Imaging Antidepressant vs. Cognitive Behavior Therapy Effects on Unipolar Depression (ssrifMRI)

Inclusion Criteria:

1. Meet DSM-IV criteria for major depressive disorder (one or more lifetime episodes, separated by at least two months of a return to normal functioning, in a current episode).
2. Male or female outpatients between the ages of 18 and 55 at time of enrollment.
3. Females only must be surgically sterile, post-menopausal for at least one year, or not pregnant and using a method of birth control that is acceptable to the investigator.
4. Have a total score of 14 or more on the first 17-items of the HRSD at both the initial and secondary interviews.
5. Be in reasonably good health. Patients with hypothyroidism, diabetes, high blood pressure, chronic respiratory, or other medical conditions may be considered candidates for study enrollment at the discretion of the investigator if their conditions are stable, they have been receiving standard therapies for the treatment of the condition, the prescribed dose and regiment of medication has been stable for at least 3 months, and all appropriate clinical and lab parameters are within normal limits for the condition that are clinically acceptable to the investigator
6. Be free of prescription psychotropic medications for two weeks (four weeks for fluoxetine) before study entry.
7. Provide written informed consent

Exclusion Criteria:

1. Being unable to complete questionnaires written in English, representing an active suicide risk (see below), active alcohol or drug dependence, having any eye problems or difficulties in corrected vision, having a North American Adult Reading Test (NAART) equivalent FSIQ < 85.
2. Pregnant women and those planning to become pregnant during the first 11 months after intake will also be excluded from the study. Pregnancy will be determined by self-report at the interview and by a pregnancy test at the time of the MRI scan. There will be no cost to the participant for the pregnancy test.
3. People who have metallic foreign objects in their body, such as aneurysm clips or pacemakers, as well as individuals prone to panicking in enclosed spaces will be excluded from the study. Subjects with a questionable history of metallic fragments will also be excluded.
4. Participants who are taking psychotropic medications, particularly antidepressant medications within two weeks of study entry (4 weeks for fluoxetine) will be excluded.
5. Participants will not be excluded on the basis of herbs, supplements, and other prescription or over the counter drugs other than those noted. HIV serostatus will not be evaluated for the research study.
6. At the initial screening visit, if girth seems to present a potential issue for the MRI, than width of participant will be assessed using a hula-hoop that is approximately the same diameter as the MR scanner. If subject exceeds the width of the hula-hoop, then they will be excluded from the study.