Examining The Effect Of Ketamine On Glutamate/Glutamine Cycling

Healthy Group

Inclusion Criteria:

- Male or female between the ages of 21-65 years.

- Able to provide written informed consent.

- Able to read and write English.

Exclusion Criteria:

- Personal or first-degree family member with history of mood, anxiety, or psychotic
axis I DSM-IV disorders confirmed after comprehensive psychiatric evaluation.

- Any history of serious medical or neurological illness.

- Any signs of major medical or neurological illness on examination or as a result of
ECG screening or laboratory studies.

- Lifetime history of psychoactive substance or alcohol dependence or substance or
alcohol abuse (other than nicotine or caffeine abuse), or drinking more that 5
drinks/week during the last year.

- Abnormality on physical examination.

- A positive pre-study (screening) urine drug screen or, at the study physician's
discretion on any drug screens given before the scans.

- Pregnant or lactating women or a positive urine pregnancy test for women of
child-bearing potential at screening or prior to any imaging day.

- Subjects who test positive for HIV or viral hepatitis (hepatitis B and/or C)

- Has received either prescribed or over-the-counter (OTC) centrally active medicine or
herbal supplements within the week prior to the MRI scan.

- Any history indicating learning disability, mental retardation, or attention deficit
disorder.

- Known sensitivity to ketamine.

- Body circumference of 52 inches or greater.

- Body weight of 280 pounds or greater.

- History of claustrophobia.

- Presence of cardiac pacemaker or other electronic device or ferromagnetic metal
foreign bodies in vulnerable positions as assessed by a standard pre-MRI screening
questionnaire.

- Donation of blood in excess of 500 mL within 56 days prior to dosing.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- Resting blood pressure lower than 90/60 or higher than 150/90,or resting heart rate
lower than 45/min or higher than 100/min.

Depression Group

Inclusion Criteria:

- Male or female between the ages of 21-65 years.

- Able to provide written informed consent.

- Current MDD Single Episode (296.2x) or Recurrent (296.3x), as determined by the
Structured Clinical Interview for DSM-IV (SCID) patient edition

- Montgomery Asberg Depression Rating Scale (MADRS) score of 18 or higher at baseline
and start of first 13C-MRS.

- Quick Inventory of Depressive Symptoms - Self-Report (QIDS-SR16) score of 19 or higher
at baseline and start of first 13C-MRS.

- No psychotropic medications for 2 or more weeks (4 weeks for Fluoxetine) prior to
first 13C-MRS.

- Be able to understand and speak English.

Exclusion Criteria:

- Patients with a history of DSM-IV-TR diagnosis of bipolar disorder or schizophrenia or
schizoaffective disorder or currently exhibiting psychotic features associated with
their depression; dementia or suspicion thereof, is also exclusionary.

- First-degree family member with history of schizophrenia or any other psychotic
disorder.

- Serious suicide or homicide risk, as assessed by evaluating clinician; A serious
suicide risk will be considered an inability to control suicide attempts, imminent
risk of suicide in the investigator's judgment, or a history of serious suicidal
behavior, which is defined using the Columbia-Suicide Severity Rating Scale (C-SSRS)
as either (1) one or more actual suicide attempts in the 3 years before study entry
with the lethality rated at 3 or higher, or (2) one or more interrupted suicide
attempts with a potential lethality judged to result in serious injury or death.

- Substance abuse or dependence during the 12 months prior to screening.

- Any history of serious medical or neurological illness.

- Any signs of major medical or neurological illness.

- Abnormality on physical examination. A subject with a clinical abnormality may be
included only if the study physician considers the abnormality will not introduce
additional risk factors and will not interfere with the study procedure.

- A positive pre-study (screening) urine drug screen or on any drug screens given before
the scans.

- Pregnant or lactating women or a positive urine pregnancy test for women of
childbearing potential at screening or prior to any imaging day.

- Any history indicating learning disability, or mental retardation.

- Known sensitivity to ketamine.

- Body weight of 280 pounds or greater.

- History of claustrophobia.

- Presence of cardiac pacemaker or other electronic device or ferromagnetic metal
foreign bodies in vulnerable positions as assessed by a standard pre-MRI screening
questionnaire.

- Donation of blood in excess of 500 mL within 56 days prior to dosing.

- History of sensitivity to heparin or heparin-induced thrombocytopenia.

- Resting blood pressure lower than 90/60 or higher than 150/90,or resting heart rate
lower than 45/min or higher than 100/min.