Inadequate treatment response occurs in approximately 40% of major depressive episodes (MDEs), and one approach to solve this is careful matching of treatment to the specific pathologies of
MDE. One such
biological abnormality is elevated
monoamine oxidase A (
MAO-A) levels, which occurs in the prefrontal and anterior cingulate cortex (PFC and ACC) during
MDE; however, the subtypes for which this abnormality is most prominent are unknown. We hypothesized that
MAO-A levels in the PFC and ACC are most elevated in
MDE with greater severity and reversed neurovegetative symptoms (
hypersomnia and either
hyperphagia or
weight gain).
MAO-A VT (an index of
MAO-A density) was measured using [(11)C]
harmine positron emission tomography (PET) in 42 subjects with MDEs secondary to
major depressive disorder and 37 healthy controls. The effect of severity and reversed neurovegetative symptoms on
MAO-A VT in the PFC and ACC was analyzed using a multivariate analysis of variance (MANOVA). Greater severity and reversed neurovegetative symptoms were associated with elevated
MAO-A VT in the PFC and ACC (MANOVA, severity: F(2,38)=5.44, p=0.008; reversed neurovegetative symptoms: F(2,38)=5.13, p=0.01). Increased
MAO-A level, when greater severity and reversed neurovegetative symptoms are present, may explain the association of these clinical features with a preferential response to
MAO inhibitors, which is especially well-evidenced for reversed neurovegetative symptoms in
MDE. As
MAO-A creates oxidative stress, facilitates apoptosis, and metabolizes monoamines,
therapeutics opposing these processes are predicted to best treat
MDE with greater severity and reversed neurovegetative symptoms.