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Biol Psychiatry. 2014 May 15;75(10):790-7. doi: 10.1016/j.biopsych.2013.10.020. Epub 2013 Nov 4.

Genetic variation in the atrial natriuretic peptide transcription factor GATA4 modulates amygdala responsiveness in alcohol dependence.

Author information

1
Department of Addictive Behavior and Addiction Medicine (AJ, PB, KB, SV-K, MK, DH, KM, FK). Electronic address: anne.jorde@zi-mannheim.de.
2
Department of Addictive Behavior and Addiction Medicine (AJ, PB, KB, SV-K, MK, DH, KM, FK).
3
Department of Genetic Epidemiology in Psychiatry (SHW, JF, JT, MR).
4
Department of Biostatistics (IR).
5
Department of Psychiatry and Psychotherapy (KC, AB, AH), Charité-Universitätsmedizin, Berlin, Germany.
6
Department of Psychiatry (LW), University Clinic Bonn, Bonn, Germany.
7
Institute of Psychopharmacology (RS); Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University.
8
Division of Mind and Brain Research (HW).

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01503931.

KEYWORDS:

ANP; Alcohol dependence; GATA4; cue-reactivity; fMRI; imaging genetics

PMID:
24314346
DOI:
10.1016/j.biopsych.2013.10.020
[Indexed for MEDLINE]

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