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Greater Monoamine Oxidase A Binding in Alcohol Dependence

  • Brittany A. Matthews
    Affiliations
    Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
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  • Stephen J. Kish
    Affiliations
    Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
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  • Xin Xu
    Affiliations
    Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
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  • Isabelle Boileau
    Affiliations
    Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
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  • Pablo M. Rusjan
    Affiliations
    Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
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  • Alan A. Wilson
    Affiliations
    Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
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  • Dan DiGiacomo
    Affiliations
    Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
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  • Sylvain Houle
    Affiliations
    Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
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  • Jeffrey H. Meyer
    Correspondence
    Address correspondence to Jeffrey H. Meyer, M.D., Ph.D., College Street Site, Centre for Addiction and Mental Health, Research Imaging Centre, 250 College Street, Toronto, Ontario, Canada M5T 1R8
    Affiliations
    Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health and Department of Psychiatry and Department of Pharmacology, University of Toronto, Toronto, Ontario, Canada
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Published:November 25, 2013DOI:https://doi.org/10.1016/j.biopsych.2013.10.010

      Background

      Alcohol dependence (AD) is a multiorgan disease in which excessive oxidative stress and apoptosis are implicated. Monoamine oxidase A (MAO-A) is an important enzyme on the outer mitochondrial membrane that participates in the cellular response to oxidative stress and mitochondrial toxicity. It is unknown whether MAO-A levels are abnormal in AD. We hypothesized that MAO-A VT, an index of MAO-A level, is elevated in the prefrontal cortex (PFC) during AD, because markers of greater oxidative stress and apoptosis are reported in the brain in AD and a microarray analysis reported greater MAO-A messenger RNA in the PFC of rodents exposed to alcohol vapor.

      Methods

      Sixteen participants with alcohol dependence and 16 healthy control subjects underwent [11C]-harmine positron emission tomography. All were nonsmoking, medication- and drug-free, and had no other past or present psychiatric or medical illnesses.

      Results

      MAO-A VT was significantly greater in the PFC (37%, independent samples t test, t30 = 3.93, p < .001), and all brain regions analyzed (mean 32%, multivariate analysis of variance, F7,24 = 3.67, p = .008). Greater duration of heavy drinking correlated positively with greater MAO-A VT in the PFC (r = .67, p = .005) and all brain regions analyzed (r = .73 to .57, p = .001–.02).

      Conclusions

      This finding represents a new pathological marker present in AD that is therapeutically targetable through direct inhibition or by novel treatments toward oxidative/pro-apoptotic processes implicated by MAO-A overexpression.

      Key Words

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