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CompletedNCT00109642Updated Jul 2, 2017

The Role of Norepinephrine in Emotional Processing

An observational study in Psychopathy and Mental Disorders, sponsored by National Institute of Mental Health (NIMH). Completed at 1 site in United States. Open to participants aged 20 Years to 50 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2017-07-02.

Sponsored by National Institute of Mental Health (NIMH) · Observational

Study type
Observational
Enrollment
216
Ages
20 Years to 50 Years
Sex
All
01

Study 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.
Read the 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.

02

Conditions studied

  • Psychopathy
  • Mental Disorders

Keywords

  • Amygdala
  • Orbitofrontal Cortex
  • Yohimbine
  • Emotion
  • Guanfacine
  • Norepinephrine
  • Healthy Volunteer
03

In context

Antisocial Personality Disorder

49 studies on the registry are indexed under Antisocial Personality Disorder; 8 are open to participants now.

This study's enrollment of 216 is close to the median of 200 across 11 observational studies indexed under Antisocial Personality Disorder.

Browse Antisocial Personality Disorder studies →

Lead sponsor

National Institute of Mental Health (NIMH) is the lead sponsor of 367 studies on the registry; 45 are open to participants now.

Of its 25 completed or terminated interventional studies of FDA-regulated products, 24 (96%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
20 Years to 50 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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.
05

Study design

Enrollment
216 participants
06

Study locations

1 site
  • National Institutes of Health Clinical Center, 9000 Rockville Pike
    Bethesda, Maryland 20892, United States
07

References and documents

Publications

  • Adolphs R. Neural systems for recognizing emotion. Curr Opin Neurobiol. 2002 Apr;12(2):169-77. doi: 10.1016/s0959-4388(02)00301-x. PubMed 12015233 ↗
  • Arnsten AF. Adrenergic targets for the treatment of cognitive deficits in schizophrenia. Psychopharmacology (Berl). 2004 Jun;174(1):25-31. doi: 10.1007/s00213-003-1724-3. Epub 2003 Dec 19. PubMed 15205875 ↗
  • Aron AR, Fletcher PC, Bullmore ET, Sahakian BJ, Robbins TW. Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans. Nat Neurosci. 2003 Feb;6(2):115-6. doi: 10.1038/nn1003. No abstract available. PubMed 12536210 ↗
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Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Apr 2005, a primary completion of Mar 2009 and a completion of Mar 2009. It does not say whether these dates are actual or estimated.

How these figures are worked out, and which studies are left out of them.

Registered
Apr 29, 2005
First posted
May 2, 2005
Start
Apr 26, 2005
Primary completionActual
Mar 15, 2009
CompletionActual
Mar 15, 2009
Last update
Jul 2, 2017
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 2, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
09

Registry details

Key details

Study ID
NCT00109642
First posted
May 2, 2005
Start date
Apr 26, 2005
Primary completion
Mar 15, 2009
Completion
Mar 15, 2009
Last update
Jul 2, 2017
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jun 2009. You cannot join it, but the record below documents what was studied.

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