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Research Studies
Brain
| PET Imaging of Mild Cognitive Impairment, Early Alzheimer’s Disease and Healthy Elderly (4863) |
Identifying the magnitude of amyloid plaque formation in human subjects is of enormous clinical value in making an early diagnosis of Alzheimer's Disease (AD) and in monitoring treatment. Further, repeat scanning will be useful to determine its potential utility for monitoring during therapy in the future. We propose to utilize the tracer [11C]-6-OH-BTA-1 in order to assess two patient populations and a control group.
We plan to study amyloid deposits using PET scanning with FDG and [11C]-6-OH-BTA-1 in 20 subjects with mild, early AD, 20 subjects with mild cognitive impairment (MCI), and 20 elderly healthy subjects. We will repeat these procedures at one-year follow-up in 16 subjects with mild, early AD, 16 subjects with mild cognitive impairment (MCI), and 16 elderly healthy subjects. An MRI scan will also be obtained to enable precise mapping of the regions of interest of each subject’s brain.
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| Neurobiology of Depression and Antidepressants (4979R) |
This study will use Positron Emission Tomography (PET) to correlate changes in state of the serotonin system to clinical responses to two types of treatments, selective serotonin reuptake inhibitors (SSRI) and electroconvulsive therapy (ECT).
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| Neurobiological Studies of Stress and Depression (4344) |
This study will use Positron Emission Tomography (PET) to identify changes in brain chemistry, specifically within the serotonin system, that may cause an episode of depression, posttraumatic stress disorder, or both.
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| Quantifying Serotonin Transporters by PET with [11C]-DASB after Interferon Treatment (4889) |
While interferon-α (INF- α) has become a standard treatment for hepatitis C, it produces a number of side effects including flu-like symptoms, e.g., fever, rapid heart rate, headache, and malaise, which tend to appear early in treatment and abate as treatment continues. In addition, it produces depression-like symptoms that emerge later in treatment and may be persistent through treatment. Thus, patients scheduled to receive INF- α treatment constitute a high-risk model of depression that can be used to examine the neurobiology of the disorder.
The mechanism by which this depression is produced is unclear. Administration of anti-depressant medications prior to beginning INF- α treatment prevents the development the depression, suggesting an effect related to the central nervous system including the serotonin system.
The aims of this study are 1) to determine whether patients undergoing INF- α treatment who develop major depression will show an increase in central nervous system serotonin activity as measured by a brain scanning method called PET scanning and 2) to compare these findings to those from PET scans taken during a major depressive episode in medically healthy untreated individuals. Finally, as a supplementary aim, we will examine whether hepatitis C patients who become depressed are more likely to have a genetic characteristics that has been linked to the development of depression.
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| Alzheimer's Disease Neuroimaging Initiative (3599) |
This multi-site study sponsored by the NIH seeks to determine whether imaging of the brain (MRI, PET or CT scans) every six months can help predict and monitor the onset and progression of Alzheimer’s disease. In addition to neuroimaging, the study will collect and test blood and, for some participants, cerebral spinal fluid, to determine if biomarkers can predict and monitor the disease.
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| Dopamine Release in Major Depression--Assessment with PET and Amphetamine Challenge (4949) |
Twelve major depressive disorder (MDD) patients (including 6 with the melancholic subtype) will complete PET imaging with [11C]raclopride before and after a single dose of amphetamine, given intravenously. They will be compared to 12 matched healthy control subjects. We hypothesize that dopamine (DA) release in response to amphetamine will be decreased in ventral striatum brain region in MDD, especially in the melancholic subtype. We further hypothesize that DA release in subregions of the striatum will be associated with MDD symptoms of loss of pleasure, decreased expression of emotions, and slowed thinking. If DA abnormalities in striatal subregions are associated with MDD, and a specific subset of MDD symptoms, this would advance understanding of brain circuitry of MDD.
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| PET Imaging of the Serotonin Transporter (SERT) and the 5HT1A Receptor in Bipolar Disorder () |
We will use the radiotracer [11C]DASB to measure serotonin (5-HT) transporter binding and [11C]WAY100635 to measure 5-HT1A serotonin receptors in the brain of depressed or recently depressed bipolar subjects and healthy subjects using PET. These receptors are markers of neurons that utilize serotonin as a neurotransmitter. Each subject will undergo a PET scan session. A MRI and fMRI scan will also be obtained to enable precise mapping of the serotonin transporters and activity in various regions of the subject’s brain.
The 5-HT1A receptor is regulated by the naturally occurring stress hormones, corticosteroids. Higher levels of glucocorticosteroids lower 5-HT1A receptor number. More severe forms of major depression are associated with over-activity of this corticosteroid stress system. We will measure plasma cortisol (a naturally-occurring corticosteroid) in response to a small challenge dose ( 0.5mg) of an artificial corticosteroid analogue called dexamethasone.
We plan to study a new cohort of 20 medication-free patients and 10 age and sex-matched healthy controls (for a total of 37 medication-free patients and 20 healthy controls). The healthy controls will be paid $250 after the studies are complete.
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Patients
