Alpha-Amino-3-Hydroxy-5-Methyl-4- Isoxazole Propionic Acid Receptor Components of the Anti-Depressant Ketamine Response

Inclusion Criteria Substudy #2: * Right-handed as determined by the Edinburgh Handedness Inventory * Current depression as indicated by a score greater than 17 on the full Hamilton Depression Rating Scale * Anti-depressant resistant depressive symptoms, defined by a history of failure of one or more adequate anti-depressant trials * Individuals who have previously received ketamine must have had a positive response. Individuals who report reduced depressive symptoms will be treated as ketamine responders and entered directly into the closed label trial. * Participants will meet DSM-5 Criteria for MDD as determined by the SCID-5 * All participants given ketamine must be engaged in treatment outside of the research protocol. Those who are not currently in treatment may be referred for treatment. * Individuals who are receiving pharmacotherapy for depression must have been receiving the current medication and dose for 4 weeks before randomization. In addition, they should have a plan to continue the current regime of pharmacotherapy for the duration of the trial. * Individuals who are receiving psychotherapy must have been in treatment for four weeks and should have a plan to continue the current regime of psychotherapy for the duration of the trial. * Willing to refrain from caffeine, drug and alcohol use for one week prior to each MRI session * Females will be included if they are not pregnant or breastfeeding and agree to utilize a medically accepted birth control method (to…