Protocol Number: 04-M-0002

Title:

The Functional Neuroanatomy of Emotion Regulation in Major Depressive Disorder (MDD)

Number:

04-M-0002

Summary:

This study will perform functional magnetic resonance imaging (fMRI) to study how the brain processes emotions in healthy control subjects and in people with major depressive disorder (MDD). It will examine what happens in the brain when people look at faces with different emotional expressions.

Healthy, normal volunteers and patients with MDD, either currently depressed or in remission, who are right-handed and between 18 and 50 years old may be eligible for this study. Healthy volunteers must have no known first-degree relatives with mood disorders. Candidates will be screened with the following:

- Medical and psychiatric history, including an electrocardiogram and blood and urine tests

- Family psychiatric history

- Psychiatric interview about current and past disturbances of mood, sleep, energy, work and school performance, and social relationships; history of paranoia, panic attacks, obsessions, compulsions, suicidal thoughts, eating disturbances, and alcohol or drug abuse

- Ratings of current symptoms of depression, anxiety and negative thinking, history of alcohol and tobacco use, physical movements, socioeconomic status, and overall level of functioning

- Neuropsychological tests to assess general intelligence, handedness, and cognitive abilities, including memory and concentration

All participants will have an fMRI scan to image brain structure while the participant performs a task while looking at pictures of faces. MRI uses a strong magnetic field and radio waves to produce images of the brain. The subject lies on a narrow bed with a plastic-encased metal coil close to the head. The bed slides into the scanner - a small tunnel about 6 feet long. Electrodes are placed on two fingers and on the inside of each wrist to measure certain heart and nervous system functions while in the scanner. During the scanning procedure, the subject is shown pictures of faces and asked to indicate whether or not the face is one of two target faces they were shown before entering the scanner. During the procedure, blood flow in different areas of the brain is measured. This completes participation for normal volunteers and MDD patients in remission.

Patients who are currently depressed will be treated with the anti-depressant medication sertraline (Zoloft). Treatment begins after screening and the first fMRI scan and continues for 8 weeks. During this time, patients come to the NIH clinic once a week to monitor progress on the medication. Follow-up includes a review of symptoms, clinical progress, and medication side effects. At the end of 8 weeks, a repeat fMRI scan is performed. At the end of the study patients are returned to the care of their primary physician or psychiatrist or given an appropriate referral.

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): None

Eligibility Criteria:

INCLUSION CRITERIA - HEALTHY VOLUNTEERS:

Healthy Control Sample (n = 30, phase 1; n = 15, phase 3): Right-handed subjects (ages 18-50) will be selected who have not met criteria for any major psychiatric disorder, have no known first-degree relatives with mood disorders, and have a current score on the Hamilton Depression Rating Scale (HDRS; 17 items) in the not depressed range (less than or equal to 7). Control subjects will be matched to depressed subjects for age, gender, and education.

INCLUSION CRITERIA - MDD SAMPLES:

MDD Sample-Currently Depressed (n = 30, phase 1; n = 15, phase 3): Right-handed subjects (ages 18-50) will be selected with primary MDD currently depressed by DSM-IV criteria for recurrent MDD and current HDRS score in the moderately-to-severely depressed range (greater than or equal to 18).

MDD Sample-Remitted Depressed (n = 15, phase 2): Right-handed subjects (ages 18-50) will be selected with a past history of MDD by DSM-IV criteria.

EXCLUSION CRITERIA:

Subjects will be recruited who are drug-naive or who have not received psychotropic drugs for at least 3 weeks (8 weeks for fluoxetine) prior to scanning. Effective medications will not be discontinued for the purposes of the study. 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 conditions or concomitant medications that are likely to influence cerebral blood flow or neurological function including cardiovascular, respiratory, endocrine and neurological diseases, 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 (as documented by pregnancy testing prior to scanning), f) general MRI exclusion criteria. Additional exclusion criteria applied to control subjects are: a) subjects with a current or past history of other axis I psychiatric conditions, b) subjects with first-degree family members with current or past history of mood disorder.

Subjects beyond age 50 are excluded to reduce the biological heterogeneity encompassed by the MDD criteria, and to reduce the variability of the BOLD signal. 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.

Special Instructions: Currently Not Provided

Keywords:

fMRI

Habituation

Extinction

Amygdala

Emotion

Major Depressive Disorder

Medial Prefrontal Cortex

Backward Masking

Depression

MDD

Healthy Volunteer

HV

Recruitment Keywords:

None

Conditions:

Major Depressive Disorder

Investigational Drug(s):

None

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:

Morris JS, Buchel C, et al. Parallel neural responses in amygdala subregions and sensory cortex during implicit fear conditioning. Neuroimage. 2001 Jun;13(6 Pt 1):1044-52. Erratum in: Neuroimage 2001 Aug;14(2):529. PMID: 11352610

Cahill L, et al. Sex-related difference in amygdala activity during emotionally influenced memory storage. Neurobiol Learn Mem. 2001 Jan;75(1):1-9. PMID: 11124043

Drevets WC. Prefrontal cortical-amygdalar metabolism in major depression. Ann N Y Acad Sci. 1999 Jun 29;877:614-37. Review. PMID: 10415674

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

Search The Studies | Help | Questions |
Clinical Center Home | NIH Home

Warren Grant Magnuson Clinical Center (CC)
National Institutes of Health (NIH)
Bethesda, Maryland 20892. Last update: 10/21/2004