Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Email this article to a Colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to My Articles & Searches Download to citation manager Citing Articles via HighWire Citing Articles via Google Scholar Articles by Bertolino, A. Articles by Nardini, M. Search for Related Content PubMed Citation Articles by Bertolino, A. Articles by Nardini, M. Atypical Neuroleptics Schizophrenia Spectrum Disorders Genetics Cognition

Interaction of COMT Val^108/158 Met Genotype and Olanzapine Treatment on Prefrontal Cortical Function in Patients With Schizophrenia

OBJECTIVE: Deficits in working memory and in prefrontal cortical physiology are important outcome measures in schizophrenia, and both have been associated with dopamine dysregulation and with a functional polymorphism (Val^108/158Met) in the catechol O-methyltransferase (COMT) gene that affects dopamine inactivation in the prefrontal cortex. The purpose of the present study was to evaluate in patients with schizophrenia the effect of COMT genotype on symptom variation, working memory performance, and prefrontal cortical physiology in response to treatment with an atypical antipsychotic drug. METHOD: Thirty patients with acute untreated schizophrenia were clinically evaluated with the Positive and Negative Syndrome Scale, underwent COMT Val/Met genotyping, and entered an 8-week prospective study of olanzapine treatment. Twenty patients completed two 3-T functional magnetic resonance imaging scans at 4 and 8 weeks during performance of N-back working memory tasks. RESULTS: There was a significant interaction of COMT genotype and the effects of olanzapine on prefrontal cortical function. Met allele load predicted improvement in working memory performance and prefrontal physiology after 8 weeks of treatment. A similar effect was found also for negative symptoms assessed with the Positive and Negative Syndrome Scale. CONCLUSIONS: These results suggest that a genetically determined variation in prefrontal dopamine catabolism impacts the therapeutic profile of olanzapine.

This article has been cited by other articles:

				S. Benetti, A. Mechelli, M. Picchioni, M. Broome, S. Williams, and P. McGuire Functional integration between the posterior hippocampus and prefrontal cortex is impaired in both first episode schizophrenia and the at risk mental state Brain, September 1, 2009; 132(9): 2426 - 2436. [Abstract] [Full Text] [PDF]

				D. P. Prata, A. Mechelli, C. H. Y. Fu, M. Picchioni, T. Toulopoulou, E. Bramon, M. Walshe, R. M. Murray, D. A. Collier, and P. McGuire Epistasis between the DAT 3' UTR VNTR and the COMT Val158Met SNP on cortical function in healthy subjects and patients with schizophrenia PNAS, August 11, 2009; 106(32): 13600 - 13605. [Abstract] [Full Text] [PDF]

				A. Bertolino, L. Fazio, G. Caforio, G. Blasi, A. Rampino, R. Romano, A. Di Giorgio, P. Taurisano, A. Papp, J. Pinsonneault, et al. Functional variants of the dopamine receptor D2 gene modulate prefronto-striatal phenotypes in schizophrenia Brain, February 1, 2009; 132(2): 417 - 425. [Abstract] [Full Text] [PDF]

				A. Bertolino, L. Fazio, A. Di Giorgio, G. Blasi, R. Romano, P. Taurisano, G. Caforio, L. Sinibaldi, G. Ursini, T. Popolizio, et al. Genetically Determined Interaction between the Dopamine Transporter and the D2 Receptor on Prefronto-Striatal Activity and Volume in Humans J. Neurosci., January 28, 2009; 29(4): 1224 - 1234. [Abstract] [Full Text] [PDF]

				J. L. Roffman, R. L. Gollub, V. D. Calhoun, T. H. Wassink, A. P. Weiss, B. C. Ho, T. White, V. P. Clark, J. Fries, N. C. Andreasen, et al. MTHFR 677C -> T genotype disrupts prefrontal function in schizophrenia through an interaction with COMT 158Val -> Met PNAS, November 11, 2008; 105(45): 17573 - 17578. [Abstract] [Full Text] [PDF]

				M. J. Arranz and S. Kapur Pharmacogenetics in Psychiatry: Are We Ready for Widespread Clinical Use? Schizophr Bull, November 1, 2008; 34(6): 1130 - 1144. [Abstract] [Full Text] [PDF]

				S. J. Bishop, J. Fossella, C. J. Croucher, and J. Duncan COMT val158met Genotype Affects Recruitment of Neural Mechanisms Supporting Fluid Intelligence Cereb Cortex, September 1, 2008; 18(9): 2132 - 2140. [Abstract] [Full Text] [PDF]

				G. D. Pearlson and B. S. Folley Schizophrenia, Psychiatric Genetics, and Darwinian Psychiatry: An Evolutionary Framework Schizophr Bull, July 1, 2008; 34(4): 722 - 733. [Abstract] [Full Text] [PDF]

				Y. Zhang, A. Bertolino, L. Fazio, G. Blasi, A. Rampino, R. Romano, M.-L. T. Lee, T. Xiao, A. Papp, D. Wang, et al. Polymorphisms in human dopamine D2 receptor gene affect gene expression, splicing, and neuronal activity during working memory PNAS, December 18, 2007; 104(51): 20552 - 20557. [Abstract] [Full Text] [PDF]

				H.-Y. Tan, Q. Chen, T. E. Goldberg, V. S. Mattay, A. Meyer-Lindenberg, D. R. Weinberger, and J. H. Callicott Catechol-O-Methyltransferase Val158Met Modulation of Prefrontal Parietal Striatal Brain Systems during Arithmetic and Temporal Transformations in Working Memory J. Neurosci., December 5, 2007; 27(49): 13393 - 13401. [Abstract] [Full Text] [PDF]

				S. Morein-Zamir, D. C. Turner, and B. J. Sahakian A Review of the Effects of Modafinil on Cognition in Schizophrenia Schizophr Bull, November 1, 2007; 33(6): 1298 - 1306. [Abstract] [Full Text] [PDF]

				L. Yavich, M. M. Forsberg, M. Karayiorgou, J. A. Gogos, and P. T. Mannisto Site-Specific Role of Catechol-O-Methyltransferase in Dopamine Overflow within Prefrontal Cortex and Dorsal Striatum J. Neurosci., September 19, 2007; 27(38): 10196 - 10209. [Abstract] [Full Text] [PDF]

				H.-Y. Tan, J. H. Callicott, and D. R. Weinberger Dysfunctional and Compensatory Prefrontal Cortical Systems, Genes and the Pathogenesis of Schizophrenia Cereb Cortex, September 1, 2007; 17(suppl_1): i171 - i181. [Abstract] [Full Text] [PDF]

				S. G. Leckband, J. R. Bishop, and V. L. Ellingrod Pharmacogenomics in Psychiatry Journal of Pharmacy Practice, June 1, 2007; 20(3): 252 - 264. [Abstract] [PDF]

				H. J. Williams, M. J. Owen, and M. C. O'Donovan Is COMT a Susceptibility Gene for Schizophrenia? Schizophr Bull, May 1, 2007; 33(3): 635 - 641. [Abstract] [Full Text] [PDF]

				A. P. Weiss Measuring the Impact of Medical Research: Moving From Outputs to Outcomes Am J Psychiatry, February 1, 2007; 164(2): 206 - 214. [Abstract] [Full Text] [PDF]

				H. M. Abdolmaleky, K.-h. Cheng, S. V. Faraone, M. Wilcox, S. J. Glatt, F. Gao, C. L. Smith, R. Shafa, B. Aeali, J. Carnevale, et al. Hypomethylation of MB-COMT promoter is a major risk factor for schizophrenia and bipolar disorder Hum. Mol. Genet., November 1, 2006; 15(21): 3132 - 3145. [Abstract] [Full Text] [PDF]

				A. Bertolino, G. Blasi, V. Latorre, V. Rubino, A. Rampino, L. Sinibaldi, G. Caforio, V. Petruzzella, A. Pizzuti, T. Scarabino, et al. Additive Effects of Genetic Variation in Dopamine Regulating Genes on Working Memory Cortical Activity in Human Brain J. Neurosci., April 12, 2006; 26(15): 3918 - 3922. [Abstract] [Full Text] [PDF]

				S. Prathikanti and D. R. Weinberger Psychiatric genetics - the new era: genetic research and some clinical implications Br. Med. Bull., December 19, 2005; 73-74(1): 107 - 122. [Abstract] [Full Text] [PDF]

				A. Breier Developing Drugs for Cognitive Impairment in Schizophrenia Schizophr Bull, October 1, 2005; 31(4): 816 - 822. [Abstract] [Full Text] [PDF]

				G. Blasi, V. S. Mattay, A. Bertolino, B. Elvevag, J. H. Callicott, S. Das, B. S. Kolachana, M. F. Egan, T. E. Goldberg, and D. R. Weinberger Effect of Catechol-O-Methyltransferase val158met Genotype on Attentional Control J. Neurosci., May 18, 2005; 25(20): 5038 - 5045. [Abstract] [Full Text] [PDF]

Get information about faster international access.

Privacy Policy

Copyright © 2004 American Psychiatric Association. All rights reserved.

Home | Search | Current Issue | Past Issues | Subscribe | All APPI Journals | Help | Contact Us