title: Dopamine DRD2/ANKK1 Taq1A and DAT1 VNTR polymorphisms are associated with a cognitive flexibility profile in pathological gamblers.
abstract: Like drug addiction, pathological gambling (PG) has been associated with impairments in executive functions and alterations in dopaminergic functioning; however, the role of dopamine (DA) in the executive profile of PG remains unclear. The aim of this study was to identify whether the DRD2/ANKK1 Taq1A-rs1800497 and the DAT1-40 bp VNTR polymorphisms are associated with cognitive flexibility (measured by Wisconsin Card Sorting Test (WCST) and Trail Making Test (TMT)) and inhibition response (measured by Stroop Color and Word Test (SCWT)), in a clinical sample of 69 PG patients. Our results showed an association between DA functioning and cognitive flexibility performance. The Taq1A A1+ (A1A2/A1A1) genotype was associated with poorer TMT performance (p<0.05), while DAT1 9-repeat homozygotes displayed better WCST performance (p<0.05) than either 10-repeat homozygotes or heterozygotes. We did not find any association between the DRD2 or DAT1 polymorphisms and the inhibition response. These results suggested that pathological gamblers with genetic predispositions toward lower availability of DA and D2 receptor density are at a higher risk of cognitive flexibility difficulties. Future studies should aim to shed more light on the genetic mechanisms underlying the executive profile in PG.
authors.affiliation: Department of Psychiatry, University Hospital of Bellvitge (IDIBELL), Barcelona, Spain CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III [Carlos III Health Institute], Barcelona, Spain.
authors.forename: Ana B
authors.initials: AB
authors.lastname: Fagundo
authors.affiliation: Department of Psychiatry, University Hospital of Bellvitge (IDIBELL), Barcelona, Spain CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III [Carlos III Health Institute], Barcelona, Spain School of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Fernando
authors.initials: F
authors.lastname: Fernández-Aranda
authors.affiliation: CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III [Carlos III Health Institute], Barcelona, Spain Neuroscience Research Program, 'Del Mar' Hospital Medical Research Institute (IMIM), Barcelona, Spain.
authors.forename: Rafael
authors.initials: R
authors.lastname: de la Torre
authors.affiliation: School of Psychology and Psychiatry, Monash University, Melbourne, VIC, Australia Institute of Neuroscience and Department of Clinical Psychology, University of Granada, Granada, Spain Red de Trastornos Adictivos [Network for Addictive Diseases], Instituto de Salud Carlos III, Madrid, Spain.
authors.forename: Antonio
authors.initials: A
authors.lastname: Verdejo-García
authors.affiliation: CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III [Carlos III Health Institute], Barcelona, Spain Department of Psychobiology and Methodology, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Granero
authors.affiliation: Department of Psychobiology and Methodology, Autonomous University of Barcelona, Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Penelo
authors.affiliation: School of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Manel
authors.initials: M
authors.lastname: Gené
authors.affiliation: School of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Carme
authors.initials: C
authors.lastname: Barrot
authors.affiliation: School of Medicine, University of Barcelona, Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Sánchez
authors.affiliation: Department of Psychiatry, University Hospital of Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Eva
authors.initials: E
authors.lastname: Alvarez-Moya
authors.affiliation: Department of Psychiatry, University Hospital of Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Cristian
authors.initials: C
authors.lastname: Ochoa
authors.affiliation: Department of Psychiatry, University Hospital of Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Maria Neus
authors.initials: MN
authors.lastname: Aymamí
authors.affiliation: Department of Psychiatry, University Hospital of Bellvitge (IDIBELL), Barcelona, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Gómez-Peña
authors.affiliation: Department of Psychiatry, University Hospital of Bellvitge (IDIBELL), Barcelona, Spain CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III [Carlos III Health Institute], Barcelona, Spain CIBER Salud Mental (CIBERsam), Instituto Salud Carlos III, Barcelona, Spain.
authors.forename: Jose M
authors.initials: JM
authors.lastname: Menchón
authors.affiliation: Department of Psychiatry, University Hospital of Bellvitge (IDIBELL), Barcelona, Spain CIBER Fisiopatología Obesidad y Nutrición (CIBERObn), Instituto de Salud Carlos III [Carlos III Health Institute], Barcelona, Spain School of Medicine, University of Barcelona, Barcelona, Spain sjimenez@bellvitgehospital.cat.
authors.forename: Susana
authors.initials: S
authors.lastname: Jiménez-Murcia
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D003071:Cognition; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005715:Gambling / Q000235:genetics* / Q000523:psychology*; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D009483:Neuropsychological Tests; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D055815:Young Adult
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; C489948:ANKK1 protein, human; D017346:Protein Serine-Threonine Kinases
keywords: Addiction; cognition; cognitive flexibility; dopamine; dopamine receptor; dopamine transport; executive functions; gambling; genetics; inhibition response; pathological gambling; polymorphism