Integrating cellular and soluble immune signatures of major depression with and without recent suicide attempts

Suicide attempts (SA) during major depressive episodes (MDE) pose a significant clinical challenge, yet its underlying biological mechanisms, particularly those associated with recent SA, remain poorly understood. In this case-control study (n = 106), we compared the immunological profiles associated with MDE without SA (n = 36), MDE with a recent SA (n = 35), and a healthy controls (n = 35). Fresh blood samples were analyzed for total cell count and using flow cytometry (FACS) to assess specific cell surface markers. Plasma proteins were quantified using multiplex ELISA or Quanterix. Multiple factorial analysis (MFA) identified three primary dimensions structuring the biological markers: soluble immune and growth factors, cellular immunity (cell ratios, CD45⁺, CD3⁺, CD8⁺, CD14⁺), and neuroinflammatory markers (GFAP, NfL, CD4+). These dimensions differentiated MDE patients from healthy controls regardless of SA status. Three parallel feature selection analyses were used to examine whether individual biomarkers could differentiate between the subgroups. Lower percentages of CD3⁺, CD8⁺CD3⁺, higher basophil count, and lower serotonin levels differentiated MDE without SA from healthy controls. An increased neutrophil-to-lymphocyte ratio and basophil count, and lower serotonin levels differentiated recent SA from healthy controls. We found no significant differences between MDE patients with and without SA, though exploratory analyses identified individual markers, such as platelet-derived factors, that warrant further investigation. These findings provide new insights into the immune landscape of MDE and recent SA and underscore the need for future longitudinal studies to disentangle state- and trait-like biological changes associated with SA.