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Sponsored by: |
National Institute of Mental Health (NIMH) |
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Information provided by: | National Institutes of Health Clinical Center (CC) |
ClinicalTrials.gov Identifier: | NCT00055575 |
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.
Condition | Intervention |
---|---|
Mood Disorders Healthy Unipolar Depression Bipolar Depression |
Drug: Transderm Scopolamine |
Study Type: | Interventional |
Study Design: | Treatment |
Official Title: | Cholinergic Modulation of Cognition and Emotion in Mood Disorders: Functional Neuroimaging Studies |
Estimated Enrollment: | 318 |
Study Start Date: | February 2003 |
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 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.
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.
Ages Eligible for Study: | 18 Years to 45 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | Yes |
Three groups of right-handed subjects will be recruited for studies under this protocol: unipolar depressives, bipolar depressives and age matched healthy controls. Subjects with both unipolar and bipolar depression appear to exhibit abnormal cholinergic function during the depressed phase (see above), and no differences are hypothesized to exist between MDD and BD depressives herein. However, while BD subjects are more difficult to recruit, the evidence for cholinergic abnormalities has been particularly compelling for BD. Therefore both groups will be recruited.
The presence of inclusion and exclusion criteria will be established using both an unstructured clinical interview with a psychiatrist and the Structured Clinical Interview for DSM-IV (SCID). Family history of mental illness will be obtained from the subject using the Family Interview of Genetic Studies. We will recruit 15 subjects per group per study, including the dose finding study for a total of 90 subjects per group.
Depressed Samples:
Subjects (ages 18-45) currently suffering from a major depressive episode falling into one of the following subgroups:
Healthy Control Sample:
Subjects (ages 18-45) who have not met criteria for any major psychiatric disorder and have no known first-degree relatives with MDD or BD will be selected. Control subjects will be matched to depressed subject for age, gender and education.
EXCLUSION CRITERIA:
Subjects will be recruited who are drug-naive or who have not received psychotropic drugs for at least 3 weeks (8 weeks for fluoxetine).
Subjects will also be excluded if they have:
Contact: Patient Recruitment and Public Liaison Office | (800) 411-1222 | prpl@mail.cc.nih.gov |
Contact: TTY | 1-866-411-1010 |
United States, Maryland | |
National Institutes of Health Clinical Center, 9000 Rockville Pike | Recruiting |
Bethesda, Maryland, United States, 20892 |
Study ID Numbers: | 030108, 03-M-0108 |
Study First Received: | March 6, 2003 |
Last Updated: | November 7, 2008 |
ClinicalTrials.gov Identifier: | NCT00055575 |
Health Authority: | United States: Federal Government |
Scopolamine Depression fMRI Cognition Emotion Brain |
Bipolar Disorder Depression Major Depressive Disorder MDD Healthy Volunteer HV |
Depression Scopolamine Bipolar Disorder Butylscopolammonium Bromide Depressive Disorder, Major Healthy Depressive Disorder |
Behavioral Symptoms Affective Disorders, Psychotic Mental Disorders Bromides Mood Disorders Psychotic Disorders |
Parasympatholytics Neurotransmitter Agents Disease Cholinergic Antagonists Molecular Mechanisms of Pharmacological Action Physiological Effects of Drugs Cholinergic Agents Pharmacologic Actions |
Muscarinic Antagonists Adjuvants, Anesthesia Pathologic Processes Mydriatics Autonomic Agents Therapeutic Uses Peripheral Nervous System Agents Central Nervous System Agents |