Function of Catecholamines in the Brain During Depression
| Status: | Archived |
|---|---|
| Conditions: | Depression |
| Therapuetic Areas: | Psychiatry / Psychology |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 7/1/2011 |
Neural Correlates of Depressive Symptoms and Reward Related Mechanisms Following AMPT Depletion in Remitted Depressed Patients Off Treatment and Healthy Controls
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:
- fMRI: While lying in the MRI scanner, the subject performs a monetary reward task that
is somewhat like playing a computer video game for money. The amount of cash the
subject can win depends on his or her performance. It is possible to lose money that
was previously won, if performance declines. This portion of the study provides
information on how the brain processes reward and about the role of catecholamines in
this process.
- PET: The subject is injected in the arm with a gluco...
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.
We found this trial at
1
site
9000 Rockville Pike
Bethesda, Maryland 20892
Bethesda, Maryland 20892
301-496-2563
National Institutes of Health Clinical Center The National Institutes of Health (NIH) Clinical Center in...
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