The Role of Norepinephrine in Emotional Processing
Condition: Psychopathy; Mental Disorders
MeSH terms: Mental Disorders
Study type: Observational

Summary: 
      This study will examine the role of a brain chemical called norepinephrine in thinking,
      decision-making, and emotional processing. After norepinephrine is released from a brain
      cell, it binds to another brain cell's receptor. Some of the receptors it binds to are called
      alpha-2 adrenergic receptors. This study will use medicines called yohimbine and guanfacine
      to look at the function of norepinephrine in the brain when it binds to the alpha-2
      adrenergic receptors. Yohimbine increases norepinephrine's function and guanfacine decreases
      its function.

      Healthy volunteers between 20 and 50 years of age who do not have heart disease, high blood
      pressure, psychiatric illness, or other serious medical conditions and who are not allergic
      to lactose may be eligible for this study. Candidates are screened with a medical and
      psychiatric history, physical examination, neuropsychological testing, blood and urine tests
      and electrocardiogram. Women are screened with a urine pregnancy test.

      Participants are given a pill of yohimbine, guanfacine, or placebo and undergo the following
      tests and procedures:

        -  Blood pressure and heart rate measurements: Blood pressure and heart rate are measured
           before the medication is taken and several times after.

        -  Blood draws: Blood is drawn before the medicine is taken and 90 minutes after to measure
           levels of norepinephrine and the hormone cortisol.

        -  Neurocognitive testing: Participants do neurocognitive tasks on the computer for up to
           90 minutes. The tasks involve looking at pictures or words on a screen and responding
           according to instructions given.

        -  Magnetic resonance imaging (MRI): Patients may undergo neurocognitive testing MRIs. This
           test uses a strong magnetic field and radio waves to show changes in brain activity. The
           subject lies on a table that slides into a narrow cylinder (the MRI scanner). Images of
           the brain are obtained while the subject performs the computer tasks.
    

Detailed description: 
      An understanding of the role of specific neurotransmitters in the neurocognitive functions
      mediating emotional processing is essential for the understanding and treatment of mood and
      anxiety disorders. One such disorder, currently regarded as untreatable, is psychopathy.
      Psychopathy has been linked with noradrenergic and amygdala disturbances. However, an
      understanding of the functional significance of the noradrenergic system in humans remains in
      its infancy. The goal of this protocol is to use targeted noradrenergic manipulations
      (yohimbine and guanfacine) in conjunction with specific neurocognitive and neuroimaging
      paradigms to consider the role of norepinephrine in reward and punishment processing. In
      particular, we wish to evaluate the hypothesis that increased norepinephrine levels following
      the administration of yohimbine will lead to enhanced formation and processing of
      stimulus-reward and stimulus-punishment associations, while decreased norepinephrine levels
      following the administration of guanfacine will reduce the formation and processing of
      stimulus-reward and stimulus-punishment associations. In addition, we aim to examine the
      hypothesis that increased norepinephrine levels will lead to increased neural response in the
      amygdala during either the formation, or processing, of stimulus-reinforcement associations.
    

Keywords: Amygdala; Orbitofrontal Cortex; Yohimbine; Emotion; Guanfacine; Norepinephrine; Healthy Volunteer