Serotonin Function During Depression

NCT00033787 | Completed

• 2 other identifiers: 02016202-M-0162
• Study Type: observational
• Target: 450
• Locations: 1 country
• Sites: 1

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 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. ...

Conditions

Depression, Involutional; Healthy

Keywords

Depression; Tryptophan Depletion; PET; Serotonin; Pathophysiology; Emotional Stimuli; GABA MRS; MDD; 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:

• subjects with rMDD (ages 18-60) will be selected. Remission is defined as a period of at least three months during which the subject has not taken an antidepressant agent, with Hamilton Depression Rating Scales (HDRS; 21-item) scores in the non-depressed range (less than 8), and with no more than one clinically significant depressive symptom. Additional 17 subjects with current MDD will be selected for the GABA MRS study.
• Twenty-four healthy subjects (ages 18-60) without a known personal or family history of psychiatric disorders in first-degree relatives will be selected.

You may not qualify if:

• 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);
• f) current breast feeding (tryptophan depletion);
• g) are smokers;
• h) current suicidal ideation or behavior;
• 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.
• j) other current axis I diagnoses beside unipolar major depressive disorder;
• k) 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.

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)

• 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.

  PMID: 2574463 BACKGROUND

• Rajkowska 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.

  PMID: 10331101 BACKGROUND

• Coppen 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.

  PMID: 4123618 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: April 9, 2002
• First Posted: April 10, 2002
• Study Start: April 5, 2002
• Primary Completion: April 30, 2005
• Study Completion: April 30, 2005
• Last Updated: July 2, 2017

Record last verified: 2009-06-08

Locations

US (1)