Effect of D-amino acid oxidase activator (DAOA; G72) on brain function during verbal fluency

Diana P Prata; Sergio A Papagni; Andrea Mechelli; Cynthia H Y Fu; Joseph Kambeitz; Marco Picchioni; Fergus Kane; Sridevi Kalidindi; Colm McDonald; Eugenia Kravariti; Timothea Toulopoulou; Elvira Bramon; Muriel Walshe; Robin Murray; David A Collier; Philip K McGuire

doi:10.1002/hbm.21198

Effect of D-amino acid oxidase activator (DAOA; G72) on brain function during verbal fluency

Diana P Prata, Sergio A Papagni, Andrea Mechelli, Cynthia H Y Fu, Joseph Kambeitz, Marco Picchioni, Fergus Kane, Sridevi Kalidindi, Colm McDonald, Eugenia Kravariti, Timothea Toulopoulou, Elvira Bramon, Muriel Walshe, Robin Murray, David A Collier, Philip K McGuire

Department of Psychosis Studies
1Department of Hepatology, Imperial College London, London, UK. 2Institute of Liver Studies at King's College School of Medicine at King's College Hospital, London, UK. 3Institute of Human Health and Performance, University College London, London, UK. 4Department of Asthma Allergy and Lung Biology, King's College London, London, UK. 5Division of Critical Care Medicine, University of Alberta, Edmonton, Canada.

Research output: Contribution to journal › Article › peer-review

Abstract

BACKGROUND: The D-Amino acid oxidase activator (G72 or DAOA) is believed to play a key role in the regulation of central glutamatergic transmission which is seen to be altered in psychosis. It is thought to regulate D-amino acid oxidase (DAO), which metabolizes D-serine, a co-agonist of NMDA-type glutamate receptors and to be involved in dendritic arborization. Linkage, genetic association and expression studies have implicated the G72 gene in both schizophrenia and bipolar disorder.

AIMS: To examine the influence of G72 variation on brain function in the healthy population.

METHOD: Fifty healthy volunteers were assessed using functional magnetic resonance imaging while performing a verbal fluency task. Regional brain activation and task-dependent functional connectivity during word generation was compared between different rs746187 genotypes.

RESULTS: G72 rs746187 genotype had a significant effect on activation in the left postcentral and supramarginal gyri (FWE P < 0.05), and on the task-dependent functional coupling of this region with the retrosplenial cingulate gyrus (FWE P < 0.05).

CONCLUSIONS: Our results may reflect an effect of G72 on glutamatergic transmission, mediated by an influence on D-amino acid oxidase activity, on brain areas particularly relevant to the hypoglutamatergic model of psychosis.

Original language	English
Pages (from-to)	143-53
Number of pages	11
Journal	Human Brain Mapping
Volume	33
Issue number	1
DOIs	https://doi.org/10.1002/hbm.21198
Publication status	Published - Jan 2012

Keywords

Adult
Brain/physiology
Brain Mapping
Carrier Proteins/genetics
Female
Genotype
Glutamic Acid/metabolism
Humans
Intracellular Signaling Peptides and Proteins
Magnetic Resonance Imaging
Male
Middle Aged
Nerve Net/physiology
Neuroimaging
Polymorphism, Single Nucleotide
Verbal Behavior/physiology

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10.1002/hbm.21198

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Prata, D. P., Papagni, S. A., Mechelli, A., Fu, C. H. Y., Kambeitz, J., Picchioni, M., Kane, F., Kalidindi, S., McDonald, C., Kravariti, E., Toulopoulou, T., Bramon, E., Walshe, M., Murray, R., Collier, D. A., & McGuire, P. K. (2012). Effect of D-amino acid oxidase activator (DAOA; G72) on brain function during verbal fluency. Human Brain Mapping, 33(1), 143-53. https://doi.org/10.1002/hbm.21198

@article{02929ba7fc494a7781b56c24db8539ac,

title = "Effect of D-amino acid oxidase activator (DAOA; G72) on brain function during verbal fluency",

abstract = "BACKGROUND: The D-Amino acid oxidase activator (G72 or DAOA) is believed to play a key role in the regulation of central glutamatergic transmission which is seen to be altered in psychosis. It is thought to regulate D-amino acid oxidase (DAO), which metabolizes D-serine, a co-agonist of NMDA-type glutamate receptors and to be involved in dendritic arborization. Linkage, genetic association and expression studies have implicated the G72 gene in both schizophrenia and bipolar disorder.AIMS: To examine the influence of G72 variation on brain function in the healthy population.METHOD: Fifty healthy volunteers were assessed using functional magnetic resonance imaging while performing a verbal fluency task. Regional brain activation and task-dependent functional connectivity during word generation was compared between different rs746187 genotypes.RESULTS: G72 rs746187 genotype had a significant effect on activation in the left postcentral and supramarginal gyri (FWE P < 0.05), and on the task-dependent functional coupling of this region with the retrosplenial cingulate gyrus (FWE P < 0.05).CONCLUSIONS: Our results may reflect an effect of G72 on glutamatergic transmission, mediated by an influence on D-amino acid oxidase activity, on brain areas particularly relevant to the hypoglutamatergic model of psychosis.",

keywords = "Adult, Brain/physiology, Brain Mapping, Carrier Proteins/genetics, Female, Genotype, Glutamic Acid/metabolism, Humans, Intracellular Signaling Peptides and Proteins, Magnetic Resonance Imaging, Male, Middle Aged, Nerve Net/physiology, Neuroimaging, Polymorphism, Single Nucleotide, Verbal Behavior/physiology",

author = "Prata, {Diana P} and Papagni, {Sergio A} and Andrea Mechelli and Fu, {Cynthia H Y} and Joseph Kambeitz and Marco Picchioni and Fergus Kane and Sridevi Kalidindi and Colm McDonald and Eugenia Kravariti and Timothea Toulopoulou and Elvira Bramon and Muriel Walshe and Robin Murray and Collier, {David A} and McGuire, {Philip K}",

note = "Copyright {\textcopyright} 2011 Wiley Periodicals, Inc.",

year = "2012",

month = jan,

doi = "10.1002/hbm.21198",

language = "English",

volume = "33",

pages = "143--53",

journal = "Human Brain Mapping",

issn = "1065-9471",

publisher = "Wiley-Liss Inc.",

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Prata, DP, Papagni, SA, Mechelli, A, Fu, CHY, Kambeitz, J, Picchioni, M , Kane, F , Kalidindi, S , McDonald, C , Kravariti, E , Toulopoulou, T, Bramon, E, Walshe, M , Murray, R , Collier, DA & McGuire, PK 2012, 'Effect of D-amino acid oxidase activator (DAOA; G72) on brain function during verbal fluency', Human Brain Mapping, vol. 33, no. 1, pp. 143-53. https://doi.org/10.1002/hbm.21198

TY - JOUR

T1 - Effect of D-amino acid oxidase activator (DAOA; G72) on brain function during verbal fluency

AU - Prata, Diana P

AU - Papagni, Sergio A

AU - Mechelli, Andrea

AU - Fu, Cynthia H Y

AU - Kambeitz, Joseph

AU - Picchioni, Marco

AU - Kane, Fergus

AU - Kalidindi, Sridevi

AU - McDonald, Colm

AU - Kravariti, Eugenia

AU - Toulopoulou, Timothea

AU - Bramon, Elvira

AU - Walshe, Muriel

AU - Murray, Robin

AU - Collier, David A

AU - McGuire, Philip K

PY - 2012/1

Y1 - 2012/1

N2 - BACKGROUND: The D-Amino acid oxidase activator (G72 or DAOA) is believed to play a key role in the regulation of central glutamatergic transmission which is seen to be altered in psychosis. It is thought to regulate D-amino acid oxidase (DAO), which metabolizes D-serine, a co-agonist of NMDA-type glutamate receptors and to be involved in dendritic arborization. Linkage, genetic association and expression studies have implicated the G72 gene in both schizophrenia and bipolar disorder.AIMS: To examine the influence of G72 variation on brain function in the healthy population.METHOD: Fifty healthy volunteers were assessed using functional magnetic resonance imaging while performing a verbal fluency task. Regional brain activation and task-dependent functional connectivity during word generation was compared between different rs746187 genotypes.RESULTS: G72 rs746187 genotype had a significant effect on activation in the left postcentral and supramarginal gyri (FWE P < 0.05), and on the task-dependent functional coupling of this region with the retrosplenial cingulate gyrus (FWE P < 0.05).CONCLUSIONS: Our results may reflect an effect of G72 on glutamatergic transmission, mediated by an influence on D-amino acid oxidase activity, on brain areas particularly relevant to the hypoglutamatergic model of psychosis.

AB - BACKGROUND: The D-Amino acid oxidase activator (G72 or DAOA) is believed to play a key role in the regulation of central glutamatergic transmission which is seen to be altered in psychosis. It is thought to regulate D-amino acid oxidase (DAO), which metabolizes D-serine, a co-agonist of NMDA-type glutamate receptors and to be involved in dendritic arborization. Linkage, genetic association and expression studies have implicated the G72 gene in both schizophrenia and bipolar disorder.AIMS: To examine the influence of G72 variation on brain function in the healthy population.METHOD: Fifty healthy volunteers were assessed using functional magnetic resonance imaging while performing a verbal fluency task. Regional brain activation and task-dependent functional connectivity during word generation was compared between different rs746187 genotypes.RESULTS: G72 rs746187 genotype had a significant effect on activation in the left postcentral and supramarginal gyri (FWE P < 0.05), and on the task-dependent functional coupling of this region with the retrosplenial cingulate gyrus (FWE P < 0.05).CONCLUSIONS: Our results may reflect an effect of G72 on glutamatergic transmission, mediated by an influence on D-amino acid oxidase activity, on brain areas particularly relevant to the hypoglutamatergic model of psychosis.

KW - Adult

KW - Brain/physiology

KW - Brain Mapping

KW - Carrier Proteins/genetics

KW - Female

KW - Genotype

KW - Glutamic Acid/metabolism

KW - Humans

KW - Intracellular Signaling Peptides and Proteins

KW - Magnetic Resonance Imaging

KW - Male

KW - Middle Aged

KW - Nerve Net/physiology

KW - Neuroimaging

KW - Polymorphism, Single Nucleotide

KW - Verbal Behavior/physiology

U2 - 10.1002/hbm.21198

DO - 10.1002/hbm.21198

M3 - Article

C2 - 21391259

SN - 1065-9471

VL - 33

SP - 143

EP - 153

JO - Human Brain Mapping

JF - Human Brain Mapping

IS - 1

ER -

Effect of D-amino acid oxidase activator (DAOA; G72) on brain function during verbal fluency

Abstract

Keywords

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