sTREM2 as a mediator in the association between life-threatening events and depression

Depression is a highly prevalent and disabling condition, affecting approximately 280 million people globally. Emerging evidence points to a significant role of neuroinflammation in the pathophysiology of depression. The soluble triggering receptor expressed on myeloid cells-2 (sTREM2) has been identified as a potential marker of neuroinflammation.

This study aims to investigate the potential mediating role of sTREM2 in the relationship between perceived stress, measured by the List of Threatening Events, and current depressive symptoms in patients with major depressive episodes (MDE).

This secondary analysis was conducted on data from a multicenter, case-control study of participants with current MDE (n = 39) and healthy controls (HC, n = 42). Plasma sTREM2 levels were measured using bead-based multiplex assays. Depression was assessed using the Hamilton Depression Rating Scale (HDRS-17) and Life-Threatening Events (LTE) were quantified with the Stressful Life Events Scale. A mediation analysis was conducted to explore the role of sTREM2 in the relationship between depression and LTE.

Patients with current MDE exhibited higher plasma sTREM2 levels compared to HC (p = 0.006). Recent stress was positively associated with sTREM2 (p = 0.032), and both LTE scores and sTREM2 levels were significant predictors of current MDE (p = 0.009, p = 0.035). Mediation analysis showed that sTREM2 accounted for 17 % of the relationship between recent stress and depression (p = 0.028).

Our findings suggest that sTREM2 may play a mediating role in the link between stress and depression, highlighting neuroinflammation as a potential pathway in the development of depression.