This study will compare serotonin transporter proteins in people with alcoholism and healthy
volunteers to examine how these proteins may be related to the inability of people with
alcoholism to appropriately regulate their alcohol consumption. Serotonin transporters
regulate levels of the brain chemical serotonin. Problems in this regulation have been
implicated in alcoholism.
Healthy normal volunteers and people who suffer from alcoholism who are between 18 and 75
years of age may be eligible for this study. Candidates are screened with a medical history
and physical examination, psychiatric diagnostic interview, blood and urine tests, an
electrocardiogram, urine toxicology screen, and written psychological evaluations.
Participants undergo positron emission tomography (PET) and magnetic resonance imaging (MRI)
scanning to measure serotonin transporter levels in the brain.
PET uses small amounts of a radioactive chemical called a tracer that "labels" the serotonin
transporters in the brain. The tracer used in this study is [11C]DASB. For the procedure,
the subject lies on the scanner bed. A special mask is fitted to the head and attached to
the bed to help keep the subject's head still during the scan so the images will be clear. A
brief scan is done just before the radioactive tracer is injected. This scan provides
measures of the brain that will help in the precise calculation of information from
subsequent scans. After the tracer is injected through a catheter (plastic tube) placed in
the arm, pictures are taken for about 2 hours.
MRI uses a magnetic field and radio waves to produce pictures of brain structure. The
subject lies on a bed that slides into the tube-like scanner, wearing earplugs to muffle
loud noises the machine makes when the magnetic fields are switched. The scan takes about an
hour, during which time the subject can communicate with the technician.
Alcoholism is characterized by the inability of individuals to regulate their consumption of
alcohol appropriately. Serotonergic dysfunction has been implicated in the pathophysiology
of this illness. Serotonin transporters (SERT) critically regulate the tone of serotonergic
transmission (Gobbi et al 2001). In a brain imaging study using the SPECT radioligand,
[123I] Beta-CIT, male alcoholics who had abstained from alcohol for more than four weeks,
had significantly reduced serotonin transporters in the raphe area of the brainstem compared
to healthy control subjects (Heinz et al 1998). However, the [123I] Beta-CIT ligand, binds
with high affinity to both the dopamine transporter (DAT) and SERT. Binding of [123I]
Beta-CIT in regions rich in SERT or DAT have been attributed to SERT and DAT respectively
but in regions of mixed innervation (e.g. cortical regions), it is not possible to
distinguish between SERT and DAT.
[11C]DASB is a PET ligand with high affinity for SERT with almost 1,000 fold selectivity
versus DAT. Using this tracer, we will be able to measure SERT binding in cortical and
subcortical brain regions including those with mixed innervation. [11C] DASB PET studies in
humans (Houle et al 2000; Meyer et al 2001) indicate the feasibility of quantifying SERT
binding in SERT rich regions. In the current protocol, we plan to use PET imaging with the
radioligand, [11C] DASB, for serotonin transporter (SERT) to delineate regional
abnormalities in SERT binding in two subject groups consisting of 30 patients with
alcoholism and 30 healthy volunteers. Our goal of the present study is to further our
understanding of the roles of the serotonergic systems in the pathophysiology of alcoholism.
- ELIGIBILITY CRITERIA:
Alcoholic and healthy subjects will be recruited from those screened by Dr. Daniel Hommer
using either protocol (Protocol number 98-AA-0009) which is used to identify and recruit
adult participants who meet DSM-IV criteria for alcohol dependence, alcohol abuse and
healthy controls or protocol (Protocol number 05-AA-0121) assessment and treatment of
people with alcohol drinking problems.
As stated in protocol 98-AA-0009, subjects will be recruited primarily from the
Washington, DC metropolitan area through newspaper advertisements. These have been
approved by the NIAAA IRB in the past and have not changed. As necessary these
advertisements which are now primarily published in the Washington Post Health Section,
will be reviewed and revised. Any revisions will be presented to the IRB. Subjects will
also be recruited through outreach to health care professionals and treatment facilities
throughout Northern Virginia, West Virginia and the Washington, DC and Baltimore
metropolitan areas. Patient referrals for sources throughout the U.S. and on occasion
international referrals also will be used.
Increased efforts will be made to recruit alcoholic subjects from the Hispanic community.
This will take the form of contacts with treatment programs that serve Hispanic
populations, as well as through advertising in Spanish language newspapers. We have
decided to exclude children from this protocol because the NIH Clinical Center currently
does not have any inpatient units capable of treating substance abusing patients who are
under the age of 18. Every effort will be made to recruit a similar number of age-matched
males and females. The two groups will not be individually matched by age. For example,
we will not seek a control subject to match a particular alcoholic patient's age. Instead
the two groups will be matched for mean age. We will obtain informed consent from all
subjects per NIH guidelines for research studies.
INCLUSION CRITERIA - PATIENTS:
DSM-IV criteria for alcohol dependence or alcohol abuse.
INCLUSION CRITERIA - CONTROLS:
PATIENTS AND CONTROLS:
Other current DSM-IV Axis I diagnostic criteria than alcohol dependence or alcohol abuse.
Psychotropic medication or other drugs that may cross the blood brain barrier.
Serious organic disease e.g. liver disease.
Prior participation in other research protocols within the past year such that a radiation
exposure together with the present study would exceed the annual limits.
Any condition that increases risk for MRI (e.g., pacemaker, metallic foreign body in the