title: Naltrexone ameliorates functional network abnormalities in alcohol-dependent individuals.
abstract: Naltrexone, an opioid receptor antagonist, is commonly used as a relapse prevention medication in alcohol and opiate addiction, but its efficacy and the mechanisms underpinning its clinical usefulness are not well characterized. In the current study, we examined the effects of 50-mg naltrexone compared with placebo on neural network changes associated with substance dependence in 21 alcohol and 36 poly-drug-dependent individuals compared with 36 healthy volunteers. Graph theoretic and network-based statistical analysis of resting-state functional magnetic resonance imaging (MRI) data revealed that alcohol-dependent subjects had reduced functional connectivity of a dispersed network compared with both poly-drug-dependent and healthy subjects. Higher local efficiency was observed in both patient groups, indicating clustered and segregated network topology and information processing. Naltrexone normalized heightened local efficiency of the neural network in alcohol-dependent individuals, to the same levels as healthy volunteers. Naltrexone failed to have an effect on the local efficiency in abstinent poly-substance-dependent individuals. Across groups, local efficiency was associated with substance, but no alcohol exposure implicating local efficiency as a potential premorbid risk factor in alcohol use disorders that can be ameliorated by naltrexone. These findings suggest one possible mechanism for the clinical effects of naltrexone, namely, the amelioration of disrupted network topology.
authors.affiliation: Department of Psychology, University of Cambridge, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK.
authors.forename: Laurel S
authors.initials: LS
authors.lastname: Morris
authors.affiliation: Department of Psychiatry, University of Cambridge, UK.
authors.forename: Kwangyeol
authors.initials: K
authors.lastname: Baek
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK.|Department of Psychiatry, University of Cambridge, UK.
authors.forename: Roger
authors.initials: R
authors.lastname: Tait
authors.affiliation: Neuroscience and Psychiatry Unit, University of Manchester, UK.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Elliott
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK.|Department of Psychiatry, University of Cambridge, UK.
authors.forename: Karen D
authors.initials: KD
authors.lastname: Ersche
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, UK.
authors.forename: Remy
authors.initials: R
authors.lastname: Flechais
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, UK.
authors.forename: John
authors.initials: J
authors.lastname: McGonigle
authors.affiliation: Neuroscience and Psychiatry Unit, University of Manchester, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Murphy
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK.|Department of Psychiatry, University of Cambridge, UK.|Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, UK.
authors.forename: Liam J
authors.initials: LJ
authors.lastname: Nestor
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, UK.
authors.forename: Csaba
authors.initials: C
authors.lastname: Orban
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK.|Department of Psychiatry, University of Cambridge, UK.|Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, UK.
authors.forename: Filippo
authors.initials: F
authors.lastname: Passetti
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, UK.
authors.forename: Louise M
authors.initials: LM
authors.lastname: Paterson
authors.affiliation: Imanova, Centre for Imaging Sciences, UK.
authors.forename: Ilan
authors.initials: I
authors.lastname: Rabiner
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, UK.
authors.forename: Laurence
authors.initials: L
authors.lastname: Reed
authors.affiliation: Department of Psychology, University of Cambridge, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK.|Department of Psychiatry, University of Cambridge, UK.
authors.forename: Dana
authors.initials: D
authors.lastname: Smith
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK.|Department of Psychiatry, University of Cambridge, UK.
authors.forename: John
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Neuroscience and Psychiatry Unit, University of Manchester, UK.
authors.forename: Eleanor M
authors.initials: EM
authors.lastname: Taylor
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK.|Department of Psychiatry, University of Cambridge, UK.
authors.forename: Edward T
authors.initials: ET
authors.lastname: Bullmore
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, UK.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Lingford-Hughes
authors.affiliation: Neuroscience and Psychiatry Unit, University of Manchester, UK.
authors.forename: Bill
authors.initials: B
authors.lastname: Deakin
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Imperial College London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK.|Department of Psychiatry, University of Cambridge, UK.
authors.forename: Barbara J
authors.initials: BJ
authors.lastname: Sahakian
authors.affiliation: Department of Psychology, University of Cambridge, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK.|Department of Psychiatry, University of Cambridge, UK.
authors.forename: Trevor W
authors.initials: TW
authors.lastname: Robbins
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, UK.|Department of Psychiatry, University of Cambridge, UK.
authors.forename: Valerie
authors.initials: V
authors.lastname: Voon
mesh_terms: D000328:Adult; D000427:Alcohol Deterrents / Q000494:pharmacology*; D000437:Alcoholism / Q000000981:diagnostic imaging* / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D059907:Functional Neuroimaging; D064368:Healthy Volunteers; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000494:pharmacology*; D009434:Neural Pathways; D019966:Substance-Related Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology; D055815:Young Adult
chemical_list: D000427:Alcohol Deterrents; D009271:Naltrexone
keywords: Addiction; alcohol; cocaine; naltrexone; opiate; substance use