Inclusion Criteria:
MDD Group
* Male or female aged 18-65 years;
* Ability for participant to comply with the requirements of the study as determined by the PI;
* Capacity to provide informed consent;
* Meets diagnostic criteria for current MDD according to the Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5);
* In a current major depressive episode (MDE) of at least moderate severity according to DSM-5;
* Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year).
* Women of childbearing potential must have a negative pregnancy test at screening and prior to the infusion.
HC Group
* Male or female aged 18-65 years;
* Capacity to provide informed consent;
* Women must be using a medically accepted reliable means of contraception (if using an oral contraceptive medication, they must also be using a barrier contraceptive) or not be of childbearing potential (i.e., surgically sterile, postmenopausal for at least one year).
* Ability for participant to comply with the requirements of the study as determined by the PI;
Exclusion Criteria:
MDD Group
* Current or history of schizophrenia or other psychotic disorder/episode, bipolar disorder, neurodevelopmental disorder, or neurocognitive disorder;
* Current major depressive disorder with psychotic features;
* Substance use disorder within the past 2 years\*;
* Lifetime history of ketamine use disorder;
* Antidepressant medication within 2 weeks of Baseline (4 weeks for fluoxetine);
* Severe current illness as reflected by a CGI score \>5;
* Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
* Clinically significant abnormalities of laboratories, physical examination, or ECG;
* Positive urine toxicology screen for drugs of abuse at the time of screening, except cannabis;
* Women who plan to become pregnant, are pregnant or are breast-feeding (because the medical risk of using ketamine during pregnancy and breast-feeding is unknown);
* Active suicidal intent or plan; CSSRS score \>2;
* Any contraindications to MRI, including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more;
* Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the participant or the quality of the data.
HC Group
* Current or history of any psychiatric, neurodevelopmental disorder, or neurocognitive disorder;
* Substance use disorder within the past 2 years\*;
* Any unstable medical illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease); endocrinologic, neurologic (including history of severe head injury), immunologic, or hematologic disease;
* Clinically significant abnormalities of laboratories or physical examination;
* Positive urine toxicology screen for drugs of abuse at the time of screening, except cannabis;
* Current pregnancy;
* Women who are breast feeding;
* Active suicidal intent or plan; CSSRS score \>2;
* Any contraindications to MRI, including claustrophobia, any trauma or surgery which may have left magnetic material in the body, magnetic implants or pacemakers, and inability to lie still for 1 hour or more.
