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Article: Differential effects of DAAO on regional activation and functional connectivity in schizophrenia, bipolar disorder and controls

TitleDifferential effects of DAAO on regional activation and functional connectivity in schizophrenia, bipolar disorder and controls
Authors
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
Citation
Neuroimage, 2011, v. 56 n. 4, p. 2283-2291 How to Cite?
Abstract
Recent 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.
Persistent Identifierhttp://hdl.handle.net/10722/141814
ISSN
2013 Impact Factor: 6.132
ISI Accession Number ID
References

 

Author Affiliations
  1. King's College London
  2. Università degli Studi di Foggia
DC FieldValueLanguage
dc.contributor.authorPapagni, SAen_HK
dc.contributor.authorMechelli, Aen_HK
dc.contributor.authorPrata, DPen_HK
dc.contributor.authorKambeitz, Jen_HK
dc.contributor.authorFu, CHYen_HK
dc.contributor.authorPicchioni, Men_HK
dc.contributor.authorWalshe, Men_HK
dc.contributor.authorToulopoulou, Ten_HK
dc.contributor.authorBramon, Een_HK
dc.contributor.authorMurray, RMen_HK
dc.contributor.authorCollier, DAen_HK
dc.contributor.authorBellomo, Aen_HK
dc.contributor.authorMcGuire, Pen_HK
dc.date.accessioned2011-09-27T03:02:31Z-
dc.date.available2011-09-27T03:02:31Z-
dc.date.issued2011en_HK
dc.identifier.citationNeuroimage, 2011, v. 56 n. 4, p. 2283-2291en_HK
dc.identifier.issn1053-8119en_HK
dc.identifier.urihttp://hdl.handle.net/10722/141814-
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.en_HK
dc.languageengen_US
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/ynimgen_HK
dc.relation.ispartofNeuroImageen_HK
dc.subjectBipolar disorderen_HK
dc.subjectDAAOen_HK
dc.subjectFMRIen_HK
dc.subjectImaging geneticsen_HK
dc.subjectSchizophreniaen_HK
dc.subjectVerbal fluencyen_HK
dc.titleDifferential effects of DAAO on regional activation and functional connectivity in schizophrenia, bipolar disorder and controlsen_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.doi10.1016/j.neuroimage.2011.03.037en_HK
dc.identifier.pmid21421061en_HK
dc.identifier.scopuseid_2-s2.0-79957446299en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-79957446299&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume56en_HK
dc.identifier.issue4en_HK
dc.identifier.spage2283en_HK
dc.identifier.epage2291en_HK
dc.identifier.eissn1095-9572-
dc.identifier.isiWOS:000291457500037-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridPapagni, SA=6506721202en_HK
dc.identifier.scopusauthoridMechelli, A=6603693131en_HK
dc.identifier.scopusauthoridPrata, DP=14632352500en_HK
dc.identifier.scopusauthoridKambeitz, J=36790051100en_HK
dc.identifier.scopusauthoridFu, CHY=8502155300en_HK
dc.identifier.scopusauthoridPicchioni, M=6507443795en_HK
dc.identifier.scopusauthoridWalshe, M=8855469300en_HK
dc.identifier.scopusauthoridToulopoulou, T=8855468700en_HK
dc.identifier.scopusauthoridBramon, E=8089378900en_HK
dc.identifier.scopusauthoridMurray, RM=35406239400en_HK
dc.identifier.scopusauthoridCollier, DA=26642980600en_HK
dc.identifier.scopusauthoridBellomo, A=6701780392en_HK
dc.identifier.scopusauthoridMcGuire, P=7101880438en_HK
dc.identifier.citeulike9080832-

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