BACKGROUND: 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 x 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.
BACKGROUND: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 x 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.
Authors: Carl Christoph Schultz; Igor Nenadic; Brien Riley; Vladimir I Vladimirov; Gerd Wagner; Kathrin Koch; Claudia Schachtzabel; Thomas W Mühleisen; Buket Basmanav; Markus M Nöthen; Thomas Deufel; Michael Kiehntopf; Marcella Rietschel; Jürgen R Reichenbach; Sven Cichon; Ralf G M Schlösser; Heinrich Sauer Journal: Schizophr Bull Date: 2013-09-27 Impact factor: 9.306
Authors: Armin Raznahan; Deanna Greenstein; Yohan Lee; Robert Long; Liv Clasen; Pete Gochman; Anjene Addington; Jay N Giedd; Judith L Rapoport; Nitin Gogtay Journal: Neuroimage Date: 2011-05-15 Impact factor: 6.556
Authors: Diana P Prata; Andrea Mechelli; Cynthia H Y Fu; Marco Picchioni; Timothea Toulopoulou; Elvira Bramon; Muriel Walshe; Robin M Murray; David A Collier; Philip McGuire Journal: Proc Natl Acad Sci U S A Date: 2009-07-28 Impact factor: 11.205
Authors: Tejas S Bhojraj; Alan N Francis; Rajaprabhakaran Rajarethinam; Shaun Eack; Shreedhar Kulkarni; Konasale M Prasad; Debra M Montrose; Diana Dworakowski; Vaibhav Diwadkar; Matcheri S Keshavan Journal: Schizophr Res Date: 2009-10-17 Impact factor: 4.939