 While Major Depressive Disorder MDD is prevalent and disabling, compelling recent data from the Sequenced Treatment Alternatives to Relieve Depression STARD study indicate that only about half of patients attain remission from MDD, even after multiple antidepressant medication trials. Further, no biomarker has been validated which can select an effective treatment for such patients, presenting critical unmet intellectual and clinical challenges. The recent landmark finding of an markedly elevated level of monoamine oxidase A MAO-A in the brains of depressed patients with MDD compared to controls, using positron emission tomography PET with a positron-emitting carbon isotope, carbon 11 11C labeled monoamine oxidase inhibitor MAOI, has provided an unparalleled opportunity to address these challenges. It has long been known that MAOIs are effective for some patients with treatment-resistant MDD, although their side effect profile makes them highly unacceptable both to patients and physicians, severely curtailing their utility. 