Brain Imaging Techniques That Predict Antidepressant Responsiveness

This is a single site, controlled, double-blind study of outpatients. There are two arms:

1. Forty participants who have a current Diagnostic and Statistical Manual of Mental
Disorders, 4th edition, text revised (DSM-IV-TR) diagnosis of Major Depression will be
recruited. These subjects will be randomized to receive one of two antidepressant
medications: Fluoxetine or Venlafaxine ER for the duration of the study. Subjects will
gradually be titrated onto the medications and will be seen in the clinic up to 18 times
for medication checks, to monitor side effects and depressive symptoms, including
suicidal ideation. In the event of suicidal ideation, subjects will be withdrawn from
the study and referred for immediate treatment.

2. Twenty normal control subjects with no current or past DSM-IV-TR diagnosis and will
receive no medication. Normal control subjects will have up to 5 visits while in the
study.

Subjects will contact study staff to complete a phone screen and then eligible subjects will
complete a clinic screen. Subjects will then be scheduled to attend the magnetic resonance
imaging (MRI) simulation visit and if subjects continue to meet entrance criteria, they will
be scheduled for the first MRI. Following the first MRI, subjects in the medication
conditions will begin receiving medication.

All subjects will undergo 3 functional magnetic resonance imaging (fMRI)s during the study:
at the beginning of the study, approximately 8 weeks and 26 weeks later. During the MRI,
subjects will view slides with positive and negative emotional content. Subjects will
complete various clinical interviews or rating scales assessing mood and side effects at each
of the visits.

Inclusion Criteria:

- Intervention Group:

- Right-handed,

- Be able to lie still on their back for about 120 minutes,

- Meet DSM-IV criteria for major depression (single or recurrent),

- Have had depressive symptoms for at least 1 month prior to screen visit,

- Must score an 18 or above on the Hamilton-D at both the initial screening visit
and first fMRI scanning session,

- Able to understand and speak English.

- Control Group: same as above with the exception of no diagnosis of psychiatric
disorder.

Exclusion Criteria:

- Any history of seizures,

- Current medical disorders that might make interpretation of scan data difficult,

- Diabetes requiring insulin treatment,

- A serious heart disorder or subjects who have had a heart attack within the last 3
months,

- Subjects who meet DSM-IV criteria for alcohol/drug abuse or dependence within the last
six months,

- Other current DSM-IV Axis I or Axis II diagnoses,

- A personal or family history of bipolar disorder,

- Current use of medication that affects central nervous system (CNS) function,

- Participation in the last 30 days in a clinical study involving an investigational
drug,

- A subject with metallic implants, such as prostheses, shrapnel or aneurysm clip-S, or
persons with electronic implants, such as cardiac pacemakers. The magnetic field
generated by the MRI machine can cause a displacement or malfunctioning of these
devices.

- A subject who is claustrophobic,

- Female subjects who are pregnant,

- A subject at serious risk for suicide,

- Diagnosis of cancer in the past 3 years and/or has active neoplastic disease,

- Nonresponse to 2 adequate trials of antidepressant treatment,

- Nonresponse to 2 adequate trials of an empirically supported psychotherapy.