* INCLUSION CRITERIA:
Phase I: Groups 1-3 and 5 (Patients)
1. 18 to 70 years of age.
2. A level of understanding sufficient to agree to all required tests and examinations, sign an informed consent document and verify understanding by a score \>= 90% on the Baseline consent quiz
3. Individuals who are able to get pregnant must be willing to remain sexually abstinent or use at least one form of effective birth control during participation in Phase I.
4. Additional Criteria for Group 1 (Active Crisis): Agree to be hospitalized
Phase I: Group 4 (Healthy Volunteers)
1. 18 to 70 years of age.
2. A level of understanding sufficient to agree to all required tests and examinations, sign an informed consent document.
3. Individuals who are able to get pregnant must be willing to remain sexually abstinent or use at least one form of effective birth control during participation in Phase I.
Phase II: Group 1 (Active Crisis) and Group 5 (Suicide Ideators)
1. Patients must have completed Study Phase I as a participant in Group 1 or 5
2. Participants must verify understanding of the protocol by a score \>= 80% on the Ketamine Response consent quiz.
3. Patients in Group 1 or 5 must report at least minimal suicidal ideation, depressive or anxiety symptoms to be eligible for this phase.
* MADRS score of over 10 (10 used as an outcome measure for remission)126
* OR HAMA score of over 7 (7 used as an outcome measure for remission)127
* OR SSI score of 2 or more (indicates any residual suicidal thoughts)
4. Individuals who are able to get pregnant must be willing to remain sexually abstinent or use at least one form of effective birth control during participation in Phase II.
Phase III: Group 1 (Active Crisis) and Group 5 (Suicide Ideators)
1. Participants must have met all inclusion criteria for and completed Study Phase II as a participant in Group 1 (active crisis) or Group 5 (Suicide Ideators).
2. Individuals who are able to get pregnant must be willing to remain sexually abstinent or use at least one form of effective birth control during participation in Phase III.
EXCLUSION CRITERIA:
Phase I: Groups 1-3 and 5 (Patients)
1. Current psychotic features or cognitive impairment that would preclude understanding of the consenting process or tests/examinations.
2. Current drug or alcohol dependence
3. Currently intoxicated or under the acute effects of an illicit substance will not be consented into the study.
4. Pregnant or nursing individuals or those who plan to become pregnant.
5. Serious, unstable medical conditions/problems including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including blood pressure, ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease.
6. Clinically significant abnormal laboratory tests.
7. Positive HIV test
8. Participants who, in the investigator s judgment, pose a current homicidal risk or pose suicide risk that cannot be managed in a secure, voluntary inpatient setting.
9. Non-English speakers
10. Additional Criteria for Group 1 (Active Crisis): For participants who still experience the effects of their suicide attempt, i.e. someone who overdosed is significantly drowsy or confused, the consenting process will occur after the patient has improved from the effects. If there is a concern around a participant's capacity to consent, the Human Subjects Protections Unit (HSPU) team member who is
monitoring the informed consent process will complete a capacity assessment. Participants who are determined not to have capacity to consent to research will not be included in the study.
Phase I: Group 4 (Healthy Volunteers)
1. Current or past Axis I diagnosis
2. Presence of medical illness likely to alter brain morphology and/or physiology (e.g., hypertension, diabetes) even if controlled by medications.
3. Current or past alcohol or substance abuse or dependence diagnosis (except for nicotine or caffeine) (or "substance abuse disorder" per DSM-V).
4. Presence of psychiatric disorders or a history of suicide attempt or death in first-degree relatives.
5. Pregnant or nursing individuals or those who plan to become pregnant.
6. No lifetime suicide attempts or ideations
7. Non-English speakers
8. Positive HIV test
Exclusions for Imaging:
1. Participants with metal objects implanted in the body, such as aneurysm clips, neural stimulators, implanted cardiac pacemakers, or auto-defibrillator, cochlear implant, or ocular foreign body which would make having an MRI scan unsafe
2. Participants who are uncomfortable in small closed spaces (have claustrophobia) and would feel uncomfortable in the MRI machine
3. Participants with a brain abnormality on an initial MRI scan
4. Subjects with hearing loss that has been clinically evaluated and diagnosed and may be worsened through participation in imaging procedures
Phase II: Group 1 (Active Crisis) and Group 5 (Suicide Ideators)
1. Treatment with a reversible MAOI within 2 weeks prior to study Phase II.
2. Treatment with any other concomitant medication not allowed within 5 1/2 half-lives prior to study Phase II.
3. Subjects with one or more seizures without a clear and resolved etiology
4. Participants with a positive urine for an illicit substance no more than 24 hours prior to the ketamine infusion.
5. Presence of current psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder as defined in the DSM-IV or DSM-V
6. Pregnant or nursing individuals or those who plan to become pregnant.
7. A medical finding or condition that in the clinical judgement of the investigator increases the risk of adverse effects from the ketamine administration (for example: findings suggesting difficulties with kidney or cardiac function that may be contraindications for an experimental intervention).
Phase III: Repeated Administration (Group 1) and Group 5 (Suicide Ideators)
1. Intolerable or serious adverse reaction to ketamine during Phase II
2. Treatment with a reversible MAOI within 2 weeks prior to study Phase III.
3. Treatment with any other concomitant medication not allowed within 5 1/2 half-lives prior to study Phase III.
4. Subjects with one or more seizures without a clear and resolved etiology
5. Participants with a positive urine for an illicit substance no more than 24 hours prior to each ketamine infusion.
6. Presence of current psychotic features or a diagnosis of Schizophrenia or any other psychotic disorder as defined in the DSM-IV or DSM-V
7. Pregnant or nursing individuals or those who plan to become pregnant.
Exclusions for Imaging:
1. Participants with metal objects implanted in the body, such as aneurysm clips, neural stimulators, implanted cardiac pacemakers, or auto-defibrillator, cochlear implant, or ocular foreign body which would make having an MRI scan unsafe
2. Participants who are uncomfortable in small closed spaces (have claustrophobia) and would feel uncomfortable in the MRI machine
3. Participants with a brain abnormality on an initial MRI scan
4. Subjects with hearing loss that has been clinically evaluated and diagnosed and may be worsened through participation in imaging procedures
