Effect of the TaqIA polymorphism on ethanol response in the brain

London, Edythe D.; Berman, Steven M.; Mohammadian, Parvenah; Ritchie, Terrie; Mandelkern, Mark A.; Susselman, Mary K.W.; Schlagenhauf, Florian; Noble, Ernest P.

doi:10.1016/j.pscychresns.2009.07.008

« Previous Next »Psychiatry Research: Neuroimaging
Volume 174, Issue 3 , Pages 163-170, 30 December 2009

Effect of the TaqIA polymorphism on ethanol response in the brain

Edythe D. London
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, United States
- Department of Molecular and Medical Pharmacology of the David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, United States
- Brain Research Institute, University of California Los Angeles, Los Angeles, CA 90095, United States
- Corresponding author. Semel Institute for Neuroscience and Human Behavior, David Geffen School of Medicine, 760 Westwood Plaza, Los Angeles, CA 90024-1759, United States. Tel.: +1 310 525 0606; fax: +1 310 825 0812.
Steven M. Berman
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, United States
- Brain Research Institute, University of California Los Angeles, Los Angeles, CA 90095, United States
Parvenah Mohammadian
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, United States
Terrie Ritchie
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, United States
Mark A. Mandelkern
- Department of Physics, University of California Irvine, Irvine, CA 92697, United States
Mary K.W. Susselman
- Ahmanson-Lovelace Brain Mapping Center, University of California Los Angeles, Los Angeles, CA 90095, United States
Florian Schlagenhauf
- Department of Psychiatry and Psychotherapy, Charité University Medicine Berlin, Campus Charité Mitte, Berlin, Germany
Ernest P. Noble
- Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, United States
- Brain Research Institute, University of California Los Angeles, Los Angeles, CA 90095, United States

Received 20 March 2009; received in revised form 17 July 2009; accepted 17 July 2009.

Abstract

Acute ethanol administration increases striatal dopamine release and decreases cerebral glucose metabolism. The A1 allele of the ANKK1 TaqIa polymorphism is associated with lower dopaminergic tone and greater risk for alcoholism, but the mechanisms are unclear. We hypothesized that ethanol would be more reinforcing in men with the A1 allele (A1+) than in men without it (A1−), as indicated by decreased anxiety and fatigue and altered activity in associated brain regions. In a pilot study, A1+ and A1− men (6/group) drank ethanol (0.75 ml/kg) or placebo beverages on each of 2 days. Positron emission tomography with [F-18]fluorodeoxyglucose (FDG) was used to assess regional cerebral glucose metabolism as a measure of relative brain activity while participants performed a vigilance task. Significant findings were as follows: Ethanol decreased anxiety and fatigue in A1+ men but increased them in A1– men. Ethanol increased activity in the striatum and insula of A1+ men, but reduced activity in the anterior cingulate of A1– men. Reduced anxiety and fatigue in A1+ men were significantly associated with greater activity within a right orbitofrontal region previously implicated in cognitive control, and less activity in structures associated with anxiety (amygdala), fatigue (thalamus), and craving/reinforcement (striatum). In contrast, anxiety and fatigue changes were unrelated to brain activity in A1− men. Although these results require replication in a larger sample, alcohol-induced negative reinforcement may explain the greater risk for alcoholism associated with the A1 allele.

Keywords: Alcohol genetics, PET, Addiction vulnerability, Cerebral glucose metabolism, Dopamine, Negative reinforcement