The modulating effect of the androgen receptor on craving in alcohol withdrawal of men is partially mediated by leptin

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Original Article

The Pharmacogenomics Journal advance online publication 3 November 2009; doi: 10.1038/tpj.2009.56

B Lenz 1,
H Frieling 1,2,
C Jacob 1,
A Heberlein 1,2,
J Kornhuber 1,
S Bleich 1,2 and
T Hillemacher 1,2

1. Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Erlangen, Germany
2. Department of Psychiatry, Socialpsychiatry and Psychotherapy, Hannover Medical School, Hannover, Germany

Correspondence: Dr B Lenz, Department of Psychiatry and Psychotherapy, Friedrich-Alexander-University of Erlangen-Nuremberg, Schwabachanlage 6-10, D-91054 Erlangen, Germany. E-mail: bernd.lenz@uk-erlangen.de

Received 3 August 2009; Revised 2 October 2009; Accepted 6 October 2009; Published online 3 November 2009.
Abstract

We reported recently that a functional relevant CAG trinucleotide repeat of the androgen receptor influences craving of men in alcohol withdrawal. It is known to modulate serum concentrations of leptin, which affects hypothalamic appetite regulation. Its plasma levels are elevated during chronic alcohol consumption, normalize within periods of abstinence and are associated with craving. The aim of this study was to further elucidate the role of leptin in mediating the effects of the mentioned polymorphism on craving in men undergoing alcohol withdrawal. We included 110 male in-patients who were admitted for detoxification treatment. Each one had an established diagnosis of alcohol dependence according to the DSM-IV. Our results show on the one hand negative associations between the number of CAG repeats and (i) leptin serum levels (P<0.01)>P<0.05),>P<0.001).>r=-0.144) accounting for 60% and indirect, leptin-mediated effects (r=-0.096) accounting for 40% of the total effect. Dysregulation of sexual hormones influences human metabolism and seems to affect leptin homeostasis. This report suggests that the investigated polymorphism mediates its effect on craving of men in alcohol withdrawal mostly through the regulation of leptin. Nevertheless future studies are needed to further explore the functionality of the androgen receptor gene in terms of craving.