Dysregulation of cytoskeletal organization, energy metabolism, complement cascade, and coagulation associated with...

Suicidal behavior is highly variable regarding severity of ideation and lethality, which may be reflected in central and systemic proteomic modifications. This study aimed to identify the proteomic profile by mass spectrometry analysis, pathways, and biological processes underlying suicidal behavior. We systematically reviewed three databases, including studies of postmortem brain tissue of suicide completers, and analyzed serum from individuals hospitalized after recent suicide attempts. The Biological General Repository for Interaction Datasets (BioGRID) was used to verify interactions between identified proteins, followed by functional enrichment analysis to determine the main biological processes and pathways. Over 700 differentially expressed proteins (DEP) were found in the postmortem brain of suicide victims, while 36 DEP were identified in the serum of individuals with suicide attempts. Four common DEPs (serum amyloid P-component, beta-2-glycoprotein 1, hemoglobin subunit beta, and S100 calcium-binding protein A9) were found in both tissues. Biological processes and pathways indicated disturbance on cytoskeletal organization, energy metabolism, complement cascade, and coagulation as key mechanisms associated with suicidal behavior. Despite preliminary findings, our work provides molecular insights into the biological underpinnings of suicidal behavior and contributes to the identification of promising candidate targets for suicide risk, an urgent and still largely unmet need in psychiatric research. Nevertheless, analytical validation using complementary molecular techniques in larger, independent samples is essential to confirm their reproducibility and quantification accuracy.