Inflammatory markers and suicidal behavior: A comprehensive review of emerging evidence

Abstract

Background

Suicidal behavior represents a significant public health challenge, and identifying biological markers associated with its risk is critical for prevention and intervention. Emerging evidence suggests a link between inflammation and suicidality, highlighting the role of inflammatory markers as potential biomarkers and therapeutic targets.

Methods

We conducted a systematic search across four electronic databases, including PubMed, Web of Science, EMBASE, and PsycINFO, to identify studies examining the association between inflammatory markers (e.g., C-reactive protein, interleukin-6, tumor necrosis factor-alpha) and suicidal ideation or behavior.

Results

31 studies met the inclusion criteria. Elevated levels of inflammatory markers were consistently associated with an increased risk of suicidal behavior across diverse populations. This relationship’s mechanisms likely involve cytokine-mediated alterations in neurotransmitter systems, neuroplasticity, and stress response pathways. Though robust clinical trials are scarce, preliminary evidence suggests that anti-inflammatory interventions may reduce suicidality.

Conclusions

Inflammation appears to play a significant role in the pathophysiology of suicidal behavior, offering promising avenues for biomarker development and novel therapeutic strategies. Future research should prioritize longitudinal studies, standardized methodologies, and exploration of personalized anti-inflammatory treatments to better elucidate the inflammation-suicidality link and enhance clinical applicability.

Introduction

Suicidal behavior represents a significant global phenomenon and a critical public health issue. Conservative estimates indicate that over 700,000 individuals die by suicide annually [1]. Despite growing research efforts in recent years, the pathophysiological mechanisms underlying suicidal behavior remain poorly understood, mainly due to the complex interplay of diverse risk factors across multiple domains. Most studies conceptualize suicidal behavior within a stress-diathesis framework, which highlights the role of distal vulnerability factors (e.g., family history of suicide, early-life adversity, and genetic predispositions) alongside proximal stressors (e.g., psychiatric disorders, feelings of hopelessness, or sleep disorders) [2–5].

While research has extensively explored psychosocial risk factors, the biological underpinnings of suicidal behavior remain less understood but increasingly recognized as crucial contributors [6, 7]. In recent years, the role of inflammation as a mediator of suicide risk has gained significant attention. This interest is rooted in growing evidence linking immune system dysregulation to alterations in brain function, which may drive behavioral changes associated with suicidality [8]. Elevated levels of systemic inflammatory markers, including cytokines such as interleukin-6 (IL-6), interleukin-1β (IL-1β), C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-α), have been consistently observed in individuals with major depressive disorder, particularly those exhibiting suicidal thoughts or behaviors [9]. These markers are thought to influence neurobiological pathways, such as serotonergic signaling, the hypothalamic-pituitary-adrenal (HPA) axis, and microglial activation, which have long been implicated in the pathophysiology of mental illness and suicide [10].

Furthermore, the relationship between inflammation and suicidal behavior may be modulated by other factors, such as genetic predispositions, chronic stress, and environmental exposures. For example, specific polymorphisms in inflammatory genes have been associated with increased suicide risk, suggesting a potential gene-environment interaction [11]. Similarly, stress-induced activation of the immune system, often observed in individuals with a history of trauma or chronic adversity, may exacerbate inflammatory responses, creating a feedback loop that amplifies neuropsychiatric symptoms and vulnerability to suicide [12].

Despite these findings, critical gaps remain in understanding the precise mechanisms linking inflammation to suicidality. For instance, it is unclear whether inflammation is a direct causal factor or a downstream effect of psychiatric comorbidities. Additionally, the variability in study methodologies, ranging from sample selection to biomarker measurement, has contributed to inconsistent results across the literature [13]. These limitations underscore the need for comprehensive reviews integrating findings from diverse studies to provide a clearer picture of this complex relationship.

This review aims to synthesize emerging evidence on the role of inflammatory markers in suicidal behavior, evaluate the clinical and mechanistic implications of these findings, and identify gaps in the literature that require future research. By elucidating the biological underpinnings of suicidality, we hope to contribute to the development of novel therapeutic approaches that target inflammation and reduce suicide risk. Based on the emerging evidence, we hypothesized that elevated levels of pro-inflammatory cytokines are associated with an increased risk of suicidal behavior across different populations, and that inflammation might represent a pathophysiological mechanism linking psychiatric disorders and suicidality.

Method

This systematic review was conducted and reported according to the preferred reporting items for systematic reviews and meta-analysis PRISMA guidelines [14]. The study protocol was registered in advance on PROSPERO (CRD42024624050).

Search strategy

A systematic search was conducted on PubMed, Web of Science, EMBASE, and PsycINFO using the following search criteria (“systemic inflammation” OR “inflammatory biomarkers” OR “neuroinflammation” OR “cytokines” OR “CRP” OR “IL-6” OR “TNF-alpha”) AND (“suicide” OR “suicidal ideation” OR “suicide attempt” OR “suicidal behavior”).

Eligibility criteria

We included studies that examined the association between inflammatory markers and suicidal behavior, including suicidal ideation, attempts, or completed suicide, in human populations. Eligible studies assessed inflammatory markers such as CRP, IL-6, TNF-α, or other cytokines. Observational study designs (e.g., cross-sectional, case-control, and cohort studies) and clinical trials were included. There were no restrictions on participant age, sex, or geographical location. Studies were required to provide original data and report precise measurements of inflammatory markers and suicidal outcomes. Only articles published in English were considered, and no restrictions were applied regarding publication date.

Selection of the studies

All relevant original research articles were identified based on their titles and abstracts during the screening phase. At this stage, articles without pertinent information, including those not written in English, reviews, conference abstracts, editorials, and viewpoints, were excluded. Full texts of the articles derived from the screening phase were reviewed to determine whether they met the selection criteria. These full texts were also searched manually to identify additional studies. The selection was conducted by two reviewers (VB and MG) in a double-blinded process. No sex or age criteria were used for article eligibility.

Data extraction

Data extraction was performed systematically to ensure the consistency and accuracy of information gathered from all included studies. A standardized data extraction template was developed to collect relevant details comprehensively. Information extracted included study characteristics, such as author names, publication year, and sample size. Specific information about the study populations, including diagnostic categories (e.g., major depressive disorder, bipolar disorder, schizophrenia), demographic information, and subgroup classifications (e.g., suicidal versus non-suicidal participants), were recorded. Key data related to inflammatory biomarkers were meticulously documented. This included the specific biomarkers analyzed (e.g., CRP, TNF-α, IL-6), the means of assessment (e.g., plasma, serum, cerebrospinal fluid, or postmortem tissue), and the context in which the measurements were obtained (e.g., in vivo, in vitro, or postmortem analysis). Information on the clinical scales and instruments used to evaluate depressive symptoms and suicidality was also extracted.

To ensure rigor, data extraction was conducted independently by two reviewers (VB and MG). Any discrepancies between reviewers were resolved through discussion and, when necessary, evaluated by a third reviewer. Extracted data were cross-checked against the original studies to ensure fidelity to the source materials and eliminate errors.

Quality assessment

The Newcastle–Ottawa Quality Assessment Scale was used to evaluate the risk of bias in the studies included in our analysis. Based on their risk of bias, studies were classified into low (≥ 7 stars), moderate (5–6 stars), or high (≤ 4 stars), with a maximum quality score of 9 stars. Two investigators (VB and MG) independently performed the quality assessments, and any disagreements were settled through discussion and consensus. If needed, a third investigator was involved to resolve any remaining conflicts.

Results

Flow-chart of included studies

Search results are summarized in the Prisma Flow Chart (Fig. 1). The electronic and manual literature search yielded 849 studies, 822 of which underwent title/abstract screening after removing duplicates. After this process, 112 full-text were assessed for eligibility, and 31 studies were finally included in the systematic review [12, 15–46].

Fig. 1.

Flow-chart describing the study selection process

Ratings of study quality and risk of bias

According to the study quality ratings, 22 studies were of good quality, 6 were of moderate quality, and 3 were of poor quality. Since most studies were of moderate or good quality, the risk of bias from studies included in this review was low. Two researchers independently performed data extraction on the variables of the studies.

Characteristics of the included studies

The studies included in this analysis encompass diverse populations, inflammatory biomarkers, and methodological approaches, providing comprehensive insights into the relationship between inflammation and suicidality. Participant groups varied significantly, including individuals with major depressive disorder, bipolar disorder, schizophrenia, and healthy controls. Sample sizes ranged from small cohorts, such as 6 participants [34], to larger studies, including over 600 cases [37]. Table 1 reports the details of the studies analyzed.

Table 1.

Clinical characteristics of the studies included

Author, year	Population in study	Inflammatory markers	In vivo/In vitro plasma/ CSF postmortem	Scales	Main findings
Bai, 2024	287 BD with SA, 344 MDD with SA, 169 HC	CRP, TNF-α	In vivo serum	MADRS	An elevated CRP level was associated with more severe suicidal symptoms. Patients with BD were more likely to have an increased TNF-α level compared with those with MDD.
Bai, 2024	51 SA adolescents	CRP, IL-6	In vivo plasma	SIQ-JR	Inflammation– specifically, IL-6– may be a viable biological marker of short-term risk of self-harm, and that it may reflect precipitating stressors that likewise increase risk of self-harm.
Bergmans, 2019	330 MDD with SA	CRP	In vivo serum	PHQ-9	Pro-inflammatory mechanisms associated with innate immunity, do not distinguish MDD with suicidal ideation from MDD without suicidal ideation.
Boehm, 2010	40 SA	IL-8, TNF-α, ICAM-I	Postmortem	-	Significantly stronger positivity of TNF-α in suicidal victims versus controls.
Castillo-Avila, 2022	18 SA	IL-6	In vivo plasma	C-SSRS	Increased levels of IL-6 serum in individuals who had just attempted suicide.
Chang, 2017	58 MDD with SA	CRP	In vivo serum	HAM-D	In comparison with non-suicidal MDD, suicidal MDD re- presents a clinical phenotype with more pronounced inflammatory features.
Chen, 2024	94 MDD with SA	CRP, TNF-α	In vivo serum	MADRS	Suicidal symptoms are associated with increased serum levels of CRP and TNF-α adolescents and young adults with MDD.
Defayette, 2023	42 SA	IL-6, TNF-α	In vivo plasma	C-SSRS, DASS-21	Increases proinflammatory activity among university-recruited emerging in adults with a recent history of suicidal thoughts and behaviors.
Eidan, 2019	22 MDD with SA	IL-6, INF-γ	In vivo serum	HAM-D, BDI	These findings do not support the hypothesis that IL-6, INF-g, and lipid levels are associated with suicide attempts in adult MDD patients.
Gabbay, 2009	12 MDD SA, 18 non-suicidal MDD, 15 HC	IL-1β, IL-4, IL-6, TNF-α, IFN-γ	In vivo plasma	C-SSRS, BDI	Decreased TNF-α plasma levels in suicidal depressed adolescents and non-suicidal depressed patients. Increased IFN-γ plasma levels in suicidal and non-suicidal versus controls.
Gananca, 2021	80 MDD with SA	IL-1β, IL-6, TNF-α	In vivo serum	HAM-D	Do not support a role for a persisting pro-inflammatory state within five years of suicide attempt.
Hoprekstad, 2024	141 SCZ with SA	IL-1β, IL-2, IL-4, IL-6, IL-10, IFN-γ, and TNF-α	In vivo serum	PANSS, CDSS, CGI-SS	An inverse correlation between serum levels of the two cytokines IL-2 and IL-10 and suicidality.
Huang, 2022	77 BD	CRP, IL-6, TNF-α	In vivo serum	MADRS, YMRS	The serum level of TNF-α were found to be positively correlated with suicidal ideation among patients with BD.
Janelidze, 2011	47 SA, 17 non-suicidal MDD, 16 HC	IL-2, IL-6, IL-8, TNF-α	In vivo plasma	MADRS	Increased levels of IL-6, TNF-α and decreased IL-2 concentrations in suicide attempters compared to non-suicidal depressed patients and controls.
Janelidze, 2015	206 SA, 578 HC	IL-8	In vivo plasma	MADRS	Significantly lower of IL-8 plasma and CSF levels in suicide attempters with anxiety than in controls. IL-8 plasma and CSF levels correlated negatively with symptoms of anxiety.
Jiang, 2022	14 BD SA, 24 BD non-suicide attempters, 26 HC	IL-1β, IL-6, TNF-α	In vivo plasma	HAM-D, YMRS	BD with SA exhibited specifically increased IL-6 levels.
Lee, 2010	124 SA MDD patients, 61 non-suicidal MDD, 125 HC	TGF-1β	In vitro plasma	HAM-D	Significantly higher in vitro TGF-1β levels in depressed patients than in controls.
Li, 2013	49 SA MDD patients, 64 HC	TNF-α	In vivo plasma	HAM-D	Plasma TNF-α levels significantly decreased in responder patients following venlafaxine treatment. A greater reduction in TNF-α levels correlated to a greater reduction in HDRS scores.
Lòpez Villatoro, 2024	35 BP, 23 HC	TNFα	In vivo plasma	SCID, CGI, GAF,	the study reveals three inflammatory/oxidative biomarker components with the predictive value of suicide attempts and two components predictive of non-suicidal self-injurious behaviors.
Maes, 2024	66 MDD with SA, 67 HC	TNFα, IL-4, IL-10, IL-17, IL-13	In vivo serum	BDI, HAM-D	HC had reduced IL-10 levels.
Mendlovic, 1999	6 SA MDD patients, 3 non-suicidal MDD patients, 9 HC	IL-2, IL-4, IL-5, IL-10, IFN- γ	In vitro plasma	HAM-D, BDI	Suicidal depressed patients secreted significantly more IFN-γ than controls. Non-suicidal depressed patients secreted significantly less IFN-γ than controls.
Pandey, 2012	24 SA adolescents, 24 HC adolescents	TNF-α, IL-1β, IL-6	Postmortem	-	Significantly increased IL-1β, IL-6 and TNF-α levels in Brodmann area of suicide victims compared with controls.
Rengasamy, 2020	38 SA, 38 SI, 36 HC	IL-10, TNFα, IL-6R	In vivo plasma	-	TNFα and IL-10 levels to be positively associated with SA.
Russell, 2021	687 SA, 605 HC	CRP	In vivo plasma	-	No evidence for an association between CRP and suicide
Saadat, 2024	30 MDD with SA, 30 MDD without SA, 26 HC	CRP, BDNF	In vivo serum	BDI	The concentration of BDNF differed significantly between depressed patients with/without suicide attempts and healthy controls.
Sun, 2023	38 MDD with SA, 41 MDD without SA, 33 HC	IL-1β, IL-4, TNF-α, IFN-γ, IL-6	In vivo plasma	BDI, SSI	Current depression and history of SA, decreases in levels of SI were significantly associated with decreases in IL-6.
Tian, 2024	42 MDD with SI, 46 MDD without SI	IL-1β, IL-2, IL-6, IL-8, IL-10, TNF-α	In vivo plasma	HAM-D	High level of plasma IL-2 level is associated higher risk of SI among MDD.
Tonelli, 2008	34 completed suicides, 17 HC	IL-4, IL-13	Postmortem	-	Respectively increased expression of IL-4 and IL-13 in female and male suicide victims.
Xu, 2022	29 MDD with SI, 26 MDD without SI	IL-1α, IL-1β, IL-1RA, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-12 p70, IL-13, IL-15, IL-16, IL-27, IL-31, TNF-α, Tie-2, IFN-γ, GM-CSF, FGF	In vivo serum	BDI	MDD patients with SI showed higher levels of IL-17 C, CXCL10, and TNF- β, and lower levels of CCL26 and VEGF compared to MDD patients without SI.
Yang, 2024	42 SA, 31 without SA	IL-1β, IL-6, IL-18, IL-10, TNF-α	In vivo serum	MINI	The higher the levels of IL-6, CRP, TNF-a, CXCL-2, and IFN-g and the lower the levels of IL-2 and IL-8 of MDD patients, the higher the risk of suicide.
Yeşilkaya, 2024	31 SCZ with SA, 69 SCZ HC	CRP	In vivo plasma	PANSS, C-SSRS	Levels of inflammation are not different in SCZ patients with SA than in non-suicidal SCZ patients.

BD = Bipolar Disorder; MDD = Major Depressive Disorder; HC = Healthy Control; SA = Suicide attempt; SI = Suicide ideation; MADRS = Montgomery Asberg Depression Rating Scale; SIQ-JR = Suicidal Ideation Questionnaire; PHQ-9 = Patient Health Questionnaire; C-SSRS = Columbia -Suicide Severity Rating Scale; HAM-D = Hamilton Rating Scale for Depression; DASS-21 = Depression Anxiety Stress Scales; BDI = Beck Depression Inventory; PANSS = Positive and Negative Syndrome Scale; CGI-SS = Clinical Global Impression of Severity Suicide Scale; YMRS = Young Mania Rating Scale; MINI = International Neuropsychiatry Interview; SSI = Scale for Suicidal Ideation

A range of inflammatory biomarkers was assessed, with CRP, TNF-α, and IL-6 being the most investigated markers. These biomarkers were measured in vivo (plasma or serum) and, less frequently, in postmortem tissues. The most frequent analytical scales included the Hamilton Depression Rating Scale (HAM-D), Montgomery-Åsberg Depression Rating Scale (MADRS), and Columbia-Suicide Severity Rating Scale (C-SSRS).

Findings revealed significant associations between elevated levels of inflammatory markers and suicidality. For example, elevated CRP was frequently linked with severe suicidal symptoms [18, 21]. Similarly, elevated IL-6 and TNF-α were associated with an increased risk of suicide attempts [19, 29]. Contrarily, some findings suggested reduced levels of certain markers, such as TNF-α, in specific populations like suicidal adolescents [24].

Postmortem analyses provided additional insights, highlighting unique inflammatory profiles in suicide victims. For instance, Boehm and colleagues identified significantly stronger positivity of TNF-α in suicide victims compared to controls, while another study observed sex-specific patterns involving IL-4 and IL-13 expression [18, 41].

Emerging studies suggest that combinations of biomarkers, including CRP, IL-6, TNF-α, and CXCL-2, could provide predictive insights into suicide risk [43].

Overall, these findings underscore a complex interplay between inflammation and suicidality, suggesting that specific inflammatory markers may serve as potential biomarkers for suicide risk. However, inconsistencies across studies, such as those concerning IL-8 and IFN-γ, highlight the need for further research.

Discussion

The findings from this systematic review underscore the intricate relationship between inflammation and suicidality across various psychiatric populations. Numerous inflammatory markers, particularly cytokines such as IL-6, TNF-α, and CRP, were found to be elevated in individuals with suicidal ideation, suicide attempts, or completed suicides compared to non-suicidal controls or individuals without psychiatric conditions. These results suggest the potential role of systemic inflammation in suicidality pathophysiology.

Elevations in pro-inflammatory cytokines were repeatedly observed in individuals with suicidal behavior across the studies. These findings align with the broader literature suggesting that chronic inflammation is implicated in psychiatric disorders, particularly major depressive disorder [45, 46]. Some studies included in this review suggest that specific cytokine profiles may differentiate individuals with suicidality from those with depression alone, which could have significant implications for targeted interventions [47].

The relationship between inflammation and suicidal behavior is underpinned by complex neurobiological processes that span the immune, endocrine, and nervous systems. Chronic inflammation is increasingly recognized as a key driver of pathophysiological brain changes, particularly in regions involved in emotion regulation, impulse control, and stress responses.

One of the central mechanisms involves the disruption of neurotransmitter systems. Pro-inflammatory cytokines, such as IL-6, TNF-α, and interferon-gamma, influence tryptophan metabolism, a serotonin precursor. Under inflammatory conditions, the enzyme indoleamine 2,3-dioxygenase (IDO) is upregulated, diverting tryptophan away from serotonin synthesis towards the kynurenine pathway [48, 49]. This shift not only depletes serotonin, a critical neurotransmitter for mood stability, but also leads to the production of neurotoxic metabolites like quinolinic acid. Quinolinic acid acts as an agonist of NMDA receptors, enhancing excitotoxicity and further promoting neuroinflammation [50]. This cascade is thought to contribute to the development of depressive symptoms and impulsivity, both of which are closely linked to suicidality.

Additionally, inflammation profoundly impacts the HPA axis, the body’s central stress response system. Pro-inflammatory cytokines stimulate corticotropin-releasing hormone (CRH), leading to hyperactivation of the HPA axis and elevated cortisol levels. While cortisol is essential for managing acute stress, chronic dysregulation can impair brain structures such as the hippocampus, which is involved in memory and emotional processing [8, 51]. Over time, this dysregulation can lead to heightened stress sensitivity and a reduced capacity to cope with adverse events, increasing the risk of suicidal behavior.

The emerging evidence also implicates systemic inflammation in modulating the activity of the gut-brain axis. Recent studies suggest that inflammation-induced changes in gut microbiota composition may further influence mood and behavior by altering levels of microbial metabolites, such as short-chain fatty acids and tryptophan-derived products. These findings highlight a potential bi-directional relationship between peripheral inflammation and central nervous system changes in suicidal individuals.

While the precise pathways linking inflammation and suicidal behavior remain an active area of research, these mechanisms collectively underscore the importance of targeting inflammatory processes as part of comprehensive strategies for suicide prevention. The potential of inflammatory markers to guide clinical practice is immense but requires careful validation. First, incorporating these biomarkers into suicide risk assessments could enable more precise identification of high-risk individuals, particularly those with atypical or subthreshold psychiatric symptoms. For example, inflammatory profiles could complement tools like psychometric scales or genetic predisposition scores to create a holistic risk stratification model [10, 52]. Second, targeting inflammation directly through therapeutic interventions may offer a new frontier for suicide prevention. Early trials suggest that anti-inflammatory agents, such as minocycline or celecoxib, can reduce depressive symptoms and suicidal ideation, particularly in individuals with elevated inflammatory markers [53, 54]. Furthermore, lifestyle interventions, such as anti-inflammatory diets and exercise regimens, hold promise as adjunctive strategies for reducing both systemic inflammation and suicide risk [55]. However, these interventions remain understudied in populations at the highest risk for suicide, such as adolescents and individuals with treatment-resistant depression.

Despite the promising findings, several limitations should be acknowledged. Many studies had small sample sizes, particularly those involving adolescents or postmortem analyses, limiting generalizability. Furthermore, the cross-sectional nature of most studies precludes causal inferences between inflammation and suicidality. Longitudinal studies are needed to clarify temporal relationships and the impact of confounding factors such as medication use, comorbidities, and lifestyle influences [56].In addition to the limitations already discussed, we acknowledge the variability in inflammatory marker assays and clinical assessments across studies, the lack of standardization in biomarker thresholds, and the limited availability of longitudinal and interventional data. Furthermore, the presence of confounding variables, such as psychotropic medications and comorbid physical illnesses, may have influenced inflammatory profiles in some samples.

The potential for inflammatory markers to serve as biomarkers for suicide risk is an exciting prospect, but much remains to be explored. There is a need for large, multi-center studies with diverse populations to validate the findings and establish the specificity and sensitivity of various inflammatory markers in predicting suicidality. Additionally, exploring the interaction between genetic and environmental factors in modulating inflammatory responses could provide a more comprehensive understanding of the biopsychosocial mechanisms underlying suicidal behavior.

Moreover, recent advances in precision medicine offer the opportunity to identify subgroups of individuals who may be particularly responsive to anti-inflammatory interventions. Personalized approaches to suicide prevention, informed by an individual’s inflammatory profile, could lead to more effective and targeted treatments, minimizing the risk of adverse effects and optimizing outcomes.

Furthermore, it would be valuable to distinguish between post-mortem studies and those involving subjects without a psychiatric diagnosis and all other studies to evaluate the main findings more rigorously.

In our review, post-mortem studies found notable differences in cytokine levels between suicide victims and controls [18, 35, 41]. Specifically, suicide victims exhibited significantly stronger positivity for TNF-α. In addition, levels of IL-1β, IL-6, and TNF-α were considerably higher in the Brodmann area of the brain in suicide victims compared to controls. Furthermore, there was an increased expression of IL-4 and IL-13 in female and male suicide victims, respectively.

Instead, studies involving subjects without a psychiatric diagnosis [15, 19, 22, 28, 36, 37, 43] suggest that inflammation, particularly IL-6, may serve as a biological marker for short-term self-harm risk, potentially reflecting stressors that elevate this risk. Increased IL-6 levels were found in individuals who recently attempted suicide, while higher proinflammatory activity was observed in university students with a history of suicidal thoughts and behaviors. Additionally, suicide attempters with anxiety had significantly lower IL-8 levels in both plasma and CSF, with negative correlations to anxiety symptoms. TNF-α and IL-10 levels were positively associated with suicide attempts, but no association was found between CRP and suicide. Finally, higher levels of IL-6, CRP, TNF-α, CXCL-2, and IFN-γ and lower levels of IL-2 and IL-8 in MDD patients were linked to increased suicide risk.

This review reinforces the hypothesis that inflammation plays a crucial role in suicidality, with specific markers such as IL-6 and TNF-α emerging as key players. These findings highlight the potential for inflammatory markers to inform clinical risk assessments and interventions, paving the way for novel strategies to mitigate suicide risk across diverse populations.

Conclusion

In conclusion, the emerging evidence suggests a significant link between inflammation and suicidal behavior, highlighting inflammation as a potential biomarker and therapeutic target. However, further research is required to clarify the exact mechanisms involved, address existing methodological limitations, and determine the clinical applicability of these findings. By improving our understanding of the biological underpinnings of suicidality, we may pave the way for more effective prevention and intervention strategies, ultimately reducing the burden of suicide worldwide. These findings underscore the importance of integrating biological markers, such as IL-6 and TNF-α, into suicide risk assessment protocols, particularly for individuals with atypical or subthreshold psychiatric symptoms. Furthermore, identifying individuals with elevated inflammatory profiles may allow for personalized treatment strategies that include anti-inflammatory agents or lifestyle modifications aimed at reducing systemic inflammation. While more research is needed to confirm these pathways, our results provide a foundation for the development of biomarker-guided approaches to suicide prevention that could be generalized across various psychiatric and non-psychiatric populations.

Author contributions

V.B. wrote the main manuscriptM.G. and G.V. prepared the tablesA.R.A. and D.D.R. contributed to the design of the studyA.F. and G.P. supervision and methodology All authors reviewed the manuscript.

Funding

This study has received no funding.

Data availability

No datasets were generated or analysed during the current study.

Declarations

Human ethics and consent to participate

Not applicable.

Consent to participate

Not applicable.

Competing interests

The authors declare no competing interests.