patients

Authors: Anna V. Kirenskaya, Zinaida I. Storozheva, Marina A. Gruden, Robert D. E. Sewell

Published in: European Archives of Psychiatry and Clinical Neuroscience | Issue 6/2018

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Abstract

Genetic influences modulating executive functions engaging prefrontal cortical brain systems were investigated in 141 male subjects. The effects of variations in two genes implicated in dopamine and GABA activities in the prefrontal cortex: rs4680 (Val158/Met polymorphism of the catechol-o-methyltransferase gene—COMT) and rs3749034 (C/T) substitution in the promoter region of the glutamic acid decarboxylase gene (GAD1) were studied on antisaccade (AS) performance in healthy subjects and schizophrenic patients. Genotyping revealed a trend towards a reduced proportion of COMT Val/Met heterozygotes and a significantly increased frequency of the GAD1 rs3749034 C allele in schizophrenic patients relative to controls. Patients had elevated error rates, increased AS latencies and increased latency variability (coefficient of variation) compared to controls. The influence of polymorphisms was observed only in patients but not in controls. A substantial effect of the COMT genotype was noted on the coefficient of variation in latency, and this measure was higher in Val homozygotes compared to Met allele carriers (p < 0.05) in the patient group. The outcome from rs3749034 was also disclosed on the error rate (higher in T carriers relative to C homozygotes, p < 0.01) and latency (increased in C homozygotes relative to T carriers, p < 0.01). Binary logistic regression showed that inclusion of the genotype factor (i.e., selective estimation of antisaccade measures in CC carriers) considerably increased the validity of the diagnostic model based on the AS measures. These findings may well be derived from specific genetic associations with prefrontal cortex functioning in schizophrenia.
Literature
14.
go back to reference Levy DL, Mendell NR, Holzman PS (2004) The antisaccade task and neuropsychological tests of prefrontal cortical integrity in schizophrenia: empirical findings and interpretative considerations. World Psychiatry 3:32–40PubMedPubMedCentral Levy DL, Mendell NR, Holzman PS (2004) The antisaccade task and neuropsychological tests of prefrontal cortical integrity in schizophrenia: empirical findings and interpretative considerations. World Psychiatry 3:32–40PubMedPubMedCentral
18.
go back to reference O’Driscoll GA, Alpert NM, Matthysse SW, Levy DL, Rauch SL, Holzman PS (1995) Functional neuroanatomy of antisaccade eye movements investigated with positron emission tomography. Proc Natl Acad Sci USA 92, 925–929CrossRefPubMed O’Driscoll GA, Alpert NM, Matthysse SW, Levy DL, Rauch SL, Holzman PS (1995) Functional neuroanatomy of antisaccade eye movements investigated with positron emission tomography. Proc Natl Acad Sci USA 92, 925–929CrossRefPubMed
25.
go back to reference Schlag-Rey M, Amador N, Sanchez H, Schlag J (1997) Antisaccade performance predicted by neuronal activity in the supplementary eye field. Nature 390(6658):398–401CrossRefPubMed Schlag-Rey M, Amador N, Sanchez H, Schlag J (1997) Antisaccade performance predicted by neuronal activity in the supplementary eye field. Nature 390(6658):398–401CrossRefPubMed
35.
go back to reference Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J, Egan MF, Kleinman JE, Weinberger DR (2004) Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet 75:807–821. https://doi.org/10.1086/425589 CrossRefPubMedPubMedCentral Chen J, Lipska BK, Halim N, Ma QD, Matsumoto M, Melhem S, Kolachana BS, Hyde TM, Herman MM, Apud J, Egan MF, Kleinman JE, Weinberger DR (2004) Functional analysis of genetic variation in catechol-O-methyltransferase (COMT): effects on mRNA, protein, and enzyme activity in postmortem human brain. Am J Hum Genet 75:807–821. https://​doi.​org/​10.​1086/​425589 CrossRefPubMedPubMedCentral
39.
go back to reference Ohnishi T, Hashimoto R, Mori T, Nemoto K, Moriguchi Y, Iida H, Noguchi H, Nakabayashi T, Hori H, Ohmori M, Tsukue R, Anami K, Hirabayashi N, Harada S, Arima K, Saitoh O, Kunugi H (2006) The association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and morphological abnormalities of the brain in chronic schizophrenia. Brain 129:399–410. https://doi.org/10.1093/brain/awh702 CrossRefPubMed Ohnishi T, Hashimoto R, Mori T, Nemoto K, Moriguchi Y, Iida H, Noguchi H, Nakabayashi T, Hori H, Ohmori M, Tsukue R, Anami K, Hirabayashi N, Harada S, Arima K, Saitoh O, Kunugi H (2006) The association between the Val158Met polymorphism of the catechol-O-methyl transferase gene and morphological abnormalities of the brain in chronic schizophrenia. Brain 129:399–410. https://​doi.​org/​10.​1093/​brain/​awh702 CrossRefPubMed
48.
go back to reference Addington AM, Gornick M, Duckworth J, Sporn A, Gogtay N, Bobb A, Greenstein D, Lenane M, Gochman P, Baker N, Balkissoon R, Vakkalanka RK, Weinberger DR, Rapoport JL, Straub RE (2005) GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss. Mol Psychiatry 10:581–588. https://doi.org/10.1038/sj.mp.4001599 CrossRefPubMed Addington AM, Gornick M, Duckworth J, Sporn A, Gogtay N, Bobb A, Greenstein D, Lenane M, Gochman P, Baker N, Balkissoon R, Vakkalanka RK, Weinberger DR, Rapoport JL, Straub RE (2005) GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss. Mol Psychiatry 10:581–588. https://​doi.​org/​10.​1038/​sj.​mp.​4001599 CrossRefPubMed
50.
go back to reference Straub RE, Lipska BK, Egan MF, Goldberg TE, Callicott JH, Mayhew MB, Vakkalanka RK, Kolachana BS, Kleinman JE, Weinberger DR (2007) Allelic variation in GAD1 (GAD67) is associated with schizophrenia and influences cortical function and gene expression. Mol Psychiatry 129:854–869. https://doi.org/10.1038/sj.mp.4001988 CrossRef Straub RE, Lipska BK, Egan MF, Goldberg TE, Callicott JH, Mayhew MB, Vakkalanka RK, Kolachana BS, Kleinman JE, Weinberger DR (2007) Allelic variation in GAD1 (GAD67) is associated with schizophrenia and influences cortical function and gene expression. Mol Psychiatry 129:854–869. https://​doi.​org/​10.​1038/​sj.​mp.​4001988 CrossRef
54.
go back to reference Tucker DM, Williamson PA (1984) Asymmetric neural control system in human self-regulation. Psychol Review 91:185–215 N 1CrossRef Tucker DM, Williamson PA (1984) Asymmetric neural control system in human self-regulation. Psychol Review 91:185–215 N 1CrossRef
56.
go back to reference Hoenicka J, Garrido E, Martínez I, Ponce G, Aragüés M, Rodríguez-Jiménez R, España-Serrano L, Alvira-Botero X, Santos JL, Rubio G, Jiménez-Arriero M, Palomo T (2010) Gender-specific COMT Val158Met polymorphism association in spanish schizophrenic patients. Am J Med Genet B Neuropsychiatr Genet 153B(1):79–85. https://doi.org/10.1002/ajmg.b.30957 PubMedCrossRef Hoenicka J, Garrido E, Martínez I, Ponce G, Aragüés M, Rodríguez-Jiménez R, España-Serrano L, Alvira-Botero X, Santos JL, Rubio G, Jiménez-Arriero M, Palomo T (2010) Gender-specific COMT Val158Met polymorphism association in spanish schizophrenic patients. Am J Med Genet B Neuropsychiatr Genet 153B(1):79–85. https://​doi.​org/​10.​1002/​ajmg.​b.​30957 PubMedCrossRef
Metadata
Title
COMT and GAD1 gene polymorphisms are associated with impaired antisaccade task performance in schizophrenic patients
Authors
Anna V. Kirenskaya
Zinaida I. Storozheva
Marina A. Gruden
Robert D. E. Sewell
Publication date
01-09-2018
Publisher
Springer Berlin Heidelberg
Published in
European Archives of Psychiatry and Clinical Neuroscience / Issue 6/2018
Print ISSN: 0940-1334
Electronic ISSN: 1433-8491
DOI
https://doi.org/10.1007/s00406-018-0881-7

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