Serotonin Function During Depression

Serotonin is a chemical involved in regulation of emotions, anxiety, sleep, stress hormones, and other body functions. The purpose of this study is to use a procedure called tryptophan depletion to study the function of serotonin in people with depression and in healthy volunteers. Major depressive disorder (MDD) has been associated with reduced functioning of central serotonergic systems. Tryptophan depletion (TD) is a procedure used to investigate the relationship between serotonergic function and depression. Evidence suggests that the mood lowering effects of TD depend upon family history and differences in genes for a specific protein called 5-HTTLPR. Healthy females with a particular gene for 5-HTTLPR and a family history of mood disorders appear to be at a greater risk for the development of depressive symptoms during TD. This study will use positron emission tomography (PET) scans of the brain to investigate the effect of variant 5-HTTLPR genotypes on response to TD. The relationship between 5-HTTLPR genotypes and the effect of TD on brain activity in individuals with different 5-HTTLPR genes will be determined. This study will also examine how the reduced serotonin function that occurs in MDD affects the brain's response to sensory stimulation. Participants in this study will be screened by telephone about their psychiatric and medical history, current emotional state, anxiety and sleep patterns, and family history of psychiatric disorders. At study entry, participants will have an interview, physical examination, electrocardiogram (EKG), and blood and laboratory tests. Menstruating women will have a pregnancy test and tests to determine menstrual phase and time of ovulation. At the second clinic visit, participants will undergo tests of intelligence and cognitive abilities and a magnetic resonance imaging (MRI) scan of the brain. Prior to Visits 3 and 4, participants will collect their saliva and urine. Menstruating women will have a pregnancy test. At Vi