Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes.
Role of translocator protein density, a marker of neuroinflammation, in the brain during major depressive episodes.
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DOI：
10.1001/jamapsychiatry.2014.2427
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发表时间：
2015-03
期刊：
影响因子：
25.8
通讯作者：
Meyer JH
中科院分区：
文献类型：
--
作者：
Setiawan E;Wilson AA;Mizrahi R;Rusjan PM;Miler L;Rajkowska G;Suridjan I;Kennedy JL;Rekkas PV;Houle S;Meyer JH
重性抑郁症（MDD）的神经炎症假说得到了几个主要发现的支持：首先，在人类和动物中，免疫系统的激活导致了重性抑郁发作（MDE）期间出现的疾病行为，如情绪低落，快感缺乏，厌食和体重减轻。其次，炎症的外周标志物在MDD中经常被报告。第三，神经炎性疾病与MDE的高发病率有关。然而，神经炎性假说的一个基本局限性是缺乏MDE期间脑炎症的证据。为了研究MDE期间是否存在小胶质细胞活化（神经炎症的一个重要方面），[18 F]FEPPA正电子发射断层扫描（PET）用于测量转运蛋白总分布体积（TSPO VT），这是TSPO密度的一个指标。在活化的小胶质细胞中转运蛋白密度升高。确定继发于MDD的MDE患者的前额叶皮层、前扣带皮层（ACC）和额叶皮层TSPO VT是否升高。病例对照研究。三级精神病院。20例继发于MDD的MDE受试者和20例健康对照者接受了[18 F]FEPPA PET扫描。MDE受试者至少6周未接受药物治疗。所有参与者都是健康的，不吸烟。TSPO VT在前额叶皮层、ACC和ACC中测量。在MDE中，所有检查的脑区TSPO VT均显著升高（多变量方差分析，F15，23=4.46，P=0.001），前额叶皮质、ACC和小脑皮质TSPO VT平均增加30%。在MDE中，ACC的TSPO VT越大，抑郁程度越严重（ACC：r=0.628，P=0.005）。这一发现为MDE中的脑炎症，更具体地说是小胶质细胞活化提供了迄今为止最令人信服的证据。这对于改善治疗是重要的，因为它意味着减少小胶质细胞活化的疗法应该对MDE有希望。较高的ACC TSPO VT与MDE严重程度之间的相关性与特定区域的神经炎症可能导致与MDE症状重叠的疾病行为的概念一致。
The neuroinflammatory hypothesis of major depressive disorder (MDD) is supported by several main findings: First, in humans and animals, activation of the immune system causes sickness behaviors that present during a major depressive episode (MDE) such as low mood, anhedonia, anorexia and weight loss. Second, peripheral markers of inflammation are frequently reported in MDD. Third, neuroinflammatory illnesses are associated with high rates of MDE. However, a fundamental limitation of the neuroinflammatory hypothesis is a paucity of evidence for brain inflammation during MDE. To investigate whether microglial activation, an important aspect of neuroinflammation, is present during MDE, [18F]FEPPA positron emission tomography (PET) was applied to measure translocator protein total distribution volume (TSPO VT), an index of TSPO density. Translocator protein density is elevated in activated microglia. To determine whether TSPO VT, is elevated in the prefrontal cortex, anterior cingulate cortex (ACC) and insula in MDE secondary to MDD. Case-control study. Tertiary care psychiatric hospital. 20 subjects with MDE secondary to MDD and 20 healthy controls, underwent an [18F]FEPPA PET scan. MDE subjects were medication-free for at least 6 weeks. All participants were otherwise healthy, and non-smoking. TSPO VT was measured in the prefrontal cortex, ACC, and insula. In MDE, TSPO VT was significantly elevated in all brain regions examined (multivariate analysis of variance, F15,23=4.46, P=0.001).TSPO VT was increased, on average, by 30% in the prefrontal cortex, ACC and insula. In MDE, greater TSPO VT in the ACC correlated with greater depression severity (ACC: r=0.628, P=0.005). This finding provides the most compelling evidence to date for brain inflammation, and more specifically microglial activation, in MDE. This is important for improving treatment since it implies that therapeutics which reduce microglial activation should be promising for MDE. The correlation between higher ACC TSPO VT with severity of MDE is consistent with the concept that neuroinflammation in specific regions may contribute to sickness behaviors which overlap with the symptoms of MDE.