Monoamine oxidase b total distribution volume in the prefrontal cortex of major depressive disorder: An ¹¹csl25.1188 positron emission tomography study

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 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. Objective: To investigate whether MAO-B V_T 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 ¹¹CSL25.1188 positron emission tomography scanning to measure MAO-B V_T. All participants were drug and medication free, nonsmoking, and otherwise healthy. Main Outcomes and Measures: The 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. 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 V_T in the PFC (mean, 26%; analysis of variance, F_1,38 = 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_1,18 = 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 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.