title: 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 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.
authors.affiliation: CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Pharmacology and Toxicology, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Lina
authors.initials: L
authors.lastname: Chiuccariello
authors.affiliation: CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Pharmacology and Toxicology, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Sylvain
authors.initials: S
authors.lastname: Houle
authors.affiliation: CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Pharmacology and Toxicology, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Laura
authors.initials: L
authors.lastname: Miler
authors.affiliation: CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Pharmacology and Toxicology, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Robert G
authors.initials: RG
authors.lastname: Cooke
authors.affiliation: CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Pharmacology and Toxicology, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Pablo M
authors.initials: PM
authors.lastname: Rusjan
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Grazyna
authors.initials: G
authors.lastname: Rajkowska
authors.affiliation: CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Pharmacology and Toxicology, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Levitan
authors.affiliation: CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Pharmacology and Toxicology, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Kish
authors.affiliation: CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Pharmacology and Toxicology, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nathan J
authors.initials: NJ
authors.lastname: Kolla
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, USA.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Ou
authors.affiliation: CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Pharmacology and Toxicology, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Alan A
authors.initials: AA
authors.lastname: Wilson
authors.affiliation: CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Pharmacology and Toxicology, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Jeffrey H
authors.initials: JH
authors.lastname: Meyer
mesh_terms: D000328:Adult; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002540:Cerebral Cortex / Q000000981:diagnostic imaging / Q000187:drug effects; D003865:Major Depressive Disorder / Q000145:classification / Q000150:complications* / Q000000981:diagnostic imaging; D006970:Disorders of Excessive Somnolence / Q000000981:diagnostic imaging / Q000209:etiology*; D005260:Female; D006247:Harmine / Q000493:pharmacokinetics; D006801:Humans; D006963:Hyperphagia / Q000000981:diagnostic imaging / Q000209:etiology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D011569:Psychiatric Status Rating Scales; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D055815:Young Adult
chemical_list: D002250:Carbon Radioisotopes; D008996:Monoamine Oxidase Inhibitors; D006247:Harmine; D008995:Monoamine Oxidase