Ignite Creation Date:
2024-05-05 @ 11:25 AM
Last Modification Date:
2024-10-26 @ 9:07 AM
Study NCT ID:
NCT00033787
Status:
COMPLETED
Last Update Posted:
2017-07-02
First Post:
2002-04-09
Brief Title:
Serotonin Function During Depression
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
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
Status:
COMPLETED
Status Verified Date:
2009-06-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief 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
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 brains 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
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 brains 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 ss 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
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 ss 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 02-M-0162 | None | None | None |