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The Role of Norepinephrine in Emotional Processing

Primary Purpose

Psychopathy, Mental Disorders

Status
Completed
Phase
Locations
United States
Study Type
Observational
Intervention
Sponsored by
National Institute of Mental Health (NIMH)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an observational trial for Psychopathy focused on measuring Amygdala, Orbitofrontal Cortex, Yohimbine, Emotion, Guanfacine, Norepinephrine, Healthy Volunteer

Eligibility Criteria

20 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
April 29, 2005
Last Updated
June 30, 2017
Sponsor
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT00109642
Brief Title
The Role of Norepinephrine in Emotional Processing
Official Title
Investigating the Role of Norepinephrine in Emotional Processing Through Alpha-2 Adrenergic Receptor Modulation
Study Type
Observational

2. Study Status

Record Verification Date
June 8, 2009
Overall Recruitment Status
Completed
Study Start Date
April 26, 2005 (undefined)
Primary Completion Date
March 15, 2009 (Actual)
Study Completion Date
March 15, 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
National Institute of Mental Health (NIMH)

4. Oversight

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Psychopathy, Mental Disorders
Keywords
Amygdala, Orbitofrontal Cortex, Yohimbine, Emotion, Guanfacine, Norepinephrine, Healthy Volunteer

7. Study Design

Enrollment
216 (false)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Facility Information:
Facility Name
National Institutes of Health Clinical Center, 9000 Rockville Pike
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20892
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
12015233
Citation
Adolphs R. Neural systems for recognizing emotion. Curr Opin Neurobiol. 2002 Apr;12(2):169-77. doi: 10.1016/s0959-4388(02)00301-x.
Results Reference
background
PubMed Identifier
15205875
Citation
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.
Results Reference
background
PubMed Identifier
12536210
Citation
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. Erratum In: Nat Neurosci. 2003 Dec;6(12):1329.
Results Reference
background

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The Role of Norepinephrine in Emotional Processing

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