Protocol Number: 04-M-0270

Title:

Investigating the Role of Serotonin in Emotional Processing Through the Use of Tryptophan Depletion

Number:

04-M-0270

Summary:

This study will examine the role of serotonin function in the brain. Serotonin, one of the brain's natural chemicals, connects with receptors on brain cells to regulate emotion, anxiety, sleep, stress hormones, and other body functions that are disturbed in various mood and anxiety disorders. Also, the research will look at the function of particular brain areas, how they are involved in regulating emotions, and how serotonin is involved in the regulation of their function. The procedures entailed are tryptophan depletion and magnetic resonance imagining (MRI). Also, researchers' understanding of the genetic causes of mood and anxiety disorders will increase through examination of participants' DNA.

Adults in good health, ages 20 through 50, may be eligible for this study. Among those not eligible are females who are pregnant or breast feeding, patients with psychiatric or central nervous system disease, and those taking medications that would interfere with study results.

At the first visit, patients will be asked about their general mood, degree of nervousness, thinking skills, and behavior. The session will last from 1.5 to 2.0 hours. A blood sample of about 2 tablespoons will be drawn, for DNA study.

Participants will undergo the following procedures and tests:

- Physical examination.

- Test of vital signs, lying and standing.

- Electrocardiogram.

- Collection of blood for chemistry and hematology.

- Urinalysis.

- HIV, urine drug, and hepatitis screening.

- Psychiatric screening.

- (Beta)-HCG pregnancy test, if applicable.

At the second visit, patients will receive either tryptophan depletion or placebo, and 5 hours later, the study will begin, to last up to 2 additional hours. Patients will be asked periodically about their emotional state or changes in their well-being. The MRI system will create images of the brain's blood flow and measure glucose metabolism as a measure of brain activity. During the MRI scan, patients will hear knocking or beeping sounds, and they will wear earplugs to reduce the noise. Patients will be able to communicate with the MRI staff at all times during the scan, and they may ask to be moved out of the machine at any time. The MRI session lasts up to 1.5 hours.

Results of any medical tests or other information will not be provided to participants, because further research may be needed before such results are meaningful. But if meaningful information develops from this study that may be important for a participant's health, he or she will be notified about it when it becomes available.

Sponsoring Institute:

National Institute of Mental Health (NIMH)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): Children

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.

Participants will be able to comprehend the purpose and procedures of the study. They will be able to provide written, informed consent for all study procedures.

EXCLUSION CRITERIA:

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 nervosa or bulimia. All participants will be free of any current anxiety disorders with the exception of specific phobias and free of current somatoform disorders. In addition, participants with a first degree relative with major depressive disorder will be excluded.

Severe acute and chronic medical illnesses (e.g., cardiac disease, diabetes, epilepsy).

CNS disease: History of brain abnormalities (e.g., neoplasms, subarachnoid cysts), cerebrovascular disease, infectious disease (e.g., abscess), or other neurological disease, or history of head trauma (defined as loss of consciousness greater than 3 min).

Currently on any regular medication that would interfere with study results (with exception of contraceptive pill).

Current use of psychotropic medication or benzodiazepine

Currently breast feeding or pregnant (as documented by pregnancy testing done within 24 hr of the study starting)

Subjects who are lactose intolerant will be excluded as the placebo capsules contain lactose. Also, those subjects who can not consume the diets provided by metabolic nutrition on the study day will be excluded.

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.

Special Instructions:

Currently Not Provided

Keywords:

Emotional Learning

Neurotransmitter

Neural Systems

Response Control

Orbitofrontal Cortex

Amygdala

Serotonin

Recruitment Keyword(s):

Healthy Volunteer

HV

Condition(s):

Healthy

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

None

Supporting Site:

National Institute of Mental Health

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Abbott FV, et al. Acute tryptophan depletion blocks morphine analgesia in the cold-pressor test in humans. Psychopharmacology (Berl). 1992;108(1-2):60-6.

Adolphs R. Neural systems for recognizing emotion. Curr Opin Neurobiol. 2002 Apr;12(2):169-77. Review.

Aron AR, et al. Stop-signal inhibition disrupted by damage to right inferior frontal gyrus in humans. Nat Neurosci. 2003 Feb;6(2):115-6. No abstract available. Erratum in: Nat Neurosci. 2003 Dec;6(12):1329.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

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