HPA axis, inflammation and suicidality in borderline personality disorder: a biomarker-focused analysis

Abstract

Dysregulation of the stress axis and low-grade inflammation may contribute to suicidal thoughts and acts in borderline personality disorder. Evidence synthesis (2020–2025) of narrative/systematic reviews and large observational studies in adults. Biomarkers included circulating and hair cortisol, diurnal cortisol profiles and dexamethasone paradigms, alongside inflammatory indices (C-reactive protein, interleukin-6, tumor necrosis factor). Outcomes were suicidal ideation, suicide attempts, suicide deaths, and self-harm. Inflammatory markers are consistently higher in borderline personality disorder with suicidality, with small-to-moderate between-group differences most frequently reported for C-reactive protein and interleukin-6. Findings for the stress axis are heterogeneous: several studies show flatter diurnal cortisol slopes or lower hair cortisol in suicidal subgroups, while acute suppression tests identify a non-suppressing subset with elevated risk. Associations generally persist after adjustment for depressive symptoms, though effect sizes attenuate and prospective data remain limited. Combining inflammatory and stress-axis measures improves discrimination over single markers, but calibration is variable across settings. Overall, biomarkers show additive, clinically meaningful signals yet lack standardized cut-offs and external validation. Research priorities include harmonized sampling protocols, preregistered prospective cohorts, and integration with sleep, impulsivity, and digital phenotypes to refine short-term risk stratification.