Proteomic insights into biology of bipolar disorder: implications for health complexity and mortality

Abstract Objective: The present study has the following objectives: 1) identify differentially expressed proteins and pathways in blood samples of bipolar disorder (BD) compared to healthy controls (HC) by employing high-throughput proteomics and bioinformatics; and 2) characterize disease-related molecular signatures through in-depth analysis of the differentially expressed proteins and pathways. Methods: Blood samples from patients with BD (n = 10) classified into high (BD+) or poor functioning (BD-), based on functional and cognitive status, and HC (n = 5) were analyzed using mass spectrometry-based proteomic analysis. Bioinformatics was performed to detect biological processes, pathways, and diseases related to BD. Results: Eight proteins exclusively characterized the molecular profile of patients with BD+ compared to HC, while 26 altered proteins were observed in the BD- group. These altered proteins were mainly enriched in biological processes related to lipid metabolism, complement system and coagulation cascade, and cardiovascular diseases; all these changes were more prominent in the BD- group. Conclusion: These findings may represent systemic alterations that occur with the progression of the illness and a possible link between BD and medical comorbidities. Such comprehensive understanding provides valuable insights for targeted interventions, addressing mental and physical health aspects in subjects with BD. Despite these promising findings, further research is warranted, encompassing larger sample cohorts and incorporating biological validation through molecular biology methods.