Immune-related biomarkers and suicidal behaviors: A meta-analysis

Biomarkers that can differentiate between psychiatric disorders with and without suicidal behavior history from each other and from healthy volunteers may explain part of the pathogenesis of suicidal behavior. We conducted the hitherto largest meta-analysis comparing immune biomarkers between subjects with and without suicide attempt history or death by suicide. The study protocol was registered with PROSPERO, CRD42020212841. Standardized mean differences (SMD) were pooled with random-effects models. Heterogeneity between studies was assessed with the I2-statistic and publication bias was evaluated by the Egger test and funnel plots. Data were based on 36 studies including 2679 persons with suicidal behaviors and 6839 comparison subjects, and four immune-related biomarkers (CRP, IL-6, TNF-α and IL-1β). Suicidal behavior was associated with higher CRP blood levels compared with: healthy controls (SMD 95%CI = 1.420.85–1.98); patients with depression alone (SMD 95%CI = 1.230.20–2.26); and patients with any psychiatric disorders (SMD 95%CI = 0.390.22–0.55). IL-6 blood level was higher in patients with suicidal behaviors compared with healthy controls (SMD 95%CI = 1.130.45–1.82) and when compared with psychiatric patients without suicidal behaviors (SMD 95%CI = 0.22 0.11–0.33). Meta-regression and subgroup analyses revealed that increased CRP in suicidal behavior is primarily driven by recent suicidal behavior. These results implicate the immune system and inflammatory response in suicidal behavior independent of a relationship to major psychiatric disorders, and that these biological measures are predominantly state-dependent markers. Future studies are needed to determine the cause-and-effect relationship of these immune system biomarkers with suicidal behavior, and their potential predictive properties.