Genetic Causes of Panic Disorder
This study will try to identify genes that increase the risk of developing panic disorder-an anxiety disorder characterized by recurrent unexpected panic attacks-and that contribute to the abnormalities associated with it. It will compare reactions in patients with panic disorder and in normal volunteers to caffeine, a compound that can induce anxiety, and to placebo, an inactive substance. Caffeine is believed to induce anxiety by blocking proteins called adenosine receptors on the surface of nerve cells in the brain. One study found that people with a specific adenosine receptor gene called 1976T/T had greater anxiety in response to caffeine challenge than did people with other adenosine receptor gene groups. There is also evidence that people with the 1976T/T genotype are more vulnerable to having panic disorder.
Normal volunteers and patients with panic disorder (with or without agoraphobia) who are between 18 and 60 years of age may be eligible for this study. Candidates are screened with physical and psychiatric examinations, a diagnostic interview, mood and anxiety ratings, an electrocardiogram, and blood and urine tests, including genetic studies.
Participants have two caffeine/placebo challenge sessions at least 3 days apart. Each session lasts about 4 hours. For at least 1 week before each session, subjects follow a diet excluding foods with caffeine and refrain from drinking alcoholic beverages for at least 48 hours before the procedure. The morning of the session, following an overnight fast, subjects swallow either a placebo capsule or a caffeine capsule that is equivalent to about 5 cups of coffee. During the session, subjects take a battery of neuropsychological tests to document changes in cognitive and emotional functioning, including attention, memory, and motor performance. In addition, heart rate and blood pressure are measured 15 minutes before and 30, 60, 90, 120, 150, and 180 minutes after the caffeine or placebo dose.
At the end of the study, patients with panic disorder are eligible to receive routine clinical treatment for up to 3 months and may participate in planning for long-term treatment under the care of their local health care provider.
|Official Title:||Association Between Adenosine Receptor Gene Polymorphisms and Physiological Responses to Caffeine in Subjects With Panic Disorder and Healthy Controls|
|Study Start Date:||May 2004|
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 A(2a) receptors. A significant association has been found in healthy infrequent caffeine users between caffeine-induced anxiety and two linked polymorphisms on the A(2a) receptor gene, the 1976C greater than T and 2592C greater than Tins polymorphisms. In one study looking at monozygotic and dizygotic twin pairs, there was much evidence that individual differences in caffeine use, intoxication, tolerance, and withdrawal were substantially influenced by genetic factors. Family and twin studies have shown that genetic factors may increase vulnerability to panic disorder. In one study a systematic mutation screening and association study of the A(1) and A(2a) adenosine receptor genes in panic disorder showed a significant association between the 1976T allele and 1976T/T genotype of the A(2a) receptor gene and panic disorder. As the 1976T/T genotype of the A(2a) 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 panic disorder patients is associated with increased caffeine-induced anxiety.
This study will study subjects with panic disorder and healthy controls. Based on previous studies the following hypotheses will be tested (2 replication and 2 new hypotheses): Replication; (1) panic disorder subjects will report higher anxiety after a caffeine challenge than the healthy control subjects. (2) healthy controls with the1976 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, New hypotheses; (3) 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 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 polymorphism will report increased anxiety after a caffeine challenge compared to healthy controls with the 1976 T/T genotype.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Daniel S Pine, M.D.||National Institute of Mental Health (NIMH)|