Article: Genetic vulnerability to psychosis and cortical function: Epistatic effects between DAAO and G72

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TitleGenetic vulnerability to psychosis and cortical function: Epistatic effects between DAAO and G72
AuthorsMechelli, A1
FusarPoli, P1 3
Prata, D1
Papagni Sergio, A1 2
Tognin, S1
Kambeitz, J1
Fu, C1
Picchioni, M1
Walshe, M1
Toulopoulou, T1
Bramon, E1
Murray, R1
Mcguire, P1
KeywordsBipolar Disorder
Daao
Functional Magnetic Resonance Imaging
G72
Glutamate
Schizophrenia
Vulnerability
Issue Date2012
PublisherBentham Science Publishers Ltd. The Journal's web site is located at http://www.bentham.org/cpd/index.htm
CitationCurrent Pharmaceutical Design, 2012, v. 18 n. 4, p. 510-517 [How to Cite?]
DOI: http://dx.doi.org/10.2174/138161212799316037
AbstractRecent studies have described G72 and DAAO as susceptibility genes for schizophrenia and bipolar disorder. Both genes modulate glutamate neurotransmission, which plays a key role in neurocognitive function and is thought to be altered in these disorders. Moreover, in vitro transcription studies indicate that the two genes interact with each other at the molecular level. However, it is unclear how these genes affect cortical function and whether their effects interact with each other. The aim of this study was therefore to examine the impact of G72 rs746187 and DAAO rs2111902 genotypes on brain function in schizophrenia, bipolar disorder and healthy volunteers. We used functional magnetic resonance imaging and an overt verbal fluency paradigm to examine brain function in a total of 120 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 47 healthy volunteers. A significant 3 way interaction between G72, DAAO and diagnosis was detected in the right middle temporal gyrus (x=60 y=-12 z=-12; z-score: 5.32; p<0.001 after family-wise error correction), accounting for 8.5% of the individual variance in activation. These data suggest that there is a nonadditive interaction between the effects of variations in the genes implicated in glutamate regulation that affects cortical function. Also, the nature of this interaction is different in patients and healthy controls, providing support for altered glutamate function in psychosis. Future studies could explore the effects of DAAO and G72 in individuals with prodromal symptoms of psychosis, in order to elucidate glutamate dysfunction in this critical phase of the disorder. © 2012 Bentham Science Publishers.
ISSN1381-6128
2011 Impact Factor: 3.87
2011 SCImago Journal Rankings: 0.341
DOIhttp://dx.doi.org/10.2174/138161212799316037
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorMechelli, A
dc.contributor.authorFusarPoli, P
dc.contributor.authorPrata, D
dc.contributor.authorPapagni Sergio, A
dc.contributor.authorTognin, S
dc.contributor.authorKambeitz, J
dc.contributor.authorFu, C
dc.contributor.authorPicchioni, M
dc.contributor.authorWalshe, M
dc.contributor.authorToulopoulou, T
dc.contributor.authorBramon, E
dc.contributor.authorMurray, R
dc.contributor.authorMcguire, P
dc.date.accessioned2012-08-23T06:11:29Z
dc.date.available2012-08-23T06:11:29Z
dc.date.issued2012
dc.description.abstractRecent studies have described G72 and DAAO as susceptibility genes for schizophrenia and bipolar disorder. Both genes modulate glutamate neurotransmission, which plays a key role in neurocognitive function and is thought to be altered in these disorders. Moreover, in vitro transcription studies indicate that the two genes interact with each other at the molecular level. However, it is unclear how these genes affect cortical function and whether their effects interact with each other. The aim of this study was therefore to examine the impact of G72 rs746187 and DAAO rs2111902 genotypes on brain function in schizophrenia, bipolar disorder and healthy volunteers. We used functional magnetic resonance imaging and an overt verbal fluency paradigm to examine brain function in a total of 120 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar I disorder and 47 healthy volunteers. A significant 3 way interaction between G72, DAAO and diagnosis was detected in the right middle temporal gyrus (x=60 y=-12 z=-12; z-score: 5.32; p<0.001 after family-wise error correction), accounting for 8.5% of the individual variance in activation. These data suggest that there is a nonadditive interaction between the effects of variations in the genes implicated in glutamate regulation that affects cortical function. Also, the nature of this interaction is different in patients and healthy controls, providing support for altered glutamate function in psychosis. Future studies could explore the effects of DAAO and G72 in individuals with prodromal symptoms of psychosis, in order to elucidate glutamate dysfunction in this critical phase of the disorder. © 2012 Bentham Science Publishers.
dc.description.natureLink_to_subscribed_fulltext
dc.identifier.citationCurrent Pharmaceutical Design, 2012, v. 18 n. 4, p. 510-517 [How to Cite?]
DOI: http://dx.doi.org/10.2174/138161212799316037
dc.identifier.doihttp://dx.doi.org/10.2174/138161212799316037
dc.identifier.epage517
dc.identifier.issn1381-6128
2011 Impact Factor: 3.87
2011 SCImago Journal Rankings: 0.341
dc.identifier.issue4
dc.identifier.scopuseid_2-s2.0-84856525206
dc.identifier.spage510
dc.identifier.urihttp://hdl.handle.net/10722/161255
dc.identifier.volume18
dc.languageeng
dc.publisherBentham Science Publishers Ltd. The Journal's web site is located at http://www.bentham.org/cpd/index.htm
dc.publisher.placeNetherlands
dc.relation.ispartofCurrent Pharmaceutical Design
dc.relation.referencesReferences in Scopus
dc.subjectBipolar Disorder
dc.subjectDaao
dc.subjectFunctional Magnetic Resonance Imaging
dc.subjectG72
dc.subjectGlutamate
dc.subjectSchizophrenia
dc.subjectVulnerability
dc.titleGenetic vulnerability to psychosis and cortical function: Epistatic effects between DAAO and G72
dc.typeArticle
Author Affiliations
  1. King's College London
  2. Università degli Studi di Foggia
  3. Università degli Studi di Pavia