NIH Clinical Research Studies

Protocol Number: 02-M-0047

Active Accrual, Protocols Recruiting New Patients

Title:
Serotonin1A Receptor and Serotonin Transporter Imaging In Mood Disorders
Number:
02-M-0047
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 Cushing's disease will undergo imaging as a comparison group.

Sponsoring Institute:
National Institute of Mental Health (NIMH)
Recruitment Detail
Type: Active Accrual Of New Subjects
Gender: Male & Female
Referral Letter Required: No
Population Exclusion(s): Children

Eligibility Criteria:
INCLUSION CRITERIA:

MDD SAMPLES:

Sixty subjects (ages 18 to 60) with MDD will be selected who additionally meet criteria for one of 3 subgroups:

A) MDD, Currently depressed with FPDD, as defined by DSM-IV criteria for recurrent MDD, currently in a major depressive episode, who have a first degree relative with MDD but no first degree relatives with mania, alcoholism, or antisocial personality disorder.

B) MDD, Currently in remission with a history of FPDD, defined as a period of at least six months with no more than one clinically significant symptom, and during which time subjects were not taking an AD agent. Subjects will thus meet the historical criteria for recurrent MDD (DSM-IV). We will also require that subjects previously had a least one antidepressant drug trial, to ensure that the severity of previous episodes warranted treatment.

C) MDD, Currently depressed, non-FPDD. To assess the specificity of the findings in MDD to FPDD, a sample meeting criteria for MDD, currently in a depressive episode, but not FPDD will also be imaged.

BIPOLAR DEPRESSED SAMPLE:

Twenty subjects (ages 18 to 60) who meet DSM-IV criteria for bipolar disorder and are currently in a major depressive episode. Subjects may be inpatients or outpatients. Because effective treatment will not be discontinued for the purposes of this protocol, subjects will be identified who have never been treated or who have discontinued medication due to lack of efficacy, noncompliance, physician order or other reasons prior to study entry.

HEALTHY, LOW RISK, CONTROL SAMPLE:

Forty subjects (ages 18 to 60) who have not met criteria for any major psychiatric disorder. The control subjects will have no known first or second degree relatives with mood disorders.

CUSHINGS DISEASE CONTROL SAMPLE:

Ten subjects (ages 18 to 60) with probable Cushing's Disease will be recruited who have both clinical and biochemical evidence of hypercortisolism (including urinary free cortisol excretion higher than the upper limit of normal (greater than 248) nmole/day, and marked central adiposity, cutaneous atrophy, proximal myopathy, and large purple striae). The diagnosis of probable Cushing's Disease will also have been established prior to referral via CRH and ACTH.

MENSTRUALLY-RELATED DYSPHORIC DISORDER SAMPLE:

(n equals 30; ages 18-50). These females are recruited, screened and diagnosed by collaboration under protocol number 81-M-0126, previously approved by IRB, entitled 'The Phenomenology and Biophysiology of Menstrually Regulated Mood and Behavioral Disorders', principal investigator, David Rubinow, M.D. As described in that protocol these subjects must have a regular menstrual cycle lasting 21 - 33 days and meet the following criteria: 1) history within the last two years of at least six months with menstrually-related mood or behavioral disturbances of at least moderate severity - that is, disturbances that are distinct in appearance and associated with a notable degree of subjective distress; 2) a 30 percent increase in mean negative mood ratings (relative to the range of the scale employed) in the premenstrual week compared with the week following the end of menses in at least two of the three cycles; 3) age 18 to 50; 4) not pregnant and in good medical health; 5) regular menses.

EXCLUSION CRITERIA:

Subjects must not have taken antidepressant or other medications likely to alter monoamine neurochemistry or cerebrovascular function for at least 3 weeks (8 weeks for fluoxetine) prior to scanning. Subjects being scanned at two points or the same point twice in their menstrual cycle must not have taken birth control pills for at least 6 months prior to scanning. However, effective medications will not be discontinued for the purposes of this study. Instead, subjects will be recruited who are not currently receiving psychotropic drugs. Subjects will also be excluded if they have:

a) serious suicidal ideation or behavior;

b) psychosis to the extent that the ability to provide informed consent is in doubt;

c) medical or neurological illnesses likely to affect physiology or anatomy;

d) a history of drug or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria);

e) current pregnancy

f) current breast feeding;

g) general MRI exclusion criteria;

h) previous exposure to ecstasy (i.e. MDMA) which has neurotoxic effects on 5-HTT expressing neurons.

Subjects beyond age 50 are excluded from the MRMD sample due to peri-menopausal status and subjects beyond age 60 are excluded to reduce the biological heterogeneity encompassed by the MDD criteria, since depressives whose age-at MDD-onset is later than 60 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 temporarily after other major medical or psychiatric conditions will also be excluded.

Special Instructions: Currently Not Provided
Keywords:
PET
Major Depression
MRI
Cerebral Blood Flow
Neuroendocrine
Bipolar Disorder
Serotonin1A
Recruitment Keywords:
Mood Disorder
Major Depressive Disorder
MDD
Depression
Healthy Volunteer
HV
Normal Control
Conditions:
Mood Disorder
Investigational Drug(s):
15 O-water
FCWAY
Investigational Device(s):
None

Contacts:
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

Citations:
PET imaging of serotonin 1A receptor binding in depression

Tracer kinetic modeling of the 5-HT1A receptor ligand [carbonyl-11C]WAY-100635 for PET

Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment

Active Accrual, Protocols Recruiting New Patients

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