Effect of Functional Genetic Polymorphisms on Brain Morphology and Function



Status:Completed
Conditions:Psychiatric
Therapuetic Areas:Psychiatry / Psychology
Healthy:No
Age Range:18 - 50
Updated:4/5/2019
Start Date:September 13, 2005
End Date:February 25, 2013

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Effect of Functional Genetic Polymorphisms on Brain Morphology

Background:

- New research on genetics and the human genome has helped to identify certain genes that
affect specific parts of the brain, including the parts that may be involved in drug use and
dependency. Researchers are interested in studying both genetic information and brain
activity to better understand variations in brain function among individuals.

Objectives:

- To study brain activity in conjunction with specific genetic information provided by
healthy volunteers including smokers, non-smokers, people with drug dependence, and those who
do not have any dependence on any substance.

Eligibility:

- Healthy volunteers between 18 and 50 years of age.

Design:

- This is an 8 10 hour study which may be completed in 1, 2, or 3 visits.

- Participants will complete questionnaires about emotional and psychological responses to
different situations, including stressful situations.

- Participants will have a training session in a mock (fake) scanner to practice tasks to
be completed in the real scanner.

- Participants will have the following two types of magnetic resonance imaging (MRI) scans
in one scan session of the brain:

- A structural MRI scan to provide basic information about each participant's brain.

- A functional MRI scanning session, in which participants will perform a memory task to
provide information about brain activity.

- Participants will provide blood samples for research and testing....

Objective:

Functional genetic polymorphisms have been identified that influence the morphology and
function of brain regions that have been implicated in addictive and neuropsychiatric
disorders. This protocol aims to integrate genotyping with both structural and functional
brain imaging to investigate the impact of specific functional polymorphisms on morphology
and function of the amygdala and the hippocampus and on behavior mediated by these brain
regions. Functional polymorphisms of the BDNF, SLC6A4, and DISC1 genes will be studied, as
these are logical candidates to influence variability in brain morphology and function. The
overall hypothesis is that variation in morphology and function of the amygdala and the
hippocampus is explained, at least in part, by specific genotype differences.

Study Population:

The study population will consist of healthy male and female adult volunteers (18-50 years
old).

Design:

After being medically cleared and giving written informed consent, each participant will
undergo a structural MRI scan of the brain to be used for volumetric measurements of the
amygdala, hippocampus, prefrontal cortex, and intracranial cavity. Each participant will
undergo an fMRI scanning session, which will include an emotional context memory task
specifically designed to require functioning of the amygdala and the hippocampus. A venous
blood sample will be collected for genotyping of BDNF, SLC6A4, and DISC1 polymorphisms.
Additionally, other functional polymorphisms that may influence brain structure may also be
evaluated, in exploratory fashion. If participants have already had a blood sample collected
for the genetics portion of another Neuroimaging Research Branch study, they may not need to
have another sample taken.

Outcome Measures:

This protocol will provide no direct benefits to research participants. Understanding the
relationship between genetic polymorphisms and brain morphology and their association to
brain function and behavior may provide further clues to the neurobiological mechanisms
underlying addictive and neuropsychiatric disorders. The potential risks are related to
acquiring MRI scans in general. Medical supervision will be provided throughout the study.

- INCLUSION CRITERIA:

To be eligible for this study, subjects must:

1. Be between the ages of 18 and 50.

2. Be in good health.

3. Be right handed.

4. Individuals with a substance abuse disorder may be included.

EXCLUSION CRITERIA:

Subjects will be excluded if they:

1. Are not suitable to undergo an MRI experiment due to pregnancy, implanted metallic
devices (cardiac pacemaker or neurostimulator, some artificial joints, metal pins,
surgical clips, or other implanted metal parts), body morphology, or claustrophobia.

2. Have coagulopathies, history of or current superficial or deep vein thrombosis,
musculoskeletal abnormalities restricting an individual s ability to lie flat for an
extended period of time.

3. Have HIV or syphilis.

4. Have a neurological illness to include, but not limited to, seizure disorders,
migraine, multiple sclerosis, movement disorders, or history of head trauma, CVA, CNS
tumor.

5. Have any current AXIS I psychiatric disorders including Attention Deficit Disorder
(ADD). Have regular use of any prescription, over-the-counter, or herbal medication
that may alter CNS function, cardiovascular function or neuronal-vascular coupling.

6. Have current dependence on any substance other than cocaine, marijuana, or nicotine.

7. Are cognitively impaired or are learning disabled.
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