Neutrophil-to-lymphocyte ratio predicting suicide risk in euthymic patients with bipolar disorder: Moderatory effect of family history

Ivković, Maja; Pantović-Stefanović, Maja; Dunjić-Kostić, Bojana; Jurišić, Vladimir; Lačković, Maja; Totić-Poznanović, Sanja; Jovanović, Aleksandar A.; Damjanović, Aleksandar

doi:10.1016/j.comppsych.2016.01.005

Cited by 90Bipolar Disorder and TreatmentSuicide and Self-Harm StudiesInflammatory Biomarkers in Disease Prognosis

Neutrophil-to-lymphocyte ratio predicting suicide risk in euthymic patients with bipolar disorder: Moderatory effect of family history

Ivković, Maja, Pantović-Stefanović, Maja, Dunjić-Kostić, Bojana, Jurišić, Vladimir, Lačković, Maja, Totić-Poznanović, Sanja, Jovanović, Aleksandar A., Damjanović, Aleksandar·2016·Comprehensive Psychiatry

DOI 10.1016/j.comppsych.2016.01.005

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Abstract

Background Neutrophil-to-lymphocyte ratio (NLR) has been independently related to bipolar disorder (BD) and factors associated with suicidal risk. The aim of our study was to explore the relationship between NLR and suicide risk in euthymic BD patients. We also sought to propose a model of interaction between NLR and stress-diathesis factors, leading to suicidal risk in BD.Methods The study group consisted of 83 patients diagnosed with BD (36 suicide attempters; 47 suicide non-attempters), compared to the healthy control group (n=73) and matched according to age, gender, and body mass index (BMI). NLR was measured according to the complete blood count. Mood symptoms have been assessed by Young Mania Rating Scale and Montgomery-Asberg Depression Rating Scale. Early trauma and acute stress were evaluated by Early Trauma Inventory Self Report-Short Form and List of Threatening Experiences Questionnaire, respectively. Suicide risk has been assessed by Suicide Behaviors Questionnaire-Revised (SBQ-R).Results Significant correlation was found between NLR and SBQ-R score. The main effects of suicide attempts on NLR, after covarying for confounders, were observed, indicating increased NLR in BD suicide attempters compared to healthy controls. We found significant moderatory effects of family history on NLR relationship to suicidal risk, with NLR being significant positive predictor of suicidal risk only in the patients with positive family history of suicide attempts.Conclusions The results suggest an enhancing effect of positive family history of suicide attempts on predictive effect of NLR on suicide risk. Our data support the idea that immune markers can predict suicide attempt risk in BD, but only in the subpopulation of BD patients with family history of suicide attempts. This could lead to prevention in suicide behavior in the patient population at particular risk of suicide.

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Lymphocytes represent the regulatory or protective component of the immune system.
“lymphocytes represent the regulatory or protective component of the immune system [11–13].”
From Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in depressed patients with suicidal behavior: A systematic review (2024) · cites this paper as [13]

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Neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and mean platelet volume as systemic inflammatory markers in different states of bipolar disorder
Inanli, I., Aydin, M., Çaliskan, A. M., & Eren, I. (2019) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2019.1640789 · Cited by 69 · see citing works
“Another study found NLR to be a significant positive predictor of suicidal risk in euthymic patients with BD, but its effects were moderated by family history of suicide attempts such that NLR was a positive predictor only in the patients with positive family history of suicide attempts [16].”
Background
Suicide attempts are associated with activated immune-inflammatory, nitro-oxidative, and neurotoxic pathways: A systematic review and meta-analysis
Vasupanrajit, A., Jirakran, K., Tunvirachaisakul, C., & Maes, M. H. J. (2021) · Journal of Affective Disorders · doi:10.1016/j.jad.2021.08.015 · Cited by 69 · see citing works
Potential usefulness of complete blood count parameters and inflammatory ratios as simple biomarkers of depression and suicide risk in drug-naive, adolescents with major depressive disorder
Puangsri, P., & Ninla-aesong, P. (2021) · Psychiatry Research · doi:10.1016/j.psychres.2021.114216 · Cited by 62 · see citing works
Neutrophil/Lymphocyte, Platelet/Lymphocyte, and Monocyte/Lymphocyte Ratios in Mood Disorders
Marazziti, D., Torrigiani, S., Carbone, M. G., Mucci, F., Flamini, W., Ivaldi, T., & Dell'Osso, L. (2022) · Current Medicinal Chemistry · doi:10.2174/0929867328666210922160116 · Cited by 61 · see citing works
Neutrophil to-lymphocyte and platelet-to-lymphocyte ratios as biomarkers for suicidal behavior in children and adolescents with depression or anxiety treated with selective serotonin reuptake inhibitors
Amitai, M., Kaffman, S., Kroizer, E., Lebow, M., Magen, I., Benaroya-Milshtein, N., Fennig, S., Weizman, A., Apter, A., & Chen, A. (2022) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2022.04.018 · Cited by 51 · see citing works
Mean platelet volume and neutrophil to lymphocyte ratio as parameters to indicate the severity of suicide attempt
Orum, M. H., Kara, M. Z., & Egilmez, O. B. (2018) · Journal of Immunoassay and Immunochemistry · doi:10.1080/15321819.2018.1529682 · Cited by 46 · see citing works
“[30–32] Ivković et al.[43] positive family history increased the predictive impact of NLR on suicide attempt and suicide risk.”
Background
Resolution of inflammation and mood disorders
Chistyakov, D. V., Astakhova, A. A., & Sergeeva, M. G. (2018) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2018.08.002 · Cited by 47 · see citing works
Clinical significance of neutrophil-lymphocyte and platelet-lymphocyte ratios in bipolar patients: an 18-month prospective study.
Melo, M. C. A., Garcia, R. F., de Araújo, C. F. C., Abreu, R. L. C., de Bruin, P. F. C., & de Bruin, V. M. S. (2019) · Psychiatry Research · doi:10.1016/j.psychres.2018.10.077 · Cited by 45 · see citing works
The association between neutrophil-to-lymphocyte ratio and post-stroke depression.
Chen, H., Luan, X., Zhao, K., Qiu, H.-H., Liu, Y.-T., Tu, X.-J., Tang, W.-J., & He, J.-C. (2018) · Clinica chimica acta; international journal of clinical chemistry · doi:10.1016/j.cca.2018.08.026 · Cited by 47 · see citing works
Elevated neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios predict post-stroke depression with acute ischemic stroke
Hu, J., Zhou, W., Zhou, Z.-M., Han, J., & Dong, W.-L. (2020) · Experimental and Therapeutic Medicine · doi:10.3892/etm.2020.8514 · Cited by 42 · see citing works
“Furthermore, an increased NLR and dysfunctional platelets have also been linked to patients with psychiatric disorders including depression (18,40-42).”
Background
Neutrophil-lymphocyte ratio is increased in elderly patients with first episode depression, but not in recurrent depression
Arabska, J., Łucka, A., Magierski, R., Sobów, T., & Wysokiński, A. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.02.043 · Cited by 38 · see citing works
Neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, and monocyte-to-lymphocyte ratio in depressed patients with suicidal behavior: A systematic review
Velasco, A., Lengvenyte, A., Rodriguez-Revuelta, J., Jimenez-Treviño, L., Courtet, P., Garcia-Portilla, M., Bobes, J., & Sáiz, P. (2024) · European Psychiatry · doi:10.1192/j.eurpsy.2023.18 · Cited by 34 · see citing works
“phagocytosis and apoptosis functions (10), and lymphocytes represent the regulatory or protective component of the immune system (11,12,13).”
Peripheral blood cellular immunophenotype in suicidal ideation, suicide attempt, and suicide: a systematic review and meta-analysis
Daray, F. M., Chiapella, L. C., Grendas, L. N., Casiani, R. I. Á., Olaviaga, A., Robetto, J., Prokopez, C. R., Silva, E. A. C., Errasti, A. E., & Neupane, S. P. (2024) · Molecular Psychiatry · doi:10.1038/s41380-024-02587-5 · Cited by 35 · see citing works
“While prior investigations have reported increased monocyte counts in patients with SB [29], our study revealed only a marginal increase that did not attain statistical signi ﬁ cance.”
Elevated Neutrophil to Lymphocyte Ratio in Older Adults with Cocaine Use Disorder as a Marker of Chronic Inflammation
Soder, H. E., Berumen, A., Gomez, K., Green, C., Suchting, R., Wardle, M. C., Vincent, J., Teixeira, A., Schmitz, J. M., & Lane, S. (2020) · Clinical Psychopharmacology and Neuroscience · doi:10.9758/cpn.2020.18.1.32 · Cited by 33 · see citing works
A comparison of inflammatory markers in manic and euthymic states of bipolar disorder
Özdin, S., & Usta, M. B. (2021) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2020.1807048 · Cited by 30 · see citing works
Evaluation of the effects of altitude on biological signatures of inflammation and anxiety- and depressive-like behavioral responses
Nguyen, K. T., Gates, C. A., Hassell, J. E., Foxx, C. L., Salazar, S. N., Luthens, A. K., Arnold, A. L., Elam, B. L., Elsayed, A. I., Leblanc, M., et al. (2021) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2021.110331 · Cited by 31 · see citing works
Can Neutrophil Lymphocyte Ratio Predict the Likelihood of Suicide in Patients with Major Depression?
Gundogdu Meydaneri, G., & Meydaneri, S. (2018) · Cureus · doi:10.7759/cureus.2510 · Cited by 29 · see citing works
“In a study investigating the efficacy of NLR in identifying suicide risk in patients with bipolar disorder, it was reported to be a successful biomarker in predicting patients with positive family history [19].”
Background
Evaluation of Simple Markers of Inflammation and Systemic Immune Inflammation Index in Schizophrenia, Bipolar Disorder Patients and Healthy Controls
Yağcı, İ., & İnaltekin, A. (2021) · Turkish Journal of Psychiatry · doi:10.5080/u26248 · Cited by 30 · see citing works
Dynamic Patterns of Threat-Associated Gene Expression in the Amygdala and Blood
Lori, A., Maddox, S. A., Sharma, S. K., Andero, R., Ressler, K. J., & Smith, A. K. (2019) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2018.00778 · Cited by 26 · see citing works
Sex-dependent grades of haematopoietic modulation in patients with major depressive episodes are associated with suicide attempts
Martínez-Botía, P., Velasco, A., Rolle, V., Jiménez-Trevino, L., De la Fuente-Tomás, L., Bernardo, Á., Arias, T., Muñoz-Turrillas, M. D. C., García-Alvarez, L., González-Blanco, L., et al. (2020) · European Neuropsychopharmacology · doi:10.1016/j.euroneuro.2020.06.006 · Cited by 27 · see citing works
“…goes beyond the inflammatory status previusly reported by others ( Courtet et al., 2016 , 2015 ; Ekinci nd Ekinci, 2017 ; Gibbs et al., 2016 ; Glaus et al., 2018a , b ; vkovic et al., 2016 ; Kayhan et al., 2017 ; Liu et al., 2012 ; azza et al., 2019 ; Miller and Raison, 2016 ; Orum et al., 018 ).”
Background
Elevated levels of monocyte-lymphocyte ratio and platelet-lymphocyte ratio in adolescents with non-suicidal self-injury
Zheng, Q., Liu, J., Ji, Y., Zhang, Y., Chen, X., & Liu, B. (2022) · BMC Psychiatry · doi:10.1186/s12888-022-04260-z · Cited by 26 · see citing works
“one study also showed that NLR in patients with bipolar disorder and SA is higher than that in healthy controls [27].”
Background
Rapidly Growing Mycobacterium Species: The Long and Winding Road from Tuberculosis Vaccines to Potent Stress-Resilience Agents
Amoroso, M., Langgartner, D., Lowry, C. A., & Reber, S. O. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222312938 · Cited by 26 · see citing works
Thiol-disulphide homeostasis, ischemia-modified albumin, complete blood count-derived inflammatory markers and C-reactive protein from acute mania to early remission in bipolar disorder
Korkmaz, Ş. A., Kızgın, S., Oğuz, E. F., Neşelioğlu, S., & Erel, Ö. (2023) · Journal of Affective Disorders · doi:10.1016/j.jad.2023.07.079 · Cited by 24 · see citing works
Leukocytes in peripheral blood in patients with bipolar disorder – Trait and state alterations and association with levels of cytokines and C-reactive protein
Munkholm, K., Jacoby, A. S., Lenskjold, T., Bruunsgaard, H., Vinberg, M., & Kessing, L. V. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.01.022 · Cited by 25 · see citing works
Neutrophil-lymphocyte and platelet-lymphocyte ratios among adolescents with bipolar disorder: A preliminary study.
Binici, N. C., Güney, S. A., & Emiroğlu, F. N. (2018) · Psychiatry Research · doi:10.1016/j.psychres.2018.08.065 · Cited by 20 · see citing works
Changes in Inflammatory Biomarkers in Patients with Schizophrenia: A 3-Year Retrospective Study
Zhu, X., Li, R., Zhu, Y., Zhou, J. L., Huang, J., Zhou, Y., Tong, J., Zhang, P., Luο, X., Chen, S., et al. (2023) · Neuropsychiatric Disease and Treatment · doi:10.2147/ndt.s411028 · Cited by 21 · see citing works
“Elevated levels of NLR, MLR, and PLR have been observed in various psychiatric disorders,(13,34,36,37) and NLR may serve as a predictor for suicide risk among certain patients with affective disorders.(18) Several studies have shown that NLR, PLR, and MLR are significantly higher in patients with schizophrenia.”
Background
Association of the neutrophil to lymphocyte ratio and white blood cell count with response to pharmacotherapy in unipolar psychotic depression: An exploratory analysis
Vos, C. F., Birkenhäger, T. K., Nolen, W. A., van den Broek, W. W., Coenen, M. J. H., ter Hark, S. E., Verkes, R., & Janzing, J. (2021) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2021.100319 · Cited by 20 · see citing works
Neutrophil to lymphocyte and monocyte to high-density lipoprotein ratios are promising inflammatory indicators of bipolar disorder
Kulacaoglu, F., Yıldırım, Y. E., Aslan, M., & İzci, F. (2023) · Nordic Journal of Psychiatry · doi:10.1080/08039488.2022.2116106 · Cited by 18 · see citing works
“Furthermore, in individuals with BD, cognitive dysfunction during even the euthymic phase, as well as suicidal risk, have been linked to elevated NLR values [24].”
Background
Neutrophil-to-lymphocyte ratio as a predictive biomarker for early diagnosis of depression: A narrative review
Ghafori, S. S., Yousefi, Z., Bakhtiari, E., hasani, M. H. M. M., & Hassanzadeh, G. (2024) · Brain Behavior & Immunity - Health · doi:10.1016/j.bbih.2024.100734 · Cited by 23 · see citing works
“There is mounting evidence that the pathophysiology of suicidal behavior includes a vital function for neuroinflammation (Ivkovi ´ c et al., 2016).”
BackgroundMethod
Exploring the role of serum lipid profile and neutrophil-to-lymphocyte ratio in violent suicide attempters: a cross sectional study
Capuzzi, E., Caldiroli, A., Capellazzi, M., Tagliabue, I., Auxilia, A. M., Ghilardi, G. I., Buoli, M., & Clerici, M. (2020) · CNS Spectrums · doi:10.1017/s1092852920002199 · Cited by 18 · see citing works
The ratio of neutrophil to lymphocyte is a predictor in endometrial cancer
Dong, Y., Cheng, Y., & Wang, J. (2019) · Open Life Sciences · doi:10.1515/biol-2019-0012 · Cited by 17 · see citing works
Biochemical predictors in presentations to the emergency department after a suicide attemp
Yagci, I., & Avci, S. (2021) · Bratislava Medical Journal · doi:10.4149/bll_2021_012 · Cited by 15 · see citing works
Haematological markers of inflammation in major depressive disorder (MDD) patients with suicidal behaviour: A systematic review and meta-analysis
Moshfeghinia, R., Kavari, K., Mostafavi, S., Sanaei, E., Farjadian, S., & Javanbakht, A. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.05.031 · Cited by 16 · see citing works
Association Between Mood Disorder Severity, Treatment Response and Systemic Inflammatory Markers: Exploring the Role of NLR, PLR, MLR, and SII
Department of Psychiatry, G. U., Kucukkarapinar, M., Erbil, D., Department of Psychiatry, G. U., Keles, İ., Department of Psychiatry, G. U., Karadag, F., & Department of Psychiatry, G. U. (2024) · Psychiatry and Clinical Psychopharmacology · doi:10.5152/pcp.2024.23760 · Cited by 14 · see citing works
“40,41 Some studies have found an increase in NLR in patients with and without suicide attempts, but this is not statistically significant.”
Background
The usefulness of a complete blood count in the prediction of the first episode of schizophrenia diagnosis and its relationship with oxidative stress
Juchnowicz, D., Dzikowski, M., Róg, J., Waszkiewicz, N., Karakuła, K. H., Zalewska, A., Maciejczyk, M., & Karakuła‐Juchnowicz, H. (2023) · PLoS ONE · doi:10.1371/journal.pone.0292756 · Cited by 14 · see citing works
“NLR is a useful marker of inflammation in schizophrenia and other psychiatric disorders, including major depression, bipolar disorder, and individuals who attempted suicide [11–14].”
Neutrophil/lymphocyte ratio: Can a non-specific marker of inflammation helps to confirm the inflammatory hypothesis of the serious mental diseases? A case-control study
Rodríguez, J. F. O., Fernández, J. D., Mira, N. O., Briz, E. L., & Gómez-Pajares, F. (2019) · Medical Hypotheses · doi:10.1016/j.mehy.2019.109279 · Cited by 14 · see citing works
“Finally, among the autoimmune processes associated with psychosis, it is worth mentioning the positive association established between autoimmune diseases and schizophrenia [27]; some studies find a significantly higher prevalence of positive titers for twenty different autoantibodies in patients with schizophrenia co…”
Background
Comparison Between Inflammatory Biomarkers (High-Sensitivity C-Reactive Protein and Neutrophil-Lymphocyte Ratio) and Psychological Morbidity in Suicide Attempt Survivors Brought to Medicine Emergency
Kumar, K., Srivastava, S., Sharma, B., Avasthi, R., & Kotru, M. (2021) · Cureus · doi:10.7759/cureus.17459 · Cited by 13 · see citing works
“NLR was higher in suicidal vs non-suicidal depressive patients and may be a biomarker of suicide attempts in major depressive disorder (MDD) [13,14].”
The role of hematological coefficients of systemic inflammation in the diagnosis and risk assessment of affective disorders
Gorbunova, A. P., Rukavishnikov, G. V., Kasyanov, E. D., & Mazo, G. E. (2024) · V M BEKHTEREV REVIEW OF PSYCHIATRY AND MEDICAL PSYCHOLOGY · doi:10.31363/2313-7053-2024-794 · Cited by 15 · see citing works
[Predictive value of inflammatory indicators for post-stroke depression in patients with ischemic stroke].
Hu, J., Zhou, W., Zhou, Z., Yang, Q., Han, J., Yan, Y., & Dong, W. (2019) · Europe PMC (PubMed Central) · doi:10.12122/j.issn.1673-4254.2019.06.06 · Cited by 13 · see citing works
Inflammation and Mental Health Disorders: Immunomodulation as a Potential Therapy for Psychiatric Conditions
Safari, H., & Mashayekhan, S. (2023) · Current Pharmaceutical Design · doi:10.2174/0113816128251883231031054700 · Cited by 10 · see citing works
The Types of Psychosocial Factors Associated with Suicidality Outcomes for People Living with Bipolar Disorder: A Scoping Review
Dempsey, R. C., Dodd, A., Gooding, P. A., & Jones, S. H. (2024) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph21050525 · Cited by 12 · see citing works
“The two studies using the St Paul-Ramsey Scale of stressful life events found no relation to suicide attempts [101,102], or suicidal ideation [102], whereas the others found an association between life events and suicide attempts [81,103].”
Background
Which Clinical and Biochemical Parameters Are Associated with Lifetime Suicide Attempts in Bipolar Disorder?
Surace, T., Capuzzi, E., Caldiroli, A., Ceresa, A., Esposito, C. M., Auxilia, A. M., Tagliabue, I., Capellazzi, M., Legnani, F., Paolo, M. D., et al. (2022) · Diagnostics · doi:10.3390/diagnostics12092215 · Cited by 10 · see citing works
“Moreover, the neutrophil–lymphocyte ratio (NLR) was suggested as a convenient and reproducible biomarker of suicide attempt risk in BD [25].”
Background
The PMN-MDSC – A key player in glucocorticoid resistance following combined physical and psychosocial trauma
Kempter, E., Amoroso, M., Kupfer, S., Lupu, L., Kustermann, M., Scheurer, J., Baumann, B., Wirth, T. C., Gündel, H., Straub, R. H., et al. (2022) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2022.11.011 · Cited by 10 · see citing works
Increased risk for mental disorders and suicide during the COVID-19 pandemic: the position statement of the Section on Suicidology and Suicide Prevention of the European Psychiatric Association.
Sarchiapone, M., López‐Castromán, J., Gramaglia, C. M., Baca‐García, E., Baralla, F., Barrigón, M. L., Bartollino, S., Beezhold, J., Bobes, J., Calati, R., et al. (2021) · GLOBAL PSYCHIATRY ARCHIVES · doi:10.52095/gp.2021.8114 · Cited by 8 · see citing works
“Increased neutrophil-to-lymphocyte ratio recently emerged as a peripheral inflammatory biomarker for suicidal behaviour in major depression and bipolar patients (Ekinci & Ekinci, 2017; Ivkovic et al., 2016; Velasco et al., 2020) and seen to be an independent risk factor for critical illness in patients with COVID-19 i…”
Background
Complete blood count-based inflammatory ratios in people with bipolar disorder: a systematic review and meta-analysis of neutrophil-to-lymphocyte, monocyte-to-lymphocyte, and platelet-to-lymphocyte ratios
Cavaleri, D., Cucchi, G., Citton, M., Monti, M., Crocamo, C., Bartoli, F., & Carrà, G. (2026) · European Psychiatry · doi:10.1192/j.eurpsy.2026.10174 · Cited by 7 · see citing works
Evaluation of inflammatory parameters in patients who attempted suicide by taking drugs
Akkuş, M., Davarcı, P. Z., Baş, S., ODLUYURT, H., & AYDOGAN, M. (2022) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.4149/bll_2022_067 · Cited by 7 · see citing works
Inflammation in Major Depressive Disorder Patients with and without Attempted Suicide
Taşçı, G., & Özsoy, F. (2023) · Clinical and Experimental Health Sciences · doi:10.33808/clinexphealthsci.1120081 · Cited by 5 · see citing works
Inflammatory Hematological Ratios in Adolescents with Mental Disorders: A Scoping Review
Popov, M. Y., Popov, Y. V., Kosterin, D. N., & Lepik, O. V. (2024) · Consortium Psychiatricum · doi:10.17816/cp15514 · Cited by 7 · see citing works
“All these findings suggest age-related differences in the associations between IHRs and suicidal behavior in adolescents (increased NLR, MLR, and PLR [76]), young adults (only MLR increased [77]), and adult patients (only NLR increased [26, 61, 78]).”
Background
Neutrophil-to-lymphocyte ratio as a potential differential diagnostic marker for Alzheimer’s disease, major depressive disorder, and Parkinson’s disease
Baykan, H., Baykan, Ö., Esen, E. C., TİRAK, A., Görgülü, S. A., & Karlıdere, T. (2018) · Dusunen Adam The Journal of Psychiatry and Neurological Sciences · doi:10.5350/dajpn2018310407 · Cited by 5 · see citing works
“In recent years, the neutrophil-to-lymphocyte ratio (NLR) has been introduced as a diagnostic tool in psychiatry (9-14) and suggested as an upcoming diagnostic method for MD (9-13) and schizophrenia (14) in the field of psychiatry, where the use of laboratory instruments for diagnosis is sparse.”
Method
Differences in biomarkers between unipolar and bipolar depression: A meta-analysis
Yang, X., Tang, Q., Xiang, R., & Liao, Q. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.120365 · Cited by 4 · see citing works
Mood disorders and 5-HTR2A genetic variants – the moderator effect of inflammation on expression of affective polarity phenotype
Pantović-Stefanović, M., Karanović, J., Jurišić, V., Dunjić-Kostić, B., Nesic, M. J., Dodić, S., Gostiljac, M., Puric, M., Pavicevic, D. S., & Ivković, M. (2024) · BMC Psychiatry · doi:10.1186/s12888-024-06207-y · Cited by 4 · see citing works
“Indirect indicators of inflammation, such as the MPV/PLT were also related to more severe pathology in mood disorders as reported previously [55].”
ResultSelf-citation
Pawsitive impact: How pet contact ameliorates adult inflammatory stress responses in individuals raised in an urban environment
Langgartner, D., Weimer, K., Brunner-Weisser, J., Winkler, R., Mannes, M., Huber-Lang, M. S., Sterrett, J. D., Lowry, C. A., Rohleder, N., Bajrami, B., et al. (2025) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2025.03.013 · Cited by 5 · see citing works
“…non-resolving low-grade inflammation and, thus, stress-related disorders (Bhat et al., 2013; Ekinci and Ekinci, 2017; Everds et al., 2013; Foertsch et al., 2017; Ivkovic et al., 2016; Liang et al., 2019; Lynall et al., 2020; Orum et al., 2018; Sutin et al., 2012; Velasco et al., 2020).”
Association between neutrophil-to-lymphocyte ratio and bipolar disorder: A systematic review and meta-analysis
Gui, L., Yu, H., Wei, Y., Huang, Q., Liu, Y., & Fu, Y. (2025) · The European Journal of Psychiatry · doi:10.1016/j.ejpsy.2025.100308 · Cited by 4 · see citing works
The potential inflammatory biomarker of bipolar disorder: Neutrophil-to-lymphocyte Ratio – A hospital-based cross-sectional study
Raj, R., Wani, Z. A., Dar, S. A., Dilawar, T., Altaf, S., Beigh, A., & Haq, I. (2024) · Journal of Neurosciences in Rural Practice · doi:10.25259/jnrp_143_2024 · Cited by 3 · see citing works
Inflammatory parameters and blood lipid values across the different mood states in patients with bipolar disorder
Ekinci, O., & Ekinci, A. E. (2020) · Journal of Clinical Psychiatry · doi:10.5505/kpd.2020.98216 · Cited by 3 · see citing works
Correlation of hematological parameters, antibodies and cytokines with disease activity in systemic lupus erythematosus: a cross-sectional study
Živković, V., Cvetković, T., Dinić, B. R., & Jurišić, V. (2023) · Egyptian Rheumatology and Rehabilitation · doi:10.1186/s43166-023-00222-9 · Cited by 3 · see citing works
“…reproducible biological markers, can be very significant clinically in numerous inflammatory diseases, such as cardiovascular [16–19], neoplastic [20–23], chronic inflammatory rheumatic diseases [3, 24–26], and psychiatric diseases [27], as well as in the early phases of metabolic syndrome [28].”
BackgroundSelf-citation
IL-4Rα signalling influences behavioural and immune responses in Trypanosoma brucei-infected mice: Evidence for iloprost as a neuroprotective agent
Olaolu, O. S., Davids, H., Dealtry, G., Abubakar, A., Obishakin, E., Iliyasu, B., Azeez, I. A., & Ajonijebu, D. C. (2025) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2025.08.014 · Cited by 2 · see citing works
Neutrophil-to-Lymphocyte Ratio Any Association with Metabolic Syndrome in Schizophrenia
Zakharova, N. V., Nasyrova, R. F., Rakhmatullin, A. I., Rumiantceva, M. N., Sizykh, K. I., & Kostin, F. N. (2024) · Personalized Psychiatry and Neurology · doi:10.52667/2712-9179-2024-4-3-12-23 · Cited by 2 · see citing works
Development and validation of a neutrophil-lymphocyte ratio-based nomogram for suicidal ideation in first-episode drug-naïve schizophrenia patients: A large-scale cross-sectional study
Ling, L., Wang, M., Du, W., Wang, J., Li, C., Zhang, X., & Lang, X. (2025) · Schizophrenia Research · doi:10.1016/j.schres.2025.05.004 · Cited by 1 · see citing works
Low-grade inflammatory parameters may be associated with recent suicide attempts – a naturalistic study among psychiatric inpatients with depressive disorders
Lovig, C., Osváth, P., Sághy, E., Molnár, C., Kovács, M. Á., Pethö, B., Simon, D., Fekete, S., Tényi, T., & Vörös, V. (2026) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2026.1707768 · Cited by 1 · see citing works
Could peripheral immunological markers discriminate schizophrenia and schizoaffective disorders from bipolar disorder?
Jeannin, J., Romeo, B. G. P., Lestra, V., Martelli, C., Amirouche, A., Benyamina, A., & Hamdani, N. (2026) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2026.02.041 · Cited by 1 · see citing works
Suicidal behavior and inflammation: neutrophil to lymphocyte ratio
Bayazıt, H., Dülgeroğlu, D., NELSON, J., SULLIVAN, Z., & Selek, S. (2022) · Minerva Psychiatry · doi:10.23736/s2724-6612.21.02206-5 · Cited by 1 · see citing works
Inflammation in Chronic Psychiatric Patients: Neutrophil/Lymphocyte Ratios, Platelet/Lymphocyte Ratios, and Mean Platelet Volume
Demir, F. Ü., Özsoy, F., & Aslan, E. A. (2023) · Kahramanmaraş Sütçü İmam Üniversitesi Tıp Fakültesi Dergisi · doi:10.17517/ksutfd.1127281 · Cited by 1 · see citing works
Increased Neurotoxicity Due to Activated Immune-Inflammatory and Nitro-Oxidative Stress Pathways in Patients with Suicide Attempts: A Systematic Review and Meta-AnalysisPreprint
Vasupanrajit, A., Jirakran, K., Tunvirachaisakul, C., & Maes, M. H. J. (2021) · Preprints.org · doi:10.20944/preprints202104.0479.v1 · Cited by 1 · see citing works
C-reactive protein, Neutrophil/lymphocyte ratio, Platelet/lymphocyte ratio, Monocyte/lymphocyte ratio among adolescents with anorexia nervosa: A preliminary studyPreprint
zhang, R., Liang, X., Wang, B., Ma, H., & Yang, L. (2022) · Research Square · doi:10.21203/rs.3.rs-1784771/v1
Change of complete blood count parameters according to blood type and smoking
İnci, H. (2023) · Journal of Experimental and Clinical Medicine · doi:10.52142/omujecm.40.1.8
Using the Bayesian variational spike and slab model in a genome‐wide association study for finding associated loci with bipolar disorder
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“…among these indicators and BD has been concluded in various epidemiological studies (Altshuler et al., 2008; Wysokiński & Margul-ska, 2017; Ivković et al., 2016; Cevher Binici et al., 2018; Çakır et al., 2015; Wysokiński et al., 2015; Wysokiński & Szczepocka, 2018; Mert & Terzi, 2016;…”
Background
Гематологические коэффициенты системного воспаления как потенциальные биомаркеры суицида
Gorbunova, A. P., Rukavishnikov, G. V., Kasyanov, E. D., Kibitov, A. O., & Mazo, G. E. (2024) · Суицидология · doi:10.32878/suiciderus.24-15-01(54)-31-52
Differences in the indicators of inflammation between patients with bipolar and unipolar depression
Dodić, S., Puric, M., Gostiljac, M., Nesic, M. J., Dunjić-Kostić, B., Mandić-Maravić, V., Erić, E., Ivković, M., & Pantović-Stefanović, M. (2024) · Medicinska istrazivanja · doi:10.5937/medi57-49899
Self-citation
Suicide during the global COVID-19 pandemic
Wasserman, D., Iosue, M., & Carli, V. (2024) · Oxford University Press eBooks · doi:10.1093/med/9780198843405.003.0021
Acute Poisonings, Suicidality and Systemic Inflammatory Load in Pregnant Women
Koçakoğlu, Ş., & Büyükaslan, H. (2025) · Psychiatry and Clinical Psychopharmacology · doi:10.5152/pcp.2025.24962
“Ivkovi ć et al 38 and Capuzzi et al 39 also reported that NLR is valuable in predicting suicidal behavior in some mental disorders.”
Correlation of Hematologic Coefficients of Inflammation and Metabolic Syndrome: Pilot Study
Kidyaeva, A. V., Eichelberg, A. V., Shnayder, N. A., & Nasyrova, R. F. (2025) · Personalized Psychiatry and Neurology · doi:10.52667/2712-9179-2025-5-2-31-36
Association between Suicidal Ideation and Immune Parameters in First-episode Patients with Schizophrenia
Xia, Y., Guan, X., Xiu, M. H., & Wu, F.-C. (2025) · Current Neuropharmacology · doi:10.2174/011570159x384619250727094057 · Cited by 1 · see citing works
“This finding is in line with previous studies in other neuropsychiatric disorders [45-47], suggesting that immune abnormalities and inflammation may play a role in the pathogenesis of SI in patients with SZ.”
Évaluation écologique des marqueurs périphériques de stress à l'aide de biocapteurs en population psychiatrique
Conejero, I. (2020) · theses.fr (ABES) · doi:10.70675/e0cb59ecz80a8z4338za3ddz2ea8e8d0334d
Development and validation of an early predictive model for acute stress disorder after trauma: a clinical cohort study
Li, X., Shi, S., Gu, J., Chu, X., Dai, X., & Shi, X. (2026) · PeerJ · doi:10.7717/peerj.21131
“NLR has garnered recognition as a novel marker for chronic low-grade inflammation and a predictor of clinical prognosis in neuroimmune diseases ( Akıl et al., 2015 ; Ivković et al., 2016 ).”
The immunophenotypes indicating suicide risk in adolescent with bipolar disorder type I
Tonyali, A., Ocakoğlu, B. K., Koç, E. B., Guney, O., Demirci, S., Soykut, A. E., Mentes, B., Şükret, A. L. E. V., & Karaçetin, G. (2026) · Medicine · doi:10.1097/md.0000000000048442
“[6] In this study, we aimed to investigate the relation between inflammatory markers such as NLR, lymphocyte-to-monocyte ratio (LMR), platelet-to-monocyte ratio, and suicide attempts in adolescents with bipolar disorder and to define a patient phenotype based on inflammatory markers.”
Cognitive Dysfunction and Suicide
Sunzeri, F. (2026) · Springer eBooks · doi:10.1007/978-3-032-14465-2_19
Peripheral immune-metabolic markers and quantitative EEG in drug-naïve first-episode mania: A case–control study
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Localization and characterization of serotonin 2A receptor in human brain postmortem
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Possible utility of neutrophil/lymphocyte ratio as a predictor of suicidal risk in mood disorders
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Neutrophil-to-lymphocyte ratio: A potential new peripheral biomarker of suicidal behavior
Velasco, Á., Rodríguez-Revuelta, J., Olié, E., Abad, I., Fernández-Peláez, A., Cazals, A., Guillaume, S., de la Fuente-Tomás, L., Jiménez-Treviño, L., Gutiérrez, L., et al. (2020) · European Psychiatry · doi:10.1192/j.eurpsy.2019.20 · Cited by 100 · see citing works
Role of depression, suicide attempt history and childhood trauma in neutrophil-to-lymphocyte ratio dynamics: A 30-week prospective study
Lion, M., Muller, M., Ibrahim, E. C., El‐Hage, W., Lengvenytė, A., Courtet, P., Antoine Lefrere, A., & Belzeaux-R, R. (2024) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2024.111227 · Cited by 4 · see citing works

Authors: Ivković, M., Pantović-Stefanović, M., Dunjić-Kostić, B., Jurišić, V., Lačković, M., Totić-Poznanović, S., Jovanović, A. A., & Damjanović, A.
Affiliations: University of Belgrade (RS)
Univerzitetski Klinički Centar Srbije (RS)
University of Kragujevac (RS)
Corresponding author: Pantović-Stefanović, Maja
ORCID: Ivković, Maja
Pantović-Stefanović, Maja
Dunjić-Kostić, Bojana
Jurišić, Vladimir
Lačković, Maja
Totić-Poznanović, Sanja
Jovanović, Aleksandar A.
Venue: Comprehensive Psychiatry
Publisher: Elsevier BV
Published: 2016-04
Volume: 66
Pages: 87-95
ISSN: 0010-440X (ISSN-L)
DOI: 10.1016/j.comppsych.2016.01.005
OpenAlex: W2258719822
Cited by: 89
References: 63
Citations by year: 2026: 7 · 2025: 9 · 2024: 12 · 2023: 10 · 2022: 9 · 2021: 13 · 2020: 9 · 2019: 8 · 2018: 10 · 2017: 2
FWCI: 5.93
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Comprehensive Psychiatry (publishedVersion)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders: Ministry of Science and Environmental Protection
Topics: Health Sciences › Medicine › Psychiatry and Mental health › Bipolar Disorder and Treatment
Social Sciences › Psychology › Clinical Psychology › Suicide and Self-Harm Studies
Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
Keywords: neutrophil-to-lymphocyte ratio, bipolar disorder, suicide risk, suicide attempts, family history of suicide, diathesis-stress model, immunological markers, early trauma, acute stress, suicide prevention, euthymic patients
MeSH terms: Adult, Bipolar Disorder, Family, Female, Humans, Leukocyte Count, Lymphocytes, Male, Middle Aged, Neutrophils, Predictive Value of Tests, Psychiatric Status Rating Scales, Surveys and Questionnaires, Risk Factors, Socioeconomic Factors, Suicide, Suicide, Attempted, Lymphocyte Count, Mood Disorders, Serbia, Self Report

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Neutrophil-to-lymphocyte ratio predicting suicide risk in euthymic patients with bipolar disorder: Moderatory effect of family history

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