Serum NLRP3 Inflammasome and BDNF: Potential Biomarkers Differentiating Reactive and Endogenous Depression

Abstract

BackgroundThe highly heterogeneous pathogenesis of depression and limited response to current antidepressants call for more objective evidence for depression subtypes. Reactive and endogenous depression are two etiologically distinct subtypes associated with different treatment responses. This study aims to explore the potential biomarkers that differentiate reactive and endogenous depressions.MethodsThe clinical manifestations and biological indicators of 64 unmedicated mild-to-moderate depression patients (32 reactive depression patients and 32 endogenous depression patients) and 21 healthy subjects were observed. The 24-item Hamilton rating scale for depression (HAMD-24) was used to evaluate the severity of depression. Serum levels of depression-related biological indicators were measured by using the enzyme-linked immunosorbent assay.ResultsThe NLRP3 level of reactive depression was significantly lower than those of endogenous depression and healthy controls. There was a significant negative correlation between the BDNF level and the HAMD-24 total scores for patients with reactive depression.ConclusionOur findings suggested the serum NLRP3 and BDNF levels could be potential biomarkers for detecting and evaluating the severity of reactive depression.

Berberine ameliorates depression-like behaviors in mice via inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing neuroplasticity disruption

“…NLRP3 was found to be overexpressed as a hub gene in the PFC of CORT-induced depression mice, suggesting that NLRP3 might play a key role and take part in the development and pathogenesis of depression. Findings from previous preclinical and clinical studies have indicated that NLRP3 inflammasome-driven pathways might be involved in numerous neuropsychiatric disorders including neuroinflammation-induced depression [ 14 , 27 – 30 ]. As revealed by western blotting and immunofluorescence labeling, the current data suggest that the NLRP3 signaling pathway was activated in CORT-induced depression mice, while berberine downregulated the NLRP3 signaling pathway in the hippocampus and PFC.…”

Recent Blood and Intracranial Molecular Biomarkers to Moderate Depression and Major Depressive Disorder

“…However, the study was only appropriate to people with mild to moderate depression, according to the article. At the same time, it was found during the experiment that after controlling for covariates, the combined dependent variable between the groups did not show any significant difference, which greatly reduced the accuracy of detection [15].…”

“…Additionally, scientists found that the expression of HDAC affects the expression of brain-derived neurotrophic factor (BDNF) [15]. BDNF is a key ligand that directs ongoing neuroplastic processes required for neurodevelopment and behavioral adaptation, and can be used to slow neuroinflammation while contributing to the development of the nervous system [15]. Through various experiments, it was found that the concentration of BDNF in most patients with depression was significantly lower.…”

“…Innate immunological responses such as infection, inflammation, and autoimmunity are mediated by NLRP3, an intracellular multiprotein complex. In a research report, it was stated that the level of NLRP3 protein in peripheral blood mononuclear cells of patients with depression was higher than that of non-depressed patients [15]. Thus, there is a relationship between the NLRP3 inflammasome and mild to moderate depressive symptoms, according to preclinical studies.…”

“…Aside from the fact that NLRP3 can be used to diagnose depression, researchers discovered that serum NLRP3 levels in the reactive depression group were considerably lower than those in the endogenous depression group and the healthy group [24]. Therefore, the concentration of serum NLRP3 inflammasome can also be used to distinguish reactive depression from endogenous depression, which can provide targeted treatment for different patients [15]. However, the study was only appropriate to people with mild to moderate depression, according to the article.…”