1. During panic there is engagement of a circuit involving deficient prefrontal cortex activity and hyperactive paleocortical and amygdala activity.
2. Pathology in the raphe-based serotonin(5-HT) system is permissive to this pathological activity pattern and therefore panic; and preclinical evidence suggests a role for the 5-HT1A receptor in this modulatory function of the 5-HT system in anxiety.
1. To measure in panic disorder subjects and healthy volunteer subjects change in regional cerebral blood flow(rCBF) in orbital prefrontal cortex (OPFC) and amygdala upon acute administration of a panicogen using [15O]-H2O positron emission tomography (PET).
2. To measure in PD patients and controls 5-HT1A binding potential (BP) in OPFC and amygdala using [carbonyl-11C]-WAY 100635 and PET.
3. To explore the relationships between change in rCBF and regional 5-HT1A BP, and to explore the relationships between components of psychopathology and the two biological outcome measures.
Medication-naïve panic disorder patients (n=14) and healthy volunteers (n=14) will have a PET scan with [11C]-WAY 100635 to measure regional 5-HT1A BP. Arterial samples will allow quantitative kinetic modeling. Next, subjects will have a series of four [15O]-H2O PET scans to measure rCBF. Before the final [15O]-H2O scan, subjects will receive a bolus challenge of i.v. pentagastrin, a polypeptide that induces a panic attack in most panic disorder subjects, and rCBF change relative to a resting scan will be measured. Anxiety scales will be administered. An MRI is acquired for coregistration. Patients will receive treatment.