Melatonin rhythm disorder is more pronounced in major depressive disorder with Non-Suicidal Self-injury

Melatonin rhythm disorder is more pronounced in major depressive disorder 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 Melatonin rhythm disorder is more pronounced in major depressive disorder with Non-Suicidal Self-injury Xiaojuan Hu, Aiguo Zhang, Chao Wang, Xulai Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4532900/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Melatonin(MT) rhythm disorders may be associated with depression and non-suicidal self-injury（NSSI）.We conducted a controlled study to investigate whether patients with major depressive disorder（MDD）comorbid NSSI have more pronounced MT disorders, and whether MT levels are associated with NSSI perception and cessation. Methods A total of 100 samples were included in the study, including 30 healthy individuals as a normal control group and 70 patients with MDD.In the subgroup of MDD,there were 35 patients with NSSI(NSSI group) and 35 patients without NSSI (non-NSSI group).We used enzyme-linked immunosorbent assay to measure the salivary MT levels (0AM, 8AM, 11AM, 1PM, 4PM, 10PM) of all participants at 6 time points. And use the Ottawa-Self- Injury Inventory (OSI) to quantitatively evaluate the self injury perception and motivation to stop self injury in patients in the NSSI group. Results The salivary MT levels in the NSSI group at 6 time points were significantly lower than those in the non- NSSI group and control group ( P <0.05), and the circadian rhythm of MT in NSSI group disappeared.We found significant correlations between MT levels and several dimensions of NSSI,specifically: 1PM MT level and intrusive/invasive urge(r=0.487， P <0.05), 8AM MT levels and desire to stop NSSI(r=-0.427， P <0.05),11AM MT levels and desire to stop NSSI(r=-0.348， P <0.05). Conclusions The decrease in MT levels and disruption of circadian rhythms may increase the risk of NSSI in patients with MDD, but its mechanism needs further exploration. Non-suicidal self-injury Melatonin Circadian rhythm Ottawa Self-Injury Scale Figures Figure 1 Figure 2 Background MDD is a mental disorder characterized by persistent low mood. In addition to the core symptoms of MDD, adolescent patients often have NSSI[ 1 ].NSSI refers to a series of socially unacceptable behaviors that individuals intentionally and directly harm their own bodies without suicidal intent[ 2 ].Previous studies have found that NSSI is associated with MDD, and MDD is the main risk factor for NSSI,depression, impulsivity, and suicidal ideation are significantly correlated with NSSI, and the levels of depression, impulsivity, and suicidal ideation are significantly higher in MDD patients with NSSI[ 3 , 4 ].NSSI often overlaps with suicidal behavior, with NSSI patients having a suicide rate 100 times higher than the general population in the following year, and still having a high suicide rate for many years, with over 5% of patients ultimately committing suicide within 9 years[ 5 – 8 ].In determining the risk of adolescent suicide, in addition to established risk factors such as depressive symptoms and suicidal tendencies, NSSI may be a particularly important assessment and prospective predictive factor[ 9 , 10 ]. Delayed circadian rhythms during adolescence and early adulthood are associated with the severity of depressive and emotional symptoms [ 11 , 12 ], and adolescents with circadian rhythm disorders are at a higher risk of mental illness [ 13 ].Disorders in circadian rhythms such as changes in the sleep wake cycle, secretion disorders of MT and cortisol are all associated with depressive symptoms[ 14 ].Cavallo et al. [ 15 ] found in their study on adolescents aged 7–15 that the 24-hour MT concentration in adolescents with depressive symptoms was lower than that in adolescents without depressive symptoms.A Swedish study found [ 16 ] that there is a negative correlation between nighttime MT secretion levels and depression levels in young people aged 18–25. That is, the less MT secretion at night, the more severe the symptoms of depression.Robillard et al. [ 17 ] found that the inositol concentration in adolescents with depressive symptoms was lower than that in adolescents without depressive symptoms, and delayed MT rhythm in adolescents with depressive symptoms was associated with lower levels of myoinositol concentration in the anterior cingulate cortex.However, a study conducted in the United States on adolescents aged 8–17 found the opposite result, that is, adolescents with depressive symptoms had higher nighttime MT levels than adolescents without depressive symptoms [ 18 ]. We attempt to explore whether MDD patients with NSSI have more pronounced MT rhythm disorders and abnormal levels, and to explore the correlation between these abnormalities and NSSI. Methods Participants The study sample includes 70 hospitalized patients aged between 14 and 24 who meet the diagnostic criteria for MDD in DSM-V-TR.The participants were hospitalized at the Affiliated Psychological Hospital of Anhui Medical University from 2020 to 2023 for treatment.All patients had no history of head injury, severe physical or neurological disorders, or abuse of psychoactive substances.They haven't used any medication in the past four weeks.And female patients were not in pregnancy or lactation.We divided the participants into NSSI group and non- NSSI group. In addition, we matched 30 healthy volunteers as the control group. Clinical evaluation The clinical evaluation was independently conducted by two experienced psychiatric attending physicians. Use the Hamilton Depression Rating Scale (HAMD) to assess the severity of the disease. Measurement of saliva MT levels Before sample collection, inform participants of the following precautions: do not eat within 1 hour, do not brush teeth within 10 minutes, and do not drink water.The collection time is 0AM, 8AM, 11AM, 1PM, 4PM, and 10PM.We used saliva cups to collected saliva samples from the subjects.We took out the cotton swab from the saliva cup and placed it under the subject's tongue for about 3 to 5 minutes, then put it back into the saliva cup and stored it in the refrigerator (0–4℃) within 30 minutes.Centrifuged the saliva sample at 3000 rpm for 15 minutes.Centrifuged saliva was stored in a -20℃ refrigerator for 4 hours for further laboratory analysis.Salivary MT concentration was detected using enzyme-linked immunosorbent assay(ELISA). According to the manufacturer's instructions, use equal portions of each saliva sample to evaluate MT levels. All specimens were measured at least twice by the same researcher.The average intra - and inter batch coefficient of variation of salivary MT is less than 2.5%, with levels expressed in pg/mL. Evaluation of the Ottawa self injury inventory(OSI) OSI [ 19 , 20 ] is a self survey questionnaire with 28 items that fully evaluates and examines the cognitive, emotional, behavioral, motivational, and environmental aspects of NSSI.The results of OSI include quantitative ratings of self harm and qualitative motivational items, categorizing the main assumed motivational factors behind NSSI.To achieve our research objectives, we utilized the following projects: -No.7 (When you have impulses that hurt yourself, how do these impulses feel to you? Pain or chaos; Comfort; Invasive or aggressive.) Each participant's scores for three possible impulses range from 0 (not at all) to 4 (extremely obvious); -No.24 (When you try to resist self harm behavior (not suicidal), how much motivation do you have to stop the behavior?)? The score ranges from 0 (not motivated at all) to 4 (extremely motivated). Statistical analysis The data analysis was performed using SPSS 22.0 statistical software. For continuous data that follow a normal distribution, group comparisons were conducted using analysis of variance (ANOVA) or t-test. For comparisons of melatonin levels at different time points between groups, repeated measures ANOVA was used. Categorical data was presented as rates (%) and group comparisons were conducted using a χ 2 test. The correlation analysis between two variables was performed using Pearson correlation. A two-tailed probability was used for calculating p-values, with P < 0.05 indicating statistically significant differences. Results Demographic and clinical characteristics This study included 35 cases in the NSSI group(MDD patients with NSSI), 35 cases in the non-NSSI group(MDD patients without NSSI), and 30 cases in the normal control group.Demographic and clinical characteristics of three groups of participants summarized in Table 1 . Table 1 Three groups of demographic and clinical characteristics NSSI group (n = 35) non-NSSI group (n = 35) control group(n = 30) P value Age(years) 18.20 ± 2.85 18.14 ± 2.68 19.17 ± 2.31 0.228 Education(years) 10.60 ± 2.38 10.80 ± 2.65 11.70 ± 2.09 0.157 gender[n(%)] male 16(45.71) 15(42.86) 15(50.00) 0.846 female 19(54.29) 20(57.14) 15(50.00) BMI(kg/m2) 20.69 ± 1.90 21.14 ± 1080 20.83 ± 2.18 0.616 HAMD 18.40 ± 4.30 19.14 ± 4.39 — 0.434 Note: BMI, body mass index;HMAD༚Hamilton Depression Scale. Group comparisons of saliva MT levels and circadian rhythm The salivary MT levels in the NSSI group decreased significantly at 6 time points compared to the other two groups(Table 2 ).The MT levels in the control group showed a significant diurnal rhythm trend, with lower levels during the day and higher levels at night.However, this circadian rhythm disappeared in the other two groups(Figure 1 ). Table 2 Analysis of variance for repeated measurements of salivary MT levels at six time points in three groups Time point NSSI group ( n = 35) Non-NSSI group( n = 35) Control group( n = 30) F value P value 0AM 4.787 ± 1.208 ab 7.315 ± 1.779 22.340 ± 4.036 438.658 < 0.001 8AM 5.067 ± 1.560 a 8.119 ± 1.963 7.059 ± 1.276 31.158 < 0.001 11AM 5.328 ± 1.639 a 8.441 ± 2.011 7.442 ± 1.409 29.819 < 0.001 1PM 4.582 ± 1.409 ab 7.078 ± 1.887 8.668 ± 1.566 51.957 < 0.001 4PM 5.040 ± 1.550 a 7.431 ± 1.981 8.198 ± 1.336 32.870 < 0.001 10PM 5.026 ± 1.269 ab 8.119 ± 1.963 19.485 ± 3.520 326.468 < 0.001 Note:”a” indicates that the salivary MT levels in the NSSI group are significantly lower than those in the non-NSSI group;”b” indicates that the salivary MT levels in the NSSI group are significantly lower than those in the Control group. Correlation between saliva MT levels and OSI In the NSSI group, OSI-7 (self injury is invasive or aggressive) was positively correlated with MT levels at 1pm (r = 0.487, P < 0.05), OSI-24 (cessation of self injury motivation) was negatively correlated with MT levels at 8AM (r=-0.427, P < 0.05), and positively correlated with MT levels at 11AM (r = 0.345, P < 0.05).(Fig. 2 ) Discussion MT follows a diurnal secretion pattern, maintaining low levels during the day, rapidly increasing at night, reaching a peak at midnight, and then gradually decreasing [ 21 ].To our knowledge, there is currently no research related to NSSI and MT.The first finding of this study was that patients with MDD accompanied by NSSI exhibited lower levels of MT, and their MT fluctuation characteristics were very similar to those of MDD patients wilhout NSSI.The MT levels of the normal population will fluctuate significantly over time. Patients with depression not only have a decrease in MT levels, but this fluctuation is also not significant. Patients with depression accompanied by NSSI have almost no fluctuation, indicating that MT level disorder is more pronounced in NSSI patients.MT is the main hormone produced by the pineal gland, and is considered a neuroprotective molecule due to its antioxidant and anti-inflammatory effects [ 22 – 24 ], as well as its inhibitory effects on the central nervous system [ 25 ].Stimulating the production of POMC/ACTH in rats fed with sucrose rich feed can induce oxidative stress and inflammation in the pituitary gland, and MT treatment can prevent these effects and normalize HPA axis activity [ 26 ].The decrease in MT levels and the disappearance of circadian rhythms can affect the functional changes of the HPA axis, thereby affecting its cognitive function. Studies have shown that MT can regulate the function of the HPA axis, while low levels of MT and rhythmic changes can reduce its regulatory function, further affecting the activity and function of the HPA axis [ 27 – 28 ].MT, as a neuroendocrine hormone, participates in stress response.Exogenous MT can improve HPA axis inhibition status [ 29 ].NSSI patients may experience more negative life events and stress, which may lead to frequent modulation of the HPA axis. By regulating stress hormone levels to cope with negative stimuli, MT, as a regulator of the HPA axis, its decrease and secretion disorder directly lead to dysfunction of the HPA axis, decreased stress capacity, increased negative emotions, and increased probability of improving emotions through self injury. Our study also found some correlations. We found a positive correlation between MT levels at 1 pm and the score of "self injury is invasive or aggressive" in item 7 of the Ottawa Injury Scale (how do these impulses feel when you have the urge to harm yourself?). In previous studies on NSSI, there have been no relevant findings.NSSI is considered a self aggressive behavior, and adrenal steroids mediate aggressive expression in different environmental contexts. Steroid hormones may play an important role in the regulation of aggression in both males and females [ 30 – 33 ].Animal experiments have shown that MT can induce aggressive behavior in female hamsters by directly regulating the levels of adrenal hormones [ 34 ], a phenomenon that may exist in other mammals, including humans.We also found a correlation between the motivation to stop self injury in the 22nd item of OSI and MT levels. The motivation of patients to stop self injury is negatively correlated with MT levels at 8am and positively correlated with MT levels at 11am, which seems contradictory.Patients with disrupted circadian rhythms usually fall asleep in the early morning or even later, and wake up near noon or even in the afternoon.A previous study by Turner et al. created a specific scale to evaluate the specific reasons for stopping NSSI, emphasizing the importance of nine individual factors related to the intention to stop self harm. These nine factors can be divided into two groups: the first group, causes related to vulnerability (i.e. fear of being discovered and stigmatized, concern about physical harm caused by NSSI, motivation arising from expectations of others, concern about NSSI addiction, and reliance on situational and environmental deterrence to prevent NSSI); The second group focuses on reasons related to resilience (i.e. desire to change and resolve pain, concerns about negative emotional consequences of NSSI, concerns about the body, and concerns about the negative impact of NSSI on human-machine relationships) [ 35 , 36 ].We believe that the disruption of MT rhythm affects factors related to vulnerability, leading to a decrease in the motivation to stop self injury. On the other hand, the decrease in MT levels at 8 a.m. enhances factors related to recovery, leading to an increase in the motivation to stop self injury (the body hopes to recover from the disrupted circadian rhythm to overcome painful emotions). Conclusions The circadian rhythm disorder of MT in patients with depression accompanied by NSSI reflects the abnormal function of the HPA axis. In order to cope with stress events, the central nervous system excessively mobilizes the function of the HPA axis to regulate the level of stress hormones, resulting in excessive HPA axis load. Through negative feedback mechanism, the function of MT is affected, and the abnormal level of MT directly affects the patient's motivation to stop self injurious behavior.Helping patients recover from the dilemma of MT circadian disorder may be beneficial for disease recovery, reduce self injurious behavior, and further reduce the risk of suicide.In addition, monitoring MT levels may be beneficial for early identification of those with depression who have a higher risk of suicide, allowing for earlier intervention. This study is a cross-sectional study with certain limitations. In the next step, we will search for NSSI patients who do not have any comorbidities or psychological disorders to further clarify the relationship between MT and NSSI. Declarations Acknowledgements We are grateful to all the participants in this study. Authors’ contributions Xiaojuan Hu performed the statistical analysis. Xiaojuan Hu, Aiguo Zhang, and Chao Wang wrote the frst draft of the manuscript. Xiaojuan Hu, Aiguo Zhang, Chao Wang and Xulai Zhang contributed to the design of the study and edited the manuscript for intellectual content. All authors read and approved the fnal manuscript. Funding This research was supported by STI2030-Major Projects of China(2021ZD0200600). Availability of data and materials The datasets used and analysed during the current study available from the corresponding author on reasonable request. Ethics approval and consent to participate The current study was approved by the Ethics Research Committee of Hefei Fourth People's Hospital (HFSY-IRB-YJ-KYXM-ZXL2023-032-001). The introductory page of the survey will provide information about the objective of the research and guarantee anonymity, confdentiality, and the freedom to decline participation in the study. Informed consent was obtained from all subjects and/or their legal guardian(s). Conflict of interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Consent for publication Not applicable. Author details 1 School of Mental Health and Psychological Science, Anhui Medical University,Hefei, China. 2 Anhui Provincial Mental Health Center,Hefei, China. 3 Anhui Medical University Affiliated Psychological Hospital,Hefei, China. 4 The Fourth People's Hospital of Hefei City,Hefei, China. References Plener PL, Schumacher TS, Munz LM, Groschwitz RC. The longitudinal course of non-suicidal self-injury and deliberate self-harm: a systematic review of the literature. Borderline Personal Disord Emot Dysregul. 2015;2:2. Nock MK. Self-injury [J]. Annu Rev Clin Psychol. 2010;6:340–63. Kinyanda E, Hjelmeland H, Musisi S. Psychological factors in deliberate self-harm as seen in a urban African population in Uganda: a case-control study. 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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-4532900","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":320533216,"identity":"1452c5ba-960d-4731-b63c-0f3548004d02","order_by":0,"name":"Xiaojuan Hu","email":"","orcid":"","institution":"School of Mental Health and Psychological Science, Anhui Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaojuan","middleName":"","lastName":"Hu","suffix":""},{"id":320533219,"identity":"bf4544a3-1af8-4263-980b-de21f45a1d1d","order_by":1,"name":"Aiguo Zhang","email":"","orcid":"","institution":"Anhui Provincial Mental Health Center","correspondingAuthor":false,"prefix":"","firstName":"Aiguo","middleName":"","lastName":"Zhang","suffix":""},{"id":320533221,"identity":"56c23a05-8023-49f4-9465-3f5bdf21ec65","order_by":2,"name":"Chao Wang","email":"","orcid":"","institution":"School of Mental Health and Psychological Science, Anhui Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chao","middleName":"","lastName":"Wang","suffix":""},{"id":320533223,"identity":"1d2a3db8-fcb9-4bbe-8e78-3d228681a0d4","order_by":3,"name":"Xulai Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA30lEQVRIiWNgGAWjYFAC5gaGBIYDIMaBAx9+EKWFEaaFLfHgzB5itTCAtfAYH+ZgI0KDwY3Exg8P/tyRN+df8+EwAw+DPL/YAfxaJGckNksk8Dwz3Dnj7YbDBRYMhjNnJ+DXwi+R2CCRIHGYccONsxsOz+BhSDC4TUALm0Ri848Eg8P2G26ceXCYh40ILUBb2iQSEg4nbjjfw0CcFsmeh20WCQcOJ2+4wWYADGQJwn4xOJ58+OaPP4dtN5w//PjDhx828vzSBLQggARYpQSxykGA/wApqkfBKBgFo2AkAQAgXk/gSzxA+QAAAABJRU5ErkJggg==","orcid":"","institution":"School of Mental Health and Psychological Science, Anhui Medical University","correspondingAuthor":true,"prefix":"","firstName":"Xulai","middleName":"","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2024-06-05 09:22:59","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4532900/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4532900/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":60185336,"identity":"f8ecb272-02bc-4ce0-b729-30b507c6ae82","added_by":"auto","created_at":"2024-07-12 18:41:51","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":133498,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eThe changing trends of MT levels in three groups at six time points.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCorrelation between saliva MT levels and OSI\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eIn the NSSI group, OSI-7 (self injury is invasive or aggressive) was positively correlated with MT levels at 1pm (r=0.487, P\u0026lt;0.05), OSI-24 (cessation of self injury motivation) was negatively correlated with MT levels at 8AM (r=-0.427, P\u0026lt;0.05), and positively correlated with MT levels at 11AM (r=0.345, P\u0026lt;0.05).(\u003cstrong\u003eFigure2\u003c/strong\u003e)\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4532900/v1/60158ad317ac7a03edbc15ab.jpg"},{"id":60185337,"identity":"1bb3a1e7-40f6-4ff8-9a60-5802108bad05","added_by":"auto","created_at":"2024-07-12 18:41:51","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1440721,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eHeat map of the correlation between MT levels and self injury perception and self injury cessation in the NSSI group\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNote:*\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05,**\u003cem\u003eP\u003c/em\u003e\u0026lt;0.01.Osi-7-a, Osi-7-b, Osi-7-c: Item 7 of the Ottawa Self Injury Scale. When you have the urge to harm yourself, how do these impulses feel to you? a: Pain or chaos; b: Comfortable; c: Invasive or aggressive.Osi-24:When you try to resist self harm behavior (not suicidal), how much motivation do you have to stop the behavior?\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-4532900/v1/4f585acb0a7bb7b50a8676a7.jpg"},{"id":71851276,"identity":"c359436b-b5c0-47ae-a53b-cf0ac1c693be","added_by":"auto","created_at":"2024-12-19 07:25:44","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2083702,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4532900/v1/3e0ee24c-2ec6-40db-a67e-ff31b3745ddf.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Melatonin rhythm disorder is more pronounced in major depressive disorder with Non-Suicidal Self-injury","fulltext":[{"header":"Background","content":"\u003cp\u003eMDD is a mental disorder characterized by persistent low mood. In addition to the core symptoms of MDD, adolescent patients often have NSSI[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e].NSSI refers to a series of socially unacceptable behaviors that individuals intentionally and directly harm their own bodies without suicidal intent[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e].Previous studies have found that NSSI is associated with MDD, and MDD is the main risk factor for NSSI,depression, impulsivity, and suicidal ideation are significantly correlated with NSSI, and the levels of depression, impulsivity, and suicidal ideation are significantly higher in MDD patients with NSSI[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].NSSI often overlaps with suicidal behavior, with NSSI patients having a suicide rate 100 times higher than the general population in the following year, and still having a high suicide rate for many years, with over 5% of patients ultimately committing suicide within 9 years[\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].In determining the risk of adolescent suicide, in addition to established risk factors such as depressive symptoms and suicidal tendencies, NSSI may be a particularly important assessment and prospective predictive factor[\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eDelayed circadian rhythms during adolescence and early adulthood are associated with the severity of depressive and emotional symptoms [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e], and adolescents with circadian rhythm disorders are at a higher risk of mental illness [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].Disorders in circadian rhythms such as changes in the sleep wake cycle, secretion disorders of MT and cortisol are all associated with depressive symptoms[\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].Cavallo et al. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] found in their study on adolescents aged 7\u0026ndash;15 that the 24-hour MT concentration in adolescents with depressive symptoms was lower than that in adolescents without depressive symptoms.A Swedish study found [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] that there is a negative correlation between nighttime MT secretion levels and depression levels in young people aged 18\u0026ndash;25. That is, the less MT secretion at night, the more severe the symptoms of depression.Robillard et al. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] found that the inositol concentration in adolescents with depressive symptoms was lower than that in adolescents without depressive symptoms, and delayed MT rhythm in adolescents with depressive symptoms was associated with lower levels of myoinositol concentration in the anterior cingulate cortex.However, a study conducted in the United States on adolescents aged 8\u0026ndash;17 found the opposite result, that is, adolescents with depressive symptoms had higher nighttime MT levels than adolescents without depressive symptoms [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eWe attempt to explore whether MDD patients with NSSI have more pronounced MT rhythm disorders and abnormal levels, and to explore the correlation between these abnormalities and NSSI.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eParticipants\u003c/h2\u003e \u003cp\u003eThe study sample includes 70 hospitalized patients aged between 14 and 24 who meet the diagnostic criteria for MDD in DSM-V-TR.The participants were hospitalized at the Affiliated Psychological Hospital of Anhui Medical University from 2020 to 2023 for treatment.All patients had no history of head injury, severe physical or neurological disorders, or abuse of psychoactive substances.They haven't used any medication in the past four weeks.And female patients were not in pregnancy or lactation.We divided the participants into NSSI group and non- NSSI group. In addition, we matched 30 healthy volunteers as the control group.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eClinical evaluation\u003c/h2\u003e \u003cp\u003eThe clinical evaluation was independently conducted by two experienced psychiatric attending physicians. Use the Hamilton Depression Rating Scale (HAMD) to assess the severity of the disease.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eMeasurement of saliva MT levels\u003c/h2\u003e \u003cp\u003eBefore sample collection, inform participants of the following precautions: do not eat within 1 hour, do not brush teeth within 10 minutes, and do not drink water.The collection time is 0AM, 8AM, 11AM, 1PM, 4PM, and 10PM.We used saliva cups to collected saliva samples from the subjects.We took out the cotton swab from the saliva cup and placed it under the subject's tongue for about 3 to 5 minutes, then put it back into the saliva cup and stored it in the refrigerator (0\u0026ndash;4℃) within 30 minutes.Centrifuged the saliva sample at 3000 rpm for 15 minutes.Centrifuged saliva was stored in a -20℃ refrigerator for 4 hours for further laboratory analysis.Salivary MT concentration was detected using enzyme-linked immunosorbent assay(ELISA). According to the manufacturer's instructions, use equal portions of each saliva sample to evaluate MT levels. All specimens were measured at least twice by the same researcher.The average intra - and inter batch coefficient of variation of salivary MT is less than 2.5%, with levels expressed in pg/mL.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eEvaluation of the Ottawa self injury inventory(OSI)\u003c/h2\u003e \u003cp\u003eOSI [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] is a self survey questionnaire with 28 items that fully evaluates and examines the cognitive, emotional, behavioral, motivational, and environmental aspects of NSSI.The results of OSI include quantitative ratings of self harm and qualitative motivational items, categorizing the main assumed motivational factors behind NSSI.To achieve our research objectives, we utilized the following projects:\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003e-No.7 (When you have impulses that hurt yourself, how do these impulses feel to you? Pain or chaos; Comfort; Invasive or aggressive.) Each participant's scores for three possible impulses range from 0 (not at all) to 4 (extremely obvious);\u003c/p\u003e \u003c/li\u003e \u003cli\u003e \u003cp\u003e-No.24 (When you try to resist self harm behavior (not suicidal), how much motivation do you have to stop the behavior?)? The score ranges from 0 (not motivated at all) to 4 (extremely motivated).\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analysis\u003c/h2\u003e \u003cp\u003eThe data analysis was performed using SPSS 22.0 statistical software. For continuous data that follow a normal distribution, group comparisons were conducted using analysis of variance (ANOVA) or t-test. For comparisons of melatonin levels at different time points between groups, repeated measures ANOVA was used. Categorical data was presented as rates (%) and group comparisons were conducted using a χ\u003csup\u003e2\u003c/sup\u003e test. The correlation analysis between two variables was performed using Pearson correlation. A two-tailed probability was used for calculating p-values, with P\u0026thinsp;\u0026lt;\u0026thinsp;0.05 indicating statistically significant differences.\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eDemographic and clinical characteristics\u003c/h2\u003e \u003cp\u003eThis study included 35 cases in the NSSI group(MDD patients with NSSI), 35 cases in the non-NSSI group(MDD patients without NSSI), and 30 cases in the normal control group.Demographic and clinical characteristics of three groups of participants 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\u003eThree groups of demographic and clinical characteristics\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=\"char\" char=\".\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNSSI group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003enon-NSSI group\u003c/p\u003e \u003cp\u003e(n\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003econtrol group(n\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eP value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.20\u0026thinsp;\u0026plusmn;\u0026thinsp;2.85\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18.14\u0026thinsp;\u0026plusmn;\u0026thinsp;2.68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e19.17\u0026thinsp;\u0026plusmn;\u0026thinsp;2.31\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.228\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEducation(years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.60\u0026thinsp;\u0026plusmn;\u0026thinsp;2.38\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.80\u0026thinsp;\u0026plusmn;\u0026thinsp;2.65\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e11.70\u0026thinsp;\u0026plusmn;\u0026thinsp;2.09\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.157\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003egender[n(%)]\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\u003emale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16(45.71)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15(42.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15(50.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.846\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003efemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19(54.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20(57.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e15(50.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBMI(kg/m2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.69\u0026thinsp;\u0026plusmn;\u0026thinsp;1.90\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.14\u0026thinsp;\u0026plusmn;\u0026thinsp;1080\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.83\u0026thinsp;\u0026plusmn;\u0026thinsp;2.18\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.616\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHAMD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e18.40\u0026thinsp;\u0026plusmn;\u0026thinsp;4.30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19.14\u0026thinsp;\u0026plusmn;\u0026thinsp;4.39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u0026mdash;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e0.434\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003eNote: BMI, body mass index;HMAD༚Hamilton Depression Scale.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003eGroup comparisons of saliva MT levels and circadian rhythm\u003c/h2\u003e \u003cp\u003eThe salivary MT levels in the NSSI group decreased significantly at 6 time points compared to the other two groups(Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).The MT levels in the control group showed a significant diurnal rhythm trend, with lower levels during the day and higher levels at night.However, this circadian rhythm disappeared in the other two groups(Figure \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\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\u003eAnalysis of variance for repeated measurements of salivary MT levels at six time points in three groups\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\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=\"char\" char=\"\u0026plusmn;\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\"\u0026plusmn;\" 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 \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTime point\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNSSI group\u003c/p\u003e \u003cp\u003e(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eNon-NSSI group(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;35)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eControl group(\u003cem\u003en\u003c/em\u003e\u0026thinsp;=\u0026thinsp;30)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cem\u003eF value\u003c/em\u003e\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003e\u003cem\u003eP value\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\u003e0AM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.787\u0026thinsp;\u0026plusmn;\u0026thinsp;1.208 \u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.315\u0026thinsp;\u0026plusmn;\u0026thinsp;1.779\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e22.340\u0026thinsp;\u0026plusmn;\u0026thinsp;4.036\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e438.658\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e8AM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.067\u0026thinsp;\u0026plusmn;\u0026thinsp;1.560 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.119\u0026thinsp;\u0026plusmn;\u0026thinsp;1.963\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e7.059\u0026thinsp;\u0026plusmn;\u0026thinsp;1.276\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e31.158\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11AM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.328\u0026thinsp;\u0026plusmn;\u0026thinsp;1.639 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.441\u0026thinsp;\u0026plusmn;\u0026thinsp;2.011\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e7.442\u0026thinsp;\u0026plusmn;\u0026thinsp;1.409\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e29.819\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1PM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.582\u0026thinsp;\u0026plusmn;\u0026thinsp;1.409 \u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.078\u0026thinsp;\u0026plusmn;\u0026thinsp;1.887\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e8.668\u0026thinsp;\u0026plusmn;\u0026thinsp;1.566\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e51.957\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e4PM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.040\u0026thinsp;\u0026plusmn;\u0026thinsp;1.550 \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e7.431\u0026thinsp;\u0026plusmn;\u0026thinsp;1.981\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e8.198\u0026thinsp;\u0026plusmn;\u0026thinsp;1.336\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e32.870\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e10PM\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.026\u0026thinsp;\u0026plusmn;\u0026thinsp;1.269 \u003csup\u003eab\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c3\"\u003e \u003cp\u003e8.119\u0026thinsp;\u0026plusmn;\u0026thinsp;1.963\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\"\u0026plusmn;\" colname=\"c4\"\u003e \u003cp\u003e19.485\u0026thinsp;\u0026plusmn;\u0026thinsp;3.520\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c5\"\u003e \u003cp\u003e326.468\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c6\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"6\"\u003eNote:\u0026rdquo;a\u0026rdquo; indicates that the salivary MT levels in the NSSI group are significantly lower than those in the non-NSSI group;\u0026rdquo;b\u0026rdquo; indicates that the salivary MT levels in the NSSI group are significantly lower than those in the Control group.\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003eCorrelation between saliva MT levels and OSI\u003c/h2\u003e \u003cp\u003eIn the NSSI group, OSI-7 (self injury is invasive or aggressive) was positively correlated with MT levels at 1pm (r\u0026thinsp;=\u0026thinsp;0.487, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), OSI-24 (cessation of self injury motivation) was negatively correlated with MT levels at 8AM (r=-0.427, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05), and positively correlated with MT levels at 11AM (r\u0026thinsp;=\u0026thinsp;0.345, P\u0026thinsp;\u0026lt;\u0026thinsp;0.05).(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e)\u003c/p\u003e "},{"header":"Discussion","content":"\u003cp\u003eMT follows a diurnal secretion pattern, maintaining low levels during the day, rapidly increasing at night, reaching a peak at midnight, and then gradually decreasing [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e].To our knowledge, there is currently no research related to NSSI and MT.The first finding of this study was that patients with MDD accompanied by NSSI exhibited lower levels of MT, and their MT fluctuation characteristics were very similar to those of MDD patients wilhout NSSI.The MT levels of the normal population will fluctuate significantly over time. Patients with depression not only have a decrease in MT levels, but this fluctuation is also not significant. Patients with depression accompanied by NSSI have almost no fluctuation, indicating that MT level disorder is more pronounced in NSSI patients.MT is the main hormone produced by the pineal gland, and is considered a neuroprotective molecule due to its antioxidant and anti-inflammatory effects [\u003cspan additionalcitationids=\"CR23\" citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], as well as its inhibitory effects on the central nervous system [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].Stimulating the production of POMC/ACTH in rats fed with sucrose rich feed can induce oxidative stress and inflammation in the pituitary gland, and MT treatment can prevent these effects and normalize HPA axis activity [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e].The decrease in MT levels and the disappearance of circadian rhythms can affect the functional changes of the HPA axis, thereby affecting its cognitive function. Studies have shown that MT can regulate the function of the HPA axis, while low levels of MT and rhythmic changes can reduce its regulatory function, further affecting the activity and function of the HPA axis [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].MT, as a neuroendocrine hormone, participates in stress response.Exogenous MT can improve HPA axis inhibition status [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e].NSSI patients may experience more negative life events and stress, which may lead to frequent modulation of the HPA axis. By regulating stress hormone levels to cope with negative stimuli, MT, as a regulator of the HPA axis, its decrease and secretion disorder directly lead to dysfunction of the HPA axis, decreased stress capacity, increased negative emotions, and increased probability of improving emotions through self injury.\u003c/p\u003e \u003cp\u003eOur study also found some correlations. We found a positive correlation between MT levels at 1 pm and the score of \"self injury is invasive or aggressive\" in item 7 of the Ottawa Injury Scale (how do these impulses feel when you have the urge to harm yourself?). In previous studies on NSSI, there have been no relevant findings.NSSI is considered a self aggressive behavior, and adrenal steroids mediate aggressive expression in different environmental contexts. Steroid hormones may play an important role in the regulation of aggression in both males and females [\u003cspan additionalcitationids=\"CR31 CR32\" citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e].Animal experiments have shown that MT can induce aggressive behavior in female hamsters by directly regulating the levels of adrenal hormones [\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e], a phenomenon that may exist in other mammals, including humans.We also found a correlation between the motivation to stop self injury in the 22nd item of OSI and MT levels. The motivation of patients to stop self injury is negatively correlated with MT levels at 8am and positively correlated with MT levels at 11am, which seems contradictory.Patients with disrupted circadian rhythms usually fall asleep in the early morning or even later, and wake up near noon or even in the afternoon.A previous study by Turner et al. created a specific scale to evaluate the specific reasons for stopping NSSI, emphasizing the importance of nine individual factors related to the intention to stop self harm. These nine factors can be divided into two groups: the first group, causes related to vulnerability (i.e. fear of being discovered and stigmatized, concern about physical harm caused by NSSI, motivation arising from expectations of others, concern about NSSI addiction, and reliance on situational and environmental deterrence to prevent NSSI); The second group focuses on reasons related to resilience (i.e. desire to change and resolve pain, concerns about negative emotional consequences of NSSI, concerns about the body, and concerns about the negative impact of NSSI on human-machine relationships) [\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e, \u003cspan citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e].We believe that the disruption of MT rhythm affects factors related to vulnerability, leading to a decrease in the motivation to stop self injury. On the other hand, the decrease in MT levels at 8 a.m. enhances factors related to recovery, leading to an increase in the motivation to stop self injury (the body hopes to recover from the disrupted circadian rhythm to overcome painful emotions).\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003eThe circadian rhythm disorder of MT in patients with depression accompanied by NSSI reflects the abnormal function of the HPA axis. In order to cope with stress events, the central nervous system excessively mobilizes the function of the HPA axis to regulate the level of stress hormones, resulting in excessive HPA axis load. Through negative feedback mechanism, the function of MT is affected, and the abnormal level of MT directly affects the patient's motivation to stop self injurious behavior.Helping patients recover from the dilemma of MT circadian disorder may be beneficial for disease recovery, reduce self injurious behavior, and further reduce the risk of suicide.In addition, monitoring MT levels may be beneficial for early identification of those with depression who have a higher risk of suicide, allowing for earlier intervention. This study is a cross-sectional study with certain limitations. In the next step, we will search for NSSI patients who do not have any comorbidities or psychological disorders to further clarify the relationship between MT and NSSI.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe are grateful to all the participants in this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eXiaojuan Hu performed the statistical analysis. Xiaojuan Hu, Aiguo Zhang, and Chao Wang wrote the frst draft of the manuscript. Xiaojuan Hu, Aiguo Zhang, \u0026nbsp;Chao Wang and Xulai Zhang contributed to the design of the study and edited the manuscript for intellectual content. All authors read and approved the fnal manuscript.\u003cbr\u003e\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by STI2030-Major Projects of China(2021ZD0200600).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe datasets used and analysed during the current study available from the\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ecorresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe current study was approved by the Ethics Research Committee of\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eHefei Fourth People\u0026apos;s Hospital (HFSY-IRB-YJ-KYXM-ZXL2023-032-001).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eThe introductory page of the survey will provide information about the objective of the research and guarantee anonymity, confdentiality, and the freedom to decline participation in the study. Informed consent was obtained from all subjects and/or their legal guardian(s).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflict of \u0026nbsp;interest\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare that the research was conducted in the absence of any\u0026nbsp;\u003c/p\u003e\n\u003cp\u003ecommercial or financial relationships that could be construed as a potential\u0026nbsp;\u003c/p\u003e\n\u003cp\u003econflict of interest.\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\u003eAuthor details\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003csup\u003e1\u003c/sup\u003eSchool of Mental Health and Psychological Science, Anhui Medical University,Hefei, China.\u003csup\u003e2\u003c/sup\u003eAnhui Provincial Mental Health Center,Hefei, China.\u003csup\u003e3\u003c/sup\u003eAnhui Medical University Affiliated Psychological Hospital,Hefei, China.\u003csup\u003e4\u003c/sup\u003eThe Fourth People\u0026apos;s Hospital of Hefei City,Hefei, China.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003ePlener PL, Schumacher TS, Munz LM, Groschwitz RC. The longitudinal course of non-suicidal self-injury and deliberate self-harm: a systematic review of the literature. Borderline Personal Disord Emot Dysregul. 2015;2:2.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNock MK. Self-injury [J]. Annu Rev Clin Psychol. 2010;6:340\u0026ndash;63.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKinyanda E, Hjelmeland H, Musisi S. Psychological factors in deliberate self-harm as seen in a urban African population in Uganda: a case-control study. Suicide Life Threat Behav. 2005;35(4):468\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRodav O, Levy S, Hamdan S. Clinical characteristics and functions of non-suicide self-injury in youth. Eur Psychiatry. 2014;29(8):503\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHarrison P, Cowen P, Burns T. et,al.Shorter Oxford textbook of psychiatry[M]. Oxfort Univ Press,2017:620\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAsarnow JR, Porta G, Spirito A, Emslie G, Clarke G, Wagner KD, Vitiello B, Keller M, Birmaher B, McCracken J, Mayes T, Berk M, Brent DA. Suicide attempts and nonsuicidal self-injury in the treatment of resistant depression in adolescents: findings from the TORDIA study. J Am Acad Child Adolesc Psychiatry. 2011;50(8):772\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTuisku V, Kiviruusu O, Pelkonen M, Karlsson L, Strandholm T, Marttunen M. Depressed adolescents as young adults - predictors of suicide attempt and non-suicidal self-injury during an 8-year follow-up. J Affect Disord. 2014;152\u0026ndash;154:313\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuan K, Fox KR, Prinstein MJ. Nonsuicidal self-injury as a time-invariant predictor of adolescent suicide ideation and attempts in a diverse community sample. J Consult Clin Psychol. 2012;80(5):842\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTuisku V, Kiviruusu O, Pelkonen M, Karlsson L, Strandholm T, Marttunen M. Depressed adolescents as young adults - predictors of suicide attempt and non-suicidal self-injury during an 8-year follow-up. J Affect Disord. 2014;152\u0026ndash;154:313\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGuan K, Fox KR, Prinstein MJ. Nonsuicidal self-injury as a time-invariant predictor of adolescent suicide ideation and attempts in a diverse community sample. J Consult Clin Psychol. 2012;80(5):842\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRANITI M B, ALLEN N B SCHWARTZO, et al. Sleep durationand sleep quality: associations with depressive symptoms across adolescence [J]. Behav Sleep Med. 2017;15(3):198\u0026ndash;215.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLEWY AJ. Depressive disorders may more commonly be related to circadian phase delaysrather than advances: time will tell [J]. Sleep Med. 2010;11(2):117\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eADDINGTON J. Prediction and prevention of psychosis in youth at clinical high risk [J]. Annu Rev Clin Psychol. 2012;8:269\u0026ndash;89.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eABREU T, BRAGANCA M. The bipolarity of light and dark: a review on bipolar disorder and circadian cycles [J]. J Affect Disord. 2015;185:219\u0026ndash;29.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCAVALLO A, HOLT K G, HEJAZI MS, et al. Melatonin circadian rhythm in childhood depression [J]. J Am Acad Child Adolesc Psychiatry. 1987;26(3):395\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSUNDBERG I, RAMKLINT M. Salivary melatonin in relation to depressive symptom severity in young adults [. J] PLoS One. 2016;11(4):e0152814.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eROBILLARD R, LAGOPOULOS J, HERMENS D F, et al. Lower In vivo myo-inositol in the anterior cingulate cortex correlates with delayed melatonin rhythms in young persons with depression [J]. Front Neurosci. 2017;11:336.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSHAFII M, MACMILLAN D R, KEY M P, et al. Nocturnal serum melatonin profile in major depression in children and adolescents [J]. Arch Gen Psychiatry. 1996;53(11):1009\u0026ndash;13.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eArtin J, Cloutier P, Levesque C, Bureau J-F. Psychometric Properties of the Functions and Addictive Features Scales of the Ottawa Self-Injury Inventory: A Preliminary Investigation Using a University Sample Mental Health in Pediatric ED View Project Emotionally Focused Therapy: Creating Connection Also in Spanish Language? View Project. 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J Pineal Res. 2019;66:e12545.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRendon NM, Rudolph LM, Sengelaub DR et al. The agonistic adrenal:melatonin elicits female aggression via regulation of adrenal androgens.Proceedings. Biol Sci. 2015;282.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou J, Zhang J, Luo X, et al. Neu-P11, a novel MT1/MT2 agonist,reverses diabetes by suppressing the hypothalamic-pituitary-adrenal axisin rats. Eur J Pharmacol. 2017;812:225\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhong LY, Yang ZH, Li XR, et al. Protective effects of melatonin againstthe damages of neuroendocrine-immune induced by lipopolysaccharidein diabetic rats. 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Horm Behav. 2004;45:40\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScotti M-AL, Schmidt KL, Newman AEM, Bonu T, Soma KK, Demas GE. 2009 Aggressive encounters differentially affect serum dehydroepiandrosterone and testosterone concentrations in male Siberian hamsters (Phodopus sungorus). Horm Behav 56, 376\u0026ndash;81.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRendon NM, Rudolph LM, Sengelaub DR et al. The agonistic adrenal: melatonin elicits female aggression via regulation of adrenal androgens. Proceedings. Biol Sci. 2015;282.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTurner BJ, Chapman AL, Gratz KL. Why Stop Self-Injuring? Development of the Reasons to Stop Self-Injury Questionnaire. Behav Modif. 2014;38:69\u0026ndash;106.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePiarulli FM, Margari A, Margari F, Matera E. Do Cortisol and Dehydroepiandrosterone Influence Motivational Factors for Non-Suicidal Self-Injury in Female Adolescents? J Clin Med. 2023;12(5):1924.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Non-suicidal self-injury, Melatonin, Circadian rhythm, Ottawa Self-Injury Scale","lastPublishedDoi":"10.21203/rs.3.rs-4532900/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4532900/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground \u003c/strong\u003eMelatonin(MT) rhythm disorders may be associated with depression and non-suicidal self-injury（NSSI）.We conducted a controlled study to investigate whether patients with major depressive disorder（MDD）comorbid NSSI have more pronounced MT disorders, and whether MT levels are associated with NSSI perception and cessation.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eA total of 100 samples were included in the study, including 30 healthy individuals as a normal control group and 70 patients with MDD.In the subgroup of MDD,there were 35 patients with NSSI(NSSI group) and 35 patients without NSSI (non-NSSI group).We used enzyme-linked immunosorbent assay to measure the salivary MT levels (0AM, 8AM, 11AM, 1PM, 4PM, 10PM) of all participants at 6 time points. And use the Ottawa-Self- Injury Inventory (OSI) to quantitatively evaluate the self injury perception and motivation to stop self injury in patients in the NSSI group.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults\u003c/strong\u003e The salivary MT levels in the NSSI group at 6 time points were significantly lower than those in the non- NSSI group and control group (\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05), and the circadian rhythm of MT in NSSI group disappeared.We found significant\u003c/p\u003e\n\u003cp\u003ecorrelations between MT levels and several dimensions of NSSI,specifically: 1PM MT level and intrusive/invasive urge(r=0.487，\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05), 8AM MT levels and desire to stop NSSI(r=-0.427，\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05),11AM MT levels and desire to stop NSSI(r=-0.348，\u003cem\u003eP\u003c/em\u003e\u0026lt;0.05).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions \u003c/strong\u003eThe decrease in MT levels and disruption of circadian rhythms may increase the risk of NSSI in patients with MDD, but its mechanism needs further exploration.\u003c/p\u003e","manuscriptTitle":"Melatonin rhythm disorder is more pronounced in major depressive disorder with Non-Suicidal Self-injury","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-07-12 18:41:46","doi":"10.21203/rs.3.rs-4532900/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"01663dca-d8d6-4ad6-b97a-6fd4ef858684","owner":[],"postedDate":"July 12th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-19T07:24:51+00:00","versionOfRecord":[],"versionCreatedAt":"2024-07-12 18:41:46","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-4532900","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4532900","identity":"rs-4532900","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}