BACKGROUND Major depressive disorder is associated with raised peripheral inflammatory markers. Mounting evidence also suggests that inflammation is involved in suicidal behavior. However, the involvement of inflammation in the brains of individuals with depression, and its association with suicidal ideation, needs further clarification. Translocator protein (TSPO), which is upregulated in activated glia (predominantly microglia), can be measured as an indication of neuroinflammation in vivo using positron emission tomography and TSPO-specific radioligands. METHODS We used [11C](R)-PK11195 positron emission tomography to compare TSPO availability in the anterior cingulate cortex (ACC), prefrontal cortex, and insula between 14 medication-free patients in a major depressive episode of at least moderate severity and 13 matched healthy control subjects. In a post hoc analysis, we also compared TSPO availability between patients with and without suicidal thoughts. RESULTS Multivariate analysis of variance indicated significantly higher TSPO in patients compared with control subjects (p = .005). The elevation was of large effect size and significant in the ACC (p = .022, Cohen's d = 0.95), with smaller nonsignificant elevations in the prefrontal cortex (p = .342, Cohen's d = 0.38) and insula (p = .466, Cohen's d = 0.29). TSPO was not elevated in patients without suicidal thinking but was significantly increased in those with suicidal thoughts compared with those without, most robustly in the ACC (p = .008) and insula (p = .023). CONCLUSIONS We confirm evidence for increased TSPO availability, suggestive of predominantly microglial activation, in the ACC during a moderate to severe major depressive episode. Our findings provide further incentive for evaluating anti-inflammatory therapies in major depressive disorder.

中文翻译：

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重度抑郁症前扣带回转运蛋白升高以及炎症在自杀念头中的作用：一项 PET 研究

背景 重度抑郁症与升高的外周炎症标志物有关。越来越多的证据还表明炎症与自杀行为有关。然而，抑郁症患者大脑中炎症的参与及其与自杀意念的关联需要进一步澄清。转运蛋白 (TSPO) 在活化的神经胶质（主要是小胶质细胞）中上调，可以使用正电子发射断层扫描和 TSPO 特异性放射性配体测量作为体内神经炎症的指示。方法我们使用 [11C](R)-PK11195 正电子发射断层扫描来比较前扣带回皮层 (ACC)、前额叶皮层、14 名处于至少中等严重程度的重度抑郁症患者和 13 名匹配的健康对照受试者之间的 14 名未用药患者和脑岛。在事后分析中，我们还比较了有和没有自杀念头的患者之间的 TSPO 可用性。结果 多变量方差分析表明，与对照受试者相比，患者的 TSPO 显着更高 (p = .005)。抬高效应大且在 ACC (p = .022, Cohen's d = 0.95) 中显着，前额叶皮层 (p = .342, Cohen's d = 0.38) 和岛叶 (p = .466) 的不显着升高，科恩的 d = 0.29）。没有自杀念头的患者的 TSPO 没有升高，但与没有自杀念头的患者相比，有自杀念头的患者的 TSPO 显着升高，在 ACC (p = .008) 和岛叶 (p = .023) 中最为明显。结论 我们证实了中度至重度重度抑郁发作期间 ACC 中 TSPO 可用性增加的证据，提示主要是小胶质细胞激活。我们的发现为评估重度抑郁症的抗炎疗法提供了进一步的动力。