Brain Chemical Receptor Effects in Patients With Panic Disorder and Post-Traumatic Stress Disorder
The purpose of this study is to examine how certain brain chemicals work in patients with Panic Disorder (PD) and Post-Traumatic Stress Disorder (PTSD) with and without major depressive disorder (MDD).
Brain chemicals that regulate emotion, anxiety, sleep, stress hormones, and other body functions bind to serotonin (5-HT1A) and benzodiazepine (BZD) receptors. Evidence suggests that 5-HT1A and BZD receptor function is abnormal in patients with PD, PTSD, and depression. This study will use positron emission tomography (PET) scans to examine BZD and 5-HT1A receptor binding potential in patients with PD and patients with PTSD with and without co-morbid MDD, as well as in healthy volunteers. This study will also determine the effects of the stress hormone cortisol on 5-HT1A and BZD receptors.
The current emotional state and psychiatric, medical, and family history of potential participants will be evaluated during an initial telephone interview. After entering the study, participants will be asked questions about general mood, degree of nervousness, and behavior. A physical examination, an electrocardiogram (EKG), and tests of intelligence and cognition will be given. Urine, blood, and saliva samples will be taken. Women will be given pregnancy tests and tests to determine menstrual phase and time of ovulation. All volunteers will undergo magnetic resonance imaging (MRI) and PET scans of the brain.
Posttraumatic Stress Disorder
Major Depressive Disorder
|Official Title:||Serotonin 1A Receptor Imaging and Benzodiazepine Receptor Imaging in Panic Disorder and Posttraumatic Stress Disorder|
|Study Start Date:||October 2001|
|Estimated Study Completion Date:||July 2008|
Evidence suggests that serotonin1A (5-HT1A) receptor, serotonin transporter (5-HTT) and benzodiazepine (BZD) receptor function is abnormal in panic disorder (PD), postraumatic stress disorder (PTSD) and depression (MDD). The hypotheses for the role of 5-HT1A receptors have been obtained by assessing behavioral, neuroendocrine and temperature responses to the selective partial 5-HT1A agonist ipsapirone in anxiety disorders subjects and healthy controls, and examining effects on 5-HT1A receptor function in rats following antidepressant drug (AD) administration. 5-HT1A receptors knockout mice show behaviors that have been used as a model for anxiety disorders in humans. Moreover, 5-HT1A receptor agonists have been shown to be effective in the treatment of patients with anxiety disorders. The serotonin transporter is implicated in these disorders by virtue of the efficacy of selective serotonin reuptake inhibitors in relieving symptoms in these subjects. 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 emission computed tomography (SPECT) suggest decreased BZD receptor binding in PD and PTSD.
Animal studies link together serotonin and GABA suggesting a pathological pathway originating from 5-HT1A receptor deficit leading towards dysfunctions within GABAergic systems, resulting in increased levels of anxiety. Yet, association between disturbed interactions between 5-HT1A receptor binding and alterations in BZD receptor binding has not been explored in humans. The proposed study will advance knowledge regarding the neurobiology of PD and PTSD by employing PET and [11C]flumazenil, [18F]FC-WAY100635([18F]FCWAY) and [11C]DASB to compare BZD receptor, 5-HT1A receptors and the serotonin transporter binding potential, respectively, 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.
The following hypotheses will be tested: 1) PD/PTSD/MDD patients have reduced GABA(A)-BZD receptor binding relative to healthy controls. 2) PD/PTSD/MDD patients have reduced 5-HT1A receptor binding potential relative to healthy controls. 3) 5-HT1A receptor binding will be more prominently reduced in PD and PTSD patients with comorbid MDD relative to anxiety disorders patients without comorbid MDD and healthy controls. 4) There will be a positive correlation between the reduction in 5-HT1A receptor binding and BZD binding in PD/PTSD/MDD patients. 5) There will be an inverse correlation between reduction in 5-HT1A receptor binding and BZD binding in PD/PTSD/MDD patients and cortisol secretion. 6) Serotonin transporter binding, measured using [11C]DASB, will be reduced in PD subjects relative to healthy controls.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|