Genetic Variation in the Atrial Natriuretic Peptide Transcription Factor GATA4 Modulates Amygdala Responsiveness in Alcohol Dependence

• Published in: Biological psychiatry (1969) Vol. 75; no. 10; pp. 790 - 797
• Main Authors: Jorde, Anne, Bach, Patrick, Witt, Stephanie H., Becker, Kathleen, Reinhard, Iris, Vollstädt-Klein, Sabine, Kirsch, Martina, Hermann, Derik, Charlet, Katrin, Beck, Anne, Wimmer, Lioba, Frank, Josef, Treutlein, Jens, Spanagel, Rainer, Mann, Karl, Walter, Henrik, Heinz, Andreas, Rietschel, Marcella, Kiefer, Falk
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 15.05.2014; Elsevier
• Subjects: Addictive behaviors; Adult and adolescent clinical studies; Alcohol dependence; Alcoholism; Alcoholism - genetics; Alcoholism and acute alcohol poisoning; Amygdala - physiopathology; ANP; Biological and medical sciences; Brain Mapping; cue-reactivity; Female; fMRI; GATA4; GATA4 Transcription Factor - genetics; Genetic Variation; Humans; imaging genetics; Magnetic Resonance Imaging; Male; Medical sciences; Middle Aged; Psychiatry; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Toxicology; fMRI; Alcohol dependence; GATA4; ANP; imaging genetics; cue-reactivity; Genetic variability; Amygdala; Central nervous system; Atrial natriuretic peptide; Genetic determinism; Encephalon; Alcoholic beverage; Natriuretic hormone; Imaging; Dependence; Functional magnetic resonance imaging; Genetics; Transcription factor; Amygdaloid nucleus; Alcoholism; Basal ganglion; Nuclear magnetic resonance imaging; Medical imagery; Functional imaging
• ISSN: 0006-3223; 1873-2402; 1873-2402
• DOI: 10.1016/j.biopsych.2013.10.020

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. 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. 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. 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.