PAID study design on the role of PKC activation in immune/inflammation-related depression:a randomised placebo-controlled trial protocol  

作　　者：Xiaoyun Guo Ruizhi Mao Lvchun Cui Fan Wang Rubai Zhou Yun Wang Jia Huang Yuncheng Zhu Yamin Yao Guoqing Zhao Zezhi Li Jun Chen Jinhui Wang Yiru Fang 

机构地区：[1]Department of Psychiatry,Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,Shanghai,China [2]Department of Psychology,Shandong Provincial Hospital affiliated to Shandong First Medical University,Jinan,Shandong,China [3]Department of Neurology,Renji Hospital,Shanghai Jiao Tong University School of Medicine,Shanghai,China [4]Clinical Research Center and Division of Mood Disorders,Shanghai Mental Health Center,Shanghai Jiao Tong University School of Medicine,Shanghai,China [5]College of Life Sciences,Chinese Academy of Sciences,Beijing,China [6]CAS Center for Excellence in Brain Science and Intelligence Technology,Chinese Academy of Science,Shanghai,China [7]Shanghai Key Laboratory of Psychotic Disorders,Shanghai,China

出　　处：《General Psychiatry》2021年第2期104-110,共7页综合精神医学（英文）

基　　金：This work was supported by the National Key R&D Program of China(2016YFC1307100);the National Natural Science Foundation of China(81930033,81771465,81201057);the Shanghai Key Project of Science&Technology(2018SHZDZX05);the National Key Technologies R&D Program of China(2012BAI01B04);the Innovative Research Team of High-level Local Universities in Shanghai.

摘　　要：Background 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.Methods and analysis 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-αinhibitor)’,‘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.Discussion 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.Trial registration number The trial protocol is registered with ClinicalTrials.gov under protocol ID 81930033 and ClinicalTrials.gov ID NCT04156425.

关 键 词：PLACEBO INFLAMMATION VITAMIN 

分 类 号：R749.4[医药卫生—神经病学与精神病学]