Article: No association of Disrupted-in-Schizophrenia-1 variation with prefrontal function in patients with schizophrenia and bipolar disorder
| Title | No association of Disrupted-in-Schizophrenia-1 variation with prefrontal function in patients with schizophrenia and bipolar disorder |
|---|---|
| Authors | Prata, DP1 3 Mechelli, A3 Picchioni, M2 3 Fu, CHY3 Kane, F3 Kalidindi, S3 Mcdonald, C4 Kravariti, E3 Toulopoulou, T3 Bramon, E3 Walshe, M3 Murray, R3 Collier, DA1 Mcguire, PK3 |
| Keywords | Bipolar disorder DISC1 Prefrontal function Psychosis Schizophrenia Verbal fluency |
| Issue Date | 2011 |
| Publisher | Blackwell 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?] DOI: http://dx.doi.org/10.1111/j.1601-183X.2010.00665.x |
| Abstract | The 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. |
| ISSN | 1601-1848 2011 Impact Factor: 3.476 2011 SCImago Journal Rankings: 0.353 |
| DOI | http://dx.doi.org/10.1111/j.1601-183X.2010.00665.x |
| References | References in Scopus |
| dc.contributor.author | Prata, DP | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Mechelli, A | ||||||||
| dc.contributor.author | Picchioni, M | ||||||||
| dc.contributor.author | Fu, CHY | ||||||||
| dc.contributor.author | Kane, F | ||||||||
| dc.contributor.author | Kalidindi, S | ||||||||
| dc.contributor.author | Mcdonald, C | ||||||||
| dc.contributor.author | Kravariti, E | ||||||||
| dc.contributor.author | Toulopoulou, T | ||||||||
| dc.contributor.author | Bramon, E | ||||||||
| dc.contributor.author | Walshe, M | ||||||||
| dc.contributor.author | Murray, R | ||||||||
| dc.contributor.author | Collier, DA | ||||||||
| dc.contributor.author | Mcguire, PK | ||||||||
| dc.date.accessioned | 2011-09-27T03:02:32Z | ||||||||
| dc.date.available | 2011-09-27T03:02:32Z | ||||||||
| dc.date.issued | 2011 | ||||||||
| dc.description.abstract | The 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.nature | link_to_subscribed_fulltext | ||||||||
| dc.identifier.citation | Genes, 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.citeulike | 8488982 | ||||||||
| dc.identifier.doi | http://dx.doi.org/10.1111/j.1601-183X.2010.00665.x | ||||||||
| dc.identifier.eissn | 1601-183X | ||||||||
| dc.identifier.epage | 285 | ||||||||
| dc.identifier.isi | WOS:000289152200003
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.issn | 1601-1848 2011 Impact Factor: 3.476 2011 SCImago Journal Rankings: 0.353 | ||||||||
| dc.identifier.issue | 3 | ||||||||
| dc.identifier.pmid | 21091867 | ||||||||
| dc.identifier.scopus | eid_2-s2.0-79953274605 | ||||||||
| dc.identifier.spage | 276 | ||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/141816 | ||||||||
| dc.identifier.volume | 10 | ||||||||
| dc.language | eng | ||||||||
| dc.publisher | Blackwell Munksgaard. The Journal's web site is located at http://www.blackwellpublishing.com/journals/G2B | ||||||||
| dc.publisher.place | Denmark | ||||||||
| dc.relation.ispartof | Genes, Brain and Behavior | ||||||||
| dc.relation.references | References in Scopus | ||||||||
| dc.subject | Bipolar disorder | ||||||||
| dc.subject | DISC1 | ||||||||
| dc.subject | Prefrontal function | ||||||||
| dc.subject | Psychosis | ||||||||
| dc.subject | Schizophrenia | ||||||||
| dc.subject | Verbal fluency | ||||||||
| dc.title | No association of Disrupted-in-Schizophrenia-1 variation with prefrontal function in patients with schizophrenia and bipolar disorder | ||||||||
| dc.type | Article |
Author Affiliations
- Social
- King's College London
- Division of Psychosis Studies
- National University of Ireland Galway