Systematic Review and Meta-Analysis on MS-Based Proteomics Applied to Human Peripheral Fluids to Assess Potential Biomarkers of Bipolar Disorder

Abstract

Bipolar disorder (BD) is a clinically heterogeneous condition, presenting a complex underlying etiopathogenesis that is not sufficiently characterized. Without molecular biomarkers being used in the clinical environment, several large screen proteomics studies have been conducted to provide valuable molecular information. Mass spectrometry (MS)-based techniques can be a powerful tool for the identification of disease biomarkers, improving prediction and diagnosis ability. Here, we evaluate the efficacy of MS proteomics applied to human peripheral fluids to assess BD biomarkers and identify relevant networks of biological pathways. Following PRISMA guidelines, we searched for studies using MS proteomics to identify proteomic differences between BD patients and healthy controls (PROSPERO database: CRD42021264955). Fourteen articles fulfilled the inclusion criteria, allowing the identification of 266 differentially expressed proteins. Gene ontology analysis identified complement and coagulation cascades, lipid and cholesterol metabolism, and focal adhesion as the main enriched biological pathways. A meta-analysis was performed for apolipoproteins (A-I, C-III, and E); however, no significant differences were found. Although the proven ability of MS proteomics to characterize BD, there are several confounding factors contributing to the heterogeneity of the findings. In the future, we encourage the scientific community to use broader samples and validation cohorts, integrating omics with bioinformatics tools towards providing a comprehensive understanding of proteome alterations, seeking biomarkers of BD, and contributing to individualized prognosis and stratification strategies, besides aiding in the differential diagnosis.

Proteomic Insights into Biology of Bipolar Disorder: Implications for Health Complexity and Mortality

“…Regarding biological processes and pathways, our findings support previous studies [16]–[19], indicating that the interplay between the complement system and coagulation cascade is involved in the etiology and progression of BD. The complement system originates from the serine protease reaction cascade, sharing a common ancestry with the coagulation factors encoded by the same ancestor genes [20], [21].…”

Systematic Review and Meta-Analysis of Mass Spectrometry Proteomics Applied to Human Peripheral Fluids to Assess Potential Biomarkers of Schizophrenia

“…In fact, of the six studies reporting the illness duration, four of them are studies that also compared SCZ and BD groups. The lack of interest in the illness duration is very different from what is observed in BD studies [110], where this parameter is reported in the majority of the studies.…”

“…Significant differences related to diagnostic criteria used, medical and psychiatric comorbidities reported, psychopharmacological treatment and its duration, as well as the sociodemographic variables such as age, illness duration, gender balance, diet, and use of tobacco, alcohol, or other psychoactive substances, among others, were observed in the selected studies. These limitations were also observed in a BD systematic review [110], suggesting common limiting factors across the psychiatric disorders studies using MS proteomics approaches, thus highlighting the need for more standardized, or at least more controlled, cohort characteristics.…”

Master Regulator Candidates in Bipolar Disorder: An in silico Transcriptome Analysis in Psychiatry

“…In addition to the in ammatory response involving cytokines, another critical and essential mechanism in in ammation is the coagulation cascade activation since thrombin -the enzyme that catalyzes the conversion of brinogen to brin -has pro-in ammatory functions [71], [72]. Data from patients' blood analyzed by mass spectrometry and gene ontology showed the involvement of complement and coagulation cascade in BD physiopathology by identifying speci c proteins such as the third component of complement and apolipoprotein A involved in these processes [73], [74]. A pilot study also indicated the dysregulation of the coagulation cascade in treated schizophrenia and BD patients through proteome analysis, reinforcing the importance of these biological processes in psychiatric disorders [75].…”