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Article: No association of Disrupted-in-Schizophrenia-1 variation with prefrontal function in patients with schizophrenia and bipolar disorder
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TitleNo association of Disrupted-in-Schizophrenia-1 variation with prefrontal function in patients with schizophrenia and bipolar disorder
 
AuthorsPrata, DP3 1
Mechelli, A3
Picchioni, M3 2
Fu, CHY3
Kane, F3
Kalidindi, S3
Mcdonald, C4
Kravariti, E3
Toulopoulou, T3
Bramon, E3
Walshe, M3
Murray, R3
Collier, DA1
Mcguire, PK3
 
KeywordsBipolar disorder
DISC1
Prefrontal function
Psychosis
Schizophrenia
Verbal fluency
 
Issue Date2011
 
PublisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/G2B
 
CitationGenes, Brain And Behavior, 2011, v. 10 n. 3, p. 276-285 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1601-183X.2010.00665.x
 
AbstractThe Disrupted-in-Schizophrenia-1 (DISC1) gene has been implicated in both schizophrenia and bipolar disorder by linkage and genetic association studies. Altered prefrontal cortical function is a pathophysiological feature of both disorders, and we have recently shown that variation in DISC1 modulates prefrontal activation in healthy volunteers. Our goal was to examine the influence of the DISC1 polymorphism Cys704Ser on prefrontal function in schizophrenia and bipolar disorder. From 2004 to 2008, patients with schizophrenia (N = 44), patients with bipolar disorder (N = 35) and healthy volunteers (N = 53) were studied using functional magnetic resonance imaging while performing a verbal fluency task. The effect of Cys704Ser on cortical activation was compared between groups as Cys704 carriers vs. Ser704 homozygotes. In contrast to the significant effect on prefrontal activation we had previously found in healthy subjects, no significant effect of Cys704Ser was detected in this or any other region in either the schizophrenia or bipolar groups. When controls were compared with patients with schizophrenia, there was a diagnosis by genotype interaction in the left middle/superior frontal gyrus [family-wise error (FWE) P = 0.002]. In this region, Ser704/ser704 controls activated more than Cys704 carriers, and there was a trend in the opposite direction in schizophrenia patients. In contrast to its effect in healthy subjects, variation in DISC1 Cys704Ser704 genotype was not associated with altered prefrontal activation in patients with schizophrenia or bipolar disorder. The absence of an effect in patients may reflect interactions of the effects of DISC1 genotype with the effects of other genes associated with these disorders, and/or with the effects of the disorders on brain function. © 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.
 
ISSN1601-1848
2012 Impact Factor: 3.597
2012 SCImago Journal Rankings: 1.793
 
DOIhttp://dx.doi.org/10.1111/j.1601-183X.2010.00665.x
 
ISI Accession Number IDWOS:000289152200003
Funding AgencyGrant Number
FCT foundation (Fundacao para a Ciencia e Tecnologia, Portugal)
Wellcome Travelling Fellowship
Wellcome Trust
Funding Information:

D.P. was supported by FCT foundation (Fundacao para a Ciencia e Tecnologia, Portugal) PhD Fellowship, C. F. by a Wellcome Travelling Fellowship and M. P. by a Wellcome Trust Research Fellowship. There were no conflicts of interest in producing this work.

 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorPrata, DP
 
dc.contributor.authorMechelli, A
 
dc.contributor.authorPicchioni, M
 
dc.contributor.authorFu, CHY
 
dc.contributor.authorKane, F
 
dc.contributor.authorKalidindi, S
 
dc.contributor.authorMcdonald, C
 
dc.contributor.authorKravariti, E
 
dc.contributor.authorToulopoulou, T
 
dc.contributor.authorBramon, E
 
dc.contributor.authorWalshe, M
 
dc.contributor.authorMurray, R
 
dc.contributor.authorCollier, DA
 
dc.contributor.authorMcguire, PK
 
dc.date.accessioned2011-09-27T03:02:32Z
 
dc.date.available2011-09-27T03:02:32Z
 
dc.date.issued2011
 
dc.description.abstractThe Disrupted-in-Schizophrenia-1 (DISC1) gene has been implicated in both schizophrenia and bipolar disorder by linkage and genetic association studies. Altered prefrontal cortical function is a pathophysiological feature of both disorders, and we have recently shown that variation in DISC1 modulates prefrontal activation in healthy volunteers. Our goal was to examine the influence of the DISC1 polymorphism Cys704Ser on prefrontal function in schizophrenia and bipolar disorder. From 2004 to 2008, patients with schizophrenia (N = 44), patients with bipolar disorder (N = 35) and healthy volunteers (N = 53) were studied using functional magnetic resonance imaging while performing a verbal fluency task. The effect of Cys704Ser on cortical activation was compared between groups as Cys704 carriers vs. Ser704 homozygotes. In contrast to the significant effect on prefrontal activation we had previously found in healthy subjects, no significant effect of Cys704Ser was detected in this or any other region in either the schizophrenia or bipolar groups. When controls were compared with patients with schizophrenia, there was a diagnosis by genotype interaction in the left middle/superior frontal gyrus [family-wise error (FWE) P = 0.002]. In this region, Ser704/ser704 controls activated more than Cys704 carriers, and there was a trend in the opposite direction in schizophrenia patients. In contrast to its effect in healthy subjects, variation in DISC1 Cys704Ser704 genotype was not associated with altered prefrontal activation in patients with schizophrenia or bipolar disorder. The absence of an effect in patients may reflect interactions of the effects of DISC1 genotype with the effects of other genes associated with these disorders, and/or with the effects of the disorders on brain function. © 2010 The Authors. Genes, Brain and Behavior © 2010 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationGenes, Brain And Behavior, 2011, v. 10 n. 3, p. 276-285 [How to Cite?]
DOI: http://dx.doi.org/10.1111/j.1601-183X.2010.00665.x
 
dc.identifier.citeulike8488982
 
dc.identifier.doihttp://dx.doi.org/10.1111/j.1601-183X.2010.00665.x
 
dc.identifier.eissn1601-183X
 
dc.identifier.epage285
 
dc.identifier.isiWOS:000289152200003
Funding AgencyGrant Number
FCT foundation (Fundacao para a Ciencia e Tecnologia, Portugal)
Wellcome Travelling Fellowship
Wellcome Trust
Funding Information:

D.P. was supported by FCT foundation (Fundacao para a Ciencia e Tecnologia, Portugal) PhD Fellowship, C. F. by a Wellcome Travelling Fellowship and M. P. by a Wellcome Trust Research Fellowship. There were no conflicts of interest in producing this work.

 
dc.identifier.issn1601-1848
2012 Impact Factor: 3.597
2012 SCImago Journal Rankings: 1.793
 
dc.identifier.issue3
 
dc.identifier.pmid21091867
 
dc.identifier.scopuseid_2-s2.0-79953274605
 
dc.identifier.spage276
 
dc.identifier.urihttp://hdl.handle.net/10722/141816
 
dc.identifier.volume10
 
dc.languageeng
 
dc.publisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/G2B
 
dc.publisher.placeDenmark
 
dc.relation.ispartofGenes, Brain and Behavior
 
dc.relation.referencesReferences in Scopus
 
dc.subjectBipolar disorder
 
dc.subjectDISC1
 
dc.subjectPrefrontal function
 
dc.subjectPsychosis
 
dc.subjectSchizophrenia
 
dc.subjectVerbal fluency
 
dc.titleNo association of Disrupted-in-Schizophrenia-1 variation with prefrontal function in patients with schizophrenia and bipolar disorder
 
dc.typeArticle
 
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Author Affiliations
  1. Social
  2. King's College London
  3. Division of Cancer Studies
  4. National University of Ireland Galway