Elevated levels of Monocyte-lymphocyte Ratio and Platelet-lymphocyte Ratio in adolescents with Non-suicidal Self-injury

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Adolescents with non-suicidal self-injury exhibited elevated monocyte-lymphocyte and platelet-lymphocyte ratios, suggesting increased systemic inflammation.

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Abstract

Background: Neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) are blood indicators of systemic inflammation. This study aims to compare the levels of inflammatory indicators derived from blood routine tests between adolescents with non-suicidal self-injury (NSSI) and those with non-NSSI. Methods: : A total of 201 adolescents with mood or emotional disorders were enrolled in this study, among which 106 had engaged in NSSI and 95 had never engaged in NSSI. NLR, MLR, and PLR were calculated based on the complete blood cell count. Results: : There was no significant difference in demographic data between the two groups. The NSSI group exhibited significantly higher MLR ( P < 0.001) and PLR ( P = 0.001) than the non-NSSI group. Multivariate logistic regression analysis revealed that MLR (OR 1.545, 95%CI [1.087-2.281], P = 0.021) and PLR (OR 1.327, 95%CI [1.215-1.450], P < 0.001) were independent predictors of NSSI. Receiver operating characteristic (ROC) curve analyses demonstrated that for predicting NSSI, the optimal cut-off value of MLR was 0.135 and the area under curve was 0.638 ([0.561- 0.715], P < 0.001), with a sensitivity of 90.60% and a specificity of 33.70%; the optimal cut-off value of PLR was 127.505 and the area under curve was of 0.611 ([0.533-0.689], P < 0.001), with a sensitivity of 39.60% and a specificity of 81.10%. Conclusions: : Systemic inflammation, as indicated by MLR and PLR, is elevated in adolescents with NSSI. MLR and PLR might serve as potential biomarkers in the assessment of NSSI in adolescents.
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Elevated levels of Monocyte-lymphocyte Ratio and Platelet-lymphocyte Ratio in adolescents with Non-suicidal Self-injury | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Elevated levels of Monocyte-lymphocyte Ratio and Platelet-lymphocyte Ratio in adolescents with Non-suicidal Self-injury Qi Zheng, Jin Liu, YaJuan Ji, XinChao Chen, BangShan Liu, Yan Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-1679507/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 10 You are reading this latest preprint version Abstract Background: Neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) are blood indicators of systemic inflammation. This study aims to compare the levels of inflammatory indicators derived from blood routine tests between adolescents with non-suicidal self-injury (NSSI) and those with non-NSSI. Methods: A total of 201 adolescents with mood or emotional disorders were enrolled in this study, among which 106 had engaged in NSSI and 95 had never engaged in NSSI. NLR, MLR, and PLR were calculated based on the complete blood cell count. Results: There was no significant difference in demographic data between the two groups. The NSSI group exhibited significantly higher MLR ( P < 0.001) and PLR ( P = 0.001) than the non-NSSI group. Multivariate logistic regression analysis revealed that MLR (OR 1.545, 95%CI [1.087-2.281], P = 0.021) and PLR (OR 1.327, 95%CI [1.215-1.450], P < 0.001) were independent predictors of NSSI. Receiver operating characteristic (ROC) curve analyses demonstrated that for predicting NSSI, the optimal cut-off value of MLR was 0.135 and the area under curve was 0.638 ([0.561- 0.715], P < 0.001), with a sensitivity of 90.60% and a specificity of 33.70%; the optimal cut-off value of PLR was 127.505 and the area under curve was of 0.611 ([0.533-0.689], P < 0.001), with a sensitivity of 39.60% and a specificity of 81.10%. Conclusions: Systemic inflammation, as indicated by MLR and PLR, is elevated in adolescents with NSSI. MLR and PLR might serve as potential biomarkers in the assessment of NSSI in adolescents. Adolescents non-suicidal self-injury (NSSI) neutrophil-lymphocyte ratio (NLR) monocyte-lymphocyte ratio (MLR) platelet-lymphocyte ratio (PLR) Figures Figure 1 Background Non-suicidal self-injury (NSSI) is defined as the direct and deliberate damage to one’s own body for reasons not socially accepted, with no observable intention to die as a consequence of the behavior [1]. It has become a proposed diagnosis in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [2]. A systematic review has shown that the prevalence of NSSI is 7.5–46.5% in adolescents [3]. Another meta-analysis found that the lifetime and 12-month prevalence of NSSI was 22.1% and 19.5%, respectively, in children and adolescents between 1989 and 2018 across the world [4]. According to the latest statistics, Chun W et al. estimated that the prevalence of NSSI in middle school students in China (aged 13–18 years) is 27.4% [5]. Numerous studies have shown that NSSI is strongly associated with suicide attempts (SAs) [6, 7] and that NSSI is the strongest predictor of future suicidal behavior [8]. The risks of both SA and completed suicide are significantly higher in those who have engaged in NSSI. Among those with a history of NSSI, 70% had at least one SA and 55% had ≥ 2 SAs [9]. Therefore, NSSI has been recognized as a major public health problem in adolescents that seriously affects their mental health and safety. Until very recently, only very few studies investigated the relationship between NSSI and inflammation. Kim et al. reported that patients with mood disorders with NSSI exhibit greater behavioral impulsivity and higher levels of serum tumor necrosis factor α (TNF-α) as compared to those without NSSI [10]. Osimo et al. suggested that low-grade systemic inflammation (defined as a serum C-reactive protein (CRP) level > 3 mg/L or white cell count (WBC) > 9.4 * 10 9 /L) is associated with NSSI in adult psychiatric inpatients through an analysis of electronic health records [11]. However, results are conflicting among different studies. Russell et al. found no association between interleukin-6 (IL-6) and NSSI; they even found a negative association between CRP and NSSI, indicating that higher levels of CRP may be protective for NSSI [12]. Despite the inconsistent findings, there is a growing interest in the relationship between inflammation and NSSI. According to previous studies, Neutrophil-Lymphocyte Ratio (NLR), Monocyte-Lymphocyte Ratio (MLR), and Platelet-Lymphocyte Ratio (PLR) are relatively stable biomarkers of systemic inflammation [13, 14]. These markers are inexpensive and easy to obtain, thus being promising for clinical application. Many studies have investigated the association between NLR, MLR, and PLR and suicide. Ekinci et al. suggested that NLR may be a marker for suicide vulnerability in patients with major depressive disorder (MDD) [15]. one study also showed that NLR in patients with bipolar disorder and SA is higher than that in healthy controls [16]. Similarly, another research also supports that SA survivors exhibited higher levels of NLR compared to normal controls [17]. Moreover, Arafat et al. revealed that the levels of CRP and NLR were significantly elevated in individuals who committed non-fatal hanging [18]. Puangsri et al. found that depressed adolescents with SA show elevated levels of MLR than those with no suicide ideation; and that the levels of MLR and NLR are positively correlated with suicidality severity [19]. To our knowledge, no studies have directly investigated the correlation between blood cell counts and NSSI. Herein we report an investigation on the associations between MLR, NLR, and PLR in adolescents with NSSI. Based on the previous findings, we hypothesized that patients with NSSI would show elevated levels of NLR, MLR, and PLR as compared with those with non-NSSI; and NLR, MLR, and PLR may be effective markers for differentiating patients with NSSI and those with non-NSSI. Methods Participants A total of 201 inpatient adolescents (aged 13–18 years) with mood or emotional disorders were recruited from the hospital. The inclusion criteria were: (1) diagnosed with mood or emotional disorders according to the International Classification of Diseases 10th Revision (ICD-10), including anxiety disorders (AD), major depressive disorder (MDD), bipolar disorder (BD), and behavioral and emotional disorders with onset usually occurring in childhood and adolescence; (2) engaged in NSSI according to the DSM-5 criteria (history of NSSI was determined using information collected through the direct interviews and medical record reviews), and having ≥ 1 self-injury at least one occasion in the past month. The participants were grouped into an NSSI group and a non-NSSI group based on whether they had a history of NSSI. The exclusion criteria were: (1) with a current diagnosis of any other psychiatric disorder; (2) with SA or suicide ideation (assessed based on the patient’s history and course of the disease); (3) with serious physical illnesses, especially those associated with systemic inflammatory responses such as active infection, fever, acute or chronic endocrinological diseases; (4) had used anti-inflammatory drugs, corticosteroids or antipyretic drugs in the past two weeks. Data collection Blood samples of all enrolled individuals were collected from the cubital vein after fasting. Complete blood cell count was measured using Sysmex XN-1000 (XN-1000, Sysmex, Japan) automatic blood cell analyzer. Data were obtained from the electronic medical records system. Laboratory results were obtained from electronic medical records, and NLR, MLR, and PLR values were calculated and compared between the two groups. Statistical analysis Data analyses were performed using the IBM SPSS Statistics version 26 for Mac OS. Continuous variables were analyzed using the student’s t-test, and categorical variables were analyzed using the chi-square test. Multivariate logistic regression analysis was conducted to determine the independent predictors of NSSI. Odds ratios (ORs) and 95% confidence interval (CI) were calculated for the predicting variables. Receiver operating characteristic (ROC) curve analysis was performed to determine the discrimination threshold of inflammatory markers in the diagnosis of NSSI. A two-tailed P < .05 was considered statistically significant for all analyses. Results A total of 201 patients were enrolled in this study, with 106 grouped into the NSSI group and 95 grouped into the non-NSSI group. In the NSSI group, there were 89 females and 17 males, with a mean age of 14.94 ± 1.56 years; among which 4 (3.77%) patients were diagnosed with anxiety disorders (AD), 56 (52.83%) with major depressive disorder (MDD), 3 (2.83%) with bipolar disorder (BD) and 43 (40.57%) with behavioral and emotional disorders with onset usually occurring in childhood and adolescence. In the non-NSSI group, there were 74 females and 21 males, with a mean age of 15.32 ± 1.71 years; among which 9 (9.47%) patients were diagnosed with AD, 42 (44.21%) with MDD, 5 (5.26%) with BD and 39 (41.05%) with behavioral and emotional disorders with onset usually occurring in childhood and adolescence. There were no significant differences in age ( p = 0.110), gender ( p = 0.359), family history ( p = 0.125), and diagnoses ( p = 0.260) between the two groups. The demographic characteristics of the subjects are summarized in Table 1 . Table 1 Demographic characteristics of the NSSI group and the non-NSSI group. Variables NSSI Non-NSSI t/x 2 p (n = 106) (n = 95) Age (y) 14.94 ± 1.56 a 15.32 ± 1.71 a -1.607 0.110 b Female (n%) 89(84.00%) 74(77.90%) 0.839 0.359 c Family history 5(4.70%) 11(11.60%) 2.351 0.125 c Diagnosis Anxiety disorders 4(3.77%) 9(9.47%) 4.030 0.260 c Major depressive disorder 56(52.83%) 42(44.21%) - - Bipolar disorder 3(2.83%) 5(5.26%) - - Behavioral and emotional disorders with onset usually occurring in childhood and adolescence 43(40.57%) 39(41.05%) - - a Expressed as mean ± standard deviation; b Student's t-test; c Chi-square test The monocyte count, MLR, and PLR were significantly higher in adolescents with NSSI than those without NSSI ( p = 0.018, p < 0.001, p = 0.001, respectively). The lymphocyte count was significantly lower in the NSSI group ( p = 0.023). There were no significant differences in white blood cell count (WBC), neutrophil count, platelet count, mean platelet volume (MPV), and NLR between the two groups (all p > 0.05) (Table 2 ). Multivariate logistic regression analysis showed that MLR (OR 1.545, 95% CI [1.087–2.281], p = 0.021) and PLR (OR 1.327, 95%CI [1.215–1.450], p < 0.001) were independently associated with NSSI (Table 3 ). Table 2 Comparison of blood cell count parameters between the NSSI group and the non-NSSI group. Variables NSSI Non-NSSI t p WBC (10 3 /uL) 6.988 ± 1.820 6.995 ± 1.810 -0.027 0.978 Lymphocyte (10 3 /uL) 2.441 ± 0.522 2.625 ± 0.606 -2.292 0.023 * Monocyte (10 3 /uL) 0.493 ± 0.168 0.441 ± 0.147 2.378 0.018 * Neutrophil (10 3 /uL) 3.843 ± 1.551 3.760 ± 1.562 0.376 0.707 Platelet (10 3 /uL) 288.642 ± 56.076 273.547 ± 59.079 1.852 0.066 MPV (fl) 9.942 ± 0.751 10.113 ± 0.927 -1.428 0.155 MLR 0.208 ± 0.078 0.173 ± 0.058 3.714 < 0.001 * NLR 1.630 ± 0.714 1.508 ± 0.733 1.200 0.231 PLR 122.391 ± 31.497 108.145 ± 28.029 3.393 0.001 * WBC: white blood cell count; MPV: mean platelet volume; MLR: monocyte-lymphocyte ratio; NLR: neutrophil-lymphocyte ratio; PLR: platelet-lymphocyte ratio; * indicates statistical significance. Table 3 Multivariate logistic regression model for the association between NSSI and inflammatory marker. Variables OR (95%CI) p MLR 1.545(1.087–2.281) 0.021 * PLR 1.327(1.215–1.450) < 0.001 * MLR: monocyte-lymphocyte ratio; PLR: platelet-lymphocyte ratio. * indicates statistical significance. Receiver-operating characteristic (ROC) curve analyses were then performed to evaluate the diagnostic ability of MLR and PLR for NSSI. According to the ROC curve, the area under curve was 0.638 ([0.561–0.715], p < 0.001) for MLR and 0.611 ([0.533–0.689], p < 0.001) for PLR. The optimal cut-off value was 0.135 for MLR, with a sensitivity of 90.60% and specificity of 33.70%; the optimal cut-off value was 127.505 for PLR, with a sensitivity of 39.60% and specificity of 81.10% (Table 4 and Fig. 1 ) . Table 4 Receiver-operating characteristic (ROC) curve of MLR and PLR as predictors of NSSI. Variables AUC 95%CI Cut-off sensitivity specificity p MLR 0.638 0.561–0.715 0.135 0.906 0.337 < 0.001 * PLR 0.611 0.533–0.689 127.505 0.396 0.811 < 0.001 * MLR: monocyte-lymphocyte ratio; PLR: platelet-lymphocyte ratio. * indicates statistical significance. Discussion To the best of our knowledge, this is the first study probing NLR, MLR, and PLR as hallmarks of systemic inflammation in adolescents with NSSI. The results showed significantly elevated levels of MLR and PLR in adolescents with NSSI compared with those with no NSSI, suggesting a potential role of MLR and PLR in the assessment and prediction of NSSI in clinical practice. Inconsistent with our hypothesis, we found no changes in NLR in adolescents with NSSI. MLR Previous studies have found that an elevated level of monocyte count is associated with overexpression of immune genes and overproduction of monocytes/macrophage-related cytokines [20]. Increased monocyte count or MLR had been observed in major psychiatric disorders, such as schizophrenia [13, 21], bipolar disorder [22, 23] and major depressive disorder [24]. It is supposed that elevated monocyte count or MLR is accompanied by an increase in the monocyte-related cytokines (such as IL-6, IL-1β, IL-12, and TNF) and activation of microglia in the brain [25], which is a biomarker of neuroinflammation. Microglia monitors the functional state of synapses and modulates neuroplasticity by synaptic pruning and phagocytosis, resulting in altered brain structure and function, including regions implicated in impulse control and emotion regulation, such as the medial prefrontal cortex, dorsolateral prefrontal cortex, insula, amygdala, and hippocampus [7, 26–28]. A previous study found that elevated monocyte count and MLR are associated with an increased risk of suicide in adolescents with major depressive disorder [19]. In sum, the elevated monocyte and MLR found in this study may play an important role in the pathology of NSSI through the release of monocyte-related cytokines and activation of microglia. PLR Platelets are closely related to stress, peripheral inflammation, and monoaminergic neurotransmission, which may be involved in the pathology of NSSI. Stress may increase platelet count and activity through sympathetic system activation [29]. The increased platelet count and activity may further induce altered endothelial permeability as well as recruitment of neutrophils and macrophages, resulting in elevated peripheral inflammation [30, 31]. Moreover, platelets contain abundant serotonin in their dense granules, and serotonin receptors (5HT 2A ) and transporters on the cell surface, are involved in the production, reuptake, and metabolism of serotonin [32, 33]. A previous study had suggested that platelet serotonin could reliably indicate the presynaptic serotonin activity in the brain [34]. Dysregulation of serotonergic neurotransmission is an important factor linked to emotion and behavior disorders, particularly impulse control disorders [35–37]. As reported in a review paper, NSSI could be considered a behavior associated with impulse control problems [38]. Previous studies found that the aggressivity and impulsivity of suicidal attempters seem to be associated with the serotonin content in platelets and the total number of 5-HT 2A receptors on platelet surface [39]. Similarly, Audenaert et al. found decreased frontal serotonin 5-HT 2A receptor binding index in patients with NSSI [40]. Similar to human behavioral data, preclinical studies also revealed a close relationship between serotonergic neurotransmission and NSSI. Dellu et al. revealed that impulsivity behavior was mainly associated with decreased serotonergic neurotransmission in the amygdala and anterior cingulate cortex by testing the different behavior of rats [41]. A recent study in the nonhuman primate model showed that primates with the s allele exhibited NSSI and impulsive behaviors, and there may be distinct the serotonin transporter (5-HTT) genotype-mediated different NSSI typologies [42]. Taken together, elevated PLR may play a role in the pathophysiology of NSSI through its influence on peripheral inflammation and serotonin neurotransmission. NLR Inconsistent with our hypothesis, we found no significant difference in NLR between adolescents with NSSI and those with no NSSI, despite a decrease in the lymphocyte count. NLR reflects the balance between innate (neutrophils) and adaptive (lymphocytes) immunity and is considered a stable peripheral biomarker of inflammation [43]. Previous studies have found that NLR is correlated with suicidality in major depression [15, 44]. The reason for the nonsignificant finding of NLR in this study remains unclear. Puangsri et al. suggested that MLR is more effective than NLR and PLR in the prediction of SAs in patients with MDD [19]. Turkmen et al. found that PLR is superior to NLR in denoting inflammation in patients with end-stage renal diseases [45]. Thus, our result may indicate that MLR and PLR are superior to NLR in the assessment of NSSI in adolescents. Cut-off values of MLR and PLR This study for the first time suggested cut-off values of MLR and PLR for predicting NSSI. With a cut-off value of 0.135, the ROC analysis of MLR reached a high sensitivity (90.60%) and low specificity (33.70%); with a cut-off value of 127.505, the ROC analysis of PLR reached a high specificity (81.10%) and low sensitivity (39.60%). Despite the relatively low areas under the curve for MLR (0.638) and PLR (0.611), a combination of MLR and PLR would be promising to improve the overall sensitivity and specificity in predicting NSSI. To be mentioned, a previous study showed that the MLR and PLR values vary with age and gender in the Chinese population, with males exhibiting higher PLR and lower MLR than females, and with age increases, PLR decreases and MLR increases [46]. In our study, females accounted for the majority of the sample, and all of the participants were aged ≤ 18. Thus, the findings of the ROC analyses should be interpreted with caution, as the optimal cut-off values obtained from our sample maybe not be suitable for males or other age groups. Future studies should investigate the cut-off values of MLR and PLR for predicting NSSI with stratification of gender and age. Limitations This study also has several limitations. First, we were not able to control factors that could influence the inflammatory status of the participants, such as menstrual cycle, and body mass index (BMI). Second, the possible association between the severity of NSSI symptoms and inflammatory indicators was not evaluated. Third, other indicators of immune functions, such as CRP and interleukins, were not evaluated. Finally, the present study is a cross-sectional study, which precludes us from identifying any causal relationship between the inflammatory indicators and NSSI. Conclusion Systemic inflammation, as indicated by MLR and PLR, is elevated in adolescents with NSSI. MLR and PLR are independent predictors of NSSI in adolescents and may serve as biomarkers in the prediction and assessment of NSSI. Abbreviations NLR: Neutrophil-lymphocyte ratio; MLR: monocyte-lymphocyte ratio; PLR: platelet-lymphocyte ratio; NSSI: non-suicidal self-injury; ROC: Receiver operating characteristic; DSM-5: the Diagnostic and Statistical Manual of Mental Disorders; SAs: suicide attempts; TNF-α: tumor necrosis factor α; CRP: C-reactive protein; WBC: white cell count; IL-6: interleukin-6; MDD: major depressive disorder; ICD-10: the International Classification of Diseases 10 th Revision; AD: anxiety disorders; BD: bipolar disorder; ORs: Odds ratios; CI: confidence interval; MPV: mean platelet volume; 5HT2A: serotonin receptors; 5-HTT: serotonin transporter; BMI: body mass index. Declarations Ethics approval and Consent to participate This study was approved by the ethics committee of Xiamen Xianyue Hospital (No. 2021-KY-06). Written informed consent was obtained from the patients’ parents or legal guardians. All methods were performed in accordance with the relevant guidelines and regulations. Consent for publication Not applicable. Availability of data and materials The datasets generated and/or analyzed during the current study are not publicly available data and anonymity but are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This study is supported by the Medical and Health Guidance Project of Xiamen City (No. 3502Z20214ZD1281). Authors' contributions QZ, XC, and BL codesigned the topic. YJ helped collect the data. JL and QZ contributed to the data analysis. QZ drafted and edited the manuscript. YZ, BL, and XC contributed valuable suggestions to the conception of the article and critically revised the manuscript. All authors approved the final version of the article. Acknowledgments The authors would like to thank all of the participants for their contribution to this study. References Hawton K, Saunders KE, O'Connor RC: Self-harm and suicide in adolescents . Lancet 2012, 379 (9834):2373–2382. APA: American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. 5th ed 2013. Rojas-Velasquez DA, Pluhar EI, Burns PA, Burton ET: Nonsuicidal Self-Injury Among African American and Hispanic Adolescents and Young Adults: a Systematic Review . Prev Sci 2021, 22 (3):367–377. Lim KS, Wong CH, McIntyre RS, Wang J, Zhang Z, Tran BX, Tan W, Ho CS, Ho RC: Global Lifetime and 12-Month Prevalence of Suicidal Behavior, Deliberate Self-Harm and Non-Suicidal Self-Injury in Children and Adolescents between 1989 and 2018: A Meta-Analysis . Int J Environ Res Public Health 2019, 16 (22). Wang C, Zhang P, Zhang N: Adolescent mental health in China requires more attention . Lancet Public Health 2020, 5 (12):e637. Mars B, Heron J, Klonsky ED, Moran P, O'Connor RC, Tilling K, Wilkinson P, Gunnell D: Predictors of future suicide attempt among adolescents with suicidal thoughts or non-suicidal self-harm: a population-based birth cohort study . Lancet Psychiatry 2019, 6 (4):327–337. Branas M, Croci MS, Ravagnani Salto AB, Doretto VF, Martinho E, Jr., Macedo M, Miguel EC, Roever L, Pan PM: Neuroimaging Studies of Nonsuicidal Self-Injury in Youth: A Systematic Review . Life (Basel) 2021, 11 (8). Chesin MS, Galfavy H, Sonmez CC, Wong A, Oquendo MA, Mann JJ, Stanley B: Nonsuicidal Self-Injury Is Predictive of Suicide Attempts Among Individuals with Mood Disorders . Suicide Life Threat Behav 2017, 47 (5):567–579. Hargus E, Hawton K, Rodham K: Distinguishing between subgroups of adolescents who self-harm . Suicide Life Threat Behav 2009, 39 (5):518–537. Kim JS, Kang E-S, Bahk YC, Jang S, Hong KS, Baek JH: Exploratory Analysis of Behavioral Impulsivity, Pro-inflammatory Cytokines, and Resting-State Frontal EEG Activity Associated With Non-suicidal Self-Injury in Patients With Mood Disorder . Frontiers in Psychiatry 2020, 11 . Osimo EF, Cardinal RN, Jones PB, Khandaker GM: Prevalence and correlates of low-grade systemic inflammation in adult psychiatric inpatients: An electronic health record-based study . Psychoneuroendocrinology 2018, 91 :226–234. Russell AE, Ford T, Gunnell D, Heron J, Joinson C, Moran P, Relton C, Suderman M, Hemani G, Mars B: Investigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study . Brain Behav Immun 2020, 89 :43–50. Mazza MG, Lucchi S, Rossetti A, Clerici M: Neutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio in non-affective psychosis: A meta-analysis and systematic review . World J Biol Psychiatry 2020, 21 (5):326–338. Mazza MG, Lucchi S, Tringali AGM, Rossetti A, Botti ER, Clerici M: Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis . Prog Neuropsychopharmacol Biol Psychiatry 2018, 84 (Pt A):229–236. Ekinci O, Ekinci A: The connections among suicidal behavior, lipid profile and low-grade inflammation in patients with major depressive disorder: a specific relationship with the neutrophil-to-lymphocyte ratio . Nord J Psychiatry 2017, 71 (8):574–580. Ivkovic M, Pantovic-Stefanovic M, Dunjic-Kostic B, Jurisic V, Lackovic M, Totic-Poznanovic S, Jovanovic AA, Damjanovic A: Neutrophil-to-lymphocyte ratio predicting suicide risk in euthymic patients with bipolar disorder: Moderatory effect of family history . Compr Psychiatry 2016, 66 :87–95. Kumar K, Srivastava S, Sharma B, Avasthi RK, Kotru M: Comparison Between Inflammatory Biomarkers (High-Sensitivity C-Reactive Protein and Neutrophil-Lymphocyte Ratio) and Psychological Morbidity in Suicide Attempt Survivors Brought to Medicine Emergency . Cureus 2021, 13 (8):e17459. Arafat SMY, Karim A, Hossain MF, Menon V, Shoib S: Neutrophil-to-lymphocyte ratio and C-reactive protein in non-fatal suicidal attempts: A cross-sectional pilot study in Bangladesh . Health Sci Rep 2021, 4 (3):e347. Puangsri P, Ninla-Aesong P: 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 . Psychiatry Res 2021, 305 :114216. Beumer W, Gibney SM, Drexhage RC, Pont-Lezica L, Doorduin J, Klein HC, Steiner J, Connor TJ, Harkin A, Versnel MA et al : The immune theory of psychiatric diseases: a key role for activated microglia and circulating monocytes . J Leukoc Biol 2012, 92 (5):959–975. Ozdin S, Sarisoy G, Boke O: A comparison of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in schizophrenia and bipolar disorder patients - a retrospective file review . Nord J Psychiatry 2017, 71 (7):509–512. Inanli I, Aydin M, Caliskan AM, Eren I: Neutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and mean platelet volume as systemic inflammatory markers in different states of bipolar disorder . Nord J Psychiatry 2019, 73 (6):372–379. Fusar-Poli L, Natale A, Amerio A, Cimpoesu P, Grimaldi Filioli P, Aguglia E, Amore M, Serafini G, Aguglia A: Neutrophil-to-Lymphocyte, Platelet-to-Lymphocyte and Monocyte-to-Lymphocyte Ratio in Bipolar Disorder . Brain Sci 2021, 11 (1). Wei Y, Feng J, Ma J, Chen D, Chen J: Neutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in patients with affective disorders . J Affect Disord 2022. Garcia-Rizo C, Casanovas M, Fernandez-Egea E, Oliveira C, Meseguer A, Cabrera B, Mezquida G, Bioque M, Kirkpatrick B, Bernardo M: Blood cell count in antipsychotic-naive patients with non-affective psychosis . Early Interv Psychiatry 2019, 13 (1):95–100. Calcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichello T, Howes OD: Stress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness . Psychopharmacology (Berl) 2016, 233 (9):1637–1650. Dahlgren MK, Hooley JM, Best SG, Sagar KA, Gonenc A, Gruber SA: Prefrontal cortex activation during cognitive interference in nonsuicidal self-injury . Psychiatry Res Neuroimaging 2018, 277 :28–38. Beauchaine TP, Sauder CL, Derbidge CM, Uyeji LL: Self-injuring adolescent girls exhibit insular cortex volumetric abnormalities that are similar to those seen in adults with borderline personality disorder . Dev Psychopathol 2019, 31 (4):1203–1212. Cognasse F, Laradi S, Berthelot P, Bourlet T, Marotte H, Mismetti P, Garraud O, Hamzeh-Cognasse H: Platelet Inflammatory Response to Stress . Front Immunol 2019, 10 :1478. Rawish E, Nording H, Munte T, Langer HF: Platelets as Mediators of Neuroinflammation and Thrombosis . Front Immunol 2020, 11 :548631. Koupenova M, Clancy L, Corkrey HA, Freedman JE: Circulating Platelets as Mediators of Immunity, Inflammation, and Thrombosis . Circ Res 2018, 122 (2):337–351. Everts P, Onishi K, Jayaram P, Lana JF, Mautner K: Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020 . Int J Mol Sci 2020, 21 (20). Mammadova-Bach E, Mauler M, Braun A, Duerschmied D: Autocrine and paracrine regulatory functions of platelet serotonin . Platelets 2018, 29 (6):541–548. Plein H, Berk M: The platelet as a peripheral marker in psychiatric illness . Hum Psychopharmacol 2001, 16 (3):229–236. Ohmura Y, Tsutsui-Kimura I, Sasamori H, Nebuka M, Nishitani N, Tanaka KF, Yamanaka A, Yoshioka M: Different roles of distinct serotonergic pathways in anxiety-like behavior, antidepressant-like, and anti-impulsive effects . Neuropharmacology 2020, 167 :107703. Bacque-Cazenave J, Bharatiya R, Barriere G, Delbecque JP, Bouguiyoud N, Di Giovanni G, Cattaert D, De Deurwaerdere P: Serotonin in Animal Cognition and Behavior . Int J Mol Sci 2020, 21 (5). da Cunha-Bang S, Knudsen GM: The Modulatory Role of Serotonin on Human Impulsive Aggression . Biol Psychiatry 2021, 90 (7):447–457. Hamza CA, Willoughby T, Heffer T: Impulsivity and nonsuicidal self-injury: A review and meta-analysis . Clin Psychol Rev 2015, 38 :13–24. Spreux-Varoquaux O, Alvarez JC, Berlin I, Batista G, Despierre PG, Gilton A, Cremniter D: Differential abnormalities in plasma 5-HIAA and platelet serotonin concentrations in violent suicide attempters: relationships with impulsivity and depression . Life Sci 2001, 69 (6):647–657. Audenaert K, Van Laere K, Dumont F, Slegers G, Mertens J, van Heeringen C, Dierckx RA: Decreased frontal serotonin 5-HT2a receptor binding index in deliberate self-harm patients . European Journal of Nuclear Medicine 2001, 28 (2):175–182. Dellu-Hagedorn F, Rivalan M, Fitoussi A, De Deurwaerdere P: Inter-individual differences in the impulsive/compulsive dimension: deciphering related dopaminergic and serotonergic metabolisms at rest . Philos Trans R Soc Lond B Biol Sci 2018, 373 (1744). Wood EK, Kruger R, Day JP, Day SM, Hunter JN, Neville L, Lindell SG, Barr CS, Schwandt ML, Goldman D et al : A nonhuman primate model of human non-suicidal self-injury: serotonin-transporter genotype-mediated typologies . Neuropsychopharmacology 2022, 47 (6):1256–1262. Zahorec R: Neutrophil-to-lymphocyte ratio, past, present and future perspectives . Bratisl Lek Listy 2021, 122 (7):474–488. Velasco A, Rodriguez-Revuelta J, Olie E, Abad I, Fernandez-Pelaez A, Cazals A, Guillaume S, de la Fuente-Tomas L, Jimenez-Trevino L, Gutierrez L et al : Neutrophil-to-lymphocyte ratio: A potential new peripheral biomarker of suicidal behavior . Eur Psychiatry 2020, 63 (1):e14. Turkmen K, Erdur FM, Ozcicek F, Ozcicek A, Akbas EM, Ozbicer A, Demirtas L, Turk S, Tonbul HZ: Platelet-to-lymphocyte ratio better predicts inflammation than neutrophil-to-lymphocyte ratio in end-stage renal disease patients . Hemodial Int 2013, 17 (3):391–396. Wang J, Zhang F, Jiang F, Hu L, Chen J, Wang Y: Distribution and reference interval establishment of neutral-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in Chinese healthy adults . J Clin Lab Anal 2021, 35 (9):e23935. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Under Review Version 1 posted Editorial decision: Major revision 29 Jul, 2022 Reviews received at journal 25 Jun, 2022 Reviewers agreed at journal 14 Jun, 2022 Reviews received at journal 11 Jun, 2022 Reviewers agreed at journal 11 Jun, 2022 Reviewers invited by journal 11 Jun, 2022 Editor assigned by journal 10 Jun, 2022 Editor invited by journal 30 May, 2022 Submission checks completed at journal 30 May, 2022 First submitted to journal 21 May, 2022 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-1679507","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":109820715,"identity":"c0f73c1a-2984-47ab-b966-0eaf12ef33c5","order_by":0,"name":"Qi Zheng","email":"","orcid":"","institution":"Department of Psychology, Xiamen Xianyue Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Qi","middleName":"","lastName":"Zheng","suffix":""},{"id":109820716,"identity":"41c46d89-8c26-4abc-88b8-411697ee7c52","order_by":1,"name":"Jin Liu","email":"","orcid":"","institution":"Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South Univers","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jin","middleName":"","lastName":"Liu","suffix":""},{"id":109820717,"identity":"92245231-6718-4937-ae8d-53a5fd5cfa3c","order_by":2,"name":"YaJuan Ji","email":"","orcid":"","institution":"Department of Psychology, Xiamen Xianyue Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"YaJuan","middleName":"","lastName":"Ji","suffix":""},{"id":109820718,"identity":"db04851f-5d2d-4579-87bd-0ede38cf32b5","order_by":3,"name":"XinChao Chen","email":"","orcid":"","institution":"Department of Psychology, Xiamen Xianyue Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"XinChao","middleName":"","lastName":"Chen","suffix":""},{"id":109820719,"identity":"ab8154b7-e748-4c5c-973b-30120def2226","order_by":4,"name":"BangShan Liu","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA80lEQVRIiWNgGAWjYBACAxDB2AAk2IHkByRBIrQwMzYwziBRCxDxEKPFnP3s4Zc/d9jlMTAzt0nb1NQlNrA3b5NgqLmDU4tlT16aNe+Z5GKgw9qkc44dTmzgOVYmwXDsGW6HHcgxM2ZsY05sAGnJbTiQ2CCRYybB2HAYt5bzb8wMf7bVQ7RYNgAdJv+GgJYbOcYPeNsOQ7QwNgCtk+DBr8VyxhszZt6244ltzIzNlj3HDhu38aQVWyQcw63FnD/H+OPPturEfvb2hzd+1NTJ9rMf3njjQw1uLUDAJgEm4VwQkYBPAzACP+CXHwWjYBSMghEPAAWFT8joVJgcAAAAAElFTkSuQmCC","orcid":"","institution":"Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South Univers","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"BangShan","middleName":"","lastName":"Liu","suffix":""},{"id":109820720,"identity":"06a1039c-bbd2-481e-b2a8-2fcacaaf7ef9","order_by":5,"name":"Yan Zhang","email":"","orcid":"","institution":"Department of Psychiatry, and National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South Univers","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Yan","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2022-05-21 11:29:05","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-1679507/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-1679507/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":22090968,"identity":"d4630a72-6fed-47af-bd9d-5fe18411b84d","added_by":"auto","created_at":"2022-05-31 17:29:04","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":13801,"visible":true,"origin":"","legend":"\u003cp\u003eThe ROC curves of MLR and PLR as predictors of NSSI. MLR is presented with a red line, with an AUC of 63.8%, a sensitivity of 90.60%, and a specificity of 33.70%. PLR is presented with a blue line, with an AUC of 61.1%, a sensitivity of 39.60%, and a specificity of 81.10%.\u003c/p\u003e","description":"","filename":"Figure1.png","url":"https://assets-eu.researchsquare.com/files/rs-1679507/v1/d6a0b58bf798a08a8f943673.png"},{"id":22090969,"identity":"5fab7a01-6613-4d93-a99d-3ab3eb412342","added_by":"auto","created_at":"2022-05-31 17:29:07","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1365621,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-1679507/v1/7556bfa2-fd86-4503-af7d-06c8ac094e28.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Elevated levels of Monocyte-lymphocyte Ratio and Platelet-lymphocyte Ratio in adolescents with Non-suicidal Self-injury","fulltext":[{"header":"Background","content":"\u003cp\u003eNon-suicidal self-injury (NSSI) is defined as the direct and deliberate damage to one\u0026rsquo;s own body for reasons not socially accepted, with no observable intention to die as a consequence of the behavior [1]. It has become a proposed diagnosis in the 5th edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) [2]. A systematic review has shown that the prevalence of NSSI is 7.5\u0026ndash;46.5% in adolescents [3]. Another meta-analysis found that the lifetime and 12-month prevalence of NSSI was 22.1% and 19.5%, respectively, in children and adolescents between 1989 and 2018 across the world [4]. According to the latest statistics, Chun W et al. estimated that the prevalence of NSSI in middle school students in China (aged 13\u0026ndash;18 years) is 27.4% [5]. Numerous studies have shown that NSSI is strongly associated with suicide attempts (SAs) [6, 7] and that NSSI is the strongest predictor of future suicidal behavior [8]. The risks of both SA and completed suicide are significantly higher in those who have engaged in NSSI. Among those with a history of NSSI, 70% had at least one SA and 55% had\u0026thinsp;\u0026ge;\u0026thinsp;2 SAs [9]. Therefore, NSSI has been recognized as a major public health problem in adolescents that seriously affects their mental health and safety.\u003c/p\u003e \u003cp\u003eUntil very recently, only very few studies investigated the relationship between NSSI and inflammation. Kim et al. reported that patients with mood disorders with NSSI exhibit greater behavioral impulsivity and higher levels of serum tumor necrosis factor α (TNF-α) as compared to those without NSSI [10]. Osimo et al. suggested that low-grade systemic inflammation (defined as a serum C-reactive protein (CRP) level\u0026thinsp;\u0026gt;\u0026thinsp;3 mg/L or white cell count (WBC)\u0026thinsp;\u0026gt;\u0026thinsp;9.4\u003csup\u003e*\u003c/sup\u003e10\u003csup\u003e9\u003c/sup\u003e/L) is associated with NSSI in adult psychiatric inpatients through an analysis of electronic health records [11]. However, results are conflicting among different studies. Russell et al. found no association between interleukin-6 (IL-6) and NSSI; they even found a negative association between CRP and NSSI, indicating that higher levels of CRP may be protective for NSSI [12]. Despite the inconsistent findings, there is a growing interest in the relationship between inflammation and NSSI.\u003c/p\u003e \u003cp\u003eAccording to previous studies, Neutrophil-Lymphocyte Ratio (NLR), Monocyte-Lymphocyte Ratio (MLR), and Platelet-Lymphocyte Ratio (PLR) are relatively stable biomarkers of systemic inflammation [13, 14]. These markers are inexpensive and easy to obtain, thus being promising for clinical application. Many studies have investigated the association between NLR, MLR, and PLR and suicide. Ekinci et al. suggested that NLR may be a marker for suicide vulnerability in patients with major depressive disorder (MDD) [15]. one study also showed that NLR in patients with bipolar disorder and SA is higher than that in healthy controls [16]. Similarly, another research also supports that SA survivors exhibited higher levels of NLR compared to normal controls [17]. Moreover, Arafat et al. revealed that the levels of CRP and NLR were significantly elevated in individuals who committed non-fatal hanging [18]. Puangsri et al. found that depressed adolescents with SA show elevated levels of MLR than those with no suicide ideation; and that the levels of MLR and NLR are positively correlated with suicidality severity [19].\u003c/p\u003e \u003cp\u003eTo our knowledge, no studies have directly investigated the correlation between blood cell counts and NSSI. Herein we report an investigation on the associations between MLR, NLR, and PLR in adolescents with NSSI. Based on the previous findings, we hypothesized that patients with NSSI would show elevated levels of NLR, MLR, and PLR as compared with those with non-NSSI; and NLR, MLR, and PLR may be effective markers for differentiating patients with NSSI and those with non-NSSI.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eA total of 201 inpatient adolescents (aged 13\u0026ndash;18 years) with mood or emotional disorders were recruited from the hospital. The inclusion criteria were: (1) diagnosed with mood or emotional disorders according to the International Classification of Diseases 10th Revision (ICD-10), including anxiety disorders (AD), major depressive disorder (MDD), bipolar disorder (BD), and behavioral and emotional disorders with onset usually occurring in childhood and adolescence; (2) engaged in NSSI according to the DSM-5 criteria (history of NSSI was determined using information collected through the direct interviews and medical record reviews), and having\u0026thinsp;\u0026ge;\u0026thinsp;1 self-injury at least one occasion in the past month. The participants were grouped into an NSSI group and a non-NSSI group based on whether they had a history of NSSI.\u003c/p\u003e \u003cp\u003eThe exclusion criteria were: (1) with a current diagnosis of any other psychiatric disorder; (2) with SA or suicide ideation (assessed based on the patient\u0026rsquo;s history and course of the disease); (3) with serious physical illnesses, especially those associated with systemic inflammatory responses such as active infection, fever, acute or chronic endocrinological diseases; (4) had used anti-inflammatory drugs, corticosteroids or antipyretic drugs in the past two weeks.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eBlood samples of all enrolled individuals were collected from the cubital vein after fasting. Complete blood cell count was measured using Sysmex XN-1000 (XN-1000, Sysmex, Japan) automatic blood cell analyzer. Data were obtained from the electronic medical records system. Laboratory results were obtained from electronic medical records, and NLR, MLR, and PLR values were calculated and compared between the two groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eData analyses were performed using the IBM SPSS Statistics version 26 for Mac OS. Continuous variables were analyzed using the student\u0026rsquo;s t-test, and categorical variables were analyzed using the chi-square test. Multivariate logistic regression analysis was conducted to determine the independent predictors of NSSI. Odds ratios (ORs) and 95% confidence interval (CI) were calculated for the predicting variables. Receiver operating characteristic (ROC) curve analysis was performed to determine the discrimination threshold of inflammatory markers in the diagnosis of NSSI. A two-tailed \u003cem\u003eP\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;.05 was considered statistically significant for all analyses.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA total of 201 patients were enrolled in this study, with 106 grouped into the NSSI group and 95 grouped into the non-NSSI group. In the NSSI group, there were 89 females and 17 males, with a mean age of 14.94\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56 years; among which 4 (3.77%) patients were diagnosed with anxiety disorders (AD), 56 (52.83%) with major depressive disorder (MDD), 3 (2.83%) with bipolar disorder (BD) and 43 (40.57%) with behavioral and emotional disorders with onset usually occurring in childhood and adolescence. In the non-NSSI group, there were 74 females and 21 males, with a mean age of 15.32\u0026thinsp;\u0026plusmn;\u0026thinsp;1.71 years; among which 9 (9.47%) patients were diagnosed with AD, 42 (44.21%) with MDD, 5 (5.26%) with BD and 39 (41.05%) with behavioral and emotional disorders with onset usually occurring in childhood and adolescence. There were no significant differences in age (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.110), gender (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.359), family history (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.125), and diagnoses (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.260) between the two groups. The demographic characteristics of the subjects are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic characteristics of the NSSI group and the non-NSSI group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNSSI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-NSSI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003et/x\u003csup\u003e2\u003c/sup\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;106)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;95)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (y)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14.94\u0026thinsp;\u0026plusmn;\u0026thinsp;1.56\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.32\u0026thinsp;\u0026plusmn;\u0026thinsp;1.71\u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-1.607\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.110\u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale (n%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89(84.00%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74(77.90%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.839\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.359\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFamily history\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5(4.70%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11(11.60%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.351\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.125\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiagnosis\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnxiety disorders\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4(3.77%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9(9.47%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.030\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.260\u003csup\u003ec\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMajor depressive disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e56(52.83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e42(44.21%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBipolar disorder\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3(2.83%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5(5.26%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBehavioral and emotional disorders with onset usually occurring in childhood and adolescence\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e43(40.57%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e39(41.05%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003csup\u003ea\u003c/sup\u003e Expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation; \u003csup\u003eb\u003c/sup\u003e Student's t-test; \u003csup\u003ec\u003c/sup\u003e Chi-square test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe monocyte count, MLR, and PLR were significantly higher in adolescents with NSSI than those without NSSI (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.018, \u003cem\u003ep\u0026thinsp;\u0026lt;\u003c/em\u003e\u0026thinsp;0.001, \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.001, respectively). The lymphocyte count was significantly lower in the NSSI group (\u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.023). There were no significant differences in white blood cell count (WBC), neutrophil count, platelet count, mean platelet volume (MPV), and NLR between the two groups (all \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026gt;\u0026thinsp;0.05) (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Multivariate logistic regression analysis showed that MLR (OR 1.545, 95% CI [1.087\u0026ndash;2.281], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;=\u0026thinsp;0.021) and PLR (OR 1.327, 95%CI [1.215\u0026ndash;1.450], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) were independently associated with NSSI (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of blood cell count parameters between the NSSI group and the non-NSSI group.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNSSI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-NSSI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003et\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWBC (10\u003csup\u003e3\u003c/sup\u003e/uL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e6.988\u0026thinsp;\u0026plusmn;\u0026thinsp;1.820\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e6.995\u0026thinsp;\u0026plusmn;\u0026thinsp;1.810\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.978\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLymphocyte (10\u003csup\u003e3\u003c/sup\u003e/uL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e2.441\u0026thinsp;\u0026plusmn;\u0026thinsp;0.522\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e2.625\u0026thinsp;\u0026plusmn;\u0026thinsp;0.606\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-2.292\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.023\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMonocyte (10\u003csup\u003e3\u003c/sup\u003e/uL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.493\u0026thinsp;\u0026plusmn;\u0026thinsp;0.168\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.441\u0026thinsp;\u0026plusmn;\u0026thinsp;0.147\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2.378\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.018\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNeutrophil (10\u003csup\u003e3\u003c/sup\u003e/uL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e3.843\u0026thinsp;\u0026plusmn;\u0026thinsp;1.551\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e3.760\u0026thinsp;\u0026plusmn;\u0026thinsp;1.562\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.376\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.707\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet (10\u003csup\u003e3\u003c/sup\u003e/uL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e288.642\u0026thinsp;\u0026plusmn;\u0026thinsp;56.076\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e273.547\u0026thinsp;\u0026plusmn;\u0026thinsp;59.079\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.852\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMPV (fl)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e9.942\u0026thinsp;\u0026plusmn;\u0026thinsp;0.751\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e10.113\u0026thinsp;\u0026plusmn;\u0026thinsp;0.927\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e-1.428\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.155\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e0.208\u0026thinsp;\u0026plusmn;\u0026thinsp;0.078\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e0.173\u0026thinsp;\u0026plusmn;\u0026thinsp;0.058\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.714\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e1.630\u0026thinsp;\u0026plusmn;\u0026thinsp;0.714\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e1.508\u0026thinsp;\u0026plusmn;\u0026thinsp;0.733\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1.200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.231\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c2\"\u003e \u003cp\u003e122.391\u0026thinsp;\u0026plusmn;\u0026thinsp;31.497\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e108.145\u0026thinsp;\u0026plusmn;\u0026thinsp;28.029\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3.393\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eWBC: white blood cell count; MPV: mean platelet volume; MLR: monocyte-lymphocyte ratio; NLR: neutrophil-lymphocyte ratio; PLR: platelet-lymphocyte ratio; \u003csup\u003e*\u003c/sup\u003e indicates statistical significance.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMultivariate logistic regression model for the association between NSSI and inflammatory marker.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOR (95%CI)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.545(1.087\u0026ndash;2.281)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.021\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e1.327(1.215\u0026ndash;1.450)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"3\"\u003eMLR: monocyte-lymphocyte ratio; PLR: platelet-lymphocyte ratio. \u003csup\u003e*\u003c/sup\u003e indicates statistical significance.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eReceiver-operating characteristic (ROC) curve analyses were then performed to evaluate the diagnostic ability of MLR and PLR for NSSI. According to the ROC curve, the area under curve was 0.638 ([0.561\u0026ndash;0.715], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for MLR and 0.611 ([0.533\u0026ndash;0.689], \u003cem\u003ep\u003c/em\u003e\u0026thinsp;\u0026lt;\u0026thinsp;0.001) for PLR. The optimal cut-off value was 0.135 for MLR, with a sensitivity of 90.60% and specificity of 33.70%; the optimal cut-off value was 127.505 for PLR, with a sensitivity of 39.60% and specificity of 81.10% (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e \u003cb\u003eand\u003c/b\u003e Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cb\u003e)\u003c/b\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eReceiver-operating characteristic (ROC) curve of MLR and PLR as predictors of NSSI.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAUC\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003e95%CI\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eCut-off\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003esensitivity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003especificity\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.638\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.561\u0026ndash;0.715\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0.135\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.906\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.337\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLR\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e0.611\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e0.533\u0026ndash;0.689\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e127.505\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.396\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e0.811\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eMLR: monocyte-lymphocyte ratio; PLR: platelet-lymphocyte ratio. \u003csup\u003e*\u003c/sup\u003e indicates statistical significance.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eTo the best of our knowledge, this is the first study probing NLR, MLR, and PLR as hallmarks of systemic inflammation in adolescents with NSSI. The results showed significantly elevated levels of MLR and PLR in adolescents with NSSI compared with those with no NSSI, suggesting a potential role of MLR and PLR in the assessment and prediction of NSSI in clinical practice. Inconsistent with our hypothesis, we found no changes in NLR in adolescents with NSSI.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eMLR\u003c/h2\u003e \u003cp\u003ePrevious studies have found that an elevated level of monocyte count is associated with overexpression of immune genes and overproduction of monocytes/macrophage-related cytokines [20]. Increased monocyte count or MLR had been observed in major psychiatric disorders, such as schizophrenia [13, 21], bipolar disorder [22, 23] and major depressive disorder [24]. It is supposed that elevated monocyte count or MLR is accompanied by an increase in the monocyte-related cytokines (such as IL-6, IL-1β, IL-12, and TNF) and activation of microglia in the brain [25], which is a biomarker of neuroinflammation. Microglia monitors the functional state of synapses and modulates neuroplasticity by synaptic pruning and phagocytosis, resulting in altered brain structure and function, including regions implicated in impulse control and emotion regulation, such as the medial prefrontal cortex, dorsolateral prefrontal cortex, insula, amygdala, and hippocampus [7, 26\u0026ndash;28]. A previous study found that elevated monocyte count and MLR are associated with an increased risk of suicide in adolescents with major depressive disorder [19]. In sum, the elevated monocyte and MLR found in this study may play an important role in the pathology of NSSI through the release of monocyte-related cytokines and activation of microglia.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003ePLR\u003c/h2\u003e \u003cp\u003ePlatelets are closely related to stress, peripheral inflammation, and monoaminergic neurotransmission, which may be involved in the pathology of NSSI. Stress may increase platelet count and activity through sympathetic system activation [29]. The increased platelet count and activity may further induce altered endothelial permeability as well as recruitment of neutrophils and macrophages, resulting in elevated peripheral inflammation [30, 31]. Moreover, platelets contain abundant serotonin in their dense granules, and serotonin receptors (5HT\u003csub\u003e2A\u003c/sub\u003e) and transporters on the cell surface, are involved in the production, reuptake, and metabolism of serotonin [32, 33]. A previous study had suggested that platelet serotonin could reliably indicate the presynaptic serotonin activity in the brain [34].\u003c/p\u003e \u003cp\u003eDysregulation of serotonergic neurotransmission is an important factor linked to emotion and behavior disorders, particularly impulse control disorders [35\u0026ndash;37]. As reported in a review paper, NSSI could be considered a behavior associated with impulse control problems [38]. Previous studies found that the aggressivity and impulsivity of suicidal attempters seem to be associated with the serotonin content in platelets and the total number of 5-HT\u003csub\u003e2A\u003c/sub\u003e receptors on platelet surface [39]. Similarly, Audenaert et al. found decreased frontal serotonin 5-HT\u003csub\u003e2A\u003c/sub\u003e receptor binding index in patients with NSSI [40]. Similar to human behavioral data, preclinical studies also revealed a close relationship between serotonergic neurotransmission and NSSI. Dellu et al. revealed that impulsivity behavior was mainly associated with decreased serotonergic neurotransmission in the amygdala and anterior cingulate cortex by testing the different behavior of rats [41]. A recent study in the nonhuman primate model showed that primates with the s allele exhibited NSSI and impulsive behaviors, and there may be distinct the serotonin transporter (5-HTT) genotype-mediated different NSSI typologies [42]. Taken together, elevated PLR may play a role in the pathophysiology of NSSI through its influence on peripheral inflammation and serotonin neurotransmission.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eNLR\u003c/h2\u003e \u003cp\u003eInconsistent with our hypothesis, we found no significant difference in NLR between adolescents with NSSI and those with no NSSI, despite a decrease in the lymphocyte count. NLR reflects the balance between innate (neutrophils) and adaptive (lymphocytes) immunity and is considered a stable peripheral biomarker of inflammation [43]. Previous studies have found that NLR is correlated with suicidality in major depression [15, 44]. The reason for the nonsignificant finding of NLR in this study remains unclear. Puangsri et al. suggested that MLR is more effective than NLR and PLR in the prediction of SAs in patients with MDD [19]. Turkmen et al. found that PLR is superior to NLR in denoting inflammation in patients with end-stage renal diseases [45]. Thus, our result may indicate that MLR and PLR are superior to NLR in the assessment of NSSI in adolescents.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eCut-off values of MLR and PLR\u003c/h2\u003e \u003cp\u003eThis study for the first time suggested cut-off values of MLR and PLR for predicting NSSI. With a cut-off value of 0.135, the ROC analysis of MLR reached a high sensitivity (90.60%) and low specificity (33.70%); with a cut-off value of 127.505, the ROC analysis of PLR reached a high specificity (81.10%) and low sensitivity (39.60%). Despite the relatively low areas under the curve for MLR (0.638) and PLR (0.611), a combination of MLR and PLR would be promising to improve the overall sensitivity and specificity in predicting NSSI.\u003c/p\u003e \u003cp\u003eTo be mentioned, a previous study showed that the MLR and PLR values vary with age and gender in the Chinese population, with males exhibiting higher PLR and lower MLR than females, and with age increases, PLR decreases and MLR increases [46]. In our study, females accounted for the majority of the sample, and all of the participants were aged\u0026thinsp;\u0026le;\u0026thinsp;18. Thus, the findings of the ROC analyses should be interpreted with caution, as the optimal cut-off values obtained from our sample maybe not be suitable for males or other age groups. Future studies should investigate the cut-off values of MLR and PLR for predicting NSSI with stratification of gender and age.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eThis study also has several limitations. First, we were not able to control factors that could influence the inflammatory status of the participants, such as menstrual cycle, and body mass index (BMI). Second, the possible association between the severity of NSSI symptoms and inflammatory indicators was not evaluated. Third, other indicators of immune functions, such as CRP and interleukins, were not evaluated. Finally, the present study is a cross-sectional study, which precludes us from identifying any causal relationship between the inflammatory indicators and NSSI.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSystemic inflammation, as indicated by MLR and PLR, is elevated in adolescents with NSSI. MLR and PLR are independent predictors of NSSI in adolescents and may serve as biomarkers in the prediction and assessment of NSSI.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNLR: Neutrophil-lymphocyte ratio; MLR: monocyte-lymphocyte ratio; PLR: platelet-lymphocyte ratio; NSSI:\u003c/p\u003e\n\u003cp\u003enon-suicidal self-injury; ROC: Receiver operating characteristic; DSM-5: the Diagnostic and Statistical Manual of Mental Disorders; SAs: suicide attempts; TNF-\u0026alpha;: tumor necrosis factor \u0026alpha;; CRP: C-reactive protein; WBC: white cell count; IL-6: interleukin-6; MDD: major depressive disorder; ICD-10: the International Classification of Diseases 10\u003csup\u003eth\u003c/sup\u003e Revision; AD: anxiety disorders; BD: bipolar disorder; ORs: Odds ratios; CI: confidence interval; MPV: mean platelet volume; 5HT2A: serotonin receptors; 5-HTT: serotonin transporter; BMI: body mass index.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and Consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by the ethics committee of Xiamen Xianyue Hospital (No. 2021-KY-06). Written informed consent was obtained from the patients\u0026rsquo; parents or legal guardians. All methods were performed in accordance with the relevant guidelines and regulations.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets generated and/or analyzed during the current study are not publicly available data and anonymity but are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study is supported by the Medical and Health Guidance Project of Xiamen City (No. 3502Z20214ZD1281).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eQZ, XC, and BL codesigned the topic. YJ helped collect the data. JL and QZ contributed to the data analysis. QZ drafted and edited the manuscript. YZ, BL, and XC contributed valuable suggestions to the conception of the article and critically revised the manuscript. All authors approved the final version of the article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors would like to thank all of the participants for their contribution to this study.\u003c/p\u003e\n"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eHawton K, Saunders KE, O\u0026apos;Connor RC: \u003cstrong\u003eSelf-harm and suicide in adolescents\u003c/strong\u003e. \u003cem\u003eLancet\u003c/em\u003e 2012, \u003cstrong\u003e379\u003c/strong\u003e(9834):2373\u0026ndash;2382.\u003c/li\u003e\n\u003cli\u003eAPA: \u003cstrong\u003eAmerican Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders. 5th ed\u003c/strong\u003e 2013.\u003c/li\u003e\n\u003cli\u003eRojas-Velasquez DA, Pluhar EI, Burns PA, Burton ET: \u003cstrong\u003eNonsuicidal Self-Injury Among African American and Hispanic Adolescents and Young Adults: a Systematic Review\u003c/strong\u003e. \u003cem\u003ePrev Sci\u003c/em\u003e 2021, \u003cstrong\u003e22\u003c/strong\u003e(3):367\u0026ndash;377.\u003c/li\u003e\n\u003cli\u003eLim KS, Wong CH, McIntyre RS, Wang J, Zhang Z, Tran BX, Tan W, Ho CS, Ho RC: \u003cstrong\u003eGlobal Lifetime and 12-Month Prevalence of Suicidal Behavior, Deliberate Self-Harm and Non-Suicidal Self-Injury in Children and Adolescents between 1989 and 2018: A Meta-Analysis\u003c/strong\u003e. \u003cem\u003eInt J Environ Res Public Health\u003c/em\u003e 2019, \u003cstrong\u003e16\u003c/strong\u003e(22).\u003c/li\u003e\n\u003cli\u003eWang C, Zhang P, Zhang N: \u003cstrong\u003eAdolescent mental health in China requires more attention\u003c/strong\u003e. \u003cem\u003eLancet Public Health\u003c/em\u003e 2020, \u003cstrong\u003e5\u003c/strong\u003e(12):e637.\u003c/li\u003e\n\u003cli\u003eMars B, Heron J, Klonsky ED, Moran P, O\u0026apos;Connor RC, Tilling K, Wilkinson P, Gunnell D: \u003cstrong\u003ePredictors of future suicide attempt among adolescents with suicidal thoughts or non-suicidal self-harm: a population-based birth cohort study\u003c/strong\u003e. \u003cem\u003eLancet Psychiatry\u003c/em\u003e 2019, \u003cstrong\u003e6\u003c/strong\u003e(4):327\u0026ndash;337.\u003c/li\u003e\n\u003cli\u003eBranas M, Croci MS, Ravagnani Salto AB, Doretto VF, Martinho E, Jr., Macedo M, Miguel EC, Roever L, Pan PM: \u003cstrong\u003eNeuroimaging Studies of Nonsuicidal Self-Injury in Youth: A Systematic Review\u003c/strong\u003e. \u003cem\u003eLife (Basel)\u003c/em\u003e 2021, \u003cstrong\u003e11\u003c/strong\u003e(8).\u003c/li\u003e\n\u003cli\u003eChesin MS, Galfavy H, Sonmez CC, Wong A, Oquendo MA, Mann JJ, Stanley B: \u003cstrong\u003eNonsuicidal Self-Injury Is Predictive of Suicide Attempts Among Individuals with Mood Disorders\u003c/strong\u003e. \u003cem\u003eSuicide Life Threat Behav\u003c/em\u003e 2017, \u003cstrong\u003e47\u003c/strong\u003e(5):567\u0026ndash;579.\u003c/li\u003e\n\u003cli\u003eHargus E, Hawton K, Rodham K: \u003cstrong\u003eDistinguishing between subgroups of adolescents who self-harm\u003c/strong\u003e. \u003cem\u003eSuicide Life Threat Behav\u003c/em\u003e 2009, \u003cstrong\u003e39\u003c/strong\u003e(5):518\u0026ndash;537.\u003c/li\u003e\n\u003cli\u003eKim JS, Kang E-S, Bahk YC, Jang S, Hong KS, Baek JH: \u003cstrong\u003eExploratory Analysis of Behavioral Impulsivity, Pro-inflammatory Cytokines, and Resting-State Frontal EEG Activity Associated With Non-suicidal Self-Injury in Patients With Mood Disorder\u003c/strong\u003e. \u003cem\u003eFrontiers in Psychiatry\u003c/em\u003e 2020, \u003cstrong\u003e11\u003c/strong\u003e.\u003c/li\u003e\n\u003cli\u003eOsimo EF, Cardinal RN, Jones PB, Khandaker GM: \u003cstrong\u003ePrevalence and correlates of low-grade systemic inflammation in adult psychiatric inpatients: An electronic health record-based study\u003c/strong\u003e. \u003cem\u003ePsychoneuroendocrinology\u003c/em\u003e 2018, \u003cstrong\u003e91\u003c/strong\u003e:226\u0026ndash;234.\u003c/li\u003e\n\u003cli\u003eRussell AE, Ford T, Gunnell D, Heron J, Joinson C, Moran P, Relton C, Suderman M, Hemani G, Mars B: \u003cstrong\u003eInvestigating evidence for a causal association between inflammation and self-harm: A multivariable Mendelian Randomisation study\u003c/strong\u003e. \u003cem\u003eBrain Behav Immun\u003c/em\u003e 2020, \u003cstrong\u003e89\u003c/strong\u003e:43\u0026ndash;50.\u003c/li\u003e\n\u003cli\u003eMazza MG, Lucchi S, Rossetti A, Clerici M: \u003cstrong\u003eNeutrophil-lymphocyte ratio, monocyte-lymphocyte ratio and platelet-lymphocyte ratio in non-affective psychosis: A meta-analysis and systematic review\u003c/strong\u003e. \u003cem\u003eWorld J Biol Psychiatry\u003c/em\u003e 2020, \u003cstrong\u003e21\u003c/strong\u003e(5):326\u0026ndash;338.\u003c/li\u003e\n\u003cli\u003eMazza MG, Lucchi S, Tringali AGM, Rossetti A, Botti ER, Clerici M: \u003cstrong\u003eNeutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis\u003c/strong\u003e. \u003cem\u003eProg Neuropsychopharmacol Biol Psychiatry\u003c/em\u003e 2018, \u003cstrong\u003e84\u003c/strong\u003e(Pt A):229\u0026ndash;236.\u003c/li\u003e\n\u003cli\u003eEkinci O, Ekinci A: \u003cstrong\u003eThe connections among suicidal behavior, lipid profile and low-grade inflammation in patients with major depressive disorder: a specific relationship with the neutrophil-to-lymphocyte ratio\u003c/strong\u003e. \u003cem\u003eNord J Psychiatry\u003c/em\u003e 2017, \u003cstrong\u003e71\u003c/strong\u003e(8):574\u0026ndash;580.\u003c/li\u003e\n\u003cli\u003eIvkovic M, Pantovic-Stefanovic M, Dunjic-Kostic B, Jurisic V, Lackovic M, Totic-Poznanovic S, Jovanovic AA, Damjanovic A: \u003cstrong\u003eNeutrophil-to-lymphocyte ratio predicting suicide risk in euthymic patients with bipolar disorder: Moderatory effect of family history\u003c/strong\u003e. \u003cem\u003eCompr Psychiatry\u003c/em\u003e 2016, \u003cstrong\u003e66\u003c/strong\u003e:87\u0026ndash;95.\u003c/li\u003e\n\u003cli\u003eKumar K, Srivastava S, Sharma B, Avasthi RK, Kotru M: \u003cstrong\u003eComparison Between Inflammatory Biomarkers (High-Sensitivity C-Reactive Protein and Neutrophil-Lymphocyte Ratio) and Psychological Morbidity in Suicide Attempt Survivors Brought to Medicine Emergency\u003c/strong\u003e. \u003cem\u003eCureus\u003c/em\u003e 2021, \u003cstrong\u003e13\u003c/strong\u003e(8):e17459.\u003c/li\u003e\n\u003cli\u003eArafat SMY, Karim A, Hossain MF, Menon V, Shoib S: \u003cstrong\u003eNeutrophil-to-lymphocyte ratio and C-reactive protein in non-fatal suicidal attempts: A cross-sectional pilot study in Bangladesh\u003c/strong\u003e. \u003cem\u003eHealth Sci Rep\u003c/em\u003e 2021, \u003cstrong\u003e4\u003c/strong\u003e(3):e347.\u003c/li\u003e\n\u003cli\u003ePuangsri P, Ninla-Aesong P: \u003cstrong\u003ePotential 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\u003c/strong\u003e. \u003cem\u003ePsychiatry Res\u003c/em\u003e 2021, \u003cstrong\u003e305\u003c/strong\u003e:114216.\u003c/li\u003e\n\u003cli\u003eBeumer W, Gibney SM, Drexhage RC, Pont-Lezica L, Doorduin J, Klein HC, Steiner J, Connor TJ, Harkin A, Versnel MA \u003cem\u003eet al\u003c/em\u003e: \u003cstrong\u003eThe immune theory of psychiatric diseases: a key role for activated microglia and circulating monocytes\u003c/strong\u003e. \u003cem\u003eJ Leukoc Biol\u003c/em\u003e 2012, \u003cstrong\u003e92\u003c/strong\u003e(5):959\u0026ndash;975.\u003c/li\u003e\n\u003cli\u003eOzdin S, Sarisoy G, Boke O: \u003cstrong\u003eA comparison of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in schizophrenia and bipolar disorder patients - a retrospective file review\u003c/strong\u003e. \u003cem\u003eNord J Psychiatry\u003c/em\u003e 2017, \u003cstrong\u003e71\u003c/strong\u003e(7):509\u0026ndash;512.\u003c/li\u003e\n\u003cli\u003eInanli I, Aydin M, Caliskan AM, Eren I: \u003cstrong\u003eNeutrophil/lymphocyte ratio, monocyte/lymphocyte ratio, and mean platelet volume as systemic inflammatory markers in different states of bipolar disorder\u003c/strong\u003e. \u003cem\u003eNord J Psychiatry\u003c/em\u003e 2019, \u003cstrong\u003e73\u003c/strong\u003e(6):372\u0026ndash;379.\u003c/li\u003e\n\u003cli\u003eFusar-Poli L, Natale A, Amerio A, Cimpoesu P, Grimaldi Filioli P, Aguglia E, Amore M, Serafini G, Aguglia A: \u003cstrong\u003eNeutrophil-to-Lymphocyte, Platelet-to-Lymphocyte and Monocyte-to-Lymphocyte Ratio in Bipolar Disorder\u003c/strong\u003e. \u003cem\u003eBrain Sci\u003c/em\u003e 2021, \u003cstrong\u003e11\u003c/strong\u003e(1).\u003c/li\u003e\n\u003cli\u003eWei Y, Feng J, Ma J, Chen D, Chen J: \u003cstrong\u003eNeutrophil/lymphocyte, platelet/lymphocyte and monocyte/lymphocyte ratios in patients with affective disorders\u003c/strong\u003e. \u003cem\u003eJ Affect Disord\u003c/em\u003e 2022.\u003c/li\u003e\n\u003cli\u003eGarcia-Rizo C, Casanovas M, Fernandez-Egea E, Oliveira C, Meseguer A, Cabrera B, Mezquida G, Bioque M, Kirkpatrick B, Bernardo M: \u003cstrong\u003eBlood cell count in antipsychotic-naive patients with non-affective psychosis\u003c/strong\u003e. \u003cem\u003eEarly Interv Psychiatry\u003c/em\u003e 2019, \u003cstrong\u003e13\u003c/strong\u003e(1):95\u0026ndash;100.\u003c/li\u003e\n\u003cli\u003eCalcia MA, Bonsall DR, Bloomfield PS, Selvaraj S, Barichello T, Howes OD: \u003cstrong\u003eStress and neuroinflammation: a systematic review of the effects of stress on microglia and the implications for mental illness\u003c/strong\u003e. \u003cem\u003ePsychopharmacology (Berl)\u003c/em\u003e 2016, \u003cstrong\u003e233\u003c/strong\u003e(9):1637\u0026ndash;1650.\u003c/li\u003e\n\u003cli\u003eDahlgren MK, Hooley JM, Best SG, Sagar KA, Gonenc A, Gruber SA: \u003cstrong\u003ePrefrontal cortex activation during cognitive interference in nonsuicidal self-injury\u003c/strong\u003e. \u003cem\u003ePsychiatry Res Neuroimaging\u003c/em\u003e 2018, \u003cstrong\u003e277\u003c/strong\u003e:28\u0026ndash;38.\u003c/li\u003e\n\u003cli\u003eBeauchaine TP, Sauder CL, Derbidge CM, Uyeji LL: \u003cstrong\u003eSelf-injuring adolescent girls exhibit insular cortex volumetric abnormalities that are similar to those seen in adults with borderline personality disorder\u003c/strong\u003e. \u003cem\u003eDev Psychopathol\u003c/em\u003e 2019, \u003cstrong\u003e31\u003c/strong\u003e(4):1203\u0026ndash;1212.\u003c/li\u003e\n\u003cli\u003eCognasse F, Laradi S, Berthelot P, Bourlet T, Marotte H, Mismetti P, Garraud O, Hamzeh-Cognasse H: \u003cstrong\u003ePlatelet Inflammatory Response to Stress\u003c/strong\u003e. \u003cem\u003eFront Immunol\u003c/em\u003e 2019, \u003cstrong\u003e10\u003c/strong\u003e:1478.\u003c/li\u003e\n\u003cli\u003eRawish E, Nording H, Munte T, Langer HF: \u003cstrong\u003ePlatelets as Mediators of Neuroinflammation and Thrombosis\u003c/strong\u003e. \u003cem\u003eFront Immunol\u003c/em\u003e 2020, \u003cstrong\u003e11\u003c/strong\u003e:548631.\u003c/li\u003e\n\u003cli\u003eKoupenova M, Clancy L, Corkrey HA, Freedman JE: \u003cstrong\u003eCirculating Platelets as Mediators of Immunity, Inflammation, and Thrombosis\u003c/strong\u003e. \u003cem\u003eCirc Res\u003c/em\u003e 2018, \u003cstrong\u003e122\u003c/strong\u003e(2):337\u0026ndash;351.\u003c/li\u003e\n\u003cli\u003eEverts P, Onishi K, Jayaram P, Lana JF, Mautner K: \u003cstrong\u003ePlatelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020\u003c/strong\u003e. \u003cem\u003eInt J Mol Sci\u003c/em\u003e 2020, \u003cstrong\u003e21\u003c/strong\u003e(20).\u003c/li\u003e\n\u003cli\u003eMammadova-Bach E, Mauler M, Braun A, Duerschmied D: \u003cstrong\u003eAutocrine and paracrine regulatory functions of platelet serotonin\u003c/strong\u003e. \u003cem\u003ePlatelets\u003c/em\u003e 2018, \u003cstrong\u003e29\u003c/strong\u003e(6):541\u0026ndash;548.\u003c/li\u003e\n\u003cli\u003ePlein H, Berk M: \u003cstrong\u003eThe platelet as a peripheral marker in psychiatric illness\u003c/strong\u003e. \u003cem\u003eHum Psychopharmacol\u003c/em\u003e 2001, \u003cstrong\u003e16\u003c/strong\u003e(3):229\u0026ndash;236.\u003c/li\u003e\n\u003cli\u003eOhmura Y, Tsutsui-Kimura I, Sasamori H, Nebuka M, Nishitani N, Tanaka KF, Yamanaka A, Yoshioka M: \u003cstrong\u003eDifferent roles of distinct serotonergic pathways in anxiety-like behavior, antidepressant-like, and anti-impulsive effects\u003c/strong\u003e. \u003cem\u003eNeuropharmacology\u003c/em\u003e 2020, \u003cstrong\u003e167\u003c/strong\u003e:107703.\u003c/li\u003e\n\u003cli\u003eBacque-Cazenave J, Bharatiya R, Barriere G, Delbecque JP, Bouguiyoud N, Di Giovanni G, Cattaert D, De Deurwaerdere P: \u003cstrong\u003eSerotonin in Animal Cognition and Behavior\u003c/strong\u003e. \u003cem\u003eInt J Mol Sci\u003c/em\u003e 2020, \u003cstrong\u003e21\u003c/strong\u003e(5).\u003c/li\u003e\n\u003cli\u003eda Cunha-Bang S, Knudsen GM: \u003cstrong\u003eThe Modulatory Role of Serotonin on Human Impulsive Aggression\u003c/strong\u003e. \u003cem\u003eBiol Psychiatry\u003c/em\u003e 2021, \u003cstrong\u003e90\u003c/strong\u003e(7):447\u0026ndash;457.\u003c/li\u003e\n\u003cli\u003eHamza CA, Willoughby T, Heffer T: \u003cstrong\u003eImpulsivity and nonsuicidal self-injury: A review and meta-analysis\u003c/strong\u003e. \u003cem\u003eClin Psychol Rev\u003c/em\u003e 2015, \u003cstrong\u003e38\u003c/strong\u003e:13\u0026ndash;24.\u003c/li\u003e\n\u003cli\u003eSpreux-Varoquaux O, Alvarez JC, Berlin I, Batista G, Despierre PG, Gilton A, Cremniter D: \u003cstrong\u003eDifferential abnormalities in plasma 5-HIAA and platelet serotonin concentrations in violent suicide attempters: relationships with impulsivity and depression\u003c/strong\u003e. \u003cem\u003eLife Sci\u003c/em\u003e 2001, \u003cstrong\u003e69\u003c/strong\u003e(6):647\u0026ndash;657.\u003c/li\u003e\n\u003cli\u003eAudenaert K, Van Laere K, Dumont F, Slegers G, Mertens J, van Heeringen C, Dierckx RA: \u003cstrong\u003eDecreased frontal serotonin 5-HT2a receptor binding index in deliberate self-harm patients\u003c/strong\u003e. \u003cem\u003eEuropean Journal of Nuclear Medicine\u003c/em\u003e 2001, \u003cstrong\u003e28\u003c/strong\u003e(2):175\u0026ndash;182.\u003c/li\u003e\n\u003cli\u003eDellu-Hagedorn F, Rivalan M, Fitoussi A, De Deurwaerdere P: \u003cstrong\u003eInter-individual differences in the impulsive/compulsive dimension: deciphering related dopaminergic and serotonergic metabolisms at rest\u003c/strong\u003e. \u003cem\u003ePhilos Trans R Soc Lond B Biol Sci\u003c/em\u003e 2018, \u003cstrong\u003e373\u003c/strong\u003e(1744).\u003c/li\u003e\n\u003cli\u003eWood EK, Kruger R, Day JP, Day SM, Hunter JN, Neville L, Lindell SG, Barr CS, Schwandt ML, Goldman D \u003cem\u003eet al\u003c/em\u003e: \u003cstrong\u003eA nonhuman primate model of human non-suicidal self-injury: serotonin-transporter genotype-mediated typologies\u003c/strong\u003e. \u003cem\u003eNeuropsychopharmacology\u003c/em\u003e 2022, \u003cstrong\u003e47\u003c/strong\u003e(6):1256\u0026ndash;1262.\u003c/li\u003e\n\u003cli\u003eZahorec R: \u003cstrong\u003eNeutrophil-to-lymphocyte ratio, past, present and future perspectives\u003c/strong\u003e. \u003cem\u003eBratisl Lek Listy\u003c/em\u003e 2021, \u003cstrong\u003e122\u003c/strong\u003e(7):474\u0026ndash;488.\u003c/li\u003e\n\u003cli\u003eVelasco A, Rodriguez-Revuelta J, Olie E, Abad I, Fernandez-Pelaez A, Cazals A, Guillaume S, de la Fuente-Tomas L, Jimenez-Trevino L, Gutierrez L \u003cem\u003eet al\u003c/em\u003e: \u003cstrong\u003eNeutrophil-to-lymphocyte ratio: A potential new peripheral biomarker of suicidal behavior\u003c/strong\u003e. \u003cem\u003eEur Psychiatry\u003c/em\u003e 2020, \u003cstrong\u003e63\u003c/strong\u003e(1):e14.\u003c/li\u003e\n\u003cli\u003eTurkmen K, Erdur FM, Ozcicek F, Ozcicek A, Akbas EM, Ozbicer A, Demirtas L, Turk S, Tonbul HZ: \u003cstrong\u003ePlatelet-to-lymphocyte ratio better predicts inflammation than neutrophil-to-lymphocyte ratio in end-stage renal disease patients\u003c/strong\u003e. \u003cem\u003eHemodial Int\u003c/em\u003e 2013, \u003cstrong\u003e17\u003c/strong\u003e(3):391\u0026ndash;396.\u003c/li\u003e\n\u003cli\u003eWang J, Zhang F, Jiang F, Hu L, Chen J, Wang Y: \u003cstrong\u003eDistribution and reference interval establishment of neutral-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in Chinese healthy adults\u003c/strong\u003e. \u003cem\u003eJ Clin Lab Anal\u003c/em\u003e 2021, \u003cstrong\u003e35\u003c/strong\u003e(9):e23935.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Adolescents, non-suicidal self-injury (NSSI), neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocyte ratio (PLR)","lastPublishedDoi":"10.21203/rs.3.rs-1679507/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-1679507/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eNeutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), and platelet-lymphocyte ratio (PLR) are blood indicators of systemic inflammation. This study aims to compare the levels of inflammatory indicators derived from blood routine tests between adolescents with non-suicidal self-injury (NSSI) and those with non-NSSI.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eA total of 201 adolescents with mood or emotional disorders were enrolled in this study, among which 106 had engaged in NSSI and 95 had never engaged in NSSI. NLR, MLR, and PLR were calculated based on the complete blood cell count. \u003c/p\u003e\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eThere was no significant difference in demographic data between the two groups. The NSSI group exhibited significantly higher MLR (\u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.001) and PLR (\u003cem\u003eP \u003c/em\u003e= 0.001) than the non-NSSI group. Multivariate logistic regression analysis revealed that MLR (OR 1.545, 95%CI [1.087-2.281], \u003cem\u003eP \u003c/em\u003e= 0.021) and PLR (OR 1.327, 95%CI [1.215-1.450], \u003cem\u003eP\u0026nbsp;\u003c/em\u003e\u0026lt; 0.001) were independent predictors of NSSI. Receiver operating characteristic (ROC) curve analyses demonstrated that for predicting NSSI, the optimal cut-off value of MLR was 0.135 and the area under curve was 0.638 ([0.561- 0.715], \u003cem\u003eP\u003c/em\u003e\u0026nbsp;\u0026lt; 0.001), with a sensitivity of 90.60% and a specificity of 33.70%; the optimal cut-off value of PLR was 127.505 and the area under curve was of 0.611 ([0.533-0.689], \u003cem\u003eP\u003c/em\u003e \u0026lt; 0.001), with a sensitivity of 39.60% and a specificity of 81.10%.\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003e\u003c/p\u003e\u003cp\u003eSystemic inflammation, as indicated by MLR and PLR, is elevated in adolescents with NSSI.\u0026nbsp;MLR and PLR might serve as potential biomarkers in the assessment of NSSI in adolescents.\u003c/p\u003e","manuscriptTitle":"Elevated levels of Monocyte-lymphocyte Ratio and Platelet-lymphocyte Ratio in adolescents with Non-suicidal Self-injury","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2022-05-31 17:29:02","doi":"10.21203/rs.3.rs-1679507/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Major revision","date":"2022-07-29T07:21:10+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-06-25T08:39:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"c49412a3-5103-4987-ad49-7fec82a2fd44","date":"2022-06-14T16:20:35+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2022-06-11T16:51:59+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"dc22a15f-fab3-4c9f-b439-9605887c69df","date":"2022-06-11T15:43:15+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2022-06-11T15:34:35+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2022-06-10T14:21:15+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2022-05-30T13:47:51+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2022-05-30T13:34:44+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Psychiatry","date":"2022-05-21T11:15:57+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-psychiatry","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bpsy","sideBox":"Learn more about [BMC Psychiatry](http://bmcpsychiatry.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bpsy/default.aspx","title":"BMC Psychiatry","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b531afe8-06a7-4038-a9dc-7f9aabe8c52d","owner":[],"postedDate":"May 31st, 2022","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2022-09-14T08:44:23+00:00","versionOfRecord":[],"versionCreatedAt":"2022-05-31 17:29:02","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-1679507","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-1679507","identity":"rs-1679507","version":["v1"]},"buildId":"uwybb5PU2iWlRI8EIam5Y","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}

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