Research Imaging Centre, Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.
JAMA Psychiatry. 2019 Jun 1;76(6):634-641. doi: 10.1001/jamapsychiatry.2019.0044.
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.
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.
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.
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.
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.
单胺氧化酶 B（MAO-B）是大脑中一种重要的高密度酶，通过产生过氧化氢来产生氧化应激，改变线粒体功能，并代谢非血清素单胺。最近在人类 MAO-B 的正电子发射断层扫描配体开发方面的进展，使 MAO-B 分布容积（MAO-B VT）的高度定量测量成为可能，这是 MAO-B 密度的一个指标。迄今为止，这是首次在重度抑郁症的大脑中评估 MAO-B 的研究，该研究评估了中缝核和杏仁核以外的区域。
探讨 MAO-B VT 是否在重度抑郁症发作（MDE）的前额叶皮层升高。
设计、地点和参与者：这项病例对照研究于 2014 年 4 月 1 日至 2018 年 8 月 30 日在一家三级精神病院进行。20 名无当前精神病合并症的 MDE 患者和 20 名年龄匹配的对照者接受了碳 11 标记的 [11C]SL25.1188 正电子发射断层扫描扫描，以测量 MAO-B VT。所有参与者均未服用药物和药物，不吸烟，且身体健康。
前额叶皮层（PFC）中的 MAO-B VT。第二个主要结果是评估 PFC 中 MAO-B VT 与重度抑郁症发病时间之间的关联。
招募了 20 名 MDE 患者（平均[标准差]年龄，34.2[13.2]岁；11 名女性）和 20 名健康对照者（平均[标准差]年龄，33.7[13.1]岁；10 名女性）。MDE 患者的 PFC 中 MAO-B VT 明显更高（平均值，26%；方差分析，F1,38=19.6，P<.001）。在 MDE 患者中，疾病持续时间与 PFC 中的 MAO-B VT 呈正相关（协方差分析，F1,18=15.2，P=.001），以及其他大多数皮层区域和丘脑。
50%（20 名患者中的 10 名）的 MDE 患者 PFC 中的 MAO-B VT 值超过了健康对照组。更高的 MAO-B VT 是 MAO-B 过度表达的指标，这可能导致线粒体功能障碍、神经毒性产物合成增加和非血清素单胺代谢增加等病理变化。因此，本研究确定了一种与常见选择性 5-羟色胺再摄取抑制剂治疗效果不佳的下游后果相关的常见病理标志物。还建议开发或重新利用与其他抗抑郁药兼容且发生高血压危象风险低的高度选择性 MAO-B 抑制剂药物，作为 MDE 的辅助治疗。
