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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: | NCT00082030 |
This study will explore brain function related to depressive symptoms and will examine DNA for genes that may be involved in depressive disorders, particularly genes that regulate synthesis and metabolism of the brain neurotransmitter catecholamine. It will compare findings in patients with major depressive disorders who are in remission with those in normal, healthy volunteers.
Patients with remitted major depressive disorders and healthy normal volunteers between 18 and 60 years of age may be eligible for this study. Candidates are screened with a psychiatric and medical history, physical examination, electrocardiogram, and blood and urine tests. Participants undergo the following tests and procedures in up to eight visits to the NIH Clinical Center:
Memory Tasks and Problem Solving and Brain Imaging
Subjects are tested with measurements of intelligence or memory ability. They also undergo magnetic resonance imaging (MRI), a test that uses a magnetic field and radio waves to produce images of the brain. For this procedure, the patient lies on a table that is moved into the scanner (a narrow cylinder), and wears earplugs to muffle loud knocking and thumping sounds that occur during the scanning process. The MRI lasts about 60 minutes.
Catecholamine Depletion Study
For this study, subjects take capsules containing either AMPT (a drug that temporarily reduces brain catecholamine activity) or a placebo (lactose capsules, which do not affect brain catecholamine activity) at 9 a.m., 2 p.m., and 7 p.m. on one visit and return the next day to take additional capsules at 7 a.m. and noon. In addition to the study medication, subjects keep a low-monoamine diet (e.g., no chocolate, cheese, smoked meats, and various other foods that will be enumerated) and do not smoke, drink alcohol, or take in food or drink containing caffeine. After taking all the study capsules, the subjects have positron emission tomography (PET) and functional MRI (fMRI) scans, as follows:
Condition |
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Depression Involutional |
Study Type: | Observational |
Official Title: | Neural Correlates of Depressive Symptoms and Reward Related Mechanisms Following AMPT Depletion in Remitted Depressed Patients Off Treatment and Healthy Controls |
Estimated Enrollment: | 220 |
Study Start Date: | April 2004 |
The depressive and anhedonic response precipitated by CD raises the possibility that dysfunction of the dopamine system is a stable, sometimes latent characteristic of MDD. Following this line of reasoning, central catecholamine dysfunction as evinced by CD may be equally salient in a subset of unaffected relatives who are at genetic risk for developing the disorder.
We plan to extend the phase I project to unaffected relatives of BD and MDD patients in order to evaluate sensitivity to CD as an endophenotype of MDD and BD. In order to maximize our statistical power, we will be recruiting equal numbers healthy low and high-risk relatives. Here, risk is defined on the basis of chronological age (see below for more detail).
Furthermore, it has recently become feasible to conduct genome-wide association studies and quantify the burden of risk alleles carried by an individual. Certainly, the identity of these risk alleles remains unknown or unproven. Nevertheless, Francis McMahon's group, with whom we are collaborating, have identified upwards of 20 common risk variants in two independent samples. Individuals carrying 19 or more of these risk alleles were found to be 4 times more likely to be cases than controls. This approach may provide us with another method of quantifying genetic risk.
The endophenotypic status of sensitivity to CD will be evaluated with psychometric instruments, FDG PET, and an fMRI-coupled appetitive learning task. We now have access to a high resolution PET scanner (High Resolution Research Tomograph) that will enable us to study hitherto irresolvable structures of importance such as the habenula and peri-aqueductal gray matter (PAG) in addition to previously implicated regions such as the ventral striatum and OFC. Analysis of the metabolic activity of these regions under sham and CD conditions in both remitted MDD and relatives of BD and MDD patients is of great theoretical import. So to is identifying regions of the brain involved in reward response that are selectively impacted by CD, a question that we hope to answer through the use of the fMRI-coupled appetitive learning task.
Ages Eligible for Study: | 18 Years to 45 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
MDD Sample: 40 subjects (ages 18-45) with remitted MDD will be selected. MDD is defined by the DSM-IV criteria, and one of the following additional criteria:
Unaffected MDD Relative Sample:
Healthy relatives of MDD probands (ages 18-45) will be recruited. Subjects will be screened to ensure that they have no history of psychiatric illness.
Unaffected BD Relative Sample:
Healthy relatives of BD probands (ages 18-45) will be recruited. Subjects will be screened to ensure that they have no history of psychiatric illness.
Healthy Control Samples:
-Healthy subjects (ages 18-45) without a known personal or first-degree family history of psychiatric disorders in first-degree relatives will be selected.
EXCLUSION CRITERIA:
Subjects who 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: | 040160, 04-M-0160 |
Study First Received: | April 28, 2004 |
Last Updated: | July 18, 2008 |
ClinicalTrials.gov Identifier: | NCT00082030 |
Health Authority: | United States: Federal Government |
Depression PET fMRI Dopamine Norepinephrine Depletion Emotional Stimuli Anhedonia |
Norepinephrine Dopamine Depletion Depression Major Depressive Disorder MDD Healthy Volunteer HV |
Dopamine Depression Mental Disorders Norepinephrine Mood Disorders |
Healthy Depressive Disorder, Major Depressive Disorder Behavioral Symptoms |