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The Journal of Neuroscience, April 12, 2006, 26(15):3918-3922; doi:10.1523/JNEUROSCI.4975-05.2006
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Brief Communications
Additive Effects of Genetic Variation in Dopamine Regulating Genes on Working Memory Cortical Activity in Human Brain
Alessandro Bertolino,1,3,4 Giuseppe Blasi,1,3 Valeria Latorre,1 Valeria Rubino,1 Antonio Rampino,1 Lorenzo Sinibaldi,2,6 Grazia Caforio,1 Vittoria Petruzzella,2 Antonio Pizzuti,5,6 Tommaso Scarabino,4 Marcello Nardini,1 Daniel R. Weinberger,3 andBruno Dallapiccola5,6 1Psychiatric Neuroscience Group, Section on Mental Disorders, Department of Neurological and Psychiatric Sciences, and 2Department of Medical Biochemistry and Medical Biology, University of Bari, 70124 Bari, Italy, 3Genes, Cognition, and Psychosis Program, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892, 4Department of Neuroradiology, Istituto di Ricovero e Cura e Carrattere Scientifico "Casa Sollievo della Sofferenza," 71013 San Giovanni Rotondo (Foggia), Italy, 5IRCCS-CSS Mendel, 00198 Rome, Italy, and 6Department of Experimental Medicine and Pathology, University La Sapienza, 00100 Rome, Italy
Correspondence should be addressed to Dr. Alessandro Bertolino, Dipartimento di Scienze Neurologiche e Psichiatriche, Universita’ degli Studi di Bari, Piazza Giulio Cesare, 9, 70124 Bari, Italy. Email: bertolia{at}psichiat.uniba.it
Functional polymorphisms in the catechol-O-methyltransferase (COMT) and the dopamine transporter (DAT) genes modulate dopamine inactivation, which is crucial for determining neuronal signal-to-noise ratios in prefrontal cortex during working memory. We show that the COMT Met158 allele and the DAT 3' variable number of tandem repeat 10-repeat allele are independently associated in healthy humans with more focused neuronal activity (as measured with blood oxygen level-dependent functional magnetic resonance imaging) in the working memory cortical network, including the prefrontal cortex. Moreover, subjects homozygous for the COMT Met allele and the DAT 10-repeat allele have the most focused response, whereas the COMT Val and the DAT 9-repeat alleles have the least. These results demonstrate additive genetic effects of genes regulating dopamine signaling on specific neuronal networks subserving working memory.
Key words: dorsolateral prefrontal cortex; anterior cingulate; working memory; dopamine; catechol-O-methyltransferase; dopamine transporter
Received Nov. 22, 2005; revised Jan. 30, 2006; accepted Feb. 27, 2006.
Correspondence should be addressed to Dr. Alessandro Bertolino, Dipartimento di Scienze Neurologiche e Psichiatriche, Universita’ degli Studi di Bari, Piazza Giulio Cesare, 9, 70124 Bari, Italy. Email: bertolia{at}psichiat.uniba.it
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