File Download
 
Links for fulltext
(May Require Subscription)
 
Supplementary

Article: Altered effect of dopamine transporter 3′UTR VNTR genotype on prefrontal and striatal function in schizophrenia
  • Basic View
  • Metadata View
  • XML View
TitleAltered effect of dopamine transporter 3′UTR VNTR genotype on prefrontal and striatal function in schizophrenia
 
AuthorsPrata, DP1 1
Mechelli, A1 1
Picchioni, MM1 1
Fu, CHY1
Toulopoulou, T1
Bramon, E1
Walshe, M1
Murray, RM1
Collier, DA1 1
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
2012 Impact Factor: 13.772
 
DOIhttp://dx.doi.org/10.1001/archgenpsychiatry.2009.147
 
ISI Accession Number IDWOS:000271427500002
 
ReferencesReferences in Scopus
 
DC FieldValue
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
2012 Impact Factor: 13.772
 
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
 
<?xml encoding="utf-8" version="1.0"?>
<item><contributor.author>Prata, DP</contributor.author>
<contributor.author>Mechelli, A</contributor.author>
<contributor.author>Picchioni, MM</contributor.author>
<contributor.author>Fu, CHY</contributor.author>
<contributor.author>Toulopoulou, T</contributor.author>
<contributor.author>Bramon, E</contributor.author>
<contributor.author>Walshe, M</contributor.author>
<contributor.author>Murray, RM</contributor.author>
<contributor.author>Collier, DA</contributor.author>
<contributor.author>McGuire, P</contributor.author>
<date.accessioned>2011-09-27T03:02:51Z</date.accessioned>
<date.available>2011-09-27T03:02:51Z</date.available>
<date.issued>2009</date.issued>
<identifier.citation>Archives Of General Psychiatry, 2009, v. 66 n. 11, p. 1162-1172</identifier.citation>
<identifier.issn>0003-990X</identifier.issn>
<identifier.uri>http://hdl.handle.net/10722/141832</identifier.uri>
<description.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&#8242; 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. &#169;2009 American Medical Association. All rights reserved.</description.abstract>
<language>eng</language>
<publisher>American Medical Association. The Journal&apos;s web site is located at http://www.archgenpsychiatry.com</publisher>
<relation.ispartof>Archives of General Psychiatry</relation.ispartof>
<subject>Chemicals And Cas Registry Numbers</subject>
<title>Altered effect of dopamine transporter 3&#8242;UTR VNTR genotype on prefrontal and striatal function in schizophrenia</title>
<type>Article</type>
<description.nature>link_to_subscribed_fulltext</description.nature>
<identifier.doi>10.1001/archgenpsychiatry.2009.147</identifier.doi>
<identifier.pmid>19884604</identifier.pmid>
<identifier.scopus>eid_2-s2.0-69449098010</identifier.scopus>
<relation.references>http://www.scopus.com/mlt/select.url?eid=2-s2.0-69449098010&amp;selection=ref&amp;src=s&amp;origin=recordpage</relation.references>
<identifier.volume>66</identifier.volume>
<identifier.issue>11</identifier.issue>
<identifier.spage>1162</identifier.spage>
<identifier.epage>1172</identifier.epage>
<identifier.eissn>1538-3636</identifier.eissn>
<identifier.isi>WOS:000271427500002</identifier.isi>
<publisher.place>United States</publisher.place>
</item>
Author Affiliations
  1. King's College London