PET-Study: Monoaminooxidase A in Postpartum Depression

Background: Postpartum depression, that is major depressive disorder with postpartum onset, is the most common complication of childbearing with a prevalence rate of approximately 13%. Furthermore, women who have experienced MDE (major depressive disorder) with postpartum onset are at greater risk of having further MDE. At the Toronto PET Centre, we intend to investigate a biological mechanism that could contribute to the neurobiology of MDE with postpartum onset. Monoamino-Oxidase-A (MAO-A) is an enzyme that breaks down serotonin, norepinephrine and dopamine. MAO-A DVS (MAO-A specific distribution volume) is highly elevated during major depressive episodes (mean, 34% or 2 STD, p<0.001). Brain MAO-A has a converse relationship to estrogen change such that its density is increased after drops in estrogen. MAO-A DVS can be measured with [ 11C] harmine positron emission tomography (PET). [ 11C] Harmine, a selective MAO-A ligand, demonstrates the properties of an excellent PET radiotracer. It provides high affinity for the MAO-A enzyme (Ki=2nM), good test/retest reliability and has a huge advantage over the MAO-A tracer, [ 11C] clorgyline, with regard to reversibility and sensitivity to artifacts of blood flow. We have completed [ 11C] harmine scans under test-retest conditions in 6 subjects. Our pilot data of 3 women with MDE with postpartum onset show promising results: MAO-A DVS is significantly higher (31%, 1.8 STD, p<0.01) as compared to healthy subjects. Hypotheses: (1) During the immediate postpartum period, in all women, MAO-A DVS, an index of MAO-A density, will be elevated shortly after the substantial drop in estrogen levels (i.e. during days 4 to 7 postpartum). (2) In women who do not have a depressive episode during the postpartum period, MAO-A DVS should normalize by week 3 postpartum (when estrogen levels plateau). (3) In women who have a depressive episode during the postpartum period, MAO-A DVS will remain elevated through to week 12 postpartum. Study design: MAO-A DVS will be measured in each subject using [ 11C] harmine PET. Group 1: 15 healthy women not recently postpartum. Group 2: 15 healthy women who are day 4 to 7 postpartum. Group 3: 15 healthy women, not having a depressive episode, during postpartum weeks 3 through 12. Group 4: 15 women with MDE with postpartum onset, during postpartum weeks 3 through 12. Clinical Relevance: Should MAO-A be elevated during the first postpartum week, this would identify a particular monoamine lowering process as a biological factor that may contribute to postpartum depression. Data obtained from our study could initiate comprehensive clinical trials with MAO-A inhibitors for MDE with postpartum onset (that have not yet been done).