Inclusion Criteria:  (i) age 18 to 80 (ii) DSM-5 diagnosis of current MDE and MDD verified by the research version of SCID for DSM-5 (iii) early onset type MDD with first MDE prior to age 40 (iv) score greater than or equal to 17 on the 17 item Hamilton Depression Rating Scale (HDRS)28 (v) antidepressant free for at least 2 weeks (by self report)  Exclusion Criteria:  (i) history of psychotic symptoms (ii) history of antisocial or borderline personality disorders (screened with the Structured Clinical Interview for Personality Disorders (SCID) for Diagnostic and Statistical Manual-5 (DSM-5) 30 (iii) history of neurodegenerative illness (iv) cigarette smoking for the past 6 months (there are reports that cigarette smoking lowers monoamine oxidase B 31, 32.) (v) currently abusing street drugs (vi) current alcohol use disorder (vii) diagnosis of liver or kidney disease (viii) positive for hepatic dysfunction as measured by AST and ALT tests (ix) diagnosis of cardiovascular disease such as hypertension/hypotension, angina or tachycardia (x) electroconvulsive therapy or mechanical brain stimulation treatment within the previous 6 months (the effects of these on MAO-B level are unknown but since they could stimulate astrogliosis which could influence MAO-B level these are included as exclusionary) (xi) positive pregnancy test (in our Centre women up to 65 years of age are given a urine pregnancy test prior to every PET scan) (xii) currently breastfeeding (xiii) recent use of MAO-B inhibitor treatments (within the previous 4 weeks) (xiv) disorders of coagulation, blood or ongoing use of anticoagulant medication (xv) presence of metal objects or implanted electrical devices in the body that would preclude MRI scanning (xvi) claustrophobia (xvii) weight over 400lbs and height over 7ft (requirements for fitting in the scanners and hospital gowns) (xviii) the total radiation dose over the currently approved guideline of 20 mSv in a 12-month period (xix) history of undergoing a number of PET scans that, including the number of PET scans under this protocol, will bring the total to more than 8 PET scans/lifetime, exceeding permissible limit for subjects participating in research set by our centre's guidelines (xx) elevated liver transaminases AST and ALT levels as shown by the laboratory test results  Additional Requirements for Receiving Tranylcypromine :  (i) not taking any anesthetics, meperidine (Demerol), anti-asthmatics, anti-hypertensives, dextromethorphan, buspirone, narcotics, codeine (e.g. found in Tylenol), over the counter medication for colds, hay fever, sinus decongestants, eye drops that contain tetrahydrozoline hydrochloride (Visine); SSRI medication including selective reuptake inhibitors (SSRI), amitriptyline, nortriptyline, protriptyline, desipramine, imipramine, doxepin, perphenazine, carbamazepine, cyclobenzaprine, amoxapine, maprotiline, trimipramine; stimulant medication such as: amphetamines, ephedrine, cocaine, methylphenidate, methyldopa, dopamine, levodopa, tryptophan as well as energy-enhancing and weight-reducing preparations for at least 2 weeks (ii) not taking fluoxetine for at least 6 weeks (iii) inadequate response to serotonin reuptake inhibitor medication (iv) inadequate response to medication that raises norepinephrine (v) inadequate response to lithium addition to an antidepressant or patient does not want to take lithium due to side effects (such as intention tremor or hypothyroidism risk) (vi) inadequate response to a medication that raises both serotonin and norepinephrine (vii) inadequate response to wellbutrin or participant is not able to take wellbutrin due to a contraindication or side effect or participant does not wish to take wellbutrin (viii) inadequate response to wellbutrin added to a second antidepressant or participant is not able to take wellbutrin due to a contraindication or side effect or participant does not wish to take wellbutrin (ix) awareness and willingness to follow medication and substance use requirements required of taking tranylcypromine or rasagiline  Exclusion  (i) previous hypersensitivity to monoamine oxidase inhibitors (ii) previous history of hypersensitivity to tyramine (iii) self report of previous diagnosis of cerebrovascular or cardiovascular disorders (iv) self report history of recurrent or frequent headaches (v) diagnosis of phaeochromocytoma and catecholamine-releasing paragangliomas (vi) systolic blood pressure not between 91 and 139 mmHg (inclusive) (vii) diastolic blood pressure not between 51 and 90 mmHg (inclusive) (viii) a decrease in systolic blood pressure of 20 mm Hg or diastolic blood pressure of 10 mm Hg within three minutes of standing when compared with BP from the sitting position (ix) use of triptans or tryptamines (e.g. sumatriptan or rizatriptan) in the past 2 weeks.  Additional Requirements for Taking Rasagiline  Inclusion  (i) Participant does not wish to take tranylcypromine due to concerns regarding side effects or the strict dietary restrictions of reduced tyramine intake required for taking tranylcypromine.  Additional Requirements for Taking Duloxetine:  Inclusion (i) Participants must be antidepressant free for at least 4 weeks prior to scanning (most antidepressants affect monoamines as does duloxetine so a longer period of being medication free is required to be able to separate effect of duloxetine from previous medication).  (ii) Participant must not have a history of non-response to duloxetine at a daily dose of 60mg daily or higher.