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Article: Differential effects of DAAO on regional activation and functional connectivity in schizophrenia, bipolar disorder and controls
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TitleDifferential effects of DAAO on regional activation and functional connectivity in schizophrenia, bipolar disorder and controls
 
AuthorsPapagni, SA1 2
Mechelli, A1
Prata, DP1
Kambeitz, J1
Fu, CHY1
Picchioni, M1
Walshe, M1
Toulopoulou, T1
Bramon, E1
Murray, RM1
Collier, DA1
Bellomo, A2
McGuire, P1
 
KeywordsBipolar disorder
DAAO
FMRI
Imaging genetics
Schizophrenia
Verbal fluency
 
Issue Date2011
 
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ynimg
 
CitationNeuroimage, 2011, v. 56 n. 4, p. 2283-2291 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.neuroimage.2011.03.037
 
AbstractRecent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene affects brain function to increase vulnerability to these disorders. We examined the impact of DAAO genotype (rs3918346) on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy controls. We tested the hypothesis that a variation in DAAO genotype would be associated with altered prefrontal function and altered functional connectivity in schizophrenia and bipolar disorder. We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype, and their interaction on brain activation and on functional connectivity. Inferences were made at p < 0.05, after correction for multiple comparisons across the whole brain. In the schizophrenia group relative to the control group, patients with one or two copies of the T allele showed lower deactivation in the left precuneus and greater activation in the right posterior cingulate gyrus than patients with two copies of the C allele. This diagnosis × genotype interaction was associated with differences in the functional connectivity of these two regions with other cortical and subcortical areas. In contrast, there were no significant effects of diagnosis or of genotype in comparisons involving bipolar patients. Our results suggest that genetic variation in DAAO has a significant impact on both regional activation and functional connectivity, and provide evidence for a diagnosis-dependent pattern of gene action. © 2011 Elsevier Inc.
 
ISSN1053-8119
2012 Impact Factor: 6.252
2012 SCImago Journal Rankings: 3.164
 
DOIhttp://dx.doi.org/10.1016/j.neuroimage.2011.03.037
 
ISI Accession Number IDWOS:000291457500037
 
ReferencesReferences in Scopus
 
DC FieldValue
dc.contributor.authorPapagni, SA
 
dc.contributor.authorMechelli, A
 
dc.contributor.authorPrata, DP
 
dc.contributor.authorKambeitz, J
 
dc.contributor.authorFu, CHY
 
dc.contributor.authorPicchioni, M
 
dc.contributor.authorWalshe, M
 
dc.contributor.authorToulopoulou, T
 
dc.contributor.authorBramon, E
 
dc.contributor.authorMurray, RM
 
dc.contributor.authorCollier, DA
 
dc.contributor.authorBellomo, A
 
dc.contributor.authorMcGuire, P
 
dc.date.accessioned2011-09-27T03:02:31Z
 
dc.date.available2011-09-27T03:02:31Z
 
dc.date.issued2011
 
dc.description.abstractRecent studies have identified DAAO as a probable susceptibility gene for schizophrenia and bipolar disorder. However, little is known about how this gene affects brain function to increase vulnerability to these disorders. We examined the impact of DAAO genotype (rs3918346) on brain function in patients with schizophrenia, patients with bipolar I disorder and healthy controls. We tested the hypothesis that a variation in DAAO genotype would be associated with altered prefrontal function and altered functional connectivity in schizophrenia and bipolar disorder. We used functional magnetic resonance imaging to measure brain responses during a verbal fluency task in a total of 121 subjects comprising 40 patients with schizophrenia, 33 patients with bipolar disorder and 48 healthy volunteers. We then used statistical parametric mapping (SPM) and psycho-physiological interaction (PPI) analyses to estimate the main effects of diagnostic group, the main effect of genotype, and their interaction on brain activation and on functional connectivity. Inferences were made at p < 0.05, after correction for multiple comparisons across the whole brain. In the schizophrenia group relative to the control group, patients with one or two copies of the T allele showed lower deactivation in the left precuneus and greater activation in the right posterior cingulate gyrus than patients with two copies of the C allele. This diagnosis × genotype interaction was associated with differences in the functional connectivity of these two regions with other cortical and subcortical areas. In contrast, there were no significant effects of diagnosis or of genotype in comparisons involving bipolar patients. Our results suggest that genetic variation in DAAO has a significant impact on both regional activation and functional connectivity, and provide evidence for a diagnosis-dependent pattern of gene action. © 2011 Elsevier Inc.
 
dc.description.naturelink_to_subscribed_fulltext
 
dc.identifier.citationNeuroimage, 2011, v. 56 n. 4, p. 2283-2291 [How to Cite?]
DOI: http://dx.doi.org/10.1016/j.neuroimage.2011.03.037
 
dc.identifier.citeulike9080832
 
dc.identifier.doihttp://dx.doi.org/10.1016/j.neuroimage.2011.03.037
 
dc.identifier.eissn1095-9572
 
dc.identifier.epage2291
 
dc.identifier.isiWOS:000291457500037
 
dc.identifier.issn1053-8119
2012 Impact Factor: 6.252
2012 SCImago Journal Rankings: 3.164
 
dc.identifier.issue4
 
dc.identifier.pmid21421061
 
dc.identifier.scopuseid_2-s2.0-79957446299
 
dc.identifier.spage2283
 
dc.identifier.urihttp://hdl.handle.net/10722/141814
 
dc.identifier.volume56
 
dc.languageeng
 
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ynimg
 
dc.publisher.placeUnited States
 
dc.relation.ispartofNeuroImage
 
dc.relation.referencesReferences in Scopus
 
dc.subjectBipolar disorder
 
dc.subjectDAAO
 
dc.subjectFMRI
 
dc.subjectImaging genetics
 
dc.subjectSchizophrenia
 
dc.subjectVerbal fluency
 
dc.titleDifferential effects of DAAO on regional activation and functional connectivity in schizophrenia, bipolar disorder and controls
 
dc.typeArticle
 
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Author Affiliations
  1. King's College London
  2. Università degli Studi di Foggia