title: Effects of naltrexone are influenced by childhood adversity during negative emotional processing in addiction recovery.
abstract: Naltrexone is an opioid receptor antagonist used in the management of alcohol dependence. Although the endogenous opioid system has been implicated in emotion regulation, the effects of mu-opioid receptor blockade on brain systems underlying negative emotional processing are not clear in addiction. Individuals meeting criteria for alcohol dependence alone (n=18, alcohol) and in combination with cocaine and/or opioid dependence (n=21, alcohol/drugs) and healthy individuals without a history of alcohol or drug dependence (n=21) were recruited. Participants were alcohol and drug abstinent before entered into this double-blind, placebo-controlled, randomized, crossover study. Functional magnetic resonance imaging was used to investigate brain response while viewing aversive and neutral images relative to baseline on 50 mg of naltrexone and placebo. We found that naltrexone modulated task-related activation in the medial prefrontal cortex and functional connectivity between the anterior cingulate cortex and the hippocampus as a function of childhood adversity (for aversive versus neutral images) in all groups. Furthermore, there was a group-by-treatment-by-condition interaction in the right amygdala, which was mainly driven by a normalization of response for aversive relative to neutral images under naltrexone in the alcohol/drugs group. We conclude that early childhood adversity is one environmental factor that influences pharmacological response to naltrexone. Pharmacotherapy with naltrexone may also have some ameliorative effects on negative emotional processing in combined alcohol and drug dependence, possibly due to alterations in endogenous opioid transmission or the kappa-opioid receptor antagonist actions of naltrexone.
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: G
authors.initials: G
authors.lastname: Savulich
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.|Department of Medical and Surgical Sciences, University Magna Graecia, Catanzaro, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Riccelli
authors.affiliation: Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK.
authors.forename: L
authors.initials: L
authors.lastname: Passamonti
authors.affiliation: Cognition and Brain Sciences Unit, Medical Research Council, Cambridge, UK.
authors.forename: M
authors.initials: M
authors.lastname: Correia
authors.affiliation: Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors.forename: J F W
authors.initials: JF
authors.lastname: Deakin
authors.affiliation: Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors.forename: R
authors.initials: R
authors.lastname: Elliott
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: R S A
authors.initials: RS
authors.lastname: Flechais
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: A R
authors.initials: AR
authors.lastname: Lingford-Hughes
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: McGonigle
authors.affiliation: Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors.forename: A
authors.initials: A
authors.lastname: Murphy
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: D J
authors.initials: DJ
authors.lastname: Nutt
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Orban
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: L M
authors.initials: LM
authors.lastname: Paterson
authors.affiliation: Centre for Neuropsychopharmacology, Imperial College London, London, UK.
authors.forename: L J
authors.initials: LJ
authors.lastname: Reed
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: D G
authors.initials: DG
authors.lastname: Smith
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: J
authors.initials: J
authors.lastname: Suckling
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: R
authors.initials: R
authors.lastname: Tait
authors.affiliation: Institute of Brain, Behaviour and Mental Health, University of Manchester, Manchester, UK.
authors.forename: E M
authors.initials: EM
authors.lastname: Taylor
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: B J
authors.initials: BJ
authors.lastname: Sahakian
authors.affiliation: Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.|Department of Psychology, University of Cambridge, Cambridge, UK.
authors.forename: T W
authors.initials: TW
authors.lastname: Robbins
authors.affiliation: Department of Psychiatry, University of Cambridge, Cambridge, UK.|Behavioural and Clinical Neuroscience Institute, University of Cambridge, Cambridge, UK.
authors.forename: K D
authors.initials: KD
authors.lastname: Ersche
mesh_terms: D000328:Adult; D000069586:Adult Survivors of Child Adverse Events; D000437:Alcoholism / Q000000981:diagnostic imaging / Q000503:physiopathology; D000679:Amygdala / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D001921:Brain / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000503:physiopathology; D016022:Case-Control Studies; D019970:Cocaine-Related Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology; D018592:Cross-Over Studies; D003463:Cues; D004311:Double-Blind Method; D005260:Female; D059907:Functional Neuroimaging; D006179:Gyrus Cinguli / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009271:Naltrexone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology*; D009434:Neural Pathways / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D009293:Opioid-Related Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology; D017397:Prefrontal Cortex / Q000000981:diagnostic imaging / Q000187:drug effects / Q000503:physiopathology; D019966:Substance-Related Disorders / Q000000981:diagnostic imaging / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D009292:Narcotic Antagonists; D009271:Naltrexone