title: Evidence for GABA-A receptor dysregulation in gambling disorder: correlation with impulsivity.
abstract: As a behavioural addiction, gambling disorder (GD) provides an opportunity to characterize addictive processes without the potentially confounding effects of chronic excessive drug and alcohol exposure. Impulsivity is an established precursor to such addictive behaviours, and GD is associated with greater impulsivity. There is also evidence of GABAergic dysregulation in substance addiction and in impulsivity. This study therefore investigated GABAAreceptor availability in 15 individuals with GD and 19 healthy volunteers (HV) using [11C]Ro15-4513, a relatively selective α5 benzodiazepine receptor PET tracer and its relationship with impulsivity. We found significantly higher [11C]Ro15-4513 total distribution volume (VT) in the right hippocampus in the GD group compared with HV. We found higher levels of the 'Negative Urgency' construct of impulsivity in GD, and these were positively associated with higher [11C]Ro15-4513 VTin the amygdala in the GD group; no such significant correlations were evident in the HV group. These results contrast with reduced binding of GABAergic PET ligands described previously in alcohol and opiate addiction and add to growing evidence for distinctions in the neuropharmacology between substance and behavioural addictions. These results provide the first characterization of GABAAreceptors in GD with [11C]Ro15-4513 PET and show greater α5 receptor availability and positive correlations with trait impulsivity. This GABAergic dysregulation is potential target for treatment.
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, UK.
authors.forename: Inge
authors.initials: I
authors.lastname: Mick
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, UK.|Department of Psychobiology, Universidade Federal de São Paulo, Brazil.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Ramos
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, UK.
authors.forename: Jim
authors.initials: J
authors.lastname: Myers
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, UK.|Centre for Affective Disorders, Department of Psychological Medicine, Institute of Psychiatry, Psychology and Neuroscience, King's College London, UK.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Stokes
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, UK.
authors.forename: Samantha
authors.initials: S
authors.lastname: Chandrasekera
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, UK.
authors.forename: David
authors.initials: D
authors.lastname: Erritzoe
authors.affiliation: Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, King's College, UK.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Mendez
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, UK.|Imanova Ltd., Centre for Imaging Sciences, UK.
authors.forename: Roger N
authors.initials: RN
authors.lastname: Gunn
authors.affiliation: Imanova Ltd., Centre for Imaging Sciences, UK.|Department of Neuroimaging, Institute of Psychiatry, King's College, UK.
authors.forename: Eugenii A
authors.initials: EA
authors.lastname: Rabiner
authors.affiliation: Imanova Ltd., Centre for Imaging Sciences, UK.
authors.forename: Graham E
authors.initials: GE
authors.lastname: Searle
authors.affiliation: Department of Psychobiology, Universidade Federal de São Paulo, Brazil.
authors.forename: José C F
authors.initials: JCF
authors.lastname: Galduróz
authors.affiliation: Department of Imaging, Division of Experimental Medicine, Department of Medicine, Imperial College, UK.
authors.forename: Adam D
authors.initials: AD
authors.lastname: Waldman
authors.affiliation: National Problem Gambling Clinic, CNWL NHS Foundation Trust, Imperial College London, UK.
authors.forename: Henrietta
authors.initials: H
authors.lastname: Bowden-Jones
authors.affiliation: Centre for Gambling Research at UBC, Department of Psychology, University of British Columbia, Canada.
authors.forename: Luke
authors.initials: L
authors.lastname: Clark
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, UK.
authors.forename: David J
authors.initials: DJ
authors.lastname: Nutt
authors.affiliation: Centre for Neuropsychopharmacology, Division of Brain Sciences, Faculty of Medicine, Imperial College London, UK.
authors.forename: Anne R
authors.initials: AR
authors.lastname: Lingford-Hughes
mesh_terms: D000328:Adult; D001386:Azides; D016739:Behavior, Addictive / Q000378:metabolism* / Q000503:physiopathology*; D001569:Benzodiazepines; D001921:Brain / Q000000981:diagnostic imaging / Q000503:physiopathology*; D002250:Carbon Radioisotopes; D005715:Gambling / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D007175:Impulsive Behavior / Q000502:physiology*; D008297:Male; D049268:Positron-Emission Tomography / Q000379:methods; D011963:Receptors, GABA-A / Q000378:metabolism*
chemical_list: D001386:Azides; D002250:Carbon Radioisotopes; D011963:Receptors, GABA-A; D001569:Benzodiazepines; C042957:Ro 15-4513
keywords: GABA system; [11C]Ro15-4513 PET; gambling disorder