Cholinergic Modulation of Condition and Emotion in Mood Disorders: Functional Neuroimaging Studies
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.
Drug: Transderm Scopolamine
|Study Design:||Primary Purpose: Treatment|
|Official Title:||Cholinergic Modulation of Cognition and Emotion in Mood Disorders: Functional Neuroimaging Studies|
- Evaluation of the antidepressant effects of the antimuscarinic agent scopolamine [ Time Frame: 5 to 10 years ]
|Study Start Date:||February 2003|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Drug: Transderm Scopolamine
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 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.
|Contact: Maura L Furey, Ph.D.||(301) email@example.com|
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike||Recruiting|
|Bethesda, Maryland, United States, 20892|
|Contact: For more information at the NIH Clinical Center contact Patient Recruitment and Public Liaison Office (PRPL) 800-411-1222 ext TTY8664111010 firstname.lastname@example.org|
|Principal Investigator:||Maura L Furey, Ph.D.||National Institute of Mental Health (NIMH)|