The Role of PKC Activation in the Immune-inflammatory Mechanism of Major Depressive Depression

Summary

Major Depressive disorder (MDD) is a heterogeneous mental illness. Treated with antidepressants that act on the neurotransmitter and/or their receptors just remitted only one third of patients with MDD, Thus, to improve the efficacy is a major unmet need for depression. Based on the scientific reports, inflammation plays a definite role in the development and treatment of depression, which may be an important way to understand and finally solve the problem. Our team found that there were significant changes in tumor necrosis factor (TNF)-α and other inflammatory factors in depressed patients, which caused neuronal apoptosis and depressive symptoms; PRKCB1(gene of protein kinase C-β) plays an anti-inflammatory role by regulating protein kinase C(PKC) activation in specific brain region, improving neuroplasticity and playing an antidepressant role. In this study, we assumes that the treatment-resistant depression patients maybe due to the immune inflammation and PKC activation inconsistency or unsynchronized, which couldn't reversible microglia polarization and neuronal apoptosis in specific brain regions, then, caused the significant changes at emotional and cognitive neural circuits, so as to exhibit such as emotional, cognitive symptoms of depression. Therefore, activating PKC and regulating immune/inflammatory process will be another way to improve the treatment outcome of depression. Take consideration, we focus on treatment-resistant depression patients, to validate the relationship between PKC activation and the immune inflammatory mechanism of depression, evaluate the antidepressant effect of golimumab or calcium tablet (a PKC activator) plus escitalopram, and initially proposes idividualized treatment strategies for MDD.

Timeline

Start

2020-07-01

Primary completion

2024-12-31

Completion

2024-12-31

Publications

• Guo X, Mao R, Cui L, Wang F, Zhou R, Wang Y, Huang J, Zhu Y, Yao Y, Zhao G, Li Z, Chen J, Wang J, Fang Y. PAID study design on the role of PKC activation in immune/inflammation-related depression: a randomised placebo-controlled trial protocol. Gen Psychiatr. 2021 Apr 5;34(2):e100440. doi: 10.1136/gpsych-2020-100440. eCollection 2021.

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Indications