File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Opposite Effects of Catechol-O-Methyltransferase Val158Met on Cortical Function in Healthy Subjects and Patients with Schizophrenia

TitleOpposite Effects of Catechol-O-Methyltransferase Val158Met on Cortical Function in Healthy Subjects and Patients with Schizophrenia
Authors
KeywordsCatechol-O-methyltransferase
cerebral cortex
cognitive symptoms
dopamine
imaging
schizophrenia
Issue Date2009
PublisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biopsychiat
Citation
Biological Psychiatry, 2009, v. 65 n. 6, p. 473-480 How to Cite?
AbstractBackground: Catechol-O-methyltransferase (COMT) is essential for dopamine metabolism in the brain, and normal variation in the COMT Val158Met polymorphism can influence regional brain function during cognitive tasks. How this is affected when central dopamine function is perturbed is unclear. We addressed this by comparing the effects of COMT Val158Met genotype on cortical activation during a task of executive functions in healthy and schizophrenic subjects. Methods: We studied 90 subjects comprising 48 healthy volunteers (15 Met158/Met158, 20 Val158/Met158, and 13 Val158/Val158) and 42 patients with DSM-IV schizophrenia (13 Met158/Met158, 17 Val158/Met158, and 12 Val158/Val158). Subjects were studied with functional magnetic resonance imaging while performing a verbal fluency task, with performance recorded online. Main effects of genotype and diagnosis and their interaction on cortical activation and functional connectivity were assessed using SPM5. Results: In the right peri-Sylvian cortex, the Met158 allele of the COMT Val158Met polymorphism was associated with greater activation than the Val158 allele in control subjects; the converse applied in patients (Z = 4.3; false discovery rate p = .04). There was also a strong trend for a group × genotype interaction on functional connectivity between this right peri-Sylvian region and the left anterior insula/operculum (Z = 3.4; p < .001, uncorrected). These findings were independent of between-group differences in task performance, medication, demographic factors, or IQ. Conclusions: Frontotemporal function during verbal generation is modulated by variation in COMT genotype. This effect is altered in schizophrenia, which may reflect the perturbation of central dopamine function associated with the disorder. © 2009 Society of Biological Psychiatry.
Persistent Identifierhttp://hdl.handle.net/10722/141837
ISSN
2015 Impact Factor: 11.212
2015 SCImago Journal Rankings: 5.823
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorPrata, DPen_HK
dc.contributor.authorMechelli, Aen_HK
dc.contributor.authorFu, CHYen_HK
dc.contributor.authorPicchioni, Men_HK
dc.contributor.authorKane, Fen_HK
dc.contributor.authorKalidindi, Sen_HK
dc.contributor.authorMcDonald, Cen_HK
dc.contributor.authorHowes, Oen_HK
dc.contributor.authorKravariti, Een_HK
dc.contributor.authorDemjaha, Aen_HK
dc.contributor.authorToulopoulou, Ten_HK
dc.contributor.authorDiforti, Men_HK
dc.contributor.authorMurray, RMen_HK
dc.contributor.authorCollier, DAen_HK
dc.contributor.authorMcGuire, PKen_HK
dc.date.accessioned2011-09-27T03:02:58Z-
dc.date.available2011-09-27T03:02:58Z-
dc.date.issued2009en_HK
dc.identifier.citationBiological Psychiatry, 2009, v. 65 n. 6, p. 473-480en_HK
dc.identifier.issn0006-3223en_HK
dc.identifier.urihttp://hdl.handle.net/10722/141837-
dc.description.abstractBackground: Catechol-O-methyltransferase (COMT) is essential for dopamine metabolism in the brain, and normal variation in the COMT Val158Met polymorphism can influence regional brain function during cognitive tasks. How this is affected when central dopamine function is perturbed is unclear. We addressed this by comparing the effects of COMT Val158Met genotype on cortical activation during a task of executive functions in healthy and schizophrenic subjects. Methods: We studied 90 subjects comprising 48 healthy volunteers (15 Met158/Met158, 20 Val158/Met158, and 13 Val158/Val158) and 42 patients with DSM-IV schizophrenia (13 Met158/Met158, 17 Val158/Met158, and 12 Val158/Val158). Subjects were studied with functional magnetic resonance imaging while performing a verbal fluency task, with performance recorded online. Main effects of genotype and diagnosis and their interaction on cortical activation and functional connectivity were assessed using SPM5. Results: In the right peri-Sylvian cortex, the Met158 allele of the COMT Val158Met polymorphism was associated with greater activation than the Val158 allele in control subjects; the converse applied in patients (Z = 4.3; false discovery rate p = .04). There was also a strong trend for a group × genotype interaction on functional connectivity between this right peri-Sylvian region and the left anterior insula/operculum (Z = 3.4; p < .001, uncorrected). These findings were independent of between-group differences in task performance, medication, demographic factors, or IQ. Conclusions: Frontotemporal function during verbal generation is modulated by variation in COMT genotype. This effect is altered in schizophrenia, which may reflect the perturbation of central dopamine function associated with the disorder. © 2009 Society of Biological Psychiatry.en_HK
dc.languageengen_US
dc.publisherElsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/biopsychiaten_HK
dc.relation.ispartofBiological Psychiatryen_HK
dc.subjectCatechol-O-methyltransferaseen_HK
dc.subjectcerebral cortexen_HK
dc.subjectcognitive symptomsen_HK
dc.subjectdopamineen_HK
dc.subjectimagingen_HK
dc.subjectschizophreniaen_HK
dc.titleOpposite Effects of Catechol-O-Methyltransferase Val158Met on Cortical Function in Healthy Subjects and Patients with 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.doi10.1016/j.biopsych.2008.09.027en_HK
dc.identifier.pmid19054502-
dc.identifier.scopuseid_2-s2.0-60349127839en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-60349127839&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume65en_HK
dc.identifier.issue6en_HK
dc.identifier.spage473en_HK
dc.identifier.epage480en_HK
dc.identifier.isiWOS:000263895900004-
dc.publisher.placeUnited Statesen_HK
dc.identifier.scopusauthoridPrata, DP=14632352500en_HK
dc.identifier.scopusauthoridMechelli, A=6603693131en_HK
dc.identifier.scopusauthoridFu, CHY=8502155300en_HK
dc.identifier.scopusauthoridPicchioni, M=6507443795en_HK
dc.identifier.scopusauthoridKane, F=24829114900en_HK
dc.identifier.scopusauthoridKalidindi, S=24366595400en_HK
dc.identifier.scopusauthoridMcDonald, C=8749594800en_HK
dc.identifier.scopusauthoridHowes, O=6602176923en_HK
dc.identifier.scopusauthoridKravariti, E=8855469000en_HK
dc.identifier.scopusauthoridDemjaha, A=23970361800en_HK
dc.identifier.scopusauthoridToulopoulou, T=8855468700en_HK
dc.identifier.scopusauthoridDiforti, M=17134536800en_HK
dc.identifier.scopusauthoridMurray, RM=35406239400en_HK
dc.identifier.scopusauthoridCollier, DA=26642980600en_HK
dc.identifier.scopusauthoridMcGuire, PK=7101880438en_HK
dc.identifier.citeulike4544883-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats