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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 1
Papagni Sergio, A1 2
Tognin, S1
Kambeitz, J1
Fu, C1
Picchioni, M1 1
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
2012 Impact Factor: 3.311
2012 SCImago Journal Rankings: 1.057
 
DOIhttp://dx.doi.org/10.2174/138161212799316037
 
ReferencesReferences in Scopus
 
DC FieldValue
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
2012 Impact Factor: 3.311
2012 SCImago Journal Rankings: 1.057
 
dc.identifier.issue4
 
dc.identifier.pmid22239582
 
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
 
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Author Affiliations
  1. King's College London
  2. Università degli Studi di Foggia
  3. Università degli Studi di Pavia