Serotonin Transporters in Alcoholism

NCT ID: NCT00085865

Last Updated: 2008-03-04

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2004-06-30
• Study Completion Date: 2006-07-31

Brief Summary

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.

Detailed Description

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.

Conditions

Alcoholism

Eligibility Criteria

Inclusion Criteria

Age: 18-75

DSM-IV criteria for alcohol dependence or alcohol abuse.

Age: 18-75

Exclusion Criteria

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.

Claustrophobia.

Pregnancy.

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 eye, etc.)

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Mental Health (NIMH)

NIH

Sponsor Role: lead

Locations

National Institute of Mental Health (NIMH)

Bethesda, Maryland, United States

Countries

United States

References

Fujita M, Charney DS, Innis RB. Imaging serotonergic neurotransmission in depression: hippocampal pathophysiology may mirror global brain alterations. Biol Psychiatry. 2000 Oct 15;48(8):801-12. doi: 10.1016/s0006-3223(00)00960-4.

Reference Type: BACKGROUND

PMID: 11063976 (View on PubMed)

Other Identifiers

04-M-0208

Identifier Type: -

Identifier Source: secondary_id

040208

Identifier Type: -

Identifier Source: org_study_id