Genetic Causes of Panic Disorder
Condition: Panic Disorder
MeSH terms: Panic Disorder
Study type: Observational

Summary: 
      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.

      ...
    

Detailed description: 
      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.
    

Keywords: Adenosine Receptor; Panic Disorder; Polymorphism; Challenge Study; Caffeine; Healthy Volunteer; HV