Developing a Biomarker to Predict Response in Treatment Resistant Depression

While Major Depressive Disorder (MDD) is prevalent and disabling, compelling recent data from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) 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.

This study seeks to: 1) replicate this study using PET scans in 20 subjects with MDD but extending it to patients with treatment-resistant depression (TRD). (Results from these participants with be compared to those from 10 non-depressed controls; 2) explore the correlation of the brain MAO-A level biomarker to treatment outcome by treating the 20 PET-imaged TRD patients with an MAOI, hypothesizing that their MAOI response will be related to their level of MAO-A. Brain MAO-A is an ideal candidate biomarker for this study since it appears to be significantly abnormally elevated in MDD, yet it has a broad range of values even among depressed patients. Most importantly, the MAO-A biomarker is known to be the single pharmacologic target of the treatment, making it appear likely that outcome with MAOI treatment will be related to MAO-A.