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Article: No association of Disrupted-in-Schizophrenia-1 variation with prefrontal function in patients with schizophrenia and bipolar disorder

TitleNo association of Disrupted-in-Schizophrenia-1 variation with prefrontal function in patients with schizophrenia and bipolar disorder
Authors
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
Citation
Genes, Brain And Behavior, 2011, v. 10 n. 3, p. 276-285 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/141816
ISSN
2014 Impact Factor: 3.661
2014 SCImago Journal Rankings: 1.729
ISI Accession Number ID
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.

References

 

DC FieldValueLanguage
dc.contributor.authorPrata, DPen_HK
dc.contributor.authorMechelli, Aen_HK
dc.contributor.authorPicchioni, Men_HK
dc.contributor.authorFu, CHYen_HK
dc.contributor.authorKane, Fen_HK
dc.contributor.authorKalidindi, Sen_HK
dc.contributor.authorMcdonald, Cen_HK
dc.contributor.authorKravariti, Een_HK
dc.contributor.authorToulopoulou, Ten_HK
dc.contributor.authorBramon, Een_HK
dc.contributor.authorWalshe, Men_HK
dc.contributor.authorMurray, Ren_HK
dc.contributor.authorCollier, DAen_HK
dc.contributor.authorMcguire, PKen_HK
dc.date.accessioned2011-09-27T03:02:32Z-
dc.date.available2011-09-27T03:02:32Z-
dc.date.issued2011en_HK
dc.identifier.citationGenes, Brain And Behavior, 2011, v. 10 n. 3, p. 276-285en_HK
dc.identifier.issn1601-1848en_HK
dc.identifier.urihttp://hdl.handle.net/10722/141816-
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.en_HK
dc.languageengen_US
dc.publisherBlackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/G2Ben_HK
dc.relation.ispartofGenes, Brain and Behavioren_HK
dc.subjectBipolar disorderen_HK
dc.subjectDISC1en_HK
dc.subjectPrefrontal functionen_HK
dc.subjectPsychosisen_HK
dc.subjectSchizophreniaen_HK
dc.subjectVerbal fluencyen_HK
dc.titleNo association of Disrupted-in-Schizophrenia-1 variation with prefrontal function in patients with schizophrenia and bipolar disorderen_HK
dc.typeArticleen_HK
dc.identifier.emailToulopoulou, T:timothea@hku.hken_HK
dc.identifier.authorityToulopoulou, T=rp01542en_HK
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1111/j.1601-183X.2010.00665.xen_HK
dc.identifier.pmid21091867-
dc.identifier.scopuseid_2-s2.0-79953274605en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79953274605&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume10en_HK
dc.identifier.issue3en_HK
dc.identifier.spage276en_HK
dc.identifier.epage285en_HK
dc.identifier.eissn1601-183X-
dc.identifier.isiWOS:000289152200003-
dc.publisher.placeDenmarken_HK
dc.identifier.scopusauthoridPrata, DP=14632352500en_HK
dc.identifier.scopusauthoridMechelli, A=6603693131en_HK
dc.identifier.scopusauthoridPicchioni, M=6507443795en_HK
dc.identifier.scopusauthoridFu, CHY=8502155300en_HK
dc.identifier.scopusauthoridKane, F=24829114900en_HK
dc.identifier.scopusauthoridKalidindi, S=24366595400en_HK
dc.identifier.scopusauthoridMcdonald, C=8749594800en_HK
dc.identifier.scopusauthoridKravariti, E=8855469000en_HK
dc.identifier.scopusauthoridToulopoulou, T=8855468700en_HK
dc.identifier.scopusauthoridBramon, E=8089378900en_HK
dc.identifier.scopusauthoridWalshe, M=8855469300en_HK
dc.identifier.scopusauthoridMurray, R=35406239400en_HK
dc.identifier.scopusauthoridCollier, DA=26642980600en_HK
dc.identifier.scopusauthoridMcguire, PK=7101880438en_HK
dc.identifier.citeulike8488982-

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