title: BDNF Val66Met and reward-related brain function in adolescents: role for early alcohol consumption.
abstract: Changes in reward processing have been identified as one important pathogenetic mechanism in alcohol addiction. The nonsynonymous single nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene (rs6265/Val66Met) modulates the central nervous system activity of neurotransmitters involved in reward processing such as serotonin, dopamine, and glutamate. It was identified as crucial for alcohol consumption in healthy adults and, in rats, specifically related to the function in the striatum, a region that is commonly involved in reward processing. However, studies in humans on the association of BDNF Val66Met and reward-related brain functions and its role for alcohol consumption, a significant predictor of later alcohol addiction, are missing. Based on an intermediate phenotype approach, we assessed the early orientation toward alcohol and alcohol consumption in 530 healthy adolescents that underwent a monetary incentive delay task during functional magnetic resonance imaging. We found a significantly lower response in the putamen to reward anticipation in adolescent Met carriers with high versus low levels of alcohol consumption. During reward feedback, Met carriers with low putamen reactivity were significantly more likely to orient toward alcohol and to drink alcohol 2 years later. This study indicates a possible effect of BDNF Val66Met on alcohol addiction-related phenotypes in adolescence.
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany. Electronic address: frauke.nees@zi-mannheim.de.
authors: F
authors: F
authors: Nees
authors: Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: S H
authors: SH
authors: Witt
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany; Department of Clinical Psychology and Psychotherapy, Ruprecht-Karls University Heidelberg, Heidelberg, Germany.
authors: R
authors: R
authors: Dinu-Biringer
authors: Institute of Psychiatry, King's College London, United Kingdom; MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, United Kingdom.
authors: A
authors: A
authors: Lourdusamy
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: J
authors: J
authors: Tzschoppe
authors: Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: S
authors: S
authors: Vollstädt-Klein
authors: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: S
authors: S
authors: Millenet
authors: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: C
authors: C
authors: Bach
authors: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: L
authors: L
authors: Poustka
authors: Department of Child and Adolescent Psychiatry and Psychotherapy, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: T
authors: T
authors: Banaschewski
authors: Institute of Psychiatry, King's College London, United Kingdom.
authors: G J
authors: GJ
authors: Barker
authors: Institute of Neuroscience and Discipline of Psychiatry, School of Medicine, Trinity College Dublin, Dublin, Ireland.
authors: A L W
authors: AL
authors: Bokde
authors: NeuroImage Nord, Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Germany.
authors: U
authors: U
authors: Bromberg
authors: NeuroImage Nord, Department of Systems Neuroscience, University Medical Center Hamburg-Eppendorf, Germany.
authors: C
authors: C
authors: Büchel
authors: Institute of Psychiatry, King's College London, United Kingdom; Department of Psychiatry, Universite de Montreal, CHU Ste Justine Hospital, Canada.
authors: P J
authors: PJ
authors: Conrod
authors: Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: J
authors: J
authors: Frank
authors: Neurospin, Commissariat à l'Energie Atomique et aux Energies Alternatives, Paris, France.
authors: V
authors: V
authors: Frouin
authors: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors: J
authors: J
authors: Gallinat
authors: Institute of Neuroscience, Trinity College Dublin, Dublin, Ireland; Department of Psychiatry, University of Vermont, USA; Department of Psychology, University of Vermont, USA.
authors: H
authors: H
authors: Garavan
authors: School of Physics and Astronomy, University of Nottingham, United Kingdom.
authors: P
authors: P
authors: Gowland
authors: Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité - Universitätsmedizin Berlin, Berlin, Germany.
authors: A
authors: A
authors: Heinz
authors: Physikalisch-Technische Bundesanstalt, Berlin, Germany.
authors: B
authors: B
authors: Ittermann
authors: Department of Addictive Behaviour and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: K
authors: K
authors: Mann
authors: INSERM CEA Unit 1000 "Imaging & Psychiatry", Institut National de la Santé et de la Recherche Médicale, University Paris Sud, Orsay, France; AP-HP Department of Adolescent Psychopathology and Medicine, Maison de Solenn, University Paris Descartes, Paris, France.
authors: J-L
authors: JL
authors: Martinot
authors: Rotman Research Institute, University of Toronto, Toronto, Canada; Montreal Neurological Institute, McGill University, QC, Canada.
authors: T
authors: T
authors: Paus
authors: The Hospital for Sick Children, Department of Physiology and Nutritional Sciences, University of Toronto, Toronto, Canada.
authors: Z
authors: Z
authors: Pausova
authors: Behavioural and Clinical Neurosciences Institute, Department of Experimental Psychology, University of Cambridge, United Kingdom.
authors: T W
authors: TW
authors: Robbins
authors: Department of Psychiatry and Psychotherapy, Neuroimaging Center, Technische Universitaet Dresden, Dresden, Germany.
authors: M N
authors: MN
authors: Smolka
authors: Division of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: M
authors: M
authors: Rietschel
authors: Institute of Psychiatry, King's College London, United Kingdom; MRC Social, Genetic and Developmental Psychiatry (SGDP) Centre, London, United Kingdom.
authors: G
authors: G
authors: Schumann
authors: Department of Cognitive and Clinical Neuroscience, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
authors: H
authors: H
authors: Flor
mesh_terms: D000293:Adolescent; D000294:Adolescent Behavior / Q000502:physiology* / Q000523:psychology; D000428:Alcohol Drinking / Q000235:genetics* / Q000523:psychology; D001921:Brain / Q000502:physiology*; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008715:Methionine / Q000235:genetics; D012201:Reward; D014633:Valine / Q000235:genetics
chemical_list: D019208:Brain-Derived Neurotrophic Factor; C579455:BDNF protein, human; D008715:Methionine; D014633:Valine
keywords: Adolescence; Alcohol; BDNF gene; Reward; Striatum