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

Abstract Bipolar disorder (BD) is a debilitating condition associated with a high prevalence of medical comorbidities and premature mortality. This is the first study to explore, through high-throughput-omics combined with bioinformatics, molecular signatures, pathways, and main medical diseases related to different stages of BD. Blood samples from BD patients (n=10) classified into high (BD+) or poor functioning (BD-), based on functional and cognitive status, and healthy controls (n=5) were analyzed using mass spectrometry-based proteomic analysis. Bioinformatics was performed to detect biological processes, pathways, and diseases related to BD. 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. 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. Competing Interest Statement The authors have declared no competing interest. Funding Statement This work was financially supported by Fundacao de Amparo a Pesquisa do Estado do Rio Grande do Sul - FAPERGS (19/ 2551-0001728-6) and Fundo de Incentivo a Pesquisa e Eventos do Hospital de Clinicas de Porto Alegre FIPE (20190640). Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Institutional Review Board of Hospital de Clinicas de Porto Alegre gave ethical approval for this work (project number 20190640). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Data Availability All data produced in the present study are available upon reasonable request to the authors.