Potential Candidates for Biomarkers in Bipolar Disorder: A Proteomic Approach through Systems Biology

Abstract

Bipolar disorder (BD) is one of the most disabling diseases characterized by severe humor fluctuation. It is accompanied by cognitive and functional impairment in addiction to high suicide rates. BD is often underdiagnosed and treated incorrectly because many of the reported symptoms are not exclusive to the disorder. Once the diagnosis is exclusively clinical, it is not possible to state precisely. From that, proteomic approaches were used to identify, in a large scale, all proteins involved in cellular or tissue processes. This review aggregate data from blood proteomes, by using protein association network, of subjects with BD and healthy controls to suggest dysfunctional molecular pathways involved in disease. Original articles containing proteomic analysis were searched in PubMed. Seven studies were selected and data were extracted for posterior analysis. A protein-protein interaction network was created by STRING database. A final set of proteins in this network were employed as input in ClueGO and, the main biological process was visualized using R package pathview. The analysis revealed proteins associated with many biological processes, including growth and endocrine regulation, iron transportation, protease inhibition, protection against pathogens and cholesterol transport. Moreover, pathway analysis indicated the association of uncovered proteins with two main metabolic pathways: complement system and coagulation cascade. Thus, a better understanding on the pathophysiology of psychiatric disorders and the identification of potential biomarker candidates are essential to improve diagnostic, prognostic and design pharmacological strategies.

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].…”

Proteomic insights into mental health status: plasma markers in young adults

“…Proteomics approaches have been utilized for the identification of protein signatures associated with specific psychological disorders [ 20 – 22 ]. For example, several growth factors (BDNF, VEGF, NGF) and cytokines (IL-1β, IL-6, IFN-α) have been linked to depression [ 23 ].…”

Proteomic insights into mental health status: plasma markers in young adults

“…Proteomics approaches have been utilized for the identification of protein signatures associated with specific psychological disorders (Comes et al 2018;Domenici et al 2010;Ziani et al 2022). For example, several growth factors (BDNF, VEGF, NGF) and cytokines (IL-1β, IL-6, IFN-α) have been linked to depression (Malik et al 2021).…”