Signaling networks in inflammatory pathways and risk for suicidal behavior
Open accessAbstract
Suicide is a leading cause of death in the young adult population, with few biological markers identified thus far to be associated with suicidality. Cytokines (including IL-6 and TNFα) may contribute to increased risk for depression and suicidality. Few studies have examined the associations of cytokine mRNA expression with depression and suicidal ideation and behavior. This study examines these associations and whether cytokine signaling networks differentiate suicide attempters (SA), suicide ideators (SI), and healthy controls (HC). Cytokine pathway marker (CPM; e.g. cytokines and proteins in cytokine signaling pathways) mRNA gene expression in whole blood was examined in suicide attempters (n = 38), suicide ideators (n = 38), and healthy controls (n = 36). Between-group differences in CPM gene expression were examined. We also examined association of the mRNA of these genes with the severity of depression and suicidal ideation. Novel Gaussian Graphical Model (GGM) techniques were utilized to examine between-network partial correlation differences in cytokine signaling networks relevant to IL-6 and TNFα signaling pathways. The severity of depression symptoms was positively associated with TNFα mRNA levels and negatively associated with IL-10 mRNA levels, but CPM expression was not associated with suicidal ideation severity. There were no between-group differences in CPM markers among healthy controls, SI and SA groups after correcting for multiple comparisons. In network analyses, we found suggestive results of between-group network differences between SI and control groups in gene pairs with IL-6R and STAT3 as common nodes. In a cohort of suicide attempters and ideators, TNFα and IL-10 mRNA levels appear to be associated with depressive symptomology, consistent with elevation of pro-inflammatory cytokine production and reduction of anti-inflammatory cytokine production. Additionally, cytokine signaling networks may differentiate suicide ideators from healthy controls based on between-network differences, with differences possibly related to relationships of IL6R or STAT3 with other components of cytokine signaling networks.
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A recent study reports no association between suicidal ideation severity and cytokine pathway marker mRNA expression.
“However, a recent study reports no association between suicidal ideation severity and cytokine pathway marker mRNA expression (217), and longitudinal studies are needed to determine whether fluctuating suicide risk correlates with severity of inflammation.”
From A brain-centric model of suicidal behavior (2020) · cites this paper as [217]
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Self-citation
- Authors
- Rengasamy, M., Zhong, Y., Marsland, A., Chen, K., Douaihy, A., Brent, D., & Melhem, N. M.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Melhem, Nadine M.
- Venue
- Brain, Behavior, & Immunity - Health
- Publisher
- Elsevier BV
- Published
- 2020-08
- Volume
- 7
- Pages
- 100122
- ISSN
- 2666-3546 (ISSN-L)
- PMC
- PMC8009526
- OpenAlex
- W3046603774
- Cited by
- 21
- References
- 51
- Citations by year
- 2026: 1 · 2025: 7 · 2024: 2 · 2023: 6 · 2022: 2 · 2021: 2 · 2020: 1
- FWCI
- 0.82
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Brain Behavior & Immunity - Health (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of Mental Health
- National Institutes of Health
- 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
- suicide, suicidal ideation, suicide attempters, interleukin-6, TNF-α, IL-10, IL-6 receptor, STAT3, depression severity, inflammatory signaling, whole blood gene expression
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