Guo Xiaoyun, Mao Ruizhi, Cui Lvchun, Wang Fan, Zhou Rubai, Wang Yun, Huang Jia, Zhu Yuncheng, Yao Yamin, Zhao Guoqing, Li Zezhi, Chen Jun, Wang Jinhui, Fang Yiru
Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Psychology, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, Shandong, China.
Gen Psychiatr. 2021 Apr 5;34(2):e100440. doi: 10.1136/gpsych-2020-100440. eCollection 2021.
Inflammation that is mediated by microglia activation plays an important role in the pathogenesis of depression. Microglia activation can lead to an increase in the levels of proinflammatory cytokines, including TNF-α, which leads to neuronal apoptosis in the specific neural circuits of some brain regions, abnormal cognition and treatment-resistant depression (TRD). Protein kinase C (PKC) is a key regulator of the microglia activation process. We assume that the abnormality in PKC might result in abnormal microglia activation, neuronal apoptosis, significant changes in emotional and cognitive neural circuits, and TRD. In the current study, we plan to target at the PKC signal pathway to improve the TRD treatment outcome.
This is a 12-week, ongoing, randomised, placebo-controlled trial. Patients with TRD (N=180) were recruited from Shanghai Mental Health Center, Shanghai Jiao Tong University. Healthy control volunteers (N=60) were recruited by advertisement. Patients with TRD were randomly assigned to 'escitalopram+golimumab (TNF-α inhibitor)', 'escitalopram+calcium tablet+vitamin D (PKC activator)' or 'escitalopram+placebo' groups. We define the primary outcome as changes in the 17-item Hamilton Depression Rating Scale (HAMD-17). The secondary outcome is defined as changes in anti-inflammatory effects, cognitive function and quality of life.
This study might be the first randomised, placebo-controlled trial to target at the PKC signal pathway in patients with TRD. Our study might help to propose individualised treatment strategies for depression.
The trial protocol is registered with ClinicalTrials.gov under protocol ID 81930033 and ClinicalTrials.gov ID NCT04156425.
由小胶质细胞激活介导的炎症在抑郁症的发病机制中起重要作用。小胶质细胞激活可导致促炎细胞因子水平升高，包括肿瘤坏死因子-α（TNF-α），这会导致某些脑区特定神经回路中的神经元凋亡、认知异常以及难治性抑郁症（TRD）。蛋白激酶C（PKC）是小胶质细胞激活过程的关键调节因子。我们假设PKC异常可能导致小胶质细胞激活异常、神经元凋亡、情绪和认知神经回路的显著变化以及TRD。在本研究中，我们计划针对PKC信号通路来改善TRD的治疗效果。
这是一项为期12周的正在进行的随机、安慰剂对照试验。难治性抑郁症患者（N = 180）从上海交通大学医学院附属精神卫生中心招募。健康对照志愿者（N = 60）通过广告招募。难治性抑郁症患者被随机分配到“艾司西酞普兰+戈利木单抗（TNF-α抑制剂）”、“艾司西酞普兰+钙片+维生素D（PKC激活剂）”或“艾司西酞普兰+安慰剂”组。我们将主要结局定义为17项汉密尔顿抑郁量表（HAMD - 17）的变化。次要结局定义为抗炎作用、认知功能和生活质量的变化。
本研究可能是首个针对难治性抑郁症患者PKC信号通路的随机、安慰剂对照试验。我们的研究可能有助于提出抑郁症的个体化治疗策略。
该试验方案已在ClinicalTrials.gov上注册，注册号为81930033，ClinicalTrials.gov标识符为NCT04156425。
