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Effects of Tryptophan Depletion on Brain Processing of Emotions in Patients With Mood Disorders

This study has been completed.
Information provided by:
National Institutes of Health Clinical Center (CC) Identifier:
First received: November 17, 2004
Last updated: April 19, 2017
Last verified: January 15, 2014

This study will investigate how the brain process emotions in healthy people and in patients who have major depression in order to better understand the causes of depression. It will examine what happens in the brain when a person responds to words related to different emotions while the brain's ability to manufacture a chemical called serotonin is reduced. Serotonin regulates functions such as emotion, anxiety and sleep, and stress hormones such as cortisol. In this study, participants' serotonin levels are reduced by depleting tryptophan, an amino acid that is the main building block for serotonin.

Healthy volunteers and patients with major depression that has been in remission for at least 3 months may be eligible for this study. Candidates must be between 18 and 50 years of age and right-handed. They are interviewed about their medical and psychiatric history, current emotional state and sleep pattern, and family history of psychiatric disorders. Screening also includes psychiatric interviews and rating scales, neuropsychological tests, physical examination, electrocardiogram (EKG), and blood, urine, and saliva tests. Women have their menstrual phase determined by a blood test and home urine ovulation test kit.

The study involves two clinic visits in which participants undergo tryptophan depletion and magnetic resonance imaging (MRI). Subjects arrive at the NIH Clinical Center in the morning after fasting overnight. They fill out questionnaires have a blood sample drawn, and then take 74 capsules that contain a mixture of amino acids found in the diet. At one visit they are given capsules that contain a balanced mixture of amino acids one would normally eat in a day; at the other visit, some of the capsules contain lactose instead of tryptophan, causing tryptophan depletion. At 2 p.m. participants fill out the same questionnaires they completed at the beginning of the day and have another blood sample drawn. Then they do a computerized test in the MRI scanner. MRI uses a magnet and radio waves to obtain pictures of the brain. For the test, subjects lie on a narrow bed that slides into the cylindrical MRI scanner. They are asked to press a button in response to words associated with different emotions that appear on a screen. Arterial spin labeling - a test that uses magnetism to measure blood flow in different areas of the brain-is also done during the procedure. After the scan, subjects eat a meal and then return home.

DNA from the participants' blood samples is also examined to try to better understand the genetic causes of depression. Some of the white cells from the samples may also be grown in the laboratory so that additional studies can be done later.

Depressive Disorder, Major

Study Type: Observational
Official Title: The Effects of Mood and Tryptophan Depletion on the Neural Correlates of Affective Shifting in Mood Disorders

Resource links provided by NLM:

Further study details as provided by National Institutes of Health Clinical Center (CC):

Enrollment: 95
Study Start Date: November 10, 2004
Estimated Study Completion Date: January 15, 2014
  Show Detailed Description


Ages Eligible for Study:   18 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes

Healthy Volunteers

Right-handed subjects (ages 18-50) will be selected who have not met criteria for any major psychiatric disorder, have no known first-degree relatives with mood disorders, and have a current score on the Hamilton Depression Rating Scale (HDRS; 17 item) in the not depressed range ( 7). Control subjects will be matched to depressed subjects and their relatives for age, gender, and education.

MDD Samples

Right-handed subjects (ages 18-50) will be selected with a past history of MDD by DSM-IV criteria.

Healthy Relatives

Healthy, right-handed, first-degree relatives of patients with MDD will be recruited.


Subjects must not have taken antidepressant drugs for at least 3 months (4 months for fluoxetine) prior to the fMRI studies or other medications likely to alter monoamine neurochemistry or cerebrovascular and cardiovascular function for at least 3 weeks prior to imaging. However, effective medications will not be discontinued for the purposes of this study. Subjects will also be excluded if they have:

  1. Psychosis
  2. Medical or neurological illnesses likely to affect physiology or anatomy, i.e. hypertension, cardiovascular disorders
  3. A history of drug (including benzodiazepines (BZD)) abuse within 1 year or a lifetime history of drug dependence (DSM IV criteria)
  4. A history of alcohol abuse within 1 year or a lifetime history of alcohol dependence (DSM IV criteria)
  5. Current pregnancy (as documented by pregnancy testing at screening or at days of the challenge studies)
  6. Current breast feeding
  7. Are smokers
  8. Serious suicidal ideation or behavior. In this study, there is a small risk of transient depressive symptoms occurring after ingesting the amino acid mixture. Therefore, if volunteers manifest evidence of serious suicidal ideation or behavior, they will be excluded from participating. Criteria for meeting suicidal ideation include but are not limited to: 1) thoughts of suicide within the past 3 months which are accompanied by intent to harm oneself, serious consideration of means or plan to attempt suicide, evidence of arranging for a suicide attempt (e.g. giving away prized possessions or updating a will), or clear desire to commit suicide, 2) severity of past suicide events, if applicable or 3) a current plan for harming themselves. All assessments will be conducted by an experienced, NIMH credentialed health professional, such as a psychiatrist or psychiatric nurse who will use their expert knowledge and experiences in determining the authenticity of a participant s information and handle the situation accordingly.
  9. General MRI exclusion criteria

Subjects must exhibit no or only moderate alcohol use. Subjects with current or previous regular use (greater than 4 weeks) of BZDs and excessive use of alcohol (greater than 8 ounces/day for men and greater than 6 ounces/day for women) in the past or present are ineligible for participation, as such drug use may confound the results. Smokers (regular use within the last 3 months) are ineligible because of the evidence for interactions between nicotine and depression, and the possibility of withdrawal symptoms that may affect behavioral and neural responses to TD.

Subjects beyond age 50 are excluded to address the biological heterogeneity encompassed by the MDD criteria, since depressives whose age-at-onset is later than 50 have a far greater likelihood of having MRI correlates of cerebrovascular disease than age-matched healthy controls or age-matched early-onset depressives. Subjects whose first major depressive episodes arose temporally after other medical or psychiatric conditions will also be excluded, since their functional imaging results generally differ from those reported in primary MDD.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00097175

United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Principal Investigator: Christian Grillon, Ph.D. National Institute of Mental Health (NIMH)
  More Information

Publications: Identifier: NCT00097175     History of Changes
Other Study ID Numbers: 050035
Study First Received: November 17, 2004
Last Updated: April 19, 2017

Keywords provided by National Institutes of Health Clinical Center (CC):
Major Depressive Disorder
Functional MRI
Negative Affect
Healthy Volunteer

Additional relevant MeSH terms:
Depressive Disorder
Depressive Disorder, Major
Mood Disorders
Pathologic Processes
Mental Disorders
Behavioral Symptoms
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs processed this record on April 26, 2017