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A Polymorphism in GABRA2 Is Associated With the Medial Frontal Response to Alcohol Cues in an fMRI Study

Authors

  • David A. Kareken,

    1. From the Departments of Neurology (DAK, MD, VB, CC), Radiology (DAK, MD), and Psychiatry (DAK, SJO), Medicine (TL), Medical & Molecular Genetics (LW, TF), Indiana University School of Medicine, Indianapolis, Indiana; and School of Electrical and Computer Engineering (TT) and Weldon School of Biomedical Engineering (TT), Purdue University, West Lafayette, Indiana.
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  • Tiebing Liang,

    1. From the Departments of Neurology (DAK, MD, VB, CC), Radiology (DAK, MD), and Psychiatry (DAK, SJO), Medicine (TL), Medical & Molecular Genetics (LW, TF), Indiana University School of Medicine, Indianapolis, Indiana; and School of Electrical and Computer Engineering (TT) and Weldon School of Biomedical Engineering (TT), Purdue University, West Lafayette, Indiana.
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  • Leah Wetherill,

    1. From the Departments of Neurology (DAK, MD, VB, CC), Radiology (DAK, MD), and Psychiatry (DAK, SJO), Medicine (TL), Medical & Molecular Genetics (LW, TF), Indiana University School of Medicine, Indianapolis, Indiana; and School of Electrical and Computer Engineering (TT) and Weldon School of Biomedical Engineering (TT), Purdue University, West Lafayette, Indiana.
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  • Mario Dzemidzic,

    1. From the Departments of Neurology (DAK, MD, VB, CC), Radiology (DAK, MD), and Psychiatry (DAK, SJO), Medicine (TL), Medical & Molecular Genetics (LW, TF), Indiana University School of Medicine, Indianapolis, Indiana; and School of Electrical and Computer Engineering (TT) and Weldon School of Biomedical Engineering (TT), Purdue University, West Lafayette, Indiana.
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  • Veronique Bragulat,

    1. From the Departments of Neurology (DAK, MD, VB, CC), Radiology (DAK, MD), and Psychiatry (DAK, SJO), Medicine (TL), Medical & Molecular Genetics (LW, TF), Indiana University School of Medicine, Indianapolis, Indiana; and School of Electrical and Computer Engineering (TT) and Weldon School of Biomedical Engineering (TT), Purdue University, West Lafayette, Indiana.
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  • Cari Cox,

    1. From the Departments of Neurology (DAK, MD, VB, CC), Radiology (DAK, MD), and Psychiatry (DAK, SJO), Medicine (TL), Medical & Molecular Genetics (LW, TF), Indiana University School of Medicine, Indianapolis, Indiana; and School of Electrical and Computer Engineering (TT) and Weldon School of Biomedical Engineering (TT), Purdue University, West Lafayette, Indiana.
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  • Thomas Talavage,

    1. From the Departments of Neurology (DAK, MD, VB, CC), Radiology (DAK, MD), and Psychiatry (DAK, SJO), Medicine (TL), Medical & Molecular Genetics (LW, TF), Indiana University School of Medicine, Indianapolis, Indiana; and School of Electrical and Computer Engineering (TT) and Weldon School of Biomedical Engineering (TT), Purdue University, West Lafayette, Indiana.
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  • Sean J. O’Connor,

    1. From the Departments of Neurology (DAK, MD, VB, CC), Radiology (DAK, MD), and Psychiatry (DAK, SJO), Medicine (TL), Medical & Molecular Genetics (LW, TF), Indiana University School of Medicine, Indianapolis, Indiana; and School of Electrical and Computer Engineering (TT) and Weldon School of Biomedical Engineering (TT), Purdue University, West Lafayette, Indiana.
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  • Tatiana Foroud

    1. From the Departments of Neurology (DAK, MD, VB, CC), Radiology (DAK, MD), and Psychiatry (DAK, SJO), Medicine (TL), Medical & Molecular Genetics (LW, TF), Indiana University School of Medicine, Indianapolis, Indiana; and School of Electrical and Computer Engineering (TT) and Weldon School of Biomedical Engineering (TT), Purdue University, West Lafayette, Indiana.
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Reprint requests: David A. Kareken, PhD, Department of Neurology, 541 Clinical Drive (CL 285), Indiana University School of Medicine, Indianapolis, IN 46202; Tel: 317-274-7327; Fax: 317-274-1337; E-mail: dkareken@iupui.edu

Abstract

Background:  Significant evidence has accumulated to suggest an association between single-nucleotide polymorphisms (SNPs) in the GABRA2 gene and alcoholism. However, research has yet to show an association between these polymorphisms and the human brain’s reward system function. In this study, we stratified subjects who had participated in an fMRI study of alcohol cue responses according to their genotype at a SNP in GABRA2 (rs279871) shown to be associated with alcohol dependence (Edenberg et al., 2004).

Methods:  Genotyping showed 13 subjects to be homozygous for the high-risk allele (AA), and 23 subjects to be heterozygous (AG). In fMRI, subjects were exposed to the aromas of their preferred alcoholic drink odors (AO), as well as to appetitive control odors (ApCO) under both alcohol intoxication and placebo control conditions.

Results:  Homozygous AA subjects had a larger [AO > ApCO] response than did AG subjects in medial frontal cortical areas thought to code reward value. However, AG subjects had a larger [AO > ApCO] effect in the ventral tegmental area. Alcohol intoxication did not alter these group differences.

Conclusions:  These are the first data to suggest that GABRA2 genotype could affect the brain’s responses to cues associated with alcohol.

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