Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00025974
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2001-11-02
Brief Title:
Brain Chemical Receptor Effects in Patients With Panic Disorder and Post-Traumatic Stress Disorder
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Serotonin 1A Receptor Imaging and Benzodiazepine Receptor Imaging in Panic Disorder and Posttraumatic Stress Disorder
Status:
COMPLETED
Status Verified Date:
2008-07-21
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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
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
Detailed Description:
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 BZDGABA 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 11Cflumazenil 18FFC-WAY10063518FFCWAY and 11CDASB 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 PDPTSDMDD patients have reduced GABAA-BZD receptor binding relative to healthy controls 2 PDPTSDMDD 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 PDPTSDMDD patients 5 There will be an inverse correlation between reduction in 5-HT1A receptor binding and BZD binding in PDPTSDMDD patients and cortisol secretion 6 Serotonin transporter binding measured using 11CDASB will be reduced in PD subjects relative to healthy controls
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 11Cflumazenil 18FFC-WAY10063518FFCWAY and 11CDASB 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 PDPTSDMDD patients have reduced GABAA-BZD receptor binding relative to healthy controls 2 PDPTSDMDD 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 PDPTSDMDD patients 5 There will be an inverse correlation between reduction in 5-HT1A receptor binding and BZD binding in PDPTSDMDD patients and cortisol secretion 6 Serotonin transporter binding measured using 11CDASB will be reduced in PD subjects relative to healthy controls
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-M-0002 | None | None | None |