Original article| Volume 54, ISSUE 1, P40-48, July 01, 2003

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Association of the G1947A COMT (Val108/158Met) gene polymorphism with prefrontal P300 during information processing

  • Jürgen Gallinat
    Address reprint requests to Jürgen Gallinat, M.D., Free University of Berlin, Department of Psychiatry, Eschenallee 3, 14050 Berlin, Germany.
    Laboratory for Clinical Psychophysiology, Department of Psychiatry, Free University, Berlin, Germany (JG, MB, PS, GW)
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  • Malek Bajbouj
    Laboratory for Clinical Psychophysiology, Department of Psychiatry, Free University, Berlin, Germany (JG, MB, PS, GW)
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  • Thomas Sander
    Gene Mapping Center, Max-Delbrueck-Center (TS), Berlin, Germany
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  • Peter Schlattmann
    Laboratory for Clinical Psychophysiology, Department of Psychiatry, Free University, Berlin, Germany (JG, MB, PS, GW)
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  • Ke Xu
    Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism (KX, EFF, DG, GW), National Institutes of Health, Rockville, Maryland, USA
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  • Erica F Ferro
    Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism (KX, EFF, DG, GW), National Institutes of Health, Rockville, Maryland, USA
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  • David Goldman
    Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism (KX, EFF, DG, GW), National Institutes of Health, Rockville, Maryland, USA
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  • Georg Winterer
    Laboratory for Clinical Psychophysiology, Department of Psychiatry, Free University, Berlin, Germany (JG, MB, PS, GW)

    Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism (KX, EFF, DG, GW), National Institutes of Health, Rockville, Maryland, USA

    Clinical Brain Disorders Branch (GW), National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland, USA
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      A common functional polymorphism, G1947A, of the catechol-O-methyltransferase (COMT) enzyme has gained interest in schizophrenia research because of its critical involvement in cortical dopamine catabolism and frontal lobe function. An assumed mechanism of dopamine is the reduction of noise in prefrontal neural networks during information processing. Therefore, the hypothesis was tested whether a variation of the COMT genotype is associated with prefrontal noise, which is in part reflected by the frontal P300 amplitude. It was predicted that homozygous Met allele carriers have a lower frontal P300 amplitude.


      The P300 component (auditory oddball) was recorded in 49 schizophrenic patients and 170 healthy control subjects. Three single nucleotide polymorphisms (SNPs) of the COMT gene (G1947A, C1883G, and G1243A) were investigated.


      We observed a significant effect of G1947A COMT genotype on frontal P300 amplitude, with evidence for a genotype × diagnosis interaction. Lower frontal P300 amplitudes occurred in homozygous carriers of the Met allele, particularly in schizophrenic patients.


      The association of the frontal P300 amplitude with the G1947A COMT genotype further emphasizes the functional role of this SNP. As the finding was mainly observed in schizophrenic patients, this may indicate that additional factors are required to interact with COMT genotype to affect prefrontal function. The smaller frontal P300 amplitude in Met carriers suggests that the amount of noise in prefrontal neural networks during information processing might be in part under genetic control, which is mediated by dopamine.


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