Ignite Creation Date:
2024-05-05 @ 11:28 AM
Last Modification Date:
2024-10-26 @ 9:08 AM
Study NCT ID:
NCT00055575
Status:
TERMINATED
Last Update Posted:
2021-03-22
First Post:
2003-03-06
Brief Title:
Cholinergic Modulation of Condition and Emotion in Mood Disorders Functional Neuroimaging Studies
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Cholinergic Modulation of Cognition and Emotion in Mood Disorders Functional Neuroimaging Studies
Status:
TERMINATED
Status Verified Date:
2015-02-02
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:
This study looks at the role of a specific brain chemical system in the mood and attention symptoms seen in major depression and bipolar disorders using functional brain imaging
Detailed Description:
1 Objective
The goal of this research project is to evaluate the role of the cholinergic system in behavioral and cognitive symptoms observed in mood disorders in humans using functional brain neuroimaging techniques Specific aspects of behavior and cognition are impaired in mood disorders including selective attention set-shifting and memory and there is also evidence that depressed subjects exhibit a mood congruent processing bias whereby they more readily process negatively toned information as compared to positively toned information This cognitive pattern lends itself to evaluation with functional brain imaging both in terms of identifying the anatomical correlates of the specific behavioral and cognitive deficits as well as characterizing the effects of pharmacological manipulation
Attention and memory functions are closely tied to the cholinergic neurotransmitter system The cholinergic system is one of the neurotransmitter systems implicated in the pathophysiology of mood disorders Evidence suggests that during major depressive episodes the cholinergic system is hypersensitive to acetylcholine Agents that enhance muscarinic cholinergic receptor function increase depressive symptoms in depressed subjects and can produce symptoms of depression in healthy subjects The preclinical literature more specifically implicates the muscarinic receptors and indicates that the use of muscarinic antagonists in the context of animal models of depression results in improvement in the behavioral analogs of depression
2 Study Population
The accrual ceiling for this protocol is 388 participants 143 currently depressed patients with major depressive disorder 100 currently depressed patients with bipolar disorder and 145 healthy controls will participate in this study
3 Design
The antimuscarinic agent scopolamine will be administered in a double-blind placebo controlled manner across all studies Clinical ratings cognitive tasks and neuroimaging will be conducted at various timepoints to evaluate the clinical effects of scopolamine on depression to assess the acute mood response to scopolamine and to study the neurobiological correlates of the clinical and behavioral drug effects
4 Outcome Measures
The proposed inpatient or outpatient project investigates the role of cholinergic neurotransmission in the behavioral and cognitive symptoms observed in the depressed phase of both major depressive disorder MDD and bipolar disorder BD The studies proposed here will identify anatomical correlates of the mood congruent processing bias working memory attention and set-shifting deficits observed in depressed subjects Further these studies will evaluate the effects of the cholinergic antagonist scopolamine both on the performance deficits and on neural activity in brain regions recruited as subjects perform these tasks
Dose escalation studies will be conducted to determine if higher doses of scopolamine will increase the antidepressant response rate in patients with major depressive disorder Based on earlier work showing the predictive value in baseline neuroimaging data to predict treatment outcome we will stratify participants at baseline into groups based on expected response to scopolamine treatment
This approach is expected to reveal how neuromodulators influence processing in brain structures recruited to perform these tasks both in healthy subjects and in major depressive disorders The combined use of functional brain imaging and pharmacological manipulation to evaluate the role of neurotransmitter dysfunction in depression may direct us to potential therapeutic approaches
The goal of this research project is to evaluate the role of the cholinergic system in behavioral and cognitive symptoms observed in mood disorders in humans using functional brain neuroimaging techniques Specific aspects of behavior and cognition are impaired in mood disorders including selective attention set-shifting and memory and there is also evidence that depressed subjects exhibit a mood congruent processing bias whereby they more readily process negatively toned information as compared to positively toned information This cognitive pattern lends itself to evaluation with functional brain imaging both in terms of identifying the anatomical correlates of the specific behavioral and cognitive deficits as well as characterizing the effects of pharmacological manipulation
Attention and memory functions are closely tied to the cholinergic neurotransmitter system The cholinergic system is one of the neurotransmitter systems implicated in the pathophysiology of mood disorders Evidence suggests that during major depressive episodes the cholinergic system is hypersensitive to acetylcholine Agents that enhance muscarinic cholinergic receptor function increase depressive symptoms in depressed subjects and can produce symptoms of depression in healthy subjects The preclinical literature more specifically implicates the muscarinic receptors and indicates that the use of muscarinic antagonists in the context of animal models of depression results in improvement in the behavioral analogs of depression
2 Study Population
The accrual ceiling for this protocol is 388 participants 143 currently depressed patients with major depressive disorder 100 currently depressed patients with bipolar disorder and 145 healthy controls will participate in this study
3 Design
The antimuscarinic agent scopolamine will be administered in a double-blind placebo controlled manner across all studies Clinical ratings cognitive tasks and neuroimaging will be conducted at various timepoints to evaluate the clinical effects of scopolamine on depression to assess the acute mood response to scopolamine and to study the neurobiological correlates of the clinical and behavioral drug effects
4 Outcome Measures
The proposed inpatient or outpatient project investigates the role of cholinergic neurotransmission in the behavioral and cognitive symptoms observed in the depressed phase of both major depressive disorder MDD and bipolar disorder BD The studies proposed here will identify anatomical correlates of the mood congruent processing bias working memory attention and set-shifting deficits observed in depressed subjects Further these studies will evaluate the effects of the cholinergic antagonist scopolamine both on the performance deficits and on neural activity in brain regions recruited as subjects perform these tasks
Dose escalation studies will be conducted to determine if higher doses of scopolamine will increase the antidepressant response rate in patients with major depressive disorder Based on earlier work showing the predictive value in baseline neuroimaging data to predict treatment outcome we will stratify participants at baseline into groups based on expected response to scopolamine treatment
This approach is expected to reveal how neuromodulators influence processing in brain structures recruited to perform these tasks both in healthy subjects and in major depressive disorders The combined use of functional brain imaging and pharmacological manipulation to evaluate the role of neurotransmitter dysfunction in depression may direct us to potential therapeutic approaches
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
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-0108 | None | None | None |