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.