RT Journal Article
SR Electronic
T1 PAID study design on the role of PKC activation in immune/inflammation-related depression: a randomised placebo-controlled trial protocol
JF General Psychiatry
JO Gen Psych
FD BMJ Publishing Group Ltd
SP e100440
DO 10.1136/gpsych-2020-100440
VO 34
IS 2
A1 Xiaoyun Guo
A1 Ruizhi Mao
A1 Lvchun Cui
A1 Fan Wang
A1 Rubai Zhou
A1 Yun Wang
A1 Jia Huang
A1 Yuncheng Zhu
A1 Yamin Yao
A1 Guoqing Zhao
A1 Zezhi Li
A1 Jun Chen
A1 Jinhui Wang
A1 Yiru Fang
YR 2021
UL http://gpsych.bmj.com/content/34/2/e100440.abstract
AB 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-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.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.Data are available upon request.