Open AccessEffect of D ‐amino acid oxidase activator (DAOA; G72) on brain function during verbal fluency
Author(s) -
Prata Diana P.,
Papagni Sergio A.,
Mechelli Andrea,
Fu Cynthia H.Y.,
Kambeitz Joseph,
Picchioni Marco,
Kane Fergus,
Kalidindi Sridevi,
McDonald Colm,
Kravariti Eugenia,
Toulopoulou Timothea,
Bramon Elvira,
Walshe Muriel,
Murray Robin,
Collier David A.,
McGuire Philip K.
Publication year - 2012
Publication title -
human brain mapping
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.005
H-Index - 191
eISSN - 1097-0193
pISSN - 1065-9471
DOI - 10.1002/hbm.21198
Subject(s) - glutamatergic , functional magnetic resonance imaging , neuroscience , psychology , glutamate receptor , medicine , endocrinology , receptor
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. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.