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Interaction between effects of genes coding for dopamine and glutamate transmission on striatal and parahippocampal function

Authors

  • Andreina Pauli,

    Corresponding author
    1. Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, University of Bern, Switzerland
    • Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Diana P. Prata,

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
    2. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Andrea Mechelli,

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Marco Picchioni,

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
    2. St Andrew's Academic Centre, King's College London, Institute of Psychiatry, Northampton, NN1
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  • Cynthia H.Y. Fu,

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Christopher A. Chaddock,

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Fergus Kane,

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Sridevi Kalidindi,

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
    2. Department of Psychology, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Colm McDonald,

    1. Department of Psychiatry, Clinical Science Institute, National University of Ireland, Galway, Ireland
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  • Eugenia Kravariti,

    1. Department of Psychiatric Neurophysiology, University Hospital of Psychiatry, University of Bern, Switzerland
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  • Timothea Toulopoulou,

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Elvira Bramon,

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Muriel Walshe,

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Natascha Ehlert,

    1. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Anna Georgiades,

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Robin Murray,

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • David A. Collier,

    1. Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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  • Philip McGuire

    1. Department of Psychosis Studies, Institute of Psychiatry, King's College London, London, SE5 8AF, United Kingdom
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Correspondence to: Andreina Pauli, Institute of Psychiatry, PO67, De Crespigny Park, London, SE5 8AF, UK. E-mail: andreina.pauli@kcl.ac.uk

Abstract

The genes for the dopamine transporter (DAT) and the D-Amino acid oxidase activator (DAOA or G72) have been independently implicated in the risk for schizophrenia and in bipolar disorder and/or their related intermediate phenotypes. DAT and G72 respectively modulate central dopamine and glutamate transmission, the two systems most robustly implicated in these disorders. Contemporary studies have demonstrated that elevated dopamine function is associated with glutamatergic dysfunction in psychotic disorders. Using functional magnetic resonance imaging we examined whether there was an interaction between the effects of genes that influence dopamine and glutamate transmission (DAT and G72) on regional brain activation during verbal fluency, which is known to be abnormal in psychosis, in 80 healthy volunteers. Significant interactions between the effects of G72 and DAT polymorphisms on activation were evident in the striatum, parahippocampal gyrus, and supramarginal/angular gyri bilaterally, the right insula, in the right pre-/postcentral and the left posterior cingulate/retrosplenial gyri (P < 0.05, FDR-corrected across the whole brain). This provides evidence that interactions between the dopamine and the glutamate system, thought to be altered in psychosis, have an impact in executive processing which can be modulated by common genetic variation. Hum Brain Mapp 34:2244–2258, 2013. © 2012 Wiley Periodicals, Inc.

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