Examination of Brain Serotonin Receptors in Patients With Mood Disorders

NCT00026832 | Completed

• 2 other identifiers: 02004702-M-0047
• Study Type: observational
• Target: 214
• Locations: 1 country
• Sites: 1

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 Cushing's disease will undergo imaging as a comparison group.

Conditions

Mood Disorder; Bipolar Disorder; Depression

Keywords

PET; Major Depression; MRI; Cerebral Blood Flow; Neuroendocrine; Bipolar Disorder; Serotonin1A; Mood Disorder; Major Depressive Disorder; MDD; Depression; Healthy Volunteer; HV; Normal Control

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• MDD SAMPLES:
• Seventy 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:
• Forty five 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:
• One hundred and four 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 12; 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.
• REMITTED MDD WITH AND WITHOUT A HISTORY OF PPD:
• (n=40; ages 18-40). These subjects are recruited, screened and diagnosed by collaboration under 95-M-0097, previously approved by IRB entitled An Endocrine Modal for Postpartum Mood Disorders. These subjects will have a history of DSM-IV MDD. Twenty will also have had a hypomanic/manic episode that occurred within three months of childbirth and twenty will have not had the latter within three months of childbirth. Women will have been well for a minimum of one year, have a regular menstrual cycle for at least three months, medication free (including birth control pill), have no history of puerperal suicide attempts or psychotic episodes requiring hospitalization. Any women with a current axis I psychiatric diagnosis will be excluded from participating in this protocol.

You may not qualify if:

• 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:
• serious suicidal ideation or behavior;
• psychosis to the extent that the ability to provide informed consent is in doubt;
• medical or neurological illnesses likely to affect physiology or anatomy;
• a history of drug or alcohol abuse within 1 year or a lifetime history of alcohol or drug dependence (DSM IV criteria);
• current pregnancy
• current breast feeding;
• 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 temporally after other major medical or psychiatric conditions will also be excluded, since their functional imaging results generally differ from those reported in primary MDD.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Drevets WC, Frank E, Price JC, Kupfer DJ, Holt D, Greer PJ, Huang Y, Gautier C, Mathis C. PET imaging of serotonin 1A receptor binding in depression. Biol Psychiatry. 1999 Nov 15;46(10):1375-87. doi: 10.1016/s0006-3223(99)00189-4.

  PMID: 10578452 BACKGROUND

• Gunn RN, Sargent PA, Bench CJ, Rabiner EA, Osman S, Pike VW, Hume SP, Grasby PM, Lammertsma AA. Tracer kinetic modeling of the 5-HT1A receptor ligand [carbonyl-11C]WAY-100635 for PET. Neuroimage. 1998 Nov;8(4):426-40. doi: 10.1006/nimg.1998.0379.

  PMID: 9811559 BACKGROUND

• Sargent PA, Kjaer KH, Bench CJ, Rabiner EA, Messa C, Meyer J, Gunn RN, Grasby PM, Cowen PJ. Brain serotonin1A receptor binding measured by positron emission tomography with [11C]WAY-100635: effects of depression and antidepressant treatment. Arch Gen Psychiatry. 2000 Feb;57(2):174-80. doi: 10.1001/archpsyc.57.2.174.

  PMID: 10665620 BACKGROUND

MeSH Terms

Conditions

Mood Disorders; Bipolar Disorder; Depression; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Mental Disorders; Bipolar and Related Disorders; Behavioral Symptoms; Behavior; Depressive Disorder

Study Officials

• Peter J Schmidt, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 14, 2001
• First Posted: November 15, 2001
• Study Start: October 4, 2001
• Study Completion: November 27, 2012
• Last Updated: July 5, 2018

Record last verified: 2012-11-27

Locations

US (1)