PAID study design on the role of PKC activation in immune/inflammation-related depression: a randomised
Xiaoyun Guo1, Ruizhi Mao1, Lvchun Cui1
1Department of Psychiatry, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
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.
Insights
This study investigates targeting the Protein Kinase C (PKC) pathway to treat treatment-resistant depression (TRD). Activating PKC may offer new therapeutic strategies for depression by modulating neuroinflammation.
Area of Science:
- Neuroscience
- Psychiatry
- Immunology
Background:
- Microglia activation-mediated inflammation is crucial in depression pathogenesis.
- Proinflammatory cytokines like TNF-α contribute to neuronal apoptosis and treatment-resistant depression (TRD).
- Protein Kinase C (PKC) regulates microglia activation; its abnormality may drive TRD.
Purpose of the Study:
- To investigate the role of the PKC signal pathway in TRD.
- To evaluate targeting the PKC pathway as a novel therapeutic strategy for TRD.
Main Methods:
- A 12-week, randomized, placebo-controlled trial involving 180 TRD patients and 60 healthy controls.
- TRD patients were assigned to escitalopram with either a TNF-α inhibitor, a PKC activator (calcium tablet+vitamin D), or placebo.
- Primary outcome: change in Hamilton Depression Rating Scale (HAMD-17); secondary outcomes: anti-inflammatory effects, cognition, and quality of life.
Main Results:
- Primary outcome data on HAMD-17 changes are pending.
- Secondary outcome data on anti-inflammatory effects, cognitive function, and quality of life are pending.
Conclusions:
- This trial may be the first to target the PKC pathway in TRD patients via a randomized, placebo-controlled design.
- Findings could inform individualized treatment strategies for depression.
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