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

Sudan Prasad Neupane*, Federico M. Daray, Elizabeth D. Ballard, Hanga Galfalvy, Liat Itzhaky, Aviv Segev, Assaf Shelef, Oren Tene, Mina M. Rizk, J. John Mann, Gil Zalsman

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


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] = 1.42[0.85–1.98]); patients with depression alone (SMD [95%CI] = 1.23[0.20–2.26]); and patients with any psychiatric disorders (SMD [95%CI] = 0.39[0.22–0.55]). IL-6 blood level was higher in patients with suicidal behaviors compared with healthy controls (SMD [95%CI] = 1.13[0.45–1.82]) 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.

Original languageEnglish
Pages (from-to)15-30
Number of pages16
JournalEuropean Neuropsychopharmacology
StatePublished - Oct 2023


  • Biomarkers
  • C-reactive protein
  • Depression
  • Immune
  • Suicidal behavior
  • Suicide


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