Depression, InvolutionalNCT00033787
Serotonin Function During Depression
An observational study of Depression, Involutional and Healthy, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Serotonin is a chemical involved in regulation of emotions, anxiety, sleep, stress hormones, and other body functions. The purpose of this study is to use a procedure called tryptophan depletion to study the function of serotonin in people with depression and in healthy volunteers. Read more about this study
- Who is it for?
- Ages 18 to 60 years
- Conditions the study is for
- Depression, Involutional, Healthy
- How many people
- 450 participants
- Where
- 1 siteUnited States
- Study dates
- 5 Apr 2002to 30 Apr 2005
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Twenty-four healthy subjects (ages 18-60) without a known personal or family history of psychiatric disorders in first-degree relatives will be selected.
Who cannot join
- Subjects must not have taken antidepressant or other medications likely to alter monoamine neurochemistry or cerebrovascular and cardiovascular function for at least 3 months prior to the studies. However, effective medications will not be discontinued for the purposes of this study.
- Subjects will also be excluded if they have:
- any form of past or current psychosis;
- medical or neurological illnesses likely to affect physiology or anatomy, i.e. hypertension, cardiovascular disorders;
- a history of drug (including benzodiazepines [BZD]) or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria) longer than 2 years;
- current pregnancy (as documented by pregnancy testing at screening or at days of the challenge studies);
Show all 16Show fewer
- current breast feeding (tryptophan depletion);
- are smokers;
- current suicidal ideation or behavior;
- general MRI exclusion criteria.
- Subjects must exhibit no or only moderate alcohol use.
- Subjects with current excessive use of alcohol (greater than 8 ounces/day for men and greater than 6 ounces/day for women) are ineligible for participation.
- other current axis I diagnoses beside unipolar major depressive disorder;
- lactose intolerance (tryptophan depletion).
- Subjects beyond the age of 60 are excluded.
- Subjects whose first major depressive episodes arose temporally after other medical or psychiatric conditions will also be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Tryptophan Depletion PET Study in Remitted Depressed Subjects and Healthy Controls, and GABA MRS Study in Remitted and Currently Depressed Subjects and Healthy Controls
Serotonin is a chemical involved in regulation of emotions, anxiety, sleep, stress hormones, and other body functions. The purpose of this study is to use a procedure called tryptophan depletion to study the function of serotonin in people with depression and in healthy volunteers.
Major depressive disorder (MDD) has been associated with reduced functioning of central serotonergic systems. Tryptophan depletion (TD) is a procedure used to investigate the relationship between serotonergic function and depression. Evidence suggests that the mood lowering effects of TD depend upon family history and differences in genes for a specific protein called 5-HTTLPR. Healthy females with a particular gene for 5-HTTLPR and a family history of mood disorders appear to be at a greater risk for the development of depressive symptoms during TD. This study will use positron emission tomography (PET) scans of the brain to investigate the effect of variant 5-HTTLPR genotypes on response to TD. The relationship between 5-HTTLPR genotypes and the effect of TD on brain activity in individuals with different 5-HTTLPR genes will be determined. This study will also examine how the reduced serotonin function that occurs in MDD affects the brain's response to sensory stimulation.
Read more
Participants in this study will be screened by telephone about their psychiatric and medical history, current emotional state, anxiety and sleep patterns, and family history of psychiatric disorders. At study entry, participants will have an interview, physical examination, electrocardiogram (EKG), and blood and laboratory tests. Menstruating women will have a pregnancy test and tests to determine menstrual phase and time of ovulation. At the second clinic visit, participants will undergo tests of intelligence and cognitive abilities and a magnetic resonance imaging (MRI) scan of the brain. Prior to Visits 3 and 4, participants will collect their saliva and urine. Menstruating women will have a pregnancy test. At Visits 3 and 4, participants will undergo TD studies and PET scanning. During one of these visits, participants will take capsules of an amino acid. On the other day, they will take lactose capsules. Throughout the study, participants will be asked about their emotional state, anxiety, ability to concentrate, and well being.
...
Read the detailed description
Major depressive disorder (MDD) has been associated with abnormally reduced function of central serotonergic systems by various types of evidence. One instructive paradigm for investigating the relationship between serotonergic function and depression has involved the mood response to tryptophan depletion (TD), achieved by oral loading with all essential amino acids excepting the 5-HT precursor, tryptophan. We obtained preliminary evidence that the mood lowering effect of TD depends upon the genotype for a functional polymorphism in the promoter region of the 5-HT transporter (5-HTT), designated 5-HTTLPR, as well as upon family history. In healthy females the s-allele and a positive family history for mood disorders appeared to be additive risk factors for the development of depressive symptoms during TD.
The current study employs quantitative PET imaging of cerebral blood flow (CBF) and glucose metabolism to investigate the effect of variant 5-HTTLPR genotypes on the neurophysiological response to TD. The current study will examine the relationship between 5-HTTLPR genotypes and the TD effect on PFC metabolic activity. We will determine whether under TD the reduction in PFC metabolism in response to TD will occur to a greater extent in subjects with the s/s allele, and in subjects with a single s allele plus a family history of depression. We will also examine whether this reduction in PFC metabolic activity is unique to subjects who develop depressive symptoms during TD.
In addition, based upon evidence that 5-HT inhibits neuronal activity in the amygdala, and modulates transmission of emotionally-salient sensory information from the sensory cortices to the amygdala, we will test the hypothesis that in MDD, reduced serotonin function associated with TD may disinhibit the amygdala response to sensory stimulation. This hypothesis will be explored by assessing the physiological responses of the amygdala to sensory stimuli that normally activate the amygdala, namely pictures of human faces that show fearful or sad emotional expressions. We are particularly interested in determining whether the amygdala CBF response to emotional stimuli during TD will be most prominently increased in subjects carrying the s-allele of the 5-HTTLPR, and whether it will be unique to subjects who develop depressive symptoms during TD.
Twenty-four unmedicated-remitted subjects with MDD and 24 healthy controls will be studied in a double-blind, placebo-controlled, randomized (according to 5-HTTLPR genotype) crossover study.
- Conditions
- Depression, Involutional, Healthy
- Keywords
- Depression, Tryptophan Depletion, PET, Serotonin, Pathophysiology, Emotional Stimuli, GABA MRS, MDD, Healthy Volunteer, HV, Normal Control
- Medical subject headings
- Depressive Disorder, Major, Depression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2002 (estimated)
- Study start5 Apr 2002
- Primary completion30 Apr 2005
- Study completion30 Apr 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Depression, InvolutionalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Enrolment
- 450 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00033787
- Sponsor's protocol ID
- 020162
- Other IDs
- 02-M-0162
- Status last verified
- 8 Jun 2009
- First submitted
- 9 Apr 2002
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Bowen DM, Najlerahim A, Procter AW, Francis PT, Murphy E. Circumscribed changes of the cerebral cortex in neuropsychiatric disorders of later life. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9504-8. doi: 10.1073/pnas.86.23.9504.
PubMed 2574463Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY, Overholser JC, Roth BL, Stockmeier CA. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry. 1999 May 1;45(9):1085-98. doi: 10.1016/s0006-3223(99)00041-4.
PubMed 10331101Coppen A, Eccleston EG, Peet M. Total and free tryptophan concentration in the plasma of depressive patients. Lancet. 1973 Jul 14;2(7820):60-3. doi: 10.1016/s0140-6736(73)93259-5. No abstract available.
PubMed 4123618
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Tryptophan Depletion PET Study in Remitted Depressed Subjects and Healthy Controls, and GABA MRS Study in Remitted and Currently Depressed Subjects and Healthy Controls
- ClinicalTrials.gov ID
- NCT00033787
- Acronym / sponsor ID
- 020162
- Conditions
- Depression, Involutional, Healthy
- Keywords
- Depression, Tryptophan Depletion, PET, Serotonin, Pathophysiology, Emotional Stimuli, GABA MRS, MDD
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 450 participants
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 5 Apr 2002
- Primary completion
- 30 Apr 2005 (actual)
- Study completion
- 30 Apr 2005 (actual)
- First posted
- 10 Apr 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Serotonin is a chemical involved in regulation of emotions, anxiety, sleep, stress hormones, and other body functions. The purpose of this study is to use a procedure called tryptophan depletion to study the function of serotonin in people with depression and in healthy volunteers.
Major depressive disorder (MDD) has been associated with reduced functioning of central serotonergic systems. Tryptophan depletion (TD) is a procedure used to investigate the relationship between serotonergic function and depression. Evidence suggests that the mood lowering effects of TD depend upon family history and differences in genes for a specific protein called 5-HTTLPR. Healthy females with a particular gene for 5-HTTLPR and a family history of mood disorders appear to be at a greater risk for the development of depressive symptoms during TD. This study will use positron emission tomography (PET) scans of the brain to investigate the effect of variant 5-HTTLPR genotypes on response to TD. The relationship between 5-HTTLPR genotypes and the effect of TD on brain activity in individuals with different 5-HTTLPR genes will be determined. This study will also examine how the reduced serotonin function that occurs in MDD affects the brain's response to sensory stimulation.
Participants in this study will be screened by telephone about their psychiatric and medical history, current emotional state, anxiety and sleep patterns, and family history of psychiatric disorders. At study entry, participants will have an interview, physical examination, electrocardiogram (EKG), and blood and laboratory tests. Menstruating women will have a pregnancy test and tests to determine menstrual phase and time of ovulation. At the second clinic visit, participants will undergo tests of intelligence and cognitive abilities and a magnetic resonance imaging (MRI) scan of the brain. Prior to Visits 3 and 4, participants will collect their saliva and urine. Menstruating women will have a pregnancy test. At Visits 3 and 4, participants will undergo TD studies and PET scanning. During one of these visits, participants will take capsules of an amino acid. On the other day, they will take lactose capsules. Throughout the study, participants will be asked about their emotional state, anxiety, ability to concentrate, and well being.
...
Detailed description
Major depressive disorder (MDD) has been associated with abnormally reduced function of central serotonergic systems by various types of evidence. One instructive paradigm for investigating the relationship between serotonergic function and depression has involved the mood response to tryptophan depletion (TD), achieved by oral loading with all essential amino acids excepting the 5-HT precursor, tryptophan. We obtained preliminary evidence that the mood lowering effect of TD depends upon the genotype for a functional polymorphism in the promoter region of the 5-HT transporter (5-HTT), designated 5-HTTLPR, as well as upon family history. In healthy females the s-allele and a positive family history for mood disorders appeared to be additive risk factors for the development of depressive symptoms during TD.
The current study employs quantitative PET imaging of cerebral blood flow (CBF) and glucose metabolism to investigate the effect of variant 5-HTTLPR genotypes on the neurophysiological response to TD. The current study will examine the relationship between 5-HTTLPR genotypes and the TD effect on PFC metabolic activity. We will determine whether under TD the reduction in PFC metabolism in response to TD will occur to a greater extent in subjects with the s/s allele, and in subjects with a single s allele plus a family history of depression. We will also examine whether this reduction in PFC metabolic activity is unique to subjects who develop depressive symptoms during TD.
In addition, based upon evidence that 5-HT inhibits neuronal activity in the amygdala, and modulates transmission of emotionally-salient sensory information from the sensory cortices to the amygdala, we will test the hypothesis that in MDD, reduced serotonin function associated with TD may disinhibit the amygdala response to sensory stimulation. This hypothesis will be explored by assessing the physiological responses of the amygdala to sensory stimuli that normally activate the amygdala, namely pictures of human faces that show fearful or sad emotional expressions. We are particularly interested in determining whether the amygdala CBF response to emotional stimuli during TD will be most prominently increased in subjects carrying the s-allele of the 5-HTTLPR, and whether it will be unique to subjects who develop depressive symptoms during TD.
Twenty-four unmedicated-remitted subjects with MDD and 24 healthy controls will be studied in a double-blind, placebo-controlled, randomized (according to 5-HTTLPR genotype) crossover study.
Study design
Who may qualify
- Ages
- 18 to 60 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Twenty-four healthy subjects (ages 18-60) without a known personal or family history of psychiatric disorders in first-degree relatives will be selected.
Key exclusion criteria (16 listed)
- Subjects must not have taken antidepressant or other medications likely to alter monoamine neurochemistry or cerebrovascular and cardiovascular function for at least 3 months prior to the studies. However, effective medications will not be discontinued for the purposes of this study.
- any form of past or current psychosis;
- medical or neurological illnesses likely to affect physiology or anatomy, i.e. hypertension, cardiovascular disorders;
- a history of drug (including benzodiazepines [BZD]) or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria) longer than 2 years;
- current pregnancy (as documented by pregnancy testing at screening or at days of the challenge studies);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 2574463Bowen DM, Najlerahim A, Procter AW, Francis PT, Murphy E. Circumscribed changes of the cerebral cortex in neuropsychiatric disorders of later life. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9504-8. doi: 10.1073/pnas.86.23.9504.
- Background: PubMed 10331101Rajkowska G, Miguel-Hidalgo JJ, Wei J, Dilley G, Pittman SD, Meltzer HY, Overholser JC, Roth BL, Stockmeier CA. Morphometric evidence for neuronal and glial prefrontal cell pathology in major depression. Biol Psychiatry. 1999 May 1;45(9):1085-98. doi: 10.1016/s0006-3223(99)00041-4.
- Background: PubMed 4123618Coppen A, Eccleston EG, Peet M. Total and free tryptophan concentration in the plasma of depressive patients. Lancet. 1973 Jul 14;2(7820):60-3. doi: 10.1016/s0140-6736(73)93259-5. No abstract available.
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Depression, Involutional and Healthy, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00033787, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.