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

File Download Links for fulltext
(May Require Subscription)
Supplementary
  • Basic View
  • Metadata View
  • XML View
TitleAltered effect of dopamine transporter 3′UTR VNTR genotype on prefrontal and striatal function in schizophrenia
AuthorsPrata, DP1
Mechelli, A1
Picchioni, MM1
Fu, CHY1
Toulopoulou, T1
Bramon, E1
Walshe, M1
Murray, RM1
Collier, DA1
McGuire, P1
KeywordsChemicals And Cas Registry Numbers
Issue Date2009
PublisherAmerican Medical Association. The Journal's web site is located at http://www.archgenpsychiatry.com
CitationArchives Of General Psychiatry, 2009, v. 66 n. 11, p. 1162-1172 [How to Cite?]
DOI: http://dx.doi.org/10.1001/archgenpsychiatry.2009.147
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.
ISSN0003-990X
2011 Impact Factor: 12.016
2011 SCImago Journal Rankings: 0.738
DOIhttp://dx.doi.org/10.1001/archgenpsychiatry.2009.147
ISI Accession Number IDWOS:000271427500002
ReferencesReferences in Scopus
DC Field
Value
dc.contributor.authorPrata, DP
dc.contributor.authorMechelli, A
dc.contributor.authorPicchioni, MM
dc.contributor.authorFu, CHY
dc.contributor.authorToulopoulou, T
dc.contributor.authorBramon, E
dc.contributor.authorWalshe, M
dc.contributor.authorMurray, RM
dc.contributor.authorCollier, DA
dc.contributor.authorMcGuire, P
dc.date.accessioned2011-09-27T03:02:51Z
dc.date.available2011-09-27T03:02:51Z
dc.date.issued2009
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.
dc.description.naturelink_to_subscribed_fulltext
dc.identifier.citationArchives Of General Psychiatry, 2009, v. 66 n. 11, p. 1162-1172 [How to Cite?]
DOI: http://dx.doi.org/10.1001/archgenpsychiatry.2009.147
dc.identifier.doihttp://dx.doi.org/10.1001/archgenpsychiatry.2009.147
dc.identifier.eissn1538-3636
dc.identifier.epage1172
dc.identifier.isiWOS:000271427500002
dc.identifier.issn0003-990X
2011 Impact Factor: 12.016
2011 SCImago Journal Rankings: 0.738
dc.identifier.issue11
dc.identifier.pmid19884604
dc.identifier.scopuseid_2-s2.0-69449098010
dc.identifier.spage1162
dc.identifier.urihttp://hdl.handle.net/10722/141832
dc.identifier.volume66
dc.languageeng
dc.publisherAmerican Medical Association. The Journal's web site is located at http://www.archgenpsychiatry.com
dc.publisher.placeUnited States
dc.relation.ispartofArchives of General Psychiatry
dc.relation.referencesReferences in Scopus
dc.subjectChemicals And Cas Registry Numbers
dc.titleAltered effect of dopamine transporter 3′UTR VNTR genotype on prefrontal and striatal function in schizophrenia
dc.typeArticle
Author Affiliations
  1. King's College London