Proinflammatory cytokines in the prefrontal cortex of teenage suicide victims
Open accessAbstract
Teenage suicide is a major public health concern, but its neurobiology is not well understood. Proinflammatory cytokines play an important role in stress and in the pathophysiology of depression—two major risk factors for suicide. Cytokines are increased in the serum of patients with depression and suicidal behavior; however, it is not clear if similar abnormality in cytokines occurs in brains of suicide victims. We therefore measured the gene and protein expression levels of proinflammatory cytokines interleukin (IL)-1β, IL-6, and tissue necrosis factor (TNF)-α in the prefrontal cortex (PFC) of 24 teenage suicide victims and 24 matched normal control subjects. Our results show that the mRNA and protein expression levels of IL-1β, IL-6, and TNF-α were significantly increased in Brodmann area 10 (BA-10) of suicide victims compared with normal control subjects. These results suggest an important role for IL-1β, IL-6, and TNF-α in the pathophysiology of suicidal behavior and that proinflammatory cytokines may be an appropriate target for developing therapeutic agents.
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Elevated IL-6 levels have been reported in serum, cerebrospinal fluid, and post-mortem prefrontal cortex of individuals with suicidal ideation or attempts.
“Elevated IL-6 levels have been reported in serum, cerebrospinal fluid (CSF), and post-mortem prefrontal cortex of individuals with suicidal ideation or attempts (64–68).”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [67]
The Discussion reports higher IL-6 in suicide attempters in studies of CSF and plasma, while Results §3.3 finds significantly higher prefrontal-cortex IL-6 mRNA in teenage suicide victims. The wording overextends the evidence: the paper discusses plasma rather than specifically demonstrating elevated serum IL-6, its post-mortem subjects were suicide victims rather than people studied for ideation or nonfatal attempts, and the cortical IL-6 protein increase did not reach significance (Results §3.1). (LLM, conf=0.84)
Experimental — accuracy not yet measuredAmong inflammatory markers, interleukin-6 (IL-6) shows the most consistent association with suicidality.
“Among inflammatory markers, interleukin-6 (IL-6) shows the most consistent association with suicidality.”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [67]
The Results (section 3.3; page unavailable) report significantly higher IL-6 mRNA in the prefrontal cortex of teenage suicide victims, supporting an association. But section 3.1 reports that the IL-6 protein increase missed statistical significance while TNF-α and IL-1β protein increases were significant. The paper does not establish that IL-6 has the most consistent association with suicidality among inflammatory markers. (LLM, conf=0.87)
Experimental — accuracy not yet measuredHeightened expression of several pro-inflammatory cytokines, such as IL-6, has been found in the prefrontal cortex of suicide decedents.
“More directly supportive of this hypothesis, heightened expression of several pro-inflammatory cytokines (e.g., IL-6) has been found in the prefrontal cortex of suicide decedents (Pandey et al., 2012; also see Lutz, Mechawar, & Turecki, 2017).”
From Sleep and suicide: A systematic review and meta-analysis of longitudinal studies (2020) · cites this paper as Pandey et al., 2012
Youths who died by suicide had higher levels of IL-6, IL-1β, and TNF-α in the prefrontal cortex than matched healthy controls.
“youths who died by suicide (N = 24) compared with matched healthy controls (N = 24) had higher levels of IL-6, IL-1β, and TNF-α in the PFC (Pandey et al. 2012)”
From Adolescent Suicide as a Failure of Acute Stress-Response Systems. (2019) · cites this paper as Pandey et al. 2012
Growing evidence implicates immune dysregulation and inflammatory signaling in the biological vulnerability underlying suicidal ideation, suicide attempt, and death by suicide.
“Growing evidence implicates immune dysregulation and inflammatory signaling in the biological vulnerability underlying suicidal ideation, suicide attempt, and death by suicide.”
From Exploring the neurobiological markers of suicidal behaviors in pediatric population: a narrative review (2026) · cites this paper as [67]
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References 55 · Cited by 378
- Authors
- Pandey, G. N., Rizavi, H. S., Ren, X., Fareed, J., Hoppensteadt, D. A., Roberts, R. C., Conley, R. R., & Dwivedi, Y.
- Affiliations
- University of Illinois Chicago (US)
- Loyola University Medical Center (US)
- University of Alabama at Birmingham (US)
- Eli Lilly (United States) (US)
- Corresponding author
- Pandey, Ghanshyam N.
- Venue
- Journal of Psychiatric Research
- Publisher
- Elsevier BV
- Published
- 2012-01
- Volume
- 46
- Issue
- 1
- Pages
- 57-63
- ISSN
- 0022-3956 (ISSN-L)
- PMC
- PMC3224201
- OpenAlex
- W1989580462
- Semantic Scholar
- a15dd899e6d489f7e457c367e00a3355f7120cd2
- Cited by
- 378
- References
- 55
- Citations by year
- 2026: 11 · 2025: 24 · 2024: 24 · 2023: 24 · 2022: 22 · 2021: 55 · 2020: 34 · 2019: 27 · 2018: 32 · 2017: 27 · 2016: 28 · 2015: 20 · 2014: 24 · 2013: 22 · 2012: 3
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Psychiatric Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Mental Health (R01-MH48153, R01MH048153)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- adolescent suicide, inflammatory cytokines, prefrontal cortex, IL-1β, interleukin-6, TNF-α, Brodmann area 10, gene expression, protein expression, neuroinflammation, depression, suicide risk factors
- MeSH terms
- Adolescent, Child, Enzyme-Linked Immunosorbent Assay, Female, Gene Expression Regulation, Humans, Male, Postmortem Changes, RNA, Messenger, Suicide, Cytokines, Prefrontal Cortex, Young Adult
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