['major depression']
['av 101 (4-chlorokynurenine)']

        -  INCLUSION CRITERIA:

          -  18 to 65 years of age.

          -  Subjects must have a level of understanding sufficient to agree to all required tests
             and examinations, sign an informed consent document and verify understanding. To
             verify this, subjects must score greater than or equal to 80% on the consent quiz.

          -  Subjects must fulfill DSM-IV or DSM-V criteria for MDD, single episode or recurrent
             without psychotic features, based on clinical assessment and confirmed by a structured
             diagnostic interview (SCID-P). Subjects must be experiencing a current major
             depressive episode of at least 4 weeks duration.

          -  Subjects must have an initial score of at least 18 on the HDRS at screening and at
             baseline of study phase I.

          -  Subjects must have a current or past history of lack of response to one adequate
             antidepressant trial (may be from the same chemical class) operationally defined using
             the modified-Antidepressant Treatment History Form (ATHF).

        EXCLUSION CRITERIA:

          -  Current psychotic features or a diagnosis of schizophrenia or any other psychotic
             disorder as defined in the DSM-IV or DSM-V.

          -  Subjects with a history of DSM-IV drug or alcohol dependency or abuse (or alcohol use
             disorder per DSM-V),except for caffeine or nicotine dependence within the preceding 3
             months.

          -  Head injury that results in loss of consciousness exceeding 5 minutes (for the imaging
             component of the study).

          -  Subjects with a DSM IV or DSM-V Axis II diagnosis of borderline or antisocial
             personality disorder.

          -  Pregnant or nursing women or women of child bearing potential not using at least 1
             medically accepted means of contraception from the time of enrollment in the study
             until 1 month after completion of the second phase. Examples of medically accepted
             means of contraception include oral, injectable, or implant birth control, condom,
             diaphragm with spermicide, intrauterine devices (IUD), tubal ligation, abstinence or
             partner with vasectomy. .

          -  Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory,
             cardiovascular (including ischemic heart disease), endocrinologic, neurologic,
             immunologic, or hematologic disease.

          -  Subjects with clinical hyperthyroidism or hypothyroidism.

          -  Subjects with one or more seizures without a clear and resolved etiology.

          -  Clinically significant abnormal laboratory tests.

          -  Treatment with a reversible monoamine oxidase inhibitor (MAOI) within 4 weeks of study
             phase II.

          -  Treatment with fluoxetine or aripirazole within 5 weeks of study phase II.

          -  Treatment with any other disallowed concomitant medication or TMS 14 days before
             randomization.

          -  Treatment with clozapine or electroconvulsive therapy (ECT) within 1 month of
             randomization.

          -  Lifetime history of deep brain stimulation.

          -  Subjects who, in the Principal Investigator s judgment, pose a current serious
             suicidal or homicidal risk.

          -  Positive HIV test

          -  Contraindications to MRS (metal in body, claustrophobia, etc for imaging)

          -  No structured psychotherapy will be permitted during the total duration of the study.
             Subjects unable or unwilling to stop psychotherapy will be unable to participate in
             the study.
      