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 stu