This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Panic disorder (PD) is an anxiety disorder characterized by recurrent and spontaneous panic attacks. The lifetime and 12-month prevalence rates of panic have been reported in the National Comorbidity Survey and include 7.2% and 4.2% for panic attack, and 3.4% and 2.2% for panic disorder (Kessler 1994). A full understanding of disease pathophysiology remains elusive, although there is increasing evidence of distinct neurochemical, neuropeptide, and neurotransmitter receptor dysregulation in PD. Caffeine, the most widely used psychoactive drug in the world, exerts its behavioral effects by antagonizing adenosine receptors (AR). Four different human AR subtypes have been found and there is evidence that the stimulatory effect of caffeine is mainly caused by an inhibition of transmission via adenosine A2a receptors. A significant association has been found in healthy infrequent caffeine users between caffeine-induced anxiety and two linked polymorphisms on the A2a receptor gene, the 1976CT and 2592CTins polymorphisms. As the 1976T/T genotype of the A2a receptor gene has been associated with both increased caffeine-induced anxiety in healthy controls, and has been associated with increased vulnerability to panic disorder, we wish to study whether the 1976T/T genotype in PD is associated with increased caffeine-induced anxiety, and whether the susceptibility to anxiety represents a state or trait abnormality in PD. In this pilot study, we will study subjects with panic disorder (n=10 currently ill, n=10 remitted), and healthy controls (n=10). The following hypotheses will be tested: (1) panic disorder subjects will report higher anxiety after a caffeine challenge than the healthy control subjects. (2) healthy controls with the 1976 T/T polymorphism will report increased anxiety after a caffeine challenge compared to healthy controls with the 1976 C/T and 1976 C/C genotypes, (3) panic patients (currently ill and remitted) with the 1976 T/T polymorphism will report increased anxiety after a caffeine challenge compared to panic patients with the 1976 C/T and 1976 C/C genotypes, (4) panic patients (two separate groups: currently ill and remitted) with the 1976 T/T polymorphism will report increased anxiety after a caffeine challenge compared to healthy controls with the 1976 T/T genotype. All diagnostically eligible participants will be genotyped the 1976 T/T polymorphism. If eligible based on genotype, subjects will undergo 2 days of testing in a randomized, double-blind, counter-balanced design with administration of oral caffeine (480mg) or placebo. This study will enhance understanding of the role of the adenosine receptor function in PD and, for the first time, help disentangle panic illness related effects (state) from genetic (trait) effects.
Showing the most recent 10 out of 869 publications
