Behavioral and Electrophysiological Effects of Ketamine in Treatment-Resistant Depression

Inclusion Criteria (MDD Subjects): * All genders, races, and ethnic origins, aged between 18 and 70; * DSM-5 diagnostic criteria for MDD (diagnosed with the use of the Structured Clinical Interview for DSM-5 (SCID-5)); * A score of ≥32 on the Inventory of Depressive Symptomatology-Clinician Rated (IDS-C30). * Capable of providing written informed consent, and fluent in English; * Right-handed; * Treatment Resistant (as assessed using the MGH Antidepressant Response Questionnaire) * Have already decided to receive ketamine treatment as part of their standard clinical care Inclusion Criteria (Control Subjects): * All genders, races, and ethnic origins, aged between 18 and 70; * Absence of medical, neurological, and psychiatric illness (including alcohol and substance abuse), as assessed by subject history and a structured clinical interview (SCID-I/NP); * A baseline Quick Inventory of Depressive Symptomatology (QIDS) score ≤ 5; * A baseline Hamilton Depression Rating Scale (HDRS) score ≤ 7; * Capable of providing written informed consent, and fluent in English; * Right-handed; * No first-degree relative with mood or psychotic disorder. Exclusion Criteria (All Subjects): * Serious or unstable medical illness, including cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic disease; * History of seizure disorder; * History or current diagnosis of any of the following DSM-5 psychiatric illnesses: schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, substance abuse disorder; * Clinical or laboratory evidence of hypothyroidism, hyperthyroidism, or other thyroid disorder that is not controlled by medication; * Substance use assessed by physician as dangerous for ketamine treatment; * Untreated glaucoma; * Complex post-traumatic stress disorder (PTSD) with dissociation; * Patients with a lifetime history of electroconvulsive therapy (ECT). * Participants with a lifetime history of ketamine use.