Structural and Functional Connectivity of Brainstem Monoamine Pathways in Treatment Resistant Depression

Potential subjects will be identified during clinical visits. If a patient qualifies to
participate in the study they will have to stop any antidepressants that they are taking to
prepare for the use of MAOIs. After a two week washout period, subjects will have an fMRI and
will be started on a MAOI. They will then be followed up for 8 weeks, which is routine and
considered standard care.

Inclusion Criteria - TRD:

1. age: 18 - 65 yrs.;

2. satisfy criteria for DSM-IV major depressive disorder (MDD);

3. 17-item Hamilton Depression Rating Scale (17-item HDRS) score > 18;

4. treatment resistance depression as defined as report of inadequate response (patient
report of minimal improvement or nonresponse) despite past treatment with at least 2
different classes of antidepressants acting on the 5-HT and/or DA monoamine
systems(except MAOIs) (as determined with the Antidepressant Treatment History Form
(ATHF)20 with score of >3 on each of the items and verified by medical records if
available);

5. able to give informed consent;

6. no use of alcohol in the past 1 week and negative urine toxicology screen;

7. MAOI treatment indicated as assessed by an independent psychiatrist not affiliated
with the study;

8. voluntary consent to treatment with an MAOI after reviewing all other options and
agree to follow safeguards and precautions during treatment.

Inclusion criteria for healthy subjects

1. ages 18-65 years and ability to give voluntary informed consent;

2. no history of psychiatric illness or substance abuse or dependence;

3. no significant family history of psychiatric or neurological illness;

4. not currently taking any prescription or centrally acting medications; no use of
alcohol in the past 1 week;

5. and no serious medical or neurological illness.

Exclusion Criteria - TRD:

1. schizophrenia, schizoaffective or primary anxiety disorder;

2. serious medical or neurological illness;

3. history of significant head injury;

4. on fluoxetine treatment;

5. on lithium or have received ECT or rTMS in the last 3 months to avoid long-term
effects of such medications;

6. substance or alcohol dependence in the past 6 months or substance abuse in the past 3
months;

7. unable to give informed consent.

Exclusion criteria for both groups:

1. pregnant or breast-feeding;

2. metallic implants or other contraindication to MRI.