Evidence suggests that serotonin1A (5-HT1A) receptor and benzodiazepine (BZD) receptor function is abnormal in panic disorder (PD), postraumatic stress disorder (PTSD), and depression (MDD). Evidence arguing for a role of BZD/GABA receptor dysfunction in anxiety disorders comes from studies showing anxiolytic and anxiogenic properties of BZD agonists and antagonists, respectively. BZD receptor sensitivity has been shown to be reduced in patients with anxiety disorders. Brain imaging studies using positron emission tomography (PET) and single photon emissison computed tomography (SPECT) suggest decreased BZD receptor binding in PD and PTSD. Yet, association between disturbed interactions between 5-HT1A receptor binding and alterations in BZD receptor binding has not been explored in humans, and so far there are no studies about 5-HT1A receptor binding potential in patients with panic disorder or PTSD. This study will advance knowledge regarding the neurobiology of PD and PTSD by employing PET and [11C]flumazenil and [18F]FC-WAY100635 ([18F]FCWAY) to compare BZD receptor and 5-HT1A receptor binding potential between PD, PTSD, and MDD patients and healthy controls. Because central 5-HT1A receptor density is down-regulated in rodents by corticosterone administration and by stress-mediated corticosterone secretion, assessments of HPA-axis activity will be assessed to determine whether down-regulation of 5-HT1A receptors correlates with cortisol hypersecretion in PD, PTSD, and MDD. During the past year, we have studied an additional 8 subjects with panic disorder, an additional 7 subjects with PTSD, and 12 additional healthy controls. These receptor image data have been analyzed, and showed a marked reduction in 5HT1A receptor binding exists in panic disorder. This was reported at international scientific meetings and in a scientific paper published in the Journal of Neuroscience. We also obtained FDA, RSC and IRB approval to use C-11 flumazenil to measure benzodiazepine receptors in these patient groups, and have now obtained these image data in 15 PTSD cases and 14 healthy controls. We are currently analyzing the data from these scans. In addition we imaged 3 patients with panic disorder. During the next year we plan to continue subject accrual for benzodiazepine receptor imaging in panic disorder. We also will publish the results of the benzodiazepine and 5HT-1A receptor binding data in PTSD. Finally, we will examine interrelationships between these functionally linked receptor species in anxiety disordered samples and in healthy controls.
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