Cholinergic Modulation of Condition and Emotion in Mood Disorders: Functional Neuroimaging Studies
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT00055575|
Recruitment Status : Terminated
First Posted : March 6, 2003
Last Update Posted : November 20, 2018
|Condition or disease||Intervention/treatment||Phase|
|Mood Disorders Healthy Unipolar Depression Bipolar Depression||Drug: Transderm Scopolamine||Not Applicable|
Hide Detailed Description
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.
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.
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.
- 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 Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||197 participants|
|Official Title:||Cholinergic Modulation of Cognition and Emotion in Mood Disorders: Functional Neuroimaging Studies|
|Study Start Date :||February 27, 2003|
|Actual Primary Completion Date :||February 2, 2015|
|Actual Study Completion Date :||February 2, 2015|
- Evaluation of the antidepressant effects of the antimuscarinic agent scopolamine [ Time Frame: 5 to 10 years ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00055575
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Carlos A Zarate, M.D.||National Institute of Mental Health (NIMH)|