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. 2019 Jun 1;76(6):634-641.
doi: 10.1001/jamapsychiatry.2019.0044.

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

Sho Moriguchi  1 , Alan A Wilson  1   2 , Laura Miler  1 , Pablo M Rusjan  1 , Neil Vasdev  1   2 , Stephen J Kish  1   2   3 , Grazyna Rajkowska  4 , Junming Wang  5 , Michael Bagby  2 , Romina Mizrahi  1   2 , Ben Varughese  1 , Sylvain Houle  1   2 , Jeffrey H Meyer  1   2   3
Affiliations

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

Sho Moriguchi et al. JAMA Psychiatry. .

Erratum in

  • Error in Scale of Y-Axis in Figure 2.
    [No authors listed] [No authors listed] JAMA Psychiatry. 2019 Jun 1;76(6):659. doi: 10.1001/jamapsychiatry.2019.0688. JAMA Psychiatry. 2019. PMID: 30969324 Free PMC article. No abstract available.

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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Conflict of interest statement

Conflict of Interest Disclosures: Drs Wilson, Houle, and Meyer reported receiving operating grant funds for studies unrelated to the present work from Janssen in the past 5 years. Dr Mizrahi reported receiving a speaker’s fee from Otsuka-Lundbeck Canada in the past 5 years. Dr Houle reported receiving grants from the Canadian Institutes of Health Research. Dr Meyer reported receiving grants from the National Institute of Mental Health, Canadian Institutes of Health Research, Brain and Behavior Research Foundation, and Janssen; reported receiving other support from Lundbeck/Takeda and Venessance outside the submitted work; reported being a consultant to Mylan, Lundbeck/Takeda, Teva, and Trius in the past 7 years; and reported being an inventor on several patents, including inflammation markers, to predict brain inflammation and/or affective disorders. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Elevated MAO-B Total Distribution Volume During Major Depressive Episodes (MDEs) in the Prefrontal Cortex
The MAO-B VT was significantly greater in the 20 patients with MDEs compared with the 20 healthy controls. Calculation of analysis of variance resulted in the following associations of diagnosis with region: prefrontal cortex (F1,38 = 19.6; P < .001), ventrolateral prefrontal cortex (F1,38 = 12.2; P = .001), dorsolateral prefrontal cortex (F1,38 = 7.4; P = .01), orbitofrontal cortex (F1,38 = 4.7; P = .04), and medial prefrontal cortex (F1,38 = 2.6; P = .12). MAO-B indicates monoamine oxidase B; MAO-B VT, MAO-B density measured by distribution volume.
Figure 2.
Figure 2.. Elevated MAO-B Total Distribution Volume During Major Depressive Episodes (MDEs)
Calculation of analysis of variance resulted in the following interactions of diagnosis with region: prefrontal cortex (F1,38 = 19.6; P < .001), thalamus (F1,38 = 8.8; P = .005), and inferior parietal cortex (F1,38 = 9.0; P = .005). MAO-B indicates monoamine oxidase B; MAO-B VT, MAO-B total distribution volume.
Figure 3.
Figure 3.. Association Between the Prefrontal Cortex MAO-B Total Distribution Volume and Duration of Illness
Analysis of covariance evaluated MAO-B VT as the dependent variable and duration of illness as the covariate (analysis of covariance, r = 0.68; F1,18 = 15.2; P = .001). After removing the highest MAO-B VT value in the prefrontal cortex, the statistical significance remained (analysis of covariance, r = 0.65; F1,17 = 12.3; P = .003). MAO-B indicates monoamine oxidase B; MAO-B VT, MAO-B total distribution volume.
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