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

• Published in: European neuropsychopharmacology Vol. 75; pp. 15 - 30
• Main Authors: Neupane, Sudan Prasad, Daray, Federico M., Ballard, Elizabeth D., Galfalvy, Hanga, Itzhaky, Liat, Segev, Aviv, Shelef, Assaf, Tene, Oren, Rizk, Mina M., Mann, J. John, Zalsman, Gil
• Format: Journal Article
• Language: English; Norwegian
• Published: Netherlands Elsevier B.V 01.10.2023
• Subjects: Biomarkers; C-reactive protein; Depression; Humans; Immune; Interleukin-6; Mental Disorders; Suicidal behavior; Suicidal Ideation; Suicide; Suicide, Attempted; Biomarkers; Depression; Suicidal behavior; C-reactive protein; Suicide; Immune
• ISSN: 0924-977X; 1873-7862
• DOI: 10.1016/j.euroneuro.2023.05.009

•We meta-analyzed immune-related biomarkers in suicidal behavior.•Suicidal behavior in depression and other psychiatric disorders is associated with increased blood CRP and IL-6.•Recent suicidal behavior is associated with further elevated blood CRP levels.•Inflammatory biomarkers are promising state-dependent markers for suicidal behavior. 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.