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Brain Monoamine Oxidase A Binding in Major Depressive Disorder: Relationship to Selective Serotonin Reuptake Inhibitor Treatment, Recovery, and Recurrence
Abstract
CONTEXT: Highly significant elevations in regional brain monoamine oxidase A (MAO-A) binding were recently reported during major depressive episodes (MDEs) of major depressive disorder (MDD). The relationship between MAO-A levels and selective serotonin reuptake inhibitor (SSRI) treatment, recovery, and recurrence in MDD is unknown. OBJECTIVES: To determine whether brain MAO-A binding changes after SSRI treatment, whether brain MAO-A binding normalizes in subjects with MDD in recovery, and whether there is a relationship between prefrontal and anterior cingulate cortex MAO-A binding in recovery and subsequent recurrence of MDE. DESIGN: Case-control study. SETTING: Tertiary care psychiatric hospital. PARTICIPANTS: Twenty-eight healthy subjects, 16 subjects with an MDE secondary to MDD, and 18 subjects with MDD in recovery underwent carbon 11-labeled harmine positron emission tomography scans. Subjects with MDE were scanned before and after 6 weeks of SSRI treatment. All were otherwise healthy, nonsmoking, and medication free. Subjects with MDD in recovery were followed up for 6 months after MAO-A binding measurement. MAIN OUTCOME MEASURE: Monoamine oxidase A V(T), an index of MAO-A density, was measured in the prefrontal cortex, anterior cingulate cortex, posterior cingulate cortex, dorsal putamen, ventral striatum, thalamus, anterior temporal cortex, midbrain, and hippocampus. RESULTS: Monoamine oxidase A V(T) was significantly elevated in each brain region both during MDE and after SSRI treatment as compared with healthy controls. During recovery, MAO-A V(T) was significantly elevated in each brain region; however, those who went on to recurrence had significantly higher MAO-A V(T) in the prefrontal and anterior cingulate cortex than those who did not. CONCLUSIONS: Elevated MAO-A binding after SSRI treatment indicates persistence of a monoamine-lowering process not present in health. This provides a strong conceptual rationale for continuing SSRI treatment during early remission. Greater MAO-A binding in the prefrontal and anterior cingulate cortex in subjects with MDD in recovery and its association with subsequent recurrence argue that deficient monoamine neuromodulation may persist into recovery and contribute to recurrence.
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“increased oxidative stress, lower antioxidant levels, and imbalanced oxidant:antioxidant levels have been well documented within the hippocampus (103,104) and mPFC (104–106), resulting in associated markers of DNA/RNA damage in these regions.”
From The Impact of Stress and Major Depressive Disorder on Hippocampal and Medial Prefrontal Cortex Morphology (2019) · cites this paper as [104]
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Metadata
- Authors
- Meyer, J. H., Wilson, A. A., Sagrati, S., Miler, L., Rusjan, P., Bloomfield, P. M., Clark, M., Sacher, J., Voineskos, A. N., & Houle, S.
- Affiliations
- Centre for Addiction and Mental Health (CA)
- Corresponding author
- Meyer, Jeffrey H.
- ORCID
- Venue
- Archives of General Psychiatry
- Publisher
- American Medical Association (AMA)
- Published
- 2009-12-01
- Volume
- 66
- Issue
- 12
- Pages
- 1304
- ISSN
- 0003-990X (ISSN-L)
- OpenAlex
- W2152918255
- Cited by
- 182
- References
- 69
- Citations by year
- 2026: 4 · 2024: 5 · 2023: 6 · 2022: 11 · 2021: 10 · 2020: 12 · 2019: 9 · 2018: 12 · 2017: 14 · 2016: 10 · 2015: 21 · 2014: 12 · 2013: 17 · 2012: 24
- FWCI
- 9.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Archives of General Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Bristol-Myers Squibb
- Eli Lilly and Company
- GlaxoSmithKline
- H. Lundbeck A/S
- Canadian Institutes of Health Research
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Treatment of Major Depression
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- major depressive disorder, monoamine oxidase A, selective serotonin reuptake inhibitors, depression remission, depression recurrence, prefrontal cortex, anterior cingulate cortex, monoamine depletion
- MeSH terms
- Adult, Brain, Brain Mapping, Carbon Radioisotopes, Major Depressive Disorder, Female, Gyrus Cinguli, Harmine, Humans, Male, Monoamine Oxidase, Recurrence, Severity of Illness Index, Tissue Distribution, Treatment Outcome, Selective Serotonin Reuptake Inhibitors, Prefrontal Cortex, Positron-Emission Tomography
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