This study will examine the use of positron emission tomography (PET) for measuring
docosahexaenoic acid (DHA) absorption from the blood into the brain. DHA is a type of fatty
acid found in fish and other seafood. It is involved in brain cell activity that underlies
the ability to think, move, and respond to the outside world. When the amount of DHA in the
brain is low, the brain may not work the same as if there were a normal amount of DHA. If
PET can be used successfully to evaluate brain DHA metabolism, this method might be useful
for future studies of alcoholism, since brain DHA levels are influenced by alcohol
Healthy normal volunteers between 18 and 65 years of age may be eligible for this study.
Because study participants must stop taking any medications, including herbal preparations,
individuals who require regular medication are excluded from this protocol. Participants
will undergo the following tests and procedures:
- Psychological questionnaires concerning thoughts and behaviors.
- Nutritional status analysis: A dietitian will assess the subject's nutritional status
through questionnaires and measurement of body fat. Body fat is measured using
bioelectrical impedance analysis. This analysis uses a low, safe electric current to
measure body composition, giving a reading of the percentage of fat in the body.
- Fat biopsy to measure the composition of fat tissue: An area on the upper half of the
buttock will be numbed and a needle will be inserted to aspirate a sample of fat tissue
- Blood drawing: Blood samples will be collected at the time of the fat biopsy and the
PET scan (see below) to measure DHA and indicators that may influence DHA.
- Diet: 3 days before the fat biopsy and at least 3 days before the PET scan, subjects
will consume a diet low in DHA and other omega-3 fats. This no seafood diet prohibits
eating fish, shellfish, seaweed, seafood, health food products or supplemental
vitamins, and foods containing canola or flaxseed oil. Caffeine-containing beverages
are limited to one per day for 3 days before the study. Alcoholic beverages are
prohibited for 2 weeks before the study. For 24 hours before the PET scan, subjects eat
only standard meals that will be provided to them.
- Magnetic resonance imaging: A brain MRI scan will be done to fit the PET scan images
onto a picture of the whole brain. During the scan, the subject lies on a table inside
a narrow metal cylinder containing a strong magnetic field.
- PET scan: Before the PET scan, catheters (small plastic tubes) are inserted into an arm
vein and into a wrist artery. The venous catheter is used for injecting a radioactive
substance that will be detected by the scanner, and the arterial catheter is used for
collecting blood samples during the scan. For the scan, the subject lies on a bed that
slides into the doughnut-shaped scanner. A mask is placed to keep the head still. A
transmission scan is done to see how much radiation the skull absorbs. Radioactive
water (15O-water) is then injected into the blood, and the brain is scanned for about
10 minutes to measure brain blood flow. Then, radioactive DHA (11C-DHA) is injected,
followed by about 1-1/2 hours of scanning to measure DHA absorption into the brain.
Docosahexaenoic acid (DHA, 22:6 n-3) is an essential omega-3 fatty acid that is selectively
concentrated in the brain. Epidemiologic studies suggest that DHA deficiency is related to
affective disorders, while clinical studies suggest that DHA is efficacious in treating
depression. DHA has also been shown to be an important second messenger involved in
phospholipase A(2)-mediated signal transduction. Although animal studies have provided a
wealth of knowledge about the role of DHA in neural function, no method exists of evaluating
DHA content or metabolism in the living human brain. Our goal is to establish a quantitative
method of examining brain DHA metabolism using PET in healthy humans and to measure regional
DHA incorporation from plasma into the brain. Utilizing the data from the pilot phase with
healthy volunteers, we will apply the method to study DHA metabolism in alcoholics. Since
alcohol consumption depletes brain DHA, we hypothesize that compared to healthy volunteers;
alcoholics will have a decreased rate of incorporation of DHA from plasma into brain.
Utilizing the method we have established, we anticipate that we will find previously
undetectable metabolic abnormalities in alcoholics. We may further find that such
abnormalities are correlated with cognitive or behavioral function. Now that the pilot phase
of the protocol has been completed, we are proceeding with the main phase of the protocol to
study non-smoking chronic alcoholics.
- INCLUSION CRITERIA:
Age 18-65 years.
1. Any Axis I diagnosis, current or past.
2. History of any intravenous drug use, or a DSM IV diagnosis of drug use or alcohol
abuse or dependence.
3. Recent use (within the past two weeks) of alcohol, or any period of extensive use,
defined as an average of one standard drink per day over a twelve-month period.
4. Abnormal laboratory or diagnostic tests that might disturb the dependent measures of
5. Inability to give a clinical history or informed consent.
6. Inability to follow dietary guidelines.
7. Serious medical problems requiring ongoing treatment (i.e., diabetes or
8. Positive test for hepatitis C or human immunodeficiency virus (HIV).
9. Metallic foreign bodies lodged in the head or neck that would be affected by the MRI
10. Head trauma resulting in a period of unconsciousness lasting longer than one hour.
11. History of central nervous system infection.
12. History of fetal alcohol syndrome or other neurodevelopment disorder.
13. History of seizures, other than in childhood and related to fever.
14. Nursing women, women with a positive pregnancy test or women of childbearing age who
are not willing to use some form of birth control during the study.
15. Recent exposure to radiation (i.e., PET from other research) which when combined with
this study would be above the allowable limits of exposure.
16. Current use of cigarettes, cigars, or other form of tobacco, defined as ten
cigarettes, two pipes or two cigars over the preceding month.
17. Current drug or medication use, or the use of any medication (i.e., Tylenol) for
three days prior to PET.
18. Positive urine drug screen.
19. Psychotropic medication use (including benzodiazepines and illicit drugs) during the
two weeks prior to the PET scan. The use of medication with a very long half life
(i.e., Prozac) during the six weeks prior to the PET scan.