The role of cytokines in the pathophysiology of suicidal behavior
Open accessAbstract
Objective Immune dysregulation has been implicated in depression and other psychiatric disorders. What is less clear is how immune dysregulation can affect risk of suicidal behavior. We reviewed the scientific literature concerning cytokines related to suicidal ideation, suicidal behavior and suicide, and surveyed clinical and neurobiological factors associated with cytokine levels that may modulate effects of inflammation on suicide risk.Methods We searched PubMed, Embase, Scopus and PsycINFO for relevant studies published from 1980 through February, 2015. Papers were included if they were written in English and focused on cytokine measurements in patients with suicidal behaviors.Results The literature search yielded 22 studies concerning cytokines and suicidal ideation, suicide attempts or suicide completion. The most consistent finding was elevated interleukin (IL)-6, found in 8 out of 14 studies, in CSF, blood, and postmortem brain. In one study, IL-6 in CSF was also found to be higher in violent than nonviolent attempters and to correlate with future suicide completion. Low plasma IL-2 was observed in 2 studies of suicide attempters, while divergent results were seen for tumor necrosis factor (TNF)-α, interferon (IFN)-γ, transforming growth factor (TGF)-β, IL-4, and soluble Il-2 receptors.Conclusions Given the complexity suggested by the heterogenous cytokine findings, putative mediators and moderators of inflammation on suicidal behavior merit further study. Elevated IL-6 was the most robust cytokine finding, associated with suicidal ideation and both nonfatal suicide attempts and suicides. Future studies should evaluate the predictive value of high IL-6, consider how this may alter brain function to impact suicidal behavior, and explore the potential beneficial effects of reducing IL-6 on suicide risk.
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Findings on IL-4, TGF-β, and other regulatory cytokines are inconsistent.
“Findings on IL-4, TGF-β, and other regulatory cytokines are further inconsistent (71).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [71]
The Results (§3.2.6; page unavailable) report mixed IL-4 findings: one postmortem study found higher levels in suicides, while three other studies found no difference. But §3.2.5 reports no TGF-β difference between depressed attempters and non-attempters, and §3.2.7 says the IL-10 studies found no association with suicidality. The paper supports inconsistency for IL-4 and describes broader heterogeneity, but not inconsistency for every regulatory cytokine named or implied. (LLM, conf=0.82)
Experimental — accuracy not yet measuredResults for IL-1β and TNF-α are inconsistent across studies, with some investigations reporting increased levels in serum or post-mortem PFC and others finding no significant differences between suicidal individuals and psychiatric or healthy controls.
“In contrast, results for other inflammatory cytokines including interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) are not consistent across studies. Some investigations report increased levels in serum or post-mortem PFC, while others find no significant differences between suicidal individuals and psychiatric or healthy controls (71).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [71]
In suicide attempters, both peripheral and central inflammation has been reported.
“In suicide attempters, both peripheral and central inflammation has been reported.30,31”
From Association Between Mood Disorder Severity, Treatment Response and Systemic Inflammatory Markers: Exploring the Role of NLR, PLR, MLR, and SII (2024) · cites this paper as [31]
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- Authors
- Ganança, L., Oquendo, M. A., Tyrka, A. R., Cisneros-Trujillo, S., Mann, J. J., & Sublette, M. E.
- Affiliations
- University of Lisbon (PT)
- Brown University (US)
- New York State Psychiatric Institute (US)
- Columbia University Irving Medical Center (US)
- Corresponding author
- Sublette, M. Elizabeth
- Venue
- Psychoneuroendocrinology
- Publisher
- Elsevier BV
- Published
- 2016-01
- Volume
- 63
- Pages
- 296-310
- ISSN
- 0306-4530 (ISSN-L)
- PMC
- PMC4910882
- OpenAlex
- W1771262887
- Cited by
- 217
- References
- 126
- Citations by year
- 2026: 9 · 2025: 21 · 2024: 28 · 2023: 16 · 2022: 22 · 2021: 26 · 2020: 19 · 2019: 21 · 2018: 29 · 2017: 18 · 2016: 8
- FWCI
- 1.03
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Psychoneuroendocrinology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (P50MH090964, R01MH083704, MH P50 MH090964, R01MH101107)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Keywords
- cytokines, suicidal behavior, suicidal ideation, suicide attempts, suicide completion, interleukin-6, immune dysregulation, inflammation, interleukin-2, TNF-α, interferon-gamma, TGF-beta, IL-4, soluble interleukin-2 receptor, cerebrospinal fluid cytokines, postmortem brain, depression
- MeSH terms
- Depression, Humans, Inflammation, Suicide, Suicide, Attempted, Cytokines, Self-Injurious Behavior, Inflammation Mediators, Suicidal Ideation
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