Elevated Monoamine Oxidase A Binding During Major Depressive Episodes Is Associated with Greater Severity and Reversed Neurovegetative Symptoms

Abstract

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 V T (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 V T 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 V T in the PFC and ACC (MANOVA, severity: F (2,38) ¼ 5.44, p ¼ 0.008; reversed neurovegetative symptoms: F (2,38) ¼ 5.13, p ¼ 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.

Role of Translocator Protein Density, a Marker of Neuroinflammation, in the Brain During Major Depressive Episodes

“…Regions of interest were automatically generated using the in-house software, ROMI, as previously described. 31 Time activity curves were used to estimate TSPO V T using a two-tissue compartment model, which has been shown previously to be an optimal model to quantitate TSPO V T with [ 18 F]FEPPA PET. 30 …”

Hypersomnia in Mood Disorders: a Rapidly Changing Landscape

“…Notably, glucocorticoid administration increases the transcription rate and catalytic activity of MAO-A in human cell lines, connecting changes in the hypothalamic-pituitary-adrenal (HPA) axis that occur in the high stress state of depression, with upregulation of MAO-A [39, 40]. In the case of hypersomnia in mood disorders, it is also noteworthy that recent evidence utilizing positron emission tomography has also demonstrated elevated MAO-A binding in the prefrontal and anterior cingulate cortices in patients with reversed neurovegetative symptoms (i.e., hypersomnia and hyperphagia) [41]. However, because patients with atypical depression demonstrate lower diurnal cortisol slopes with normal serum cortisol levels [42], connections between hypersomnia in mood disorders and the HPA axis are speculative, and if present, may be due to negative feedback and/or altered sensitivity of the system.…”

Increased Seasonal Variation in Serotonin Transporter Binding in Seasonal Affective Disorder

“…The second hypothesis was that seasonal variation in [ 11 C]DASB 5-HTT BP ND in the PFC and ACC would be associated with severity of SAD symptoms. The rationale for the second hypothesis is that SAD is well known to be a dimensional illness with a continuous distribution within health (such that 25% of healthy individuals experience mild seasonal symptoms) through to SAD of moderate to high severity Kasper et al, 1989;Rohan et al, 2011); and in MDD the magnitude of brain biomarker abnormalities is often correlated with severity, reflecting that MDD is a complex neuropsychiatric illness for which any individual pathology is more likely to present when MDD is more severe (Chiuccariello et al, 2014;Deschwanden et al, 2011;Fujita et al, 2012;Meyer, 2012;Sanacora et al, 2004;Setiawan et al, 2015). Criteria for all included being age 18-40, non-smoking and in good physical health, no history of alcohol or substance abuse, no antidepressant use within the past 6 months, and no use of prescription medications or herbal supplements within the past 2 months.…”