title: Genetic variation in the atrial natriuretic peptide transcription factor GATA4 modulates amygdala responsiveness in alcohol dependence.
abstract: BACKGROUND
  Two genome-wide association studies recently showed alcohol dependence to be associated with a single-nucleotide polymorphism (rs13273672) located on a gene (GATA4) that encodes a transcription factor of atrial natriuretic peptide (ANP). A growing body of evidence suggests that ANP might be involved in the symptomology of alcohol dependence. This study examined whether reactivity to alcohol cues in the ANP target region amygdala, a key area implicated in addictive behavior, differs depending on the GATA4 genotype of a patient. We also investigated potential associations between these differences in amygdala activation and relapse behavior.
  
  
  METHODS
  Eighty-one abstinent, alcohol-dependent patients completed a functional magnetic resonance imaging cue-reactivity task in a 3-Tesla scanner and provided blood samples for DNA extraction.
  
  
  RESULTS
  The results showed significantly lower alcohol-cue-induced activations in G-allele carriers as compared with AA-homozygotes in the bilateral amygdala. A survival analysis revealed that a stronger alcohol-specific amygdala response predicted a lowered risk for relapse to heavy drinking in the AA-homozygotes, whereas this effect could not be observed in G-allele carriers.
  
  
  CONCLUSIONS
  These results illuminate potential underlying mechanisms of the involvement of the GATA4 gene in the etiology of alcohol dependence via its influence on ANP and amygdala processing.
authors: Department of Addictive Behavior and Addiction Medicine (AJ, PB, KB, SV-K, MK, DH, KM, FK). Electronic address: anne.jorde@zi-mannheim.de.
authors: Anne
authors: A
authors: Jorde
authors: Department of Addictive Behavior and Addiction Medicine (AJ, PB, KB, SV-K, MK, DH, KM, FK).
authors: Patrick
authors: P
authors: Bach
authors: Department of Genetic Epidemiology in Psychiatry (SHW, JF, JT, MR).
authors: Stephanie H
authors: SH
authors: Witt
authors: Department of Addictive Behavior and Addiction Medicine (AJ, PB, KB, SV-K, MK, DH, KM, FK).
authors: Kathleen
authors: K
authors: Becker
authors: Department of Biostatistics (IR).
authors: Iris
authors: I
authors: Reinhard
authors: Department of Addictive Behavior and Addiction Medicine (AJ, PB, KB, SV-K, MK, DH, KM, FK).
authors: Sabine
authors: S
authors: Vollstädt-Klein
authors: Department of Addictive Behavior and Addiction Medicine (AJ, PB, KB, SV-K, MK, DH, KM, FK).
authors: Martina
authors: M
authors: Kirsch
authors: Department of Addictive Behavior and Addiction Medicine (AJ, PB, KB, SV-K, MK, DH, KM, FK).
authors: Derik
authors: D
authors: Hermann
authors: Department of Psychiatry and Psychotherapy (KC, AB, AH), Charité-Universitätsmedizin, Berlin, Germany.
authors: Katrin
authors: K
authors: Charlet
authors: Department of Psychiatry and Psychotherapy (KC, AB, AH), Charité-Universitätsmedizin, Berlin, Germany.
authors: Anne
authors: A
authors: Beck
authors: Department of Psychiatry (LW), University Clinic Bonn, Bonn, Germany.
authors: Lioba
authors: L
authors: Wimmer
authors: Department of Genetic Epidemiology in Psychiatry (SHW, JF, JT, MR).
authors: Josef
authors: J
authors: Frank
authors: Department of Genetic Epidemiology in Psychiatry (SHW, JF, JT, MR).
authors: Jens
authors: J
authors: Treutlein
authors: Institute of Psychopharmacology (RS); Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University.
authors: Rainer
authors: R
authors: Spanagel
authors: Department of Addictive Behavior and Addiction Medicine (AJ, PB, KB, SV-K, MK, DH, KM, FK).
authors: Karl
authors: K
authors: Mann
authors: Division of Mind and Brain Research (HW).
authors: Henrik
authors: H
authors: Walter
authors: Department of Psychiatry and Psychotherapy (KC, AB, AH), Charité-Universitätsmedizin, Berlin, Germany.
authors: Andreas
authors: A
authors: Heinz
authors: Department of Genetic Epidemiology in Psychiatry (SHW, JF, JT, MR).
authors: Marcella
authors: M
authors: Rietschel
authors: Department of Addictive Behavior and Addiction Medicine (AJ, PB, KB, SV-K, MK, DH, KM, FK).
authors: Falk
authors: F
authors: Kiefer
mesh_terms: D000437:Alcoholism / Q000235:genetics*; D000679:Amygdala / Q000503:physiopathology*; D001931:Brain Mapping; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics*; D014644:Genetic Variation; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged
chemical_list: D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human
keywords: ANP; Alcohol dependence; GATA4; cue-reactivity; fMRI; imaging genetics