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Article: Altered effect of dopamine transporter 3′UTR VNTR genotype on prefrontal and striatal function in schizophrenia

TitleAltered effect of dopamine transporter 3′UTR VNTR genotype on prefrontal and striatal function in schizophrenia
Authors
KeywordsChemicals And Cas Registry Numbers
Issue Date2009
PublisherAmerican Medical Association. The Journal's web site is located at http://www.archgenpsychiatry.com
Citation
Archives Of General Psychiatry, 2009, v. 66 n. 11, p. 1162-1172 How to Cite?
Abstract
Context: The dopamine transporter plays a key role in the regulation of central dopaminergic transmission, which modulates cognitive processing. Disrupted dopamine function and impaired executive processing are robust features of schizophrenia. Objective: To examine the effect of a polymorphism in the dopamine transporter gene (the variable number of tandem repeats in the 3′ untranslated region) on brain function during executive processing in healthy volunteers and patients with schizophrenia. We hypothesized that this variation would have a different effect on prefrontal and striatal activation in schizophrenia, reflecting altered dopamine function. Design: Case-control study. Setting: Psychiatric research center. Participants: Eighty-five subjects, comprising 44 healthy volunteers (18 who were 9-repeat carriers and 26 who were 10-repeat homozygotes) and 41 patients with DSM-IV schizophrenia (18 who were 9-repeat carriers and 23 who were 10-repeat homozygotes). Main Outcome Measures: Regional brain activation during word generation relative to repetition in an overt verbal fluency task measured by functional magnetic resonance imaging. Main effects of genotype and diagnosis on activation and their interaction were estimated with analysis of variance in SPM5. Results: Irrespective of diagnosis, the 10-repeat allele was associated with greater activation than the 9-repeat allele in the left anterior insula and right caudate nucleus. Trends for the same effect in the right insula and for greater deactivation in the rostral anterior cingulate cortex were also detected. There were diagnosis x genotype interactions in the left middle frontal gyrusandleft nucleus accumbens,wherethe 9-repeat allele was associated with greater activation than the 10-repeat allele in patients but not controls. Conclusions: Insular, cingulate, and striatal function during an executive task is normally modulated by variation in thedopaminetransporter gene. Its effect on activation in the dorsolateral prefrontal cortex and ventral striatum is altered in patients with schizophrenia. This may reflect altered dopamine function in these regions in schizophrenia. ©2009 American Medical Association. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/141832
ISSN
2013 Impact Factor: 13.747
ISI Accession Number ID
References

 

Author Affiliations
  1. King's College London
DC FieldValueLanguage
dc.contributor.authorPrata, DPen_HK
dc.contributor.authorMechelli, Aen_HK
dc.contributor.authorPicchioni, MMen_HK
dc.contributor.authorFu, CHYen_HK
dc.contributor.authorToulopoulou, Ten_HK
dc.contributor.authorBramon, Een_HK
dc.contributor.authorWalshe, Men_HK
dc.contributor.authorMurray, RMen_HK
dc.contributor.authorCollier, DAen_HK
dc.contributor.authorMcGuire, Pen_HK
dc.date.accessioned2011-09-27T03:02:51Z-
dc.date.available2011-09-27T03:02:51Z-
dc.date.issued2009en_HK
dc.identifier.citationArchives Of General Psychiatry, 2009, v. 66 n. 11, p. 1162-1172en_HK
dc.identifier.issn0003-990Xen_HK
dc.identifier.urihttp://hdl.handle.net/10722/141832-
dc.description.abstractContext: The dopamine transporter plays a key role in the regulation of central dopaminergic transmission, which modulates cognitive processing. Disrupted dopamine function and impaired executive processing are robust features of schizophrenia. Objective: To examine the effect of a polymorphism in the dopamine transporter gene (the variable number of tandem repeats in the 3′ untranslated region) on brain function during executive processing in healthy volunteers and patients with schizophrenia. We hypothesized that this variation would have a different effect on prefrontal and striatal activation in schizophrenia, reflecting altered dopamine function. Design: Case-control study. Setting: Psychiatric research center. Participants: Eighty-five subjects, comprising 44 healthy volunteers (18 who were 9-repeat carriers and 26 who were 10-repeat homozygotes) and 41 patients with DSM-IV schizophrenia (18 who were 9-repeat carriers and 23 who were 10-repeat homozygotes). Main Outcome Measures: Regional brain activation during word generation relative to repetition in an overt verbal fluency task measured by functional magnetic resonance imaging. Main effects of genotype and diagnosis on activation and their interaction were estimated with analysis of variance in SPM5. Results: Irrespective of diagnosis, the 10-repeat allele was associated with greater activation than the 9-repeat allele in the left anterior insula and right caudate nucleus. Trends for the same effect in the right insula and for greater deactivation in the rostral anterior cingulate cortex were also detected. There were diagnosis x genotype interactions in the left middle frontal gyrusandleft nucleus accumbens,wherethe 9-repeat allele was associated with greater activation than the 10-repeat allele in patients but not controls. Conclusions: Insular, cingulate, and striatal function during an executive task is normally modulated by variation in thedopaminetransporter gene. Its effect on activation in the dorsolateral prefrontal cortex and ventral striatum is altered in patients with schizophrenia. This may reflect altered dopamine function in these regions in schizophrenia. ©2009 American Medical Association. All rights reserved.en_HK
dc.languageengen_US
dc.publisherAmerican Medical Association. The Journal's web site is located at http://www.archgenpsychiatry.comen_HK
dc.relation.ispartofArchives of General Psychiatryen_HK
dc.subjectChemicals And Cas Registry Numbersen_US
dc.titleAltered effect of dopamine transporter 3′UTR VNTR genotype on prefrontal and striatal function in schizophreniaen_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.doi10.1001/archgenpsychiatry.2009.147en_HK
dc.identifier.pmid19884604en_HK
dc.identifier.scopuseid_2-s2.0-69449098010en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-69449098010&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume66en_HK
dc.identifier.issue11en_HK
dc.identifier.spage1162en_HK
dc.identifier.epage1172en_HK
dc.identifier.eissn1538-3636-
dc.identifier.isiWOS:000271427500002-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridPrata, DP=14632352500en_HK
dc.identifier.scopusauthoridMechelli, A=6603693131en_HK
dc.identifier.scopusauthoridPicchioni, MM=6507443795en_HK
dc.identifier.scopusauthoridFu, CHY=8502155300en_HK
dc.identifier.scopusauthoridToulopoulou, T=8855468700en_HK
dc.identifier.scopusauthoridBramon, E=8089378900en_HK
dc.identifier.scopusauthoridWalshe, M=8855469300en_HK
dc.identifier.scopusauthoridMurray, RM=35406239400en_HK
dc.identifier.scopusauthoridCollier, DA=26642980600en_HK
dc.identifier.scopusauthoridMcGuire, P=7101880438en_HK

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