PT  - JOURNAL ARTICLE
AU  - Xiaoyun Guo
AU  - Ruizhi Mao
AU  - Lvchun Cui
AU  - Fan Wang
AU  - Rubai Zhou
AU  - Yun Wang
AU  - Jia Huang
AU  - Yuncheng Zhu
AU  - Yamin Yao
AU  - Guoqing Zhao
AU  - Zezhi Li
AU  - Jun Chen
AU  - Jinhui Wang
AU  - Yiru Fang
TI  - PAID study design on the role of PKC activation in immune/inflammation-related depression: a randomised placebo-controlled trial protocol
AID  - 10.1136/gpsych-2020-100440
DP  - 2021 Apr 01
TA  - General Psychiatry
PG  - e100440
VI  - 34
IP  - 2
4099  - http://gpsych.bmj.com/content/34/2/e100440.short
4100  - http://gpsych.bmj.com/content/34/2/e100440.full
SO  - Gen Psych2021 Apr 01; 34
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.