1. ¹Department of Psychiatry, The University of Chicago, Chicago, IL, USA
2. ²Department of Psychiatry, University of Munster Albert-Schweitzer-Strae, Münster, Germany
3. ³Department of Psychiatry, University of Würzburg Füchsleinstrae, Würzburg, Germany

Correspondence: Dr H de Wit, Department of Psychiatry, The University of Chicago, MC3077, 5841 S. Maryland Avenue, Chicago, IL 60637, USA. Tel: +1 773 702 1537; Fax: +1 773 834 7698; E-mail: hdew@midway.uchicago.edu

⁴Neuroscience Training Program, University of Wisconsin Madison, USA.

Received 13 November 2002; Revised 30 April 2003; Accepted 5 May 2003; Published online 25 June 2003.

Abstract

The adenosine receptor system, which mediates the psychoactive effects of caffeine, is also thought to be involved in the regulation of anxiety. In this study, we examined the association between variations in anxiogenic responses to caffeine and polymorphisms in the A₁ and A_2a adenosine receptor genes. Healthy, infrequent caffeine users (N=94) recorded their subjective mood states following a 150 mg oral dose of caffeine freebase or placebo in a double-blind study. We found a significant association between self-reported anxiety after caffeine administration and two linked polymorphisms on the A_2a receptor gene, the 1976C>T and 2592C>Tins polymorphisms. Individuals with the 1976T/T and the 2592Tins/Tins genotypes reported greater increases in anxiety after caffeine administration than the other genotypic groups. The study shows that an adenosine receptor gene polymorphism that has been associated with Panic Disorder is also associated with anxiogenic responses to an acute dose of caffeine.