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Original Investigation
March 6, 2019

Monoamine Oxidase B Total Distribution Volume in the Prefrontal Cortex of Major Depressive Disorder: An [11C]SL25.1188 Positron Emission Tomography Study

Author Affiliations
  • 1Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
  • 2Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
  • 3Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada
  • 4Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson
  • 5Department of Pathology, University of Mississippi Medical Center, Jackson
JAMA Psychiatry. 2019;76(6):634-641. doi:10.1001/jamapsychiatry.2019.0044
Key Points

Question  Is monoamine oxidase B (MAO-B) distribution volume, an index of MAO-B density, greater in the prefrontal cortex during major depressive episodes of MDD?

Findings  This case-control study demonstrated that MAO-B distribution volume was significantly elevated in the prefrontal cortex of patients with major depressive episodes (n = 20) compared with healthy controls (n = 20) (mean, 26%). Duration of illness was significantly and positively correlated with MAO-B distribution volume in the prefrontal cortex.

Meaning  Results suggest that there is a novel phenotype of elevated MAO-B level in the prefrontal cortex of patients with major depressive episodes secondary to major depressive disorder for which low-cost identifiers and selective therapeutics compatible with serotonin reuptake inhibitors should be developed.

Abstract

Importance  Monoamine oxidase B (MAO-B) is an important, high-density enzyme in the brain that generates oxidative stress by hydrogen peroxide production, alters mitochondrial function, and metabolizes nonserotonergic monoamines. Recent advances in positron emission tomography radioligand development for MAO-B in humans enable highly quantitative measurement of MAO-B distribution volume (MAO-B VT), an index of MAO-B density. To date, this is the first investigation of MAO-B in the brain of major depressive disorder that evaluates regions beyond the raphe and amygdala.

Objective  To investigate whether MAO-B VT is elevated in the prefrontal cortex in major depressive episodes (MDEs) of major depressive disorder.

Design, Setting, and Participants  This case-control study was performed at a tertiary care psychiatric hospital from April 1, 2014, to August 30, 2018. Twenty patients with MDEs without current psychiatric comorbidities and 20 age-matched controls underwent carbon 11–labeled [11C]SL25.1188 positron emission tomography scanning to measure MAO-B VT. All participants were drug and medication free, nonsmoking, and otherwise healthy.

Main Outcomes and Measures  The MAO-B VT in the prefrontal cortex (PFC). The second main outcome was to evaluate the association between MAO-B VT in the PFC and duration of major depressive disorder illness.

Results  Twenty patients with MDEs (mean [SD] age, 34.2 [13.2] years; 11 women) and 20 healthy controls (mean [SD] age, 33.7 [13.1] years; 10 women) were recruited. Patients with MDEs had significantly greater MAO-B VT in the PFC (mean, 26%; analysis of variance, F1,38 = 19.6, P < .001). In individuals with MDEs, duration of illness covaried positively with MAO-B VT in the PFC (analysis of covariance, F1,18 = 15.2, P = .001), as well as most other cortex regions and the thalamus.

Conclusions and Relevance  Fifty percent (10 of 20) of patients with MDEs had MAO-B VT values in the PFC exceeding those of healthy controls. Greater MAO-B VT is an index of MAO-B overexpression, which may contribute to pathologies of mitochondrial dysfunction, elevated synthesis of neurotoxic products, and increased metabolism of nonserotonergic monoamines. Hence, this study identifies a common pathological marker associated with downstream consequences poorly targeted by the common selective serotonin reuptake inhibitor treatments. It is also recommended that the highly selective MAO-B inhibitor medications that are compatible for use with other antidepressants and have low risk for hypertensive crisis should be developed or repurposed as adjunctive treatment for MDEs.

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