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

ImportanceMonoamine 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 V-T), 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. ObjectiveTo investigate whether MAO-B V-T is elevated in the prefrontal cortex in major depressive episodes (MDEs) of major depressive disorder. Design, Setting, and ParticipantsThis 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 [C-11]SL25.1188 positron emission tomography scanning to measure MAO-B V-T. All participants were drug and medication free, nonsmoking, and otherwise healthy. Main Outcomes and MeasuresThe MAO-B V-T in the prefrontal cortex (PFC). The second main outcome was to evaluate the association between MAO-B V-T in the PFC and duration of major depressive disorder illness. ResultsTwenty 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 V-T in the PFC (mean, 26%; analysis of variance, F-1,F-38=19.6, P<.001). In individuals with MDEs, duration of illness covaried positively with MAO-B V-T in the PFC (analysis of covariance, F-1,F-18=15.2, P=.001), as well as most other cortex regions and the thalamus. Conclusions and RelevanceFifty percent (10 of 20) of patients with MDEs had MAO-B V-T values in the PFC exceeding those of healthy controls. Greater MAO-B V-T 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.