Serotonin Transporter Genetic Variation and Amygdalar Activation Correlates of Antidepressant Response

Inclusion Criteria:Inclusion criteria for Depressed Subjects 1. Ages 18-45 years and able to give voluntary informed consent. 2. Satisfy criteria for Major Depression using the Structured Clinical Interview for DSM-IV (SCID-IV). 3. 17-item Hamilton Depression Rating Scale score \> 18 4. Satisfy criteria to undergo an MRI scan based on MRI screening questionnaire 5. Able to be managed as outpatients for initial assessment and during treatment as ascertained by the following - 6. Symptoms not worsening by more than 5 point on either the HDRS during the course of the study. 7. No danger to self or others. 8. No psychotic symptoms. 9. If genetically the patient is a match/meets our requirements for the study. The ratio of s genotype and the l/l genotype is 3:2. Therefore, at some stage in the study we may have more of one type of genotype and may not be able to include a patient for whose genotype we already have sufficient number of subjects. Inclusion criteria for healthy subjects: 1. Ages 18-60 years and able to give voluntary informed consent. 2. No history of psychiatric illness or substance abuse or dependence as assessed by SCID for non-patients (SCID-NP). 3. No significant family history of psychiatric or neurological illness. 4. Not currently taking any prescription or centrally acting medications. 5. No serious medical or neurological illness as assessed by history, physical examination and laboratory examination including CBC and blood chemistry. 6. If genetically the subject is a match/meets our requirements for the study. The ratio of s genotype and the l/l genotype is 4:1. Therefore, at some stage in the study we may have more of one type of genotype and may not be able to include a patient for whose genotype we already have sufficient number of subjects. Exclusion Criteria: * Exclusion criteria for patients 1. Meeting DSM-IV criteria for schizophrenia, schizophreniform disorder, schizoaffective disorder, atypical psychosis, mental retardation, or organic mental (including organic mood) disorder. 2. Use of neuroleptic past 2 weeks 3. Use of antidepressants in the past 2 weeks. If on fluoxetine in the past then should not have been on this medication for 4 weeks. 4. Use of mood stabilizers in the past 2 weeks 5. Use of benzodiazepines in the past 2 weeks. 6. Acutely suicidal or homicidal or requiring inpatient treatment. 7. Meeting DSM-IV criteria for other substance dependence within the past year, except caffeine or nicotine. The criteria will be evaluated by interview and urinary toxicology screening initially and on test days. 8. Use of alcohol in the past 1 week. 9. No serious medical or neurological illness as assessed by physical examination and laboratory examination including CBC and blood chemistry. 10. Current pregnancy or breast feeding. 11. Metallic implants. 12. Previously known positive HIV blood test as reported by the subject.