title: Greater monoamine oxidase a binding in alcohol dependence.
abstract: 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 [(11)C]-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.
authors.affiliation: 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.
authors.forename: Brittany A
authors.initials: BA
authors.lastname: Matthews
authors.affiliation: 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.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
authors.affiliation: 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.
authors.forename: Xin
authors.initials: X
authors.lastname: Xu
authors.affiliation: 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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Boileau
authors.affiliation: 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.
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Rusjan
authors.affiliation: 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.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.affiliation: 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.
authors.forename: Dan
authors.initials: D
authors.lastname: DiGiacomo
authors.affiliation: 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.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.affiliation: 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. Electronic address: jeff.meyer@camhpet.ca.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Meyer
mesh_terms: D000328:Adult; D000437:Alcoholism / Q000000981:diagnostic imaging / Q000201:enzymology*; D001921:Brain / Q000000981:diagnostic imaging / Q000201:enzymology; D005260:Female; D006801:Humans; D008297:Male; D008995:Monoamine Oxidase / Q000032:analysis*; D049268:Positron-Emission Tomography; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000201:enzymology*
chemical_list: D008995:Monoamine Oxidase
keywords: Addictions; alcohol dependence; monoamine oxidase A; neurotoxicity; oxidative stress; positron emission tomography