Recently (R)-[(11)C]rolipram has been successfully used to image PDE4 in animals and humans. We have confirmed that PDE4 levels can be measured reliably by performing (R)-[(11)C]rolipram positron emission tomography (PET) with multiple arterial sampling even in rats. The primary purpose of this protocol is to compare PDE4 levels before and after starting a selective serotonin reuptake inhibitor (SSRI) sertraline, citalopram or escitalopram in unmedicated depressed patients. The secondary purpose is to compare PDE4 levels between unmedicated depressed patients and healthy subjects. Baseline scans of patients will be used for this second comparison. For the first time, these comparisons have become possible with the new PET agent (R)-[(11)C]rolipram. The findings will advance understanding on the role of cAMP signal transduction system in the pathology of depression and the mechanisms of antidepressant effects.