CAMH Research Imaging Centre and Campbell Family Mental Health Research Institute, Centre for Addiction and Mental Health, Department of Psychiatry, Pharmacology and Toxicology, Institute of Medical Sciences, University of Toronto, Toronto, Ontario, Canada.
Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, Jackson, Mississippi, USA.
Neuropsychopharmacology. 2014 Mar;39(4):973-80. doi: 10.1038/npp.2013.297. Epub 2013 Oct 24.
Inadequate treatment response occurs in approximately 40% of major depressive episodes (MDEs), and one approach to solve this is careful matching of treatment to the specific pathologies of MDE. One such biological abnormality is elevated monoamine oxidase A (MAO-A) levels, which occurs in the prefrontal and anterior cingulate cortex (PFC and ACC) during MDE; however, the subtypes for which this abnormality is most prominent are unknown. We hypothesized that MAO-A levels in the PFC and ACC are most elevated in MDE with greater severity and reversed neurovegetative symptoms (hypersomnia and either hyperphagia or weight gain). MAO-A VT (an index of MAO-A density) was measured using [(11)C]harmine positron emission tomography (PET) in 42 subjects with MDEs secondary to major depressive disorder and 37 healthy controls. The effect of severity and reversed neurovegetative symptoms on MAO-A VT in the PFC and ACC was analyzed using a multivariate analysis of variance (MANOVA). Greater severity and reversed neurovegetative symptoms were associated with elevated MAO-A VT in the PFC and ACC (MANOVA, severity: F(2,38)=5.44, p=0.008; reversed neurovegetative symptoms: F(2,38)=5.13, p=0.01). Increased MAO-A level, when greater severity and reversed neurovegetative symptoms are present, may explain the association of these clinical features with a preferential response to MAO inhibitors, which is especially well-evidenced for reversed neurovegetative symptoms in MDE. As MAO-A creates oxidative stress, facilitates apoptosis, and metabolizes monoamines, therapeutics opposing these processes are predicted to best treat MDE with greater severity and reversed neurovegetative symptoms.
在大约 40%的重度抑郁发作（MDE）中，治疗反应不足，解决这个问题的一种方法是根据 MDE 的具体病理情况仔细匹配治疗方法。一种这样的生物学异常是单胺氧化酶 A（MAO-A）水平升高，这种异常在 MDE 期间发生在前额皮质和前扣带皮质（PFC 和 ACC）中；然而，这种异常最突出的亚型尚不清楚。我们假设，在 MDE 中，MAO-A 水平在严重程度更高和神经生殖症状（过度嗜睡和贪食或体重增加）逆转的情况下升高最明显。使用[(11)C]harmine 正电子发射断层扫描（PET）测量 42 名患有与重度抑郁障碍相关的 MDE 和 37 名健康对照者的 PFC 和 ACC 中的 MAO-A VT（MAO-A 密度指数）。使用多变量方差分析（MANOVA）分析严重程度和逆转神经生殖症状对 PFC 和 ACC 中 MAO-A VT 的影响。严重程度和逆转神经生殖症状与 PFC 和 ACC 中的 MAO-A VT 升高相关（MANOVA，严重程度：F(2,38)=5.44，p=0.008；逆转神经生殖症状：F(2,38)=5.13，p=0.01）。当严重程度和逆转神经生殖症状存在时，MAO-A 水平升高可能解释了这些临床特征与 MAO 抑制剂的优先反应之间的关联，尤其是在 MDE 中逆转神经生殖症状方面证据确凿。由于 MAO-A 会产生氧化应激、促进细胞凋亡并代谢单胺，因此预计对抗这些过程的治疗方法最适合治疗严重程度更高和逆转神经生殖症状的 MDE。
