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Hum Brain Mapp. 2012 Jan;33(1):143-53. doi: 10.1002/hbm.21198. Epub 2011 Mar 9.

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

Author information

1
Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, UK. diana.prata@kcl.ac.uk

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.

PMID:
21391259
DOI:
10.1002/hbm.21198
[Indexed for MEDLINE]
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