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.
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: Anita C Hansson; Anne Koopmann; Stefanie Uhrig; Sina Bühler; Esi Domi; Eva Kiessling; Roberto Ciccocioppo; Robert C Froemke; Valery Grinevich; Falk Kiefer; Wolfgang H Sommer; Sabine Vollstädt-Klein; Rainer Spanagel Journal: Neuropsychopharmacology Date: 2017-11-01 Impact factor: 7.853
Authors: Mehran Zare-Bidoky; Arshiya Sangchooli; Hamed Ekhtiari; Amy C Janes; Marc J Kaufman; Jason A Oliver; James J Prisciandaro; Torsten Wüstenberg; Raymond F Anton; Patrick Bach; Alex Baldacchino; Anne Beck; James M Bjork; Judson Brewer; Anna Rose Childress; Eric D Claus; Kelly E Courtney; Mohsen Ebrahimi; Francesca M Filbey; Dara G Ghahremani; Peyman Ghobadi Azbari; Rita Z Goldstein; Anna E Goudriaan; Erica N Grodin; J Paul Hamilton; Colleen A Hanlon; Peyman Hassani-Abharian; Andreas Heinz; Jane E Joseph; Falk Kiefer; Arash Khojasteh Zonoozi; Hedy Kober; Rayus Kuplicki; Qiang Li; Edythe D London; Joseph McClernon; Hamid R Noori; Max M Owens; Martin P Paulus; Irene Perini; Marc Potenza; Stéphane Potvin; Lara Ray; Joseph P Schacht; Dongju Seo; Rajita Sinha; Michael N Smolka; Rainer Spanagel; Vaughn R Steele; Elliot A Stein; Sabine Steins-Loeber; Susan F Tapert; Antonio Verdejo-Garcia; Sabine Vollstädt-Klein; Reagan R Wetherill; Stephen J Wilson; Katie Witkiewitz; Kai Yuan; Xiaochu Zhang; Anna Zilverstand Journal: Nat Protoc Date: 2022-02-04 Impact factor: 17.021
Authors: Alecia D Dager; D Reese McKay; Jack W Kent; Joanne E Curran; Emma Knowles; Emma Sprooten; Harald H H Göring; Thomas D Dyer; Godfrey D Pearlson; Rene L Olvera; Peter T Fox; William R Lovallo; Ravi Duggirala; Laura Almasy; John Blangero; David C Glahn Journal: Neuropsychopharmacology Date: 2014-07-31 Impact factor: 7.853