Increased neutrophil-lymphocyte ratios in depressive adolescents is correlated with the severity of depression
Abstract
We aimed to investigate the neutrophil-lymphocyte ratio and platelet-lymphocyte ratio in adolescents with major depression. Sixty-seven adolescents and 121 healthy controls were enrolled in the study. The diagnosis was made by using both the Kiddie and Young Adult Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version and the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition. The severity of depressive symptoms was evaluated using the Beck depression inventory (BDI). The neutrophil-lymphocyte ratios of the adolescents with depression were significantly higher than those of the control group, even after adjusting for age, sex, BMI, and BDI scores, whereas there was no significant difference in platelet-lymphocyte ratios. A positive correlation between the severity of depression and neutrophil-lymphocyte ratios and platelet-lymphocyte ratios were determined in the case group. The results of this study may promote the hypothesis that inflammation plays an important role in the etiology of major depression in adolescents.
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Neutrophil-to-lymphocyte ratio and PLR were found to be related to depression severity.
“Neutrophil-to-lymphocyte ratio and PLR were found to be related to depression severity.24”
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 [24]
NLR, PLR, and MLR are being investigated in neuropsychiatric disorders such as Alzheimer's disease, schizophrenia, bipolar disorder, and major depressive disorder.
“are also being investigated in neuropsychiatric disorders such as Alzheimer’s disease, schizophrenia, bipolar disorder, and major depressive disorder (MDD) [11, 18].”
Lymphocytes represent the regulatory or protective component of the immune system.
“lymphocytes represent the regulatory or protective component of the immune system [11–13].”
It has not been determined whether inflammation is a causative factor or a consequence of depression.
“(iii) it has not been determined whether inflammation is a causative factor or a consequence of depression [11].”
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“A study also found that adolescents with depression had higher NLR, which was positively correlated with the severity of depression [25].”
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“However, in the studies by Uçar et al. and Ozyurt et al. no significant differences were observed in PLR [28,29].”
Zhou, L., Ma, X., & Wang, W. (2024) · BMC Psychiatry · doi:10.1186/s12888-023-05430-3 · Cited by 16 · see citing works
“The relationship between NLR and depression severity in patients with depression [22] and NRL and psychotic depression [23] has been previously reported, and depression has many similarities with negative symptoms, prompt NLR, negative symptoms of SCZ, and depressive symptoms.”
BackgroundFourrier, C., Sampson, E., Hori, H., Schubert, K. O., Clark, S. R., Mills, N. T., & Baune, B. T. (2020) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2020.06.007 · Cited by 16 · see citing works
Shan, M., Lü, S., Cui, R., Yang, Y., Sun, Z., & Pan, Y. (2022) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2022.111041 · Cited by 15 · see citing works
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
“24 On the other hand, Kayhan et al 23 found no difference in NLR values between different levels of depression severity and suggested that PLR might be more related to severity.”
BackgroundChild and Adolescent Psychiatry, U. O. H. S., Önen, Ö., Erkuran, H. Ö., Child and Adolescent Psychiatry, U. O. H. S., Bağ, Ö., Department of Social Pediatrics, U. O. H. S., Abacıgil, F., & Department of Public Health, A. A. M. U. F. O. M. (2021) · Psychiatry and Clinical Psychopharmacology · doi:10.5152/pcp.2021.21137 · Cited by 13 · see citing works
“9 No significant relationship was found between BCPI levels and depression scale scores in our study.”
ResultWen, X., Wang, F., Tang, T. F., Xu, B., Yuan, M., Li, Y., Ding, H., Tao, F., Su, P., & Wang, G. (2024) · Journal of Affective Disorders · doi:10.1016/j.jad.2024.06.098 · Cited by 16 · see citing works
Zhang, Y. P., Mei, H., Xiao, H., Zhang, Y., Gao, W., Qi, H., & Zhang, J. (2022) · Journal of Psychosomatic Research · doi:10.1016/j.jpsychores.2022.111101 · Cited by 13 · see citing works
Blood cell ratios in mood and cognitive outcomes following electroconvulsive therapy.
Ryan, K., Lynch, M., & McLoughlin, D. (2022) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2022.11.016 · Cited by 9 · see citing works
Sharifan, P., Darroudi, S., Rafiee, M., Toosi, M. S. E., Doust, F. N. S., Taghizadeh, N., Mashhadi, M. R. F., Ghazizadeh, H., Mohammadi, M. A., Dabagh, A. E., et al. (2023) · International Journal of Geriatric Psychiatry · doi:10.1002/gps.5972 · Cited by 11 · see citing works
“Previous studies have also found that NLR and PLR are associated with depression, and some studies have further found that PLR is a more significant factor in the severity of depression cases compared to NLR.(40) Additionally, previous research has suggested that vitamin D deficiency is related to depression, which is…”
ResultInflammatory burden index is correlated with increased depression: a population-based study
Shao, X., Xie, Z., & Zhu, L. (2025) · BMC Psychiatry · doi:10.1186/s12888-025-06730-6 · Cited by 10 · see citing works
“Sunbul and Ozyurt identified a positive correlation between NLR and the severity of depression [31].”
Avşar, P. A., Kara, T., Kocaman, O., & Akkuş, M. (2024) · Biomarkers in Medicine · doi:10.1080/17520363.2024.2404387 · Cited by 9 · see citing works
Li, S., Nan, W., Peng, Z., Huang, Q., Chen, Q., & He, B. (2025) · European Journal of Psychotraumatology · doi:10.1080/20008066.2025.2450109 · Cited by 8 · see citing works
“Özyurt et al. demonstrated that white blood cells and neutrophils, recognized as clinical biomarkers of inflammation, were higher in depressive adolescents compared to the healthy controls (Özyurt & Binici, 2018).”
He, Y., Wei, Y., Wang, Y., Liang, F., & Ma, T. (2024) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2024.1359400 · Cited by 7 · see citing works
“However, evidence in this area remains controversial (20 – 22).”
BackgroundKigar, S. L., Lynall, M.-E., DePuyt, A. E., Atkinson, R., Sun, V. H., Samuels, J. D., Eassa, N. E., Poffenberger, C. N., Lehmann, M. L., Listwak, S. J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-62840-5 · Cited by 10 · see citing works
“In parallel, multiple clinical studies have documented an increased ratio of neutrophils relative to lymphocytes in people with MDD 10,11 .”
Matits, L., Munk, M., Bizjak, D. A., Kolassa, I.-T., Karrasch, S., Vollrath, S., Jerg, A., & Steinacker, J. M. (2023) · Brain, Behavior, & Immunity - Health · doi:10.1016/j.bbih.2023.100614 · Cited by 10 · see citing works
The role of inflammation in children with specific learning disorders
Öz, B. O., & Ardiç, B. (2022) · Annals of Indian Psychiatry · doi:10.4103/aip.aip_129_22 · Cited by 6 · see citing works
Serum peripheral markers for inflammation in adolescents with anorexia nervosa
Ünver, H., Ceylan, B. G., Yıldırım, A. B. E., & Fiş, N. P. (2024) · International Journal of Psychiatry in Clinical Practice · doi:10.1080/13651501.2024.2343482 · Cited by 6 · see citing works
“…between the groups in terms of PlR value, and it is stated that NlR is a more reliable marker for inflammation compared to PlR (aydin et al., 2015; Özyurt & Binici, 2018; Uçar et al., 2019). studies show that patients with different mental disorders have elevated platelet counts (almis & aksoy,…”
BackgroundResultInfluentialLi, J., Zhang, Y., Yang, N., Du, J., Liu, P., Dai, W., & Dong, Q. (2025) · Psychiatry Investigation · doi:10.30773/pi.2024.0295 · Cited by 8 · see citing works
A new interpretation of neutrophil-lymphocyte ratio from psychiatric aspect
Kalelioğlu, T., & Karamustafalıoğlu, N. (2019) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.4149/bll_2019_099 · Cited by 6 · 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
“One of the studies included in our review demonstrated a correlation between NLR and the severity of depressive symptoms in adolescents with MDD [51].”
BackgroundMethodResultInfluentialDrapisz, A., Avrahami, M., Dor, D. H. B., Bustan, Y., Mekori‐Domachevsky, E., Weizman, A., & Barzilay, R. (2022) · International Clinical Psychopharmacology · doi:10.1097/yic.0000000000000412 · Cited by 5 · see citing works
“Literature on the association between severe mood disorders and inflammation in children and adolescents with neuropsychiatric disorders is limited (Goldstein et al., 2011; Mitchell and Goldstein, 2014; Binici et al., 2018; Özyurt and Binici, 2018).”
BackgroundZhou, Y., Jiang, X., Hu, Y., Zheng, Y., Yan, J., Zhang, B., Gao, Q., & Chen, Y. (2025) · Harvard Review of Psychiatry · doi:10.1097/hrp.0000000000000444 · Cited by 4 · see citing works
Schumacher, A., Tu, E., Albaum, C. S., & Korczak, D. J. (2025) · Comprehensive Psychoneuroendocrinology · doi:10.1016/j.cpnec.2025.100302 · Cited by 4 · see citing works
“…with individual studies reporting lymphocytes to be either elevated [19] or unchanged [20 – 23], reporting neutrophils to be either increased [20,21, 23] or unchanged [22], platelets to be either increased [21,23] or unchanged [20,22], and NLR to be either increased [20 – 22] or unchanged [23]…”
Cheng, J., Liu, Z., Zhu, R., Liu, Q., Han, H., Liu, N., Shi, J., Han, S., & Ma, N. (2025) · Journal of Affective Disorders · doi:10.1016/j.jad.2025.119734 · Cited by 4 · see citing works
Yu, J., Zhang, Z., Li, C., Zhang, J., Ding, Z., Zhu, W., & Wang, Q. (2021) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2021.773338 · Cited by 4 · see citing works
“Notably, neutrophil to lymphocyte ratio, but not absolute lymphocytes counts, was used to explore the biological mechanisms underlying psychiatric disorders (14, 15).”
MethodMarkiewicz, M. G., Madetko‐Alster, N., Otto‐Ślusarczyk, D., Duszyńska-Wąs, K., Migda, B., Chunowski, P., Struga, M., & Alster, P. (2025) · Diseases · doi:10.3390/diseases13040119 · Cited by 3 · see citing works
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
Soedjana, H., Hasibuan, L. Y., Riestiano, B. E., Andayani, S., Nurfitriani, A., Sundoro, A., Putri, A. C., & Prasetyo, A. T. (2024) · JPRAS Open · doi:10.1016/j.jpra.2024.04.005 · Cited by 3 · see citing works
“22 , 23 Inflammatory processes in the brain resulting in an imbalance of inflammatory mediators can affect neurotransmitter metabolism (glutamate and serotonin), which has an impact on neuropsychiatric disorders such as depression.”
BackgroundSydorova, N. M., & Kazmirchuk, K. (2024) · Ukrainian Journal of Military Medicine · doi:10.46847/ujmm.2024.3(5)-057 · Cited by 4 · see citing works
Inagawa, Y., Kurata, K., Obi, S., Onuki, Y., Monden, Y., Kurane, K., Furukawa, R., Mitani, T., Nakamura, H., Suda, S., et al. (2025) · Journal of Eating Disorders · doi:10.1186/s40337-025-01282-2 · Cited by 3 · see citing works
Zhu, M., & Li, W. (2025) · Frontiers in Psychiatry · doi:10.3389/fpsyt.2025.1671777 · Cited by 2 · see citing works
Öztürk, M., Özkan, Y., Sapmaz, Ş. Y., & Kandemır, H. (2022) · Journal of Clinical Psychiatry · doi:10.5505/kpd.2022.48091 · Cited by 2 · see citing works
“In studies conducted with adolescents who did not use medication recently and had depression; no significant difference was found between the depressive group and the healthy control group in terms of PLR although NLR was found to be significantly higher in patients with depression compared to healthy control group (2…”
BackgroundResultApplicability of the Neutrophil/Lymphocyte Ratio in Behavioral Studies
de, S. R. B. N., Henrique, A. L., Caetano, C. V., da Silva, M. C., Medeiros, A. F., Pereira, A. A. G., da Silva, P. D., de Camargo, N. C., de Camargo, L. C., do Nascimento, S. H., et al. (2022) · International Journal of Blood Research and Disorders · doi:10.23937/2469-5696/1410075 · Cited by 2 · see citing works
“This has been observed for patients with Schizoaffective Disorder and Schizophrenia [ 12], Attention Deficit Hyperactivity Disorder [16 ], Obsessive Compulsive Disorder [56], Hypomania in Bipolar Mood Disorder [ 10 ] and Major Depressive Disorder [57 , 58 ].”
BackgroundRengasamy, M. L., Kovats, T., Wears, A., Griffo, A., Saul, M. I., Spada, M. L., & Price, R. B. (2023) · Journal of Affective Disorders Reports · doi:10.1016/j.jadr.2023.100684 · Cited by 2 · see citing works
Yurteri, N., & ŞAHİN, İ. E. (2020) · Konuralp Tıp Dergisi · doi:10.18521/ktd.789566 · Cited by 1 · see citing works
Cognitive function and inflammatory markers of survivors of MIS-C
Üstündağ, G., Özyurt, G., Tüz, A. E., Çıldır, D. A., Akman, S., Aksay, A. K., Yılmaz, D., & Öncel, E. K. (2025) · Applied Neuropsychology Child · doi:10.1080/21622965.2025.2526378 · Cited by 1 · see citing works
Self-citationZhang, W., Zhang, Y., Xu, T., Wang, Y., Yu, E., & Jing, Y. (2025) · BMC Psychiatry · doi:10.1186/s12888-025-07705-3 · Cited by 1 · see citing works
“One recent study found that adolescents with depression had a significantly higher NLR than the control group, whereas no significant difference was observed in PLR [37].”
Examining Subclinical Inflammation in Major Depressive Disorder Subtypes
Aslan, E., & Demir, B. (2025) · Genel Tıp Dergisi · doi:10.54005/geneltip.1609236 · Cited by 1 · see citing works
Özmen, Ç., Akray, A., İltaş, A., Yıldız, P. Ö., Yıldız, İ., & Aktaş, H. (2021) · Çukurova medical journal (Online)/Çukurova medical journal · doi:10.17826/cumj.977656 · Cited by 1 · see citing works
Chronic social defeat stress induces meningeal neutrophilia via type I interferon signalingPreprint
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Efe, A., & Tok, A. (2023) · Journal of Clinical Psychiatry · doi:10.5505/kpd.2023.23471
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“different types of cancer, SIRS, sepsis, behavioural and psychiatric pathologies, MI and different autoimmune disorders [16].”
BackgroundNeurophysiological cognitive assessment and its association with neutrophil to lymphocyte ratio
Rajprabha, Sharma, A., Sorout, J., Kacker, S., & Jangid, N. (2023) · RUDN Journal of Medicine · doi:10.22363/2313-0245-2023-27-3-285-292
“This has been observed for patients with schizoaffective disorder and schizophrenia [8], attention deficit hyperactivity disorder [9], obsessive compulsive disorder [10], hypomania in bipolar mood disorder [11], and major depressive disorders [12, 13].”
Interlinking Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios and Depressive Disorders
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Interlinking Neutrophil-Lymphocyte and Platelet-Lymphocyte Ratios and Depressive Disorders
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“Additionally, there was a positive correlation between the NLRs, the PLR, and the severity of depression (Ozyurt and Binici 2018 ).”
Self-citationLin, K., Wang, P., Li, S., Ma, C., Wen, D., Wang, X., & Liao, L. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1712425
- Authors
- Özyurt, G., & Binici, N. C.
- Affiliations
- Izmir Kâtip Çelebi University (TR)
- Dr. Behçet Uz Çocuk Hastalıkları Hastanesi (TR)
- Corresponding author
- Özyurt, Gonca
- Venue
- Psychiatry Research
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 268
- Pages
- 426-431
- ISSN
- 0165-1781 (ISSN-L)
- OpenAlex
- W2887651376
- Semantic Scholar
- ff5a7b96469015d6ee2bf20aa3ffd1d43dd354b9
- Cited by
- 74
- References
- 68
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 13 · 2023: 10 · 2022: 13 · 2021: 8 · 2020: 5 · 2019: 1
- FWCI
- 1.11
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Psychiatry Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Health Sciences › Medicine › Oncology › Inflammatory Biomarkers in Disease Prognosis
- Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
- Keywords
- neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio, adolescent depression, major depressive disorder, depression severity, inflammation, inflammatory markers
- MeSH terms
- Adolescent, Blood Platelets, Child, Depression, Depressive Disorder, Major, Major Depressive Disorder, Female, Humans, Inflammation, Leukocyte Count, Lymphocytes, Male, Neutrophils, Psychiatric Status Rating Scales, Severity of Illness Index, Case-Control Studies
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