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:

• age: 18 - 65 yrs.;
• satisfy criteria for DSM-IV major depressive disorder (MDD);
• 17-item Hamilton Depression Rating Scale (17-item HDRS) score > 18;
• 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);
• able to give informed consent;
• no use of alcohol in the past 1 week and negative urine toxicology screen;
• MAOI treatment indicated as assessed by an independent psychiatrist not affiliated with the study;
• 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

• ages 18-65 years and ability to give voluntary informed consent;
• no history of psychiatric illness or substance abuse or dependence;
• no significant family history of psychiatric or neurological illness;
• not currently taking any prescription or centrally acting medications; no use of alcohol in the past 1 week;
• and no serious medical or neurological illness.

Exclusion criteria

- TRD:

• schizophrenia, schizoaffective or primary anxiety disorder;
• serious medical or neurological illness;
• history of significant head injury;
• on fluoxetine treatment;
• on lithium or have received ECT or rTMS in the last 3 months to avoid long-term effects of such medications;
• substance or alcohol dependence in the past 6 months or substance abuse in the past 3 months;
• unable to give informed consent.

Exclusion criteria

for both groups:

• pregnant or breast-feeding;
• metallic implants or other contraindication to MRI.