Glutamatergic and GABAergic Mediators of Antidepressant Response in Major Depression

Inclusion Criteria:

1. Male or female age ≥ 18 and ≤ 65

2. Meets DSM-IV criteria for MDD

3. Current score of ≥ 18 on the 21-item Hamilton Depression Rating Scale (HAM-D).

Exclusion Criteria:

1. Unwillingness or inability to provide written informed consent.

2. Current suicidal ideation

3. Active psychotic symptoms

4. Lifetime history of bipolar disorder, schizophrenia, or OCD

5. Failed treatment with an adequate trial of ≥ 2 antidepressants during the current
major depressive episode ("failure" will be defined as ≤ 50% subjective improvement,
and an "adequate trial" will be defined as at least 4 weeks of treatment using at
least the minimum dose of the antidepressant recommended by the manufacturer in
product labeling)

6. DSM-IV diagnosis of alcohol or substance dependence, with the exception of nicotine
dependence, within three months prior to screening

7. Any history of treatment with electroconvulsive therapy

8. Positive urine toxicology screen for any drug of abuse or excluded medication at
screening. Opiate pain medication being taken for a medical condition is exempt from
needing a negative opiate screen.

9. Clinically significant medical or neurologic disease, as judged by the principal
investigator, which would increase the risk to the participant or interfere with
interpretation of results

10. Female participants with a positive urine pregnancy test at screening

12. Pregnancy. Females of childbearing potential must be using an effective contraceptive
method (e.g., abstinence, prescription oral contraceptives, contraceptive injections,
double-barrier method, male partner sterilization).

13. Any screening laboratory abnormality deemed clinically significant by the investigator
14. A QTc interval on screening ECG of ≥ 450 msec. 15. Use of any excluded medications
(see Section 6.7 below) that cannot be discontinued during the screening phase 16.
Previous failure to respond to treatment with citalopram that would, in the judgment of
the investigator, constitute an adequate trial in MDD 17. Treatment with any
investigational medications within 30 days prior to screening 18. Any contraindications to
having an MRI scan, including cardiac pacemakers, metal vascular clips or stents,
artificial heart valves, certain kinds of prostheses, brain stimulator devices, implanted
drug pumps, ear implants, eye implants or known metal fragments in eyes, exposure to
shrapnel or metal filings (wounded in military combat, sheetmetal workers, welders, and
others), transdermal drug delivery systems, and certain tattoos with metallic ink 19.
Left-handedness