1. ¹Uppsala University Centre for Clinical Research, Central Hospital, Västerås, Sweden
2. ²Laboratory of Neurogenetics, NIH/NIAAA, Rockville, MD, USA
3. ³Laboratory of Clinical and Translational Studies, NIH/NIAAA, Poolesville, MD, USA
4. ⁴Department of Psychiatry, University of Cape Town, Cape Town, South Africa
5. ⁵Department of Psychiatry, University of Pisa, Pisa, Italy
6. ⁶Department of Psychiatry, University of Helsinki School of Medicine, Helsinki, Finland

Correspondence: Dr RL Sjöberg, Laboratory for Neurogenetics, NIH/NIAAA, 5625 Fishers Lane, Rockville, MD 20852, USA. Tel: +1 301 443 3242; Fax: +1 301 480 2839; E-mail: sjobergr@mail.nih.gov

⁷These authors contributed equally to this work.

Received 13 December 2006; Revised 6 March 2007; Accepted 9 March 2007; Published online 11 April 2007.

Abstract

A functional VNTR polymorphism in the promoter of the monoamine oxidase A gene (MAOA-LPR) has previously been shown to be an important predictor of antisocial behavior in men. Testosterone analogues are known to interact with the MAOA promoter in vitro to influence gene transcription as well as in vivo to influence CSF levels of the MAO metabolite 3-methoxy-4-hydroxyphenylglycol (MHPG) in human males. We examined the possible joint effects of testosterone (measured in CSF) and MAOA-LPR genotype on antisocial personality disorder and scores on the Brown–Goodwin Aggression scale in 95 unrelated male criminal alcoholics and 45 controls. The results confirm that MAOA genotype and CSF testosterone interact to predict antisocial behaviors. The MAOA/testosterone interaction also predicted low levels of CSF MHPG, which tentatively suggests the possibility that the interaction may be mediated by a direct effect on gene transcription. If replicated these findings offer plausible explanations for previous inconsistencies in studies of the relationship between testosterone and male human aggression, as well as for how MAOA genotype may influence aggressive behavior in human males.