Brain Connectivity in Treatment Resistant Depression

Eligibility Details: Inclusion Criteria - TRD: 1. age: 18 - 65 yrs.; 2. satisfy criteria for DSM-IV major depressive disorder (MDD); 3. 17-item Hamilton Depression Rating Scale (17-item HDRS) score > 18; 4. treatment resistance depression as defined as report of inadequate response (patient report of minimal improvement or nonresponse) despite past treatment with at least 2 different classes of antidepressants acting on the 5-HT and/or DA monoamine systems(except MAOIs) (as determined with the Antidepressant Treatment History Form (ATHF)20 with score of >3 on each of the items and verified by medical records if available); 5. able to give informed consent; 6. no use of alcohol in the past 1 week and negative urine toxicology screen; 7. MAOI treatment indicated as assessed by an independent psychiatrist not affiliated with the study; 8. voluntary consent to treatment with an MAOI after reviewing all other options and agree to follow safeguards and precautions during treatment. Inclusion criteria for healthy subjects 1. ages 18-65 years and ability to give voluntary informed consent; 2. no history of psychiatric illness or substance abuse or dependence; 3. no significant family history of psychiatric or neurological illness; 4. not currently taking any prescription or centrally acting medications; no use of alcohol in the past 1 week; 5. and no serious medical or neurological illness. Exclusion Criteria - TRD: 1. schizophrenia, schizoaffective or primary anxiety disorder; 2. serious medical or neurological illness; 3. history of significant head injury; 4. on fluoxetine treatment; 5. on lithium or have received ECT or rTMS in the last 3 months to avoid long-term effects of such medications; 6. substance or alcohol dependence in the past 6 months or substance abuse in the past 3 months; 7. unable to give informed consent. Exclusion criteria for both groups: 1. pregnant or breast-feeding; 2. metallic implants or other contraindication to MRI.