The Role of Norepinephrine in Emotional Processing

June 30, 2017 updated by: National Institute of Mental Health (NIMH)

Investigating the Role of Norepinephrine in Emotional Processing Through Alpha-2 Adrenergic Receptor Modulation

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.

Study Overview

Status

Completed

Conditions

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.

Study Type

Observational

Enrollment

216

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

20 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:

Age: Participants will be males and females, 20-50 years of age.

IQ: IQ, as measured by 4 subscales from the Wechsler Adult Intelligence Scale-Revised (WAIS-R), must be greater than 80.

Medication status: No current use of any psychotropic medication or benzodiazepine.

EXCLUSION CRITERIA:

Because factors such as psychiatric disease, or CNS disease, can influence functional brain activity, these factors are exclusionary:

  • Psychiatric History: Participants will be assessed using DSM-IV criteria via standardized psychiatric interviews conducted by trained examiners (SCID). All participants will be free of any current or past major affective disorder, psychotic disorder, substance dependence, anorexia, somatoform disorder, or anxiety disorders with the exception of specific phobias.
  • Severe acute and chronic medical illnesses (e.g. cardiac disease, diabetes, epilepsy).
  • CNS disease: Known history of brain abnormalities (e.g., neoplasms, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g., abscess), other central nervous system disease, or history of head trauma which resulted in a persistent neurologic deficit or loss of consciousness greater than 3 minutes.
  • Currently on regular medication that would interfere with study results. This includes alpha and beta adrenergic medications, other anti-hypertensive medications, glucocorticoid and mineralocorticoid medications, and medications causing sedation or stimulation. For example, current use of tylenol or ibuprofen is permitted, while current use of benadryl or methylphenidate is not. Use of oral contraceptive pills is permitted.
  • Currently breast feeding or pregnant (as documented by pregnancy testing at screening or at days of the challenge studies).

Additional exclusion criteria for fMRI studies:

  • Metal or electronic objects: Metal plates, certain types of dental braces, cardiac pacemakers, etc., that are sensitive to electromagnetic fields contraindicate MRI scans.
  • Claustrophobia: participants will be questioned about potential discomfort in being in an enclosed space, such as an MRI scanner.
  • Body weight - to reduce the likelihood of significant orthostasis from guanfacine, participants must weigh 60kg or greater. Those weighing less than 60 kg will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Mental Health (NIMH)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 26, 2005

Primary Completion (Actual)

March 15, 2009

Study Completion (Actual)

March 15, 2009

Study Registration Dates

First Submitted

April 29, 2005

First Submitted That Met QC Criteria

April 29, 2005

First Posted (Estimate)

May 2, 2005

Study Record Updates

Last Update Posted (Actual)

July 2, 2017

Last Update Submitted That Met QC Criteria

June 30, 2017

Last Verified

June 8, 2009

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 050147
  • 05-M-0147

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Mental Disorders

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Uzbekistan

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe