Ignite Creation Date:
2024-05-05 @ 11:28 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00050700
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2002-12-17
Brief Title:
Brain Imaging in Depression
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Muscarinic Cholinergic Receptor Imaging in Depression
Status:
COMPLETED
Status Verified Date:
2010-05-14
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 use brain imaging technology to examine the role of certain brain receptors and the nervous system chemical acetylcholine in major depression
The cholinergic system involves the regulation of neurotransmitters and the brain receptors to which they bind Evidence suggests that the cholinergic system may play a role in the development of depression Acetylcholine is a neurotransmitter that binds to certain brain receptors called muscarinic cholinergic receptors Cholinomimetic drugs drugs that stimulate the cholinergic system often exacerbate depressive symptoms in people with mood disorders and in healthy individuals This increase in depressive symptoms may be caused by stimulation of muscarinic acetylcholine receptors mAChRs but further study is needed to confirm this This study will use positron emission tomography PET and magnetic resonance imaging MRI to study the function of mAChRs in individuals with depression
Participants in this study will undergo a physical examination psychiatric interviews neuropsychological tests PET and MRI scans and rating scales of depression anxiety and negative thinking symptoms Questions about behavior and functioning will be asked and blood samples will be collected for genetic analysis
The cholinergic system involves the regulation of neurotransmitters and the brain receptors to which they bind Evidence suggests that the cholinergic system may play a role in the development of depression Acetylcholine is a neurotransmitter that binds to certain brain receptors called muscarinic cholinergic receptors Cholinomimetic drugs drugs that stimulate the cholinergic system often exacerbate depressive symptoms in people with mood disorders and in healthy individuals This increase in depressive symptoms may be caused by stimulation of muscarinic acetylcholine receptors mAChRs but further study is needed to confirm this This study will use positron emission tomography PET and magnetic resonance imaging MRI to study the function of mAChRs in individuals with depression
Participants in this study will undergo a physical examination psychiatric interviews neuropsychological tests PET and MRI scans and rating scales of depression anxiety and negative thinking symptoms Questions about behavior and functioning will be asked and blood samples will be collected for genetic analysis
Detailed Description:
Several paths of evidence converge in implicating a role for the cholinergic system in the pathophysiology of affective illness In both unipolar depressed and euthymic bipolar subjects cholinomimetic drugs ie muscarinic agonists acetylcholinesterase inhibitors exacerbate depressive signs and symptoms such as dysphoria psychomotor retardation impairment of attention and memory hypothalamic pituitary adrenal axis hyperactivity and sleep EEG abnormalities In healthy subjects the acetylcholinesterase inhibitor physostigmine elicits a range of depressive symptoms including dysphoria anergia psychomotor slowing emotional lability sleep disturbances memory and concentration impairment and with higher doses tearfulness and depression These effects have been shown to reflect stimulation of muscarinic receptors Cholinomimetics also exacerbate behavioral despair in putative animal models of depression Conversely the anticholinergic agent biperidine improved symptoms of depression in a placebo controlled study Moreover muscarinic cholinomimetics and a choline rich nutrient lecithin phosphatidylcholine exert antimanic effects in bipolar subjects
Potentially consistent with these observations depressed subjects exhibit hypersensitivity to cholinomimetic agents Administration of muscarinic cholinergic agonists ACh releasing agents or acetylcholinesterase inhibitors induce exaggerated effects on REM density and latency in depressed subjects than in healthy controls In addition both manic and depressed bipolar subjects show increased pupillary sensitivity to the muscarinic cholinergic agonist pilocarpine relative to controls
Despite the data implicating the mAChR receptor system in mood disorders no direct in vivo investigations of the central mAChR have been performed in depressed subjects A novel PET radioligand 18FFP-TZTP was recently developed by Eckelman as a selective agonist of M2 receptors Because the M2 receptor functions predominately as a presynaptic release-controlling autoreceptor decreased distribution volume V of this receptor could conceivably give rise to increased postsynaptic muscarinic receptor sensitivity
This application proposes a pilot PET study of M2 receptor distribution volume in currently depressed subjects with major depressive disorder n30 currently depressed subjects with bipolar disorder n30 and psychiatrically healthy controls n30 The proposed pilot study will test the central hypothesis that M2 receptor V is decreased in regions where they are primarily located presynaptically in depressed subjects relative to healthy controls The proposed study will advance knowledge regarding the pathophysiology of depression
Potentially consistent with these observations depressed subjects exhibit hypersensitivity to cholinomimetic agents Administration of muscarinic cholinergic agonists ACh releasing agents or acetylcholinesterase inhibitors induce exaggerated effects on REM density and latency in depressed subjects than in healthy controls In addition both manic and depressed bipolar subjects show increased pupillary sensitivity to the muscarinic cholinergic agonist pilocarpine relative to controls
Despite the data implicating the mAChR receptor system in mood disorders no direct in vivo investigations of the central mAChR have been performed in depressed subjects A novel PET radioligand 18FFP-TZTP was recently developed by Eckelman as a selective agonist of M2 receptors Because the M2 receptor functions predominately as a presynaptic release-controlling autoreceptor decreased distribution volume V of this receptor could conceivably give rise to increased postsynaptic muscarinic receptor sensitivity
This application proposes a pilot PET study of M2 receptor distribution volume in currently depressed subjects with major depressive disorder n30 currently depressed subjects with bipolar disorder n30 and psychiatrically healthy controls n30 The proposed pilot study will test the central hypothesis that M2 receptor V is decreased in regions where they are primarily located presynaptically in depressed subjects relative to healthy controls The proposed study will advance knowledge regarding the pathophysiology of depression
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 |
|---|---|---|---|
| 03-M-0001 | None | None | None |