CatecholO-Methyltransferase Val158Met Polymorphism in Schizophrenia: Differential Effects of Val and Met Alleles on Cognitive Stability and Flexibility
- 1 February 2004
- journal article
- research article
- Published by American Psychiatric Association Publishing in American Journal of Psychiatry
- Vol. 161 (2) , 359-361
- https://doi.org/10.1176/appi.ajp.161.2.359
Abstract
OBJECTIVE: The catechol O-methyltransferase (COMT) Val158Met polymorphism has been associated with cognitive and behavioral phenotypes in schizophrenia. Whether COMT genotype is beneficial may depend on phenotype definition. The authors examined the effects of COMT genotype on a task that distinguishes imitation from reversal learning. They hypothesized that the Val and Met alleles would be associated with deficits in imitation learning and reversal learning, respectively. METHOD: Twenty-six patients with schizophrenia and schizoaffective disorder completed a task requiring alternation between imitation and reversal rules. RESULTS: Met homozygotes showed better acquisition of the imitation rule but greater deficit shifting from imitation to reversal. Val homozygotes had poorer imitation performance and slower reaction times. CONCLUSIONS: The Met allele, by increasing tonic dopamine, may promote cognitive stability but limit cognitive flexibility.Keywords
This publication has 15 references indexed in Scilit:
- Catechol O -methyltransferase val
158
-met genotype and individual variation in the brain response to amphetamineProceedings of the National Academy of Sciences, 2003
- Neurocognitive correlates of the COMT Val158Met polymorphism in chronic schizophreniaBiological Psychiatry, 2002
- The computational role of dopamine D1 receptors in working memoryNeural Networks, 2002
- Computational perspectives on dopamine function in prefrontal cortexCurrent Opinion in Neurobiology, 2002
- Improved short-term spatial memory but impaired reversal learning following the dopamine D2 agonist bromocriptine in human volunteersPsychopharmacology, 2001
- Task set switching in schizophrenia.Neuropsychology, 2000
- The regulation of forebrain dopamine transmission: relevance to the pathophysiology and psychopathology of schizophreniaBiological Psychiatry, 1999
- Analysis of a functional catechol-O-methyltransferase gene polymorphism in schizophrenia: evidence for association with aggressive and antisocial behaviorPsychiatry Research, 1997
- Cortical regulation of subcortical dopamine systems and its possible relevance to schizophreniaJournal Of Neural Transmission-Parkinsons Disease and Dementia Section, 1993
- Phasic versus tonic dopamine release and the modulation of dopamine system responsivity: A hypothesis for the etiology of schizophreniaNeuroscience, 1991