Effect of Functional Genetic Polymorphisms on Brain Morphology and Function
Condition: Drug Abuse
MeSH terms: Substance-Related Disorders
Study type: Observational

Summary: 
      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....
    

Detailed description: 
      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.
    

Time perspective: Other
Keywords: Prefrontal Cortex; Hippocampus; Amygdala; MRI; Cognitive Tasks