PET Biomarkers in Treatment Resistant Depression

INCLUSION: 1. Primary diagnosis of Major Depressive Disorder 2. Subjects aged 18-65 3. Depressed subjects must have Treatment-Resistant Depression (TRD) two previous adequate antidepressant treatment trial failures within the current depressive episode from different classes 4. Minimum baseline Montgomery Asberg Depression Rating Scale (MADRS) score of 22 5. Signs informed consent form 6. Subjects must be willing to be have a PET scan 7. Subjects must be antidepressant medication free for 3 weeks prior to PET scan EXCLUSION 1. Significant past or present neurological disorder, including seizures, stroke, or head trauma 2. History of bipolar disorder, psychosis, schizoaffective disorder, or schizophrenia 3. Moderate or high level of suicide risk, as determined by a score of 3 or 4 on item 3 of the HAM-D scale. Also excluded will be those who present a significant suicide risk by history or current psychiatrist's assessment. 4. Personality disorder which might interfere with compliance or increase suicide risk 5. Alcohol or drug abuse or dependence in the past year; history of lifetime IV drug use or use of methylene diamine methamphetamine (MDMA or "ecstasy") more than twice 6. Current thyroid dysfunction (past or currently treated dysfunction is acceptable) 7. Clinically significant or unstable medical conditions or laboratory abnormalities, including hypertension (repeated BP \> 140 systolic, \> 90 diastolic) 8. Intake of investigational (unapproved) drug in the past 3 months 9. Electroconvulsive therapy (ECT) in three months prior to screening 10. Use of Vagal Nerve Stimulation (VNS) 11. Positive drug of abuse screen 12. Anticoagulant treatment which cannot be discontinued for 10 days prior to PET scanning 13. Pregnancy, currently lactating; planning to conceive during the course of study participation or abortion in the past two months. 14. Dementia (clinical and neurocognitive criteria) 15. Claustrophobia of a severity which would not permit the participant to undergo an MRI or a PET scan 16. Recent (\< 7 days) consumption of Ayahuasca Tea or other South American non-standard decoction. 17. Presence of metallic devices, implants and other contraindications to scanning 18. Current, past or anticipated exposure to radiation, that may include being badged for radiation exposure in the workplace or participation in nuclear medicine research protocols 19. Smokers (use of tobacco products in the previous 3 months) 20. Potential participants having taken an antidepressant medication in the last 3 weeks. Participants otherwise eligible may elect to discontinue medication which has not been significantly helpful according to their report, their current psychiatrist's report (if available), and the evaluating psychiatrist. No patient will be asked to discontinue an effective antidepressant medication to participate. 21. History of previous MAO-I treatment