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 languageEnglish
Pages (from-to)143-53
Number of pages11
JournalHuman Brain Mapping
Volume33
Issue number1
DOIs
Publication statusPublished - 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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