Functional MRI Before and After Treatment for Depression

You were selected as a possible participant because you are suffering from a major depressive
episode, and you have not previously tried the medication used in this study to treat
depression. Approximately 60 subjects will participate in this study: 30 subjects who are
currently suffering from a major depressive episode and 30 subjects who have never suffered
from a major depressive episode.

If you choose to participate, you will be seen at the clinic for a total of five times plus
three MRI scans. You will be seen once for a screening visit. If you choose to enroll, you
will return a week later for the baseline visit and again at weeks 2, 4 and 8. Around the
time of week one (baseline), week 2 and week 8 you will also undergo an MRI scan of the
brain.

Screening Visit: The study physician and the research study staff will first screen you for
eligibility. The screening visit includes meeting with a physician for a discussion of your
medical history and current medications, taking your blood pressure, and checking your
weight. Women of childbearing potential will also have a urine pregnancy test. You will meet
with a member of the research staff for an interview to collect information about your
depression and other psychiatric symptoms you have experienced. The purpose of the interview
is to confirm your diagnosis and assess the current severity of your depression. The
screening visit will take approximately 2 hours.

Week 1 (baseline): If you are eligible to continue with the study, you will return to the
clinic within 7 days for a baseline visit. At your baseline visit, you will complete several
tests to assess your memory and concentration. These tests are being conducted because
problems with memory and concentration are common in people who are depressed and the
researchers want to find out if there is a difference in your memory and concentration before
and after taking the study medication. We also wish to compare the results to any findings
from the brain imaging. Following the baseline visit, you will begin treatment with the
antidepressant citalopram. The starting dose is 20 mg once per day.

Week 1 MRI: Around the time of your week one (baseline) visit and before starting
medications, you will have your first MRI.

Week 2 visit: At the end of your second week, the study physician will meet with you to
assess your overall condition. Your antidepressant medication will be counted to verify that
you have been taking it as prescribed. Your dose will likely not change, but it is possible
that it will be increased to as much as 40 mg. If you are experiencing side effects, your
dose may be decreased. We will provide you with enough medication to last until your next
visit.

Week 2 MRI: Around the time of your week 2 visit you will have your second MRI.

Week 4 visit: The study physician will meet with you to assess your overall condition. Your
antidepressant medication will be counted to verify that you have been taking it as
prescribed. The dose may be left unchanged, increased up to a total of 40 mg daily or
decreased, if you are experiencing side effects (to a minimum of 20 mg daily). You will also
be asked about any other medications you have taken since your last visit. We will provide
you with enough medication to last until your next visit.

Week 6 (Telephone check-in): The study physician will check in with you by telephone to
assess your overall condition. The dose of the citalopram may be left unchanged, increased to
a maximum of 60 mg daily or decreased (to a minimum to 20 m daily) if you are experiencing
side effects.

Week 8: (End-of-study visit) In addition to the usual visit procedures, the end-of-study
visit will include repeated tests of memory and concentration. The study physician will also
discuss recommendations for further treatment of your depression. No study medication will be
dispensed at this visit.

Week 8 MRI: Around the time of your week 8 visit you will have your third and final MRI.

Inclusion Criteria:

Patients will be aged 18-65, have no significant neurologic history, must meet DSM-IV
criteria for a diagnosis of major depression and be free of antidepressant or other
psychotropic medication for a minimum of two weeks before enrollment. If a subject is
talking psychiatric medication he/she may be weaned off of the medication by their treating
physician prior to study enrollment. Such a course of action would only be advised if the
current medication was not considered to be of any benefit to the subject. In particular,
if a patient is on antidepressant medication which is of benefit, we would not advise
tapering off medication -- and subsequent risk of relapse -- in order to participate in the
study. The same line of thinking applies to all psychiatric diagnoses and associated
medications candidate subjects may be taking.

Exclusion Criteria:

1. Significant head trauma with loss of consciousness.

2. Active abuse of alcohol or illegal substances.

3. Excluded psychiatric diagnoses include: Bipolar Affective Disorder, primary psychotic
disorders (Schizophrenia, Schizoaffective disorder), Obsessive-Compulsive Disorder

4. Pregnant or nursing women.

5. Any contraindication to being scanned in the 3T scanner at the Lucas Center such as
having a pacemaker or any implanted device that has not been cleared for scanning at 3
Tesla.

6. Any significant neurologic history (i.e. seizure, stroke, multiple sclerosis).

7. Use of psychotropic medications within 2 weeks of enrollment.