Ignite Creation Date:
2024-05-05 @ 11:24 AM
Last Modification Date:
2024-10-26 @ 9:06 AM
Study NCT ID:
NCT00026832
Status:
COMPLETED
Last Update Posted:
2018-07-05
First Post:
2001-11-14
Brief Title:
Examination of Brain Serotonin Receptors in Patients With Mood Disorders
Sponsor:
National Institute of Mental Health NIMH
Organization:
National Institutes of Health Clinical Center CC
Study Overview
Official Title:
Serotonin1A Receptor and Serotonin Transporter Imaging In Mood Disorders
Status:
COMPLETED
Status Verified Date:
2012-11-27
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:
The purpose of this study is to evaluate the function of certain brain chemicals and receptors in patients with mood disorders This study will also examine how the stress hormone cortisol affects brain function
Data suggest that serotonin 1A 5-HT1A receptor function is abnormal in patients with mood disorders such as major depressive disorder MDD and bipolar disorder BP However these data are limited because they are based on small sample sizes In this study PET scans will be used to compare 5-HT1A receptor binding potential between mood disorder patients and healthy volunteers
All participants will have an initial medical and psychiatric evaluation Depression severity anxiety negative thinking level of functioning intelligence and cognitive functions will be measured Urine saliva and blood will be collected Women will have a pregnancy test and tests to determine menstrual phase and time of ovulation Participants will undergo magnetic resonance imaging MRI and PET scans of the brain Some participants will have other procedures such as a lumbar puncture Participants with Cushings disease will undergo imaging as a comparison group
Data suggest that serotonin 1A 5-HT1A receptor function is abnormal in patients with mood disorders such as major depressive disorder MDD and bipolar disorder BP However these data are limited because they are based on small sample sizes In this study PET scans will be used to compare 5-HT1A receptor binding potential between mood disorder patients and healthy volunteers
All participants will have an initial medical and psychiatric evaluation Depression severity anxiety negative thinking level of functioning intelligence and cognitive functions will be measured Urine saliva and blood will be collected Women will have a pregnancy test and tests to determine menstrual phase and time of ovulation Participants will undergo magnetic resonance imaging MRI and PET scans of the brain Some participants will have other procedures such as a lumbar puncture Participants with Cushings disease will undergo imaging as a comparison group
Detailed Description:
Multiple lines of evidence suggest that serotonin1A 5-HT1A receptor and serotonin transporter 5-HTT function is abnormal in major depressive disorder MDD and that somatic antidepressant treatments effect changes in the function of these systems that are relevant to their therapeutic mechanisms The data supporting these hypotheses have been obtained by assessing neuroendocrine and temperature responses to 5-HT1A agonists in MDD subjects measuring 5-HT1A receptor and 5-HTT binding in brain tissue acquired post mortem from small samples of MDD subjects and examining effects on 5-HT1A receptor function in rats following antidepressant drug AD administration The recent development of highly selective 5-HT1A receptor and 5-HTT radioligands for positron emission tomography PET imaging made direct noninvasive exploration of the central serotonin sites binding possible Two studies conducted using one of these carbonyl-11C-WAY-100635 found reduced 5-HT1A receptor binding potential BP in the mesiotemporal cortex the raphe and the prefrontal cortex PFC Pilot data from these studies suggested that the abnormal reduction in 5-HT1A receptor BP is more prominent in bipolar disorder BD than MDD subjects ie unipolar depressives who did not have bipolar relatives and that it exists independently of mood state
However these data have the limitations that the subject samples studied in these preliminary post mortem and PET series have been small and that carbonyl-11CWAY-100635 uptake is difficult to quantitate in PET images Therefore these observations require replication in subject samples large enough to establish main effects of diagnostic subtype using a 5-HT1A receptor radioligand that can be validly quantitated A selective 5-HT1A receptor radioligand suitable for this purpose 18FFC-WAY100635 18FFCWAY has recently been developed at the NIH In addition a recently developed selective 5-HTT ligand 11C DASB provides a unique opportunity to image the 5-HTT in the same depressed sample
The proposed study will advance knowledge regarding the neurobiology of mood disorders by employing PET and 18FFCWAY and 11C DASB to compare 5-HT1A receptor BP between mood disordered and healthy control subjects in the mesiotemporal cortex raphe anterior cingulate gyrus and left orbital cortex The following hypotheses based upon pilot data acquired using carbonyl-11C-WAY-100636 will be tested 1 Depressives have reduced 5-HT1A receptor binding relative to healthy controls 2 Bipolar depressives will have significantly greater reductions in 5-HT1A receptor binding than unipolar depressives with only unipolar relatives A pilot study in which bipolar depressives are treated with lithium or divalproex and then re-imaged will test the third hypothesis that 5-HT1A receptor binding will increase in bipolar subjects during mood stabilizer therapy
Finally because central 5-HT1A receptor density is down-regulated in rodents by corticosterone administration and by stress-mediated corticosterone secretion assessments of hypothalamic-pituitary-adrenal HPA axis activity which is commonly elevated in MDD and BD will be assessed to determine whether down-regulation of 5-HT1A receptors correlates with cortisol hypersecretion in mood disorders Because this down-regulation may play a compensatory role to reduce cortisol secretion neuroendocrine assessments of long-standing rather than acute hypercortisolism and of the pathophysiological diathesis to hypersecrete cortisol will be emphasized as providing the most sensitive correlates of reduced 5-HT1A receptor binding A medical control group with Cushings Disease will also be imaged to determine whether pathological elevation of glucocorticoid levels down-regulates 5-HT1A receptor expression in humans as it does in rats
However these data have the limitations that the subject samples studied in these preliminary post mortem and PET series have been small and that carbonyl-11CWAY-100635 uptake is difficult to quantitate in PET images Therefore these observations require replication in subject samples large enough to establish main effects of diagnostic subtype using a 5-HT1A receptor radioligand that can be validly quantitated A selective 5-HT1A receptor radioligand suitable for this purpose 18FFC-WAY100635 18FFCWAY has recently been developed at the NIH In addition a recently developed selective 5-HTT ligand 11C DASB provides a unique opportunity to image the 5-HTT in the same depressed sample
The proposed study will advance knowledge regarding the neurobiology of mood disorders by employing PET and 18FFCWAY and 11C DASB to compare 5-HT1A receptor BP between mood disordered and healthy control subjects in the mesiotemporal cortex raphe anterior cingulate gyrus and left orbital cortex The following hypotheses based upon pilot data acquired using carbonyl-11C-WAY-100636 will be tested 1 Depressives have reduced 5-HT1A receptor binding relative to healthy controls 2 Bipolar depressives will have significantly greater reductions in 5-HT1A receptor binding than unipolar depressives with only unipolar relatives A pilot study in which bipolar depressives are treated with lithium or divalproex and then re-imaged will test the third hypothesis that 5-HT1A receptor binding will increase in bipolar subjects during mood stabilizer therapy
Finally because central 5-HT1A receptor density is down-regulated in rodents by corticosterone administration and by stress-mediated corticosterone secretion assessments of hypothalamic-pituitary-adrenal HPA axis activity which is commonly elevated in MDD and BD will be assessed to determine whether down-regulation of 5-HT1A receptors correlates with cortisol hypersecretion in mood disorders Because this down-regulation may play a compensatory role to reduce cortisol secretion neuroendocrine assessments of long-standing rather than acute hypercortisolism and of the pathophysiological diathesis to hypersecrete cortisol will be emphasized as providing the most sensitive correlates of reduced 5-HT1A receptor binding A medical control group with Cushings Disease will also be imaged to determine whether pathological elevation of glucocorticoid levels down-regulates 5-HT1A receptor expression in humans as it does in rats
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-0047 | None | None | None |