November 21, 2025Annals of General PsychiatryOpen Access

Pro-inflammatory cytokines level in depressed patients with suicidal behaviour: a systematic review and meta-analysis

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Why the study?

Proinflammatory factors were evaluated in major depressive disorder patients with and without suicidal behaviors versus healthy controls to identify potential biomarkers for suicidal behaviors and prevention strategies.

Do pro-inflammatory cytokine levels differ in depressed patients with suicidal behavior compared to those without suicidal behavior and healthy controls?

Structured PICO

Do pro-inflammatory cytokine levels differ in depressed patients with suicidal behavior compared to those without suicidal behavior and healthy controls?

Population

2,669 participants from 24 observational studies, including individuals diagnosed with depressive disorder (MDD or major depressive episodes) with suicidal behavior, depressed patients without suicidal behavior, and healthy controls.

Intervention

Assessment of pro-inflammatory cytokine levels (TNF-α, IF-y, TGF-β1, IL-6, IL-10, IL-4, IL-2, IL-1β)

Comparator

Depressed patients without suicidal behavior and healthy controls

Outcome

Levels of pro-inflammatory cytokines (TNF-α, IF-y, TGF-β1, IL-6, IL-10, IL-4, IL-2, IL-1β)surrogate

While IL-6 is elevated in depressed patients with suicidal behavior compared to healthy controls, there are no significant differences in pro-inflammatory cytokines between depressed patients with and without suicidal behavior, suggesting these markers may relate more to depression itself than suicidality.

Limitations

High heterogeneity across studies (I² > 90% for most analyses)
Methodological differences between included studies

Implication

IL-6 elevation may reflect depression rather than suicidality; leaves open whether cytokines independently predict suicidal behavior.

Abstract

INTRODUCTION: The study assesses proinflammatory factors in major depressive disorder (MDD) patients with and without suicidal behaviors, and healthy controls, to identify potential biomarkers for suicidal behaviors and prevention strategies. METHODS: We conducted a systematic review, which we have registered in Prospero (#CRD42024547764), and searched through five databases until March 2024. We included observational studies in English that reported on depressed patients with and without suicidal behaviors, as well as healthy controls, and measured the levels of pro-inflammatory cytokines. The Newcastle- Ottawa Scale was used for quality evaluation of the studies and the main analysis was performed using Stata 17. RESULTS: One systematic review resulted in 4,369 articles but only 24 were selected for the review. The meta-analysis showed depressed patients with suicidal behaviors had significantly higher interleukin (IL)-6 levels compared to the control group with a standardized mean difference (SMD) of 1.26 [0.07, 2.45]; I² = 98.81%. There was no significant difference noted between the depressed patients suffering from suicidal behaviors and those not suffering (SMD 0.42 [-0.58, 1.42]; I² = 98.50%). There is no significant difference between the groups in the levels of tumor necrosis factor-alpha (TNF-α) and IL-10. Further analysis of IL-4, IL-2, IL-1β, IF-γ, and TGF-β1 also indicated no significant group differences. CONCLUSION: The review found no significant cytokine differences (including IFN-γ, IL-1β, IL-2, IL-4, IL-8, IL-10, TGF-β1, TNF-α) between depressed individuals with or without suicidal ideation and controls. Variations likely reflect methodological differences, highlighting the need for standardized, longitudinal research.