Brain Imaging, Genetics and Treatment for Major Depression

Background: \- Antidepressants help many people with depression, however, some do not seem to benefit as much. Currently, it is not possible to determine who will improve with certain antidepressants. Studies have shown that genes may influence whether an antidepressant works for an individual. Other studies have shown that depressed people tend to have lower levels of a chemical called glutamate in parts of their brain, and that glutamate levels increase after recovering from depression. Researchers want to study the antidepressant citalopram (Celexa) to see how it affects glutamate levels in the brain. They also want to study how a person s genes affect their response to this treatment. Objectives: \- To see whether glutamate levels and certain genes affect how a person responds to a particular antidepressant medication. Eligibility: \- Individuals between 25 and 55 years of age who have been diagnosed with major depression (without psychotic features). Participants may not have tried more than three antidepressant treatments. Design: * Participants will be screened with a physical exam and medical history. They will answer questions about mood and current feelings of depression, as well as family history of depression. Blood and urine samples will be collected. * This study will have two phases. The first phase may last up to 7 weeks depending on current antidepressant use and involves one to seven outpatient visits. The second phase lasts 8 weeks and involves five outpatient visits, one every 2 weeks. * In the first phase, participants will stop taking their current antidepressant medications for at least 2 weeks before the next phase of the study. Participants who are on fluoxetine (Prozac) will need to be off it for 6 weeks. * At the end of this phase, participants will have brain imaging studies to look at brain function and chemistry. * In the second phase, participants will take citalopram at the standard dose. They will answer questions about mood a