Characteristics of Self-Injury Behavior and Its Associations with Thyroid and Sex Hormones in Major Depressive Disorder and Bipolar Disorder

Characteristics of Self-Injury Behavior and Its Associations with Thyroid and Sex Hormones in Major Depressive Disorder and Bipolar Disorder | 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 Characteristics of Self-Injury Behavior and Its Associations with Thyroid and Sex Hormones in Major Depressive Disorder and Bipolar Disorder Na Zhang, Yuanyuan Dai, lin Zhao, Chengcong Wu, Zhihai Zhou, Cheng Yang, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-9139380/v1 This work is licensed under a CC BY 4.0 License Status: Under Review Version 1 posted 12 You are reading this latest preprint version Abstract Background Non-suicidal self-injury (NSSI) is prevalent among adolescents with mood disorders. However, differences in NSSI characteristics between major depressive disorder (MDD) and bipolar disorder (BD), and their endocrine correlates, remain insufficiently explored. This study examined NSSI characteristics and their associations with thyroid and sex hormones in adolescents with MDD and BD. Methods This retrospective study included 484 adolescents diagnosed with MDD or BD. Demographic characteristics and hormone levels were compared within each diagnostic group. Sex-stratified binary logistic regression analyses were conducted to identify factors associated with NSSI. Additionally, adolescents with NSSI were compared between the MDD and BD groups. Results NSSI prevalence was 56.6% in BD and 65.9% in MDD. Females were significantly more frequent than males in both groups. In BD, adolescents with NSSI had lower testosterone and free thyroxine (FT4) than those without NSSI. Sex-stratified logistic regression showed that, in females, thyroid-stimulating hormone (TSH) and FT4independently predicted NSSI. There were no significant predictors in males. In MDD, adolescents with NSSI had lower testosterone, but no hormones significantly predicted NSSI by sex. Among adolescents with NSSI, there were no demographic or hormonal differences between the BD and MDD groups. Conclusions Thyroid hormones predicted NSSI mainly in females with BD. After NSSI, hormone levels and demographic characteristics did not differ significantly between BD and MDD patients, suggesting hormones levels have limited value for distinguishing diagnostic subtypes. Identification of high-risk individuals should consider both diagnoses and sex, with close attention to thyroid function in females with BD. Major depressive disorder Bipolar disorder Testosterone Thyroid hormones Non-suicidal self-injury Figures Figure 1 1. Background Non-suicidal self-injury (NSSI) is defined as the deliberate, repetitive destruction of one's own body tissue without suicidal intent, such as cutting, scratching, or hitting oneself (Kruzan et al., 2025). This behavior is particularly prevalent among adolescents and has increased globally in recent years. The lifetime prevalence among adolescents is approximately 22.0%, with a recurrence rate of up to 20.3% (Xiao et al., 2022). In China, prevalence is higher, reaching 24.7%; children and adolescents show higher rates than university students(Qu et al., 2023), highlighting the need for prompt identification and intervention. NSSI is associated with an elevated risk of subsequent suicidal behaviors(Muehlenkamp et al., 2019), is especially common among individuals with mood disorders, and correlates with emotional dysregulation, impulse control difficulties, and other psychiatric conditions (He et al., 2023; McHugh et al., 2019). Numerous studies have focused on psychosocial factors contributing to NSSI. These include childhood trauma, school bullying, and family dysfunction(Zhang et al., 2025). However, systematic research on the biological mechanisms of NSSI remains limited. Recent neurobiological and endocrine studies suggest that the endocrine system—particularly the hypothalamic–pituitary–thyroid (HPT) axis and hypothalamic–pituitary–gonadal (HPG) axis, which are closely involved in emotional regulation—may play a critical role in the pathogenesis of NSSI (Peng et al., 2024). Thyroid hormones, the end products of the HPT axis, regulate metabolic functions and play key roles in neuronal differentiation, synaptogenesis, and neurotransmitter metabolism(Bernal, 2007). Hormones such as thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) have been implicated in depression and suicidal behaviors (Ma et al., 2022). Duval (2017)proposed that a blunted TSH response to thyrotropin-releasing hormone (TRH) may represent a risk factor for suicide. One study found FT4 levels were significantly lower in individuals who attempted suicide compared with non-attempters, while differences in TSH and FT3 were inconsistent(Peng et al., 2018). Other studies have reported elevated TSH levels in patients with mood disorders(Toloza et al., 2021). This suggests that thyroid function may influence self-injurious impulses through complex mechanisms. However, heterogeneity in study samples, including medication use and comorbidities, has limited the consistency of findings. Puberty is a critical period for rapid brain remodeling. During this time, emotional regulation and impulse control are not yet fully mature. This increases the risk of impulsive behaviors such as self-injury and suicide(Johnston et al., 2017). Testosterone levels rise significantly in puberty and are considered an important factor influencing central nervous system development and behavioral changes in adolescents(Varlinskaya et al., 2013). Testosterone is the end product of the HPG axis. It is closely linked to risk-taking behaviors, impulse control, and emotional regulation(Terburg et al., 2009; Rice & Sher, 2015). Testosterone can cross the blood–brain barrier and modulate neurotransmitter systems, including dopamine, GABA, and serotonin. These actions influence emotional and behavioral responses(McHenry et al., 2014). Some studies have reported that adolescents with depression who engage in self-injury may have higher testosterone levels than their non-injurious peers(Ma et al., 2022). However, contradictory findings have also been reported(Sher, 2023). Previous studies have preliminarily examined abnormalities in thyroid and sex hormones in patients with mood disorders. They have looked at how these hormones may be linked to NSSI. However, systematic investigations of the relationship between these hormones and self-injurious behaviors across mood disorder subtypes remain scarce. MDD and BD are both mood disorders. However, they differ significantly in pathophysiological mechanisms, neuroendocrine profiles, and emotional regulation strategies. Some studies suggest that individuals with BD may exhibit distinct neuroendocrine characteristics compared with those with MDD. This may influence patterns of self-injurious behavior(Wei et al., 2025). Changes in specific biological markers have also been proposed as early indicators of suicide risk. These indicators could provide clinicians with potential tools for identifying high-risk individuals(Johnston et al., 2022). Investigating the associations between these hormones and NSSI, especially differences across mood disorder subtypes, holds important theoretical and clinical significance. 2. Methods 2.1 Participants This retrospective cross-sectional study included adolescent inpatients with mood disorders. These patients were hospitalized at the Fourth People’s Hospital of Wuhu, Anhui Province, China, between January 2020 and December 2021. A total of 484 patients were enrolled: 311 with MDD and 173 with BD. The inclusion criteria were as follows: (1) a diagnosis of MDD or BD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The diagnosis was confirmed jointly by experienced attending psychiatrists and senior physicians; (2) age between 10 and 19 years; (3) complete, reliable medical records. The exclusion criteria were as follows: (1) comorbid psychiatric disorders (e.g., schizophrenia spectrum disorders or pervasive developmental disorders) or serious neurological conditions; (2) history of or current endocrine, andrological, or gynecological disorders; thyroid dysfunction; metabolic syndrome; gout; hypertension; long-term liver or kidney problems; asthma; or any other major physical illness; (3) pregnancy or lactation at the time of hospitalization; (4) recent (within three months) use of medications that could affect hormones, such as hormone medicines, oral contraceptives, or any kind of corticosteroids; (5) substance or alcohol abuse or dependence, confirmed by urine screening; (6) evident intellectual disability. This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Ethics Committee of Wuhu Fourth People’s Hospital (approval number: [2021]-KY-06). Due to the retrospective nature of the study, the ethics committee waived the requirement for informed consent. All patient data were anonymized during analysis. 2.2 Clinical data collection All demographic and clinical data were obtained from the electronic medical record system and standardized assessment forms of Wuhu Fourth People’s Hospital. Two trained researchers independently extracted and entered the data, which were cross-checked by a third researcher for accuracy and completeness. Demographic variables included sex, age, place of residence, only-child status, and family structure. Clinical variables included somatic symptoms and positive psychotic symptoms. NSSI was assessed independently by two psychiatrists using medical history, examination records, and psychiatric evaluations, with consensus required for a DSM-5 diagnosis. 2.3 Hormone assays Serum levels of thyroid and sex hormones were measured using fasting venous blood samples collected between 6:30 and 7:00 a.m. on the morning following hospital admission. All samples were delivered to the laboratory within 30 minutes of collection and analyzed immediately. Sex hormone levels were measured using the Atellica Solution analyzer (Siemens Healthineers, Germany) with a chemiluminescent immunoassay. Thyroid function indices were assessed with the Roche Cobas e601 electrochemiluminescence immunoassay system (Shanghai Lanwei Clinical Testing Co., Ltd.). All assays were performed by laboratory physicians who had completed standardized training and followed established procedures. 2.4 Statistical analysis Statistical analyses were performed using IBM SPSS Statistics version 26.0. Demographic characteristics and hormone levels were compared within each diagnostic group using independent-samples t tests for continuous variables and chi-square tests for categorical variables. To examine the predictive effects of hormone levels on NSSI risk while controlling for sex-related confounding, sex-stratified binary logistic regression analyses were conducted within each group, with hormone variables entered using the enter method. All statistical tests were two-tailed, and a p < 0.05 was considered statistically significant. 3. Results 3.1 Statistical analyses in patients with BD 3.1.1 Demographic characteristics of patients with BD Table 1 presents the demographic characteristics of adolescents with BD with and without NSSI. Compared with those without NSSI, adolescents with NSSI were more likely to be female ( χ² = 21.546， p < 0 .001)、had an earlier age at onset ( t = 2.86， p = 0.005) , and exhibited more positive psychotic symptoms ( χ² = 4.067， p = 0.044). The proportion of only children was also lower in the NSSI group ( χ² =5.700， p = 0.017) . No significant differences were found in age, place of residence, family structure, or somatic symptoms ( p > 0.05). Table 1. Comparison of demographic characteristics between adolescents with and without NSSI in the BD group Variable NSSI group (n=98) Non-NSSI group (n=75) χ²/t p Female, n (%) 89（65.9%） 46（34.1%） 21.546 0.001 *** Age, years, M(SD) 15.92±1.43 16.03±1.34 1.03 0.612 Age at onset, years, M(SD) 13.97±1.80 13.03±1.99 2.86 0.005 ** Urban residence, n (%) 42（42.9%） 30（40.0%） 0.143 0.706 Only-child status, n (%) 37（56.0%） 42（53.2%） 5.700 0.017 * Nuclear family, n (%) 73（74.5%） 59（78.7%） 0.410 0.522 Somatic symptoms, n (%) 22（22.4%） 16（21.3%） 0.031 0.861 Positive psychotic symptoms, n (%) 49（50.0%） 26（34.7%） 4.067 0.044 * 3.1.2 Relationship between testosterone, thyroid hormones, and non-suicidal self-injury in adolescents with BD As shown in Figure 1, compared with adolescents with BD without NSSI, those with NSSI had significantly lower levels of Testosterone ( p < 0.001) and FT4 ( p = 0.03). No significant differences were observed in FT3 ( p = 0.09) or TSH ( p = 0.06) between the two groups. 3.1.3 Binary logistic regression analysis of hormone levels and NSSI in patients with BD To further clarify the role of hormone levels in predicting the risk of NSSI, binary logistic regression analyses were conducted in patients with BD. Previous analyses revealed a significant difference in sex distribution between the NSSI and non-NSSI groups. Considering the potential confounding effect of sex on hormonal associations, sex-stratified analyses were therefore performed. As shown in Table 2, TSH was a significant negative predictor of NSSI risk in female patients ( OR = 0.777, p = 0.024). FT4 also showed a significant negative association with NSSI risk ( OR = 0.784, p = 0.028), indicating that lower levels of TSH and FT4 were associated with an increased risk of NSSI. In contrast, neither TSH nor FT4 significantly predicted NSSI risk in male patients ( p > 0.05). In addition, testosterone and FT3 were not significant predictors of NSSI in either sex ( p > 0.05). Table 2. Sex-stratified binary logistic regression analyses of factors associated with NSSI in patients with BD Variable male Female B OR 95% CI p B OR 95% CI p Testosterone,ng/mL,M(SD) 0.118 1.125 0.997-1.269 0.057 0.586 1.796 0.805-4.008 0.153 TSH, mIU/L, M(SD) -0.102 0.903 0.523-1.558 0.714 -0.252 0.777 0.624-0.968 0.024 * FT3, pmol/L, M(SD) 0.024 1.024 0.440-2.384 0.956 -0.135 0.874 0.512-1.491 0.621 FT4, pmol/L, M(SD) -0.037 0.964 0.753-1.233 0.770 -0.243 0.784 0.632-0.974 0.028 * Note: TSH: Thyroid-stimulating hormone; FT3: Free triiodothyronine; FT4: Free thyroxine. 3.2 Statistical analyses in patients with MDD 3.2.1 Demographic characteristics of patients with MDD Table 3 presents the demographic characteristics of adolescents with MDD with and without NSSI.The NSSI group showed significantly higher proportions of females ( χ ² = 44.412, p < 0.001), only-child status ( χ ² = 4.514, p = 0.034), and positive psychotic symptoms ( χ ² = 5.166, p = 0.023). In contrast, age ( t = 3.539, p = 0.047) and age at onset ( t = 5.84, p = 0.001) were significantly lower in the NSSI group. No significant differences were found in place of residence, family structure, or somatic symptoms ( p > 0.05). Table 3. Comparison of demographic characteristics between adolescents with and without NSSI in the MDD group Variable NSSI group (n=98) Non-NSSI group (n=75) χ²/t p Female, n (%) 190（92.7%） 66（62.3%） 44.412 0.001 *** Age, years, M(SD) 15.90±1.46 16.24±13.3 3.539 0.047 * Age at onset, years, M(SD) 12.75±1.71 14.01±1.96 5.84 <0.001 *** Urban residence, n (%) 94（45.9%） 45（42.5%） 0.327 0.567 Only-child status, n (%) 90（43.9%） 60（56.6%） 4.514 0.034 * Nuclear family, n (%) 155（75.6%） 90（84.9%） 3.612 0.057 Somatic symptoms, n (%) 39（19.0%） 24（22.6%） 0.566 0.452 Positive psychotic symptoms, n (%) 87（42.4%） 31（29.2%） 5.166 0.023 * 3.2.2 Relationship between testosterone, thyroid hormones, and non-suicidal self-injury in adolescents with MDD As shown in Figure1, compared with adolescents with MDD without NSSI, those with NSSI had significantly lower testosterone levels than those without NSSI (p < 0.001). No significant differences were observed in TSH (p = 0.56), FT3 (p = 0.92), and FT4 (p = 0.11)between the two groups. 3.2.3 Binary logistic regression analysis of hormone levels and NSSI in patients with MDD To further examine the predictive effects of hormone levels on the risk of NSSI while controlling for potential sex-related confounding, gender-stratified binary logistic regression analyses were conducted in patients with MDD. As shown in Table 4, none of the hormone variables significantly predicted NSSI risk in either male or female patients ( p > 0.05). Table 4. Sex-stratified binary logistic regression analyses of factors associated with NSSI in patients with BD Variable male Female B OR 95% CI p B OR 95% CI p Testosterone,ng/mL,M(SD) 0.014 1.014 0.940-1.093 0.723 -0.061 0.941 0.562-1.576 0.817 TSH, mIU/L, M(SD) -0.110 0.330 0.102-1.063 0.063 0.209 1.232 0.946-1.605 0.121 FT3, pmol/L, M(SD) -0.325 0.723 0.222-2.353 0.590 0.240 1.271 0.821-1.966 0.282 FT4, pmol/L, M(SD) 0.088 1.092 0.699-1.708 0.699 -0.095 0.909 0.758-1.090 0.303 Note: TSH: Thyroid-stimulating hormone; FT3: Free triiodothyronine; FT4: Free thyroxine. 3.3 Comparison between BD and MDD groups with NSSI Among adolescents with NSSI, no significant differences were observed between the BD and MDD groups with respect to sex, age, place of residence, only-child status, family structure, somatic symptoms, positive psychotic symptoms, or hormone levels ( p > 0.05; see Table 5). Table 5. Comparison of Demographics and Hormone Levels Between Adolescents With NSSI in the BD and MDD Groups (M ± SD) Variable BD group (n=98) MDD group (n=205) χ²/t p Female, n (%) 89（90.8%） 190（92.7%） 0.317 0.574 Age, years, M(SD) 15.92±1.43 15.90±1.46 0.576 0.907 Age at onset, years, M(SD) 13.03±1.99 12.75±1.71 1.26 0.209 Urban residence, n (%) 42（42.9%） 94（45.9%） 0.241 0.624 Only-child status, n (%) 37（37.8%） 90（43.9%） 1.029 0.310 Nuclear family, n (%) 73（74.5%） 155（75.6%） 0.045 0.833 Somatic symptoms, n (%) 22（22.4%） 39（19.0%） 0.484 0.487 Positive psychotic symptoms, n (%) 49（50.0%） 87（42.4%） 1.532 0.216 Testosterone,ng/mL,M(SD) 3.204±6.993 2.805±6.296 -1.098 0.273 TSH, mIU/L, M(SD) 2.092±1.604 1.821±1.276 -0.142 0.887 FT3, pmol/L, M(SD) 4.344±0.669 4.439±0.720 0.496 0.620 FT4, pmol/L, M(SD) 11.767±1.968 11.800±1.873 1.585 0.114 Note: TSH: Thyroid-stimulating hormone; FT3: Free triiodothyronine; FT4: Free thyroxine. 4. Discussion This study examined the associations between thyroid hormones, sex hormones, and NSSI in adolescents with MDD and BD. To our knowledge, research focusing on the endocrine correlates of NSSI in these clinical populations remains limited. In the present sample, the prevalence of NSSI was 56.6% among adolescents with BD and 65.9% among those with MDD. In both diagnostic groups, female adolescents showed a significantly higher prevalence of NSSI than males. Further analyses indicated that, among female adolescents with BD, TSH and FT4 levels significantly predicted NSSI risk. These findings suggest that thyroid hormone levels, particularly TSH and FT4, may be associated with NSSI risk in female adolescents with BD. 4.1 Association between hormone levels and NSSI in patients with BD Among adolescents with BD, this study found that NSSI was significantly associated with lower levels of testosterone and FT4, suggesting that reduced T and FT4 levels may increase vulnerability to NSSI. Building on this, Sex-stratified logistic regression analyses further showed that only TSH and FT4 levels significantly predicted NSSI risk in female patients, whereas no hormone showed a significant association with NSSI in male patients. Together, these findings suggest that the influence of thyroid axis dysfunction on NSSI in BD may differ by sex. Some previous studies have reported fluctuations in testosterone levels in adolescents with BD during depressive episodes and remission, with notable sex differences in the direction of these changes (Yin et al., 2025 ; Wooderson et al., 2015 ). In the present study, group-level analyses showed that BD patients with NSSI had significantly lower testosterone levels than those without NSSI. However, in sex-stratified logistic regression analyses, testosterone did not emerge as an independent predictor of NSSI.These findings suggest that testosterone may not be directly associated with NSSI through a simple causal pathway in adolescents with BD. Consistent with previous research on emotion regulation and neural functioning, the influence of testosterone on NSSI risk may operate through indirect mechanisms. Evidence indicates that testosterone exerts neuroprotective and anti-inflammatory effects and may influence emotional regulation by modulating GABAergic and glutamatergic neurotransmission(Radaghdam et al., 2021 ).Moreover, McHenry(2014) reported that testosterone may buffer anxiety and depressive symptoms and contribute to the regulation of impulsive behavior through its effects on limbic neurotransmission and neural plasticity. Taken together, these mechanisms suggest that testosterone may indirectly influence NSSI risk under certain conditions. Nevertheless, this association appears to be complex, and further studies with larger samples and longitudinal designs are required to clarify the role of testosterone across different pathological states. In addition to sex hormones, thyroid hormones also appear to play an important role in adolescents with BD. Previous studies have suggested that reduced levels of FT4 may be associated with impaired plasticity in the prefrontal cortex and hippocampus, which could weaken stress-coping capacity and increase vulnerability to NSSI(Norman et al., 2024 ). Moreover, even mild reductions in thyroid hormone levels may be linked to disruptions in hippocampal and prefrontal functioning, potentially contributing to greater emotional instability and a higher propensity for impulsive behaviors (Zhong et al., 2019 ). Accordingly, in adolescents with BD, lower levels of FT4 and TSH may jointly represent an endocrine basis for NSSI, offering potential biological markers for identifying individuals at elevated risk. Importantly, sex differences may moderate this association. In the present study, reductions in both TSH and FT4 were significantly associated with increased NSSI risk among female adolescents with BD, whereas no significant associations between thyroid hormones and NSSI were observed in male patients. One possible explanation is that thyroid hormone–related emotion regulation pathways may function differently across sexes. Previous research has shown that estrogen can influence deiodinase activity, modulate TSH feedback sensitivity, and increase the expression of thyroid hormone–binding proteins, thereby rendering females more sensitive to fluctuations in thyroid function. In contrast, males may show noticeable emotional or behavioral changes only under conditions of more pronounced thyroid dysfunction(Poppe & Velkeniers, 2003 ; Santin & Furlanetto, 2011 ). Another possible explanation is that the relatively smaller male BD sample in the present study may have limited statistical power, potentially obscuring weaker associations. Future studies with larger, sex-stratified samples are therefore needed to further clarify the endocrine mechanisms underlying NSSI risk. 4.2 Association between hormone levels and NSSI in patients with MDD In adolescents with MDD, we observed that those engaging in NSSI exhibited significantly lower testosterone levels compared with their counterparts without NSSI. However, in subsequent sex-stratified logistic regression analyses, testosterone did not emerge as an independent predictor of NSSI. Additionally, no significant group differences or predictive effects were found for TSH, FT3, or FT4. Thus, hormone level variations in adolescents with MDD may reflect depressive state rather than NSSI risk. Previous studies have indicated that patients with depression often exhibit HPA axis dysfunction and heightened inflammatory responses. These factors may modulate the risk of NSSI and obscure the independent predictive effects of testosterone and thyroid hormones(Leistner & Menke, 2020 ). Moreover, sex hormone levels in depressed populations are influenced by many physiological and environmental factors. These include age, disease status, medication use, and psychological stress(Zarrouf et al., 2009 ). Testosterone shows considerable variability among adolescents with MDD, which limits its stability as a predictor of NSSI. In addition, hormone levels display pronounced diurnal and cyclical fluctuations. Single measurements, therefore, are insufficient to reflect long-term status. There may also be lagged effects between hormonal changes and NSSI behaviors. Cross-sectional or single-time-point designs are thus inadequate to capture their dynamic associations. 4.3 Comparison between BD and MDD groups with NSSI Among adolescents with NSSI, there were no significant differences between the BD and MDD groups in hormone levels or demographic characteristics. Taken together, these findings suggest that while TSH and FT4 independently predicted NSSI risk among female adolescents with BD, demographic variables and single-time-point hormone measures were insufficient to distinguish BD from MDD after the onset of NSSI. This pattern suggests that thyroid function may serve better as a biological marker of risk during the vulnerability stage, rather than as a marker for diagnostic differentiation after NSSI has begun. Clinically, these findings underscore the importance of considering both diagnostic subtype and sex when identifying adolescents at high risk for NSSI. In particular, assessment and ongoing monitoring of thyroid function may be especially relevant in female adolescents with BD. In summary, the present study found that FT4 and TSH levels were predictive of NSSI among female adolescents with BD. In adolescents with MDD, however, testosterone levels were significantly reduced but did not independently predict NSSI. These findings indicate that identifying adolescents at high risk for NSSI should take into account both diagnostic subtypes and sex differences. In particular, thyroid function assessment may be especially relevant in female adolescents with BD. Building on these findings, this study provides preliminary evidence linking endocrine indicators to NSSI across different adolescent mood disorder subtypes, offering potential biological clues for early identification and individualized intervention. Nevertheless, several limitations should be noted. First, the cross-sectional design and reliance on a single morning hormone measurement limited the ability to assess dynamic hormonal changes. The sample size was also relatively small. Therefore, future studies should use longitudinal designs with repeated hormone measurements to validate these findings and further explore the endocrine mechanisms underlying NSSI in various mood disorder subtypes. Ultimately, these findings may help inform individualized intervention strategies. 5. Conclusions Among female adolescents with BD, FT4 and TSH levels independently predicted the risk of NSSI, whereas testosterone was not an independent predictor in adolescents with MDD. These findings suggest that reduced thyroid function may increase vulnerability to NSSI in female adolescents with BD. Monitoring thyroid function in this group may help identify individuals at higher risk for NSSI. Larger longitudinal studies are needed to confirm these findings. Declarations Ethics approval and consent to participate This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Ethics Committee of Wuhu Fourth People’s Hospital (approval number: [2021]-KY-06). Due to the retrospective nature of the study, the ethics committee waived the requirement for informed consent. All patient data were anonymized during analysis. Consent for publication Not applicable. Availability of data and materials The datasets used and/or analysed during the current study are available from the corresponding author on reasonable request. Competing interests The authors declare that they have no competing interests. Funding This work was supported by the Shandong Provincial Medical and Health Science and Technology Program (Youth Fund) [202303090348]; the National Key Research and Development Program of China[SQ2023YFC3300058]. Authors' contributions ： HSC, ZN, and DYY designed the study. ZL, YC, ZZH, and WCC analyzed the data. ZN and DYY wrote the first draft of the manuscript. HSC, ZL, SHX, and ZK provided supervision, resources, and critical review and editing. All authors contributed to the interpretation of the data, critically revised the manuscript for important intellectual content, approved the final version to be published, and agreed to be accountable for all aspects of the work. Acknowledgements ： We would like to express our sincere gratitude to all the researchers who contributed to completion of the work and the execution of the experiment, as well as to all participants for their invaluable assistance in this study. References Bernal J. Thyroid hormone receptors in brain development and function. Nat Clin Pract Endocrinol Metab. 2007;3:249–59. https://doi.org/10.1038/ncpendmet0424 . Duval F, Mokrani MC, Erb A, Gonzalez Opera F, Calleja C, Paris V. 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Low serum free thyroxine level is correlated with lipid profile in depressive patients with suicide attempt. Psychiatry Res. 2018;266:111–5. https://doi.org/10.1016/j.psychres.2018.05.059 . Poppe K, Velkeniers B. Thyroid disorders in infertile women. Ann Endocrinol (Paris). 2003;64:45–50. Qu D, Wen X, Liu B, Zhang X, He Y, Chen D, Chen R. Non-suicidal self-injury in Chinese population: a scoping review of prevalence, method, risk factors and preventive interventions. Lancet Reg Health West Pac. 2023;37:100794. https://doi.org/10.1016/j.lanwpc.2023.100794 . Radaghdam S, Karamad V, Nourazarian A, Shademan B, Khaki-Khatibi F, Nikanfar M. Molecular mechanisms of sex hormones in the development and progression of Alzheimer's disease. Neurosci Lett. 2021;764:136221. https://doi.org/10.1016/j.neulet.2021.136221 . Rice TR, Sher L. Adolescent suicide and testosterone. Int J Adolesc Med Health. 2015;29. https://doi.org/10.1515/ijamh-2015-0058 . Santin AP, Furlanetto TW. 2011. Role of estrogen in thyroid function and growth regulation. J. Thyroid Res. 2011, 875125. https://doi.org/10.4061/2011/875125 Sher L. Testosterone and suicidal behavior in bipolar disorder. Int J Environ Res Public Health. 2023;20:2502. https://doi.org/10.3390/ijerph20032502 . Terburg D, Morgan B, van Honk J. The testosterone–cortisol ratio: a hormonal marker for proneness to social aggression. Int J Law Psychiatry. 2009;32:216–23. https://doi.org/10.1016/j.ijlp.2009.04.008 . Toloza FJK, Mao Y, Menon L, George G, Borikar M, Thumma S, Maraka S. Association of thyroid function with suicidal behavior: a systematic review and meta-analysis. Med (Kaunas). 2021;57:714. https://doi.org/10.3390/medicina57070714 . Varlinskaya EI, Vetter-O'Hagen CS, Spear LP. Puberty and gonadal hormones: role in adolescent-typical behavioral alterations. Horm Behav. 2013;64:343–9. https://doi.org/10.1016/j.yhbeh.2012.11.012 . Wei Y, Zhang C, Sun B, Lin J, Zhao Y, Chen Y, Chen J. Gender-specific differences in the association of HDL and HDL-related oxidative stress indicators with the occurrence of major depressive disorder and bipolar disorder: a large-scale study. J Affect Disord. 2025;388:119530. https://doi.org/10.1016/j.jad.2025.119530 . Wooderson SC, Gallagher P, Watson S, Young AH. An exploration of testosterone levels in patients with bipolar disorder. BJPsych Open. 2015;1:136–8. https://doi.org/10.1192/bjpo.bp.115.001008 . Xiao Q, Song X, Huang L, Hou D, Huang X. Global prevalence and characteristics of non-suicidal self-injury between 2010 and 2021 among a non-clinical sample of adolescents: a meta-analysis. Front Psychiatry. 2022;13:912441. https://doi.org/10.3389/fpsyt.2022.912441 . Yin J, Huang D, Zhang J, Zhang R, Zhong S, He J, Wu Y, Luo S, Sun J, Liu Y, Song X, Lai S, Gao Y, Chen Z, Jia Y. The differences in testosterone and stress hormones between unipolar and bipolar depression in adolescents and adults. Psychoneuroendocrinology. 2025;172:107227. https://doi.org/10.1016/j.psyneuen.2025.107227 . Zarrouf FA, Artz S, Griffith J, Sirbu C, Kommor M. Testosterone and depression: systematic review and meta-analysis. J Psychiatr Pract. 2009;15:289–305. https://doi.org/10.1097/01.pra.0000358315.88931.fc . Zhang W, Song X, Wang X, Jiang Z, Zhang Y, Cui Y. Network analysis of core factors related to non-suicidal self-injury in adolescents with mood disorders. Front Psychiatry. 2025;16:1557351. https://doi.org/10.3389/fpsyt.2025.1557351 . Zhong S, Chen G, Zhao L, Jia Y, Chen F, Qi Z, Wang Y. Correlation between intrinsic brain activity and thyroid-stimulating hormone level in unmedicated bipolar II depression. Neuroendocrinology. 2019;108:232–43. https://doi.org/10.1159/000497182 . Additional Declarations No competing interests reported. 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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-9139380","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":623053009,"identity":"371920b0-a1cb-4355-847c-dd452812042a","order_by":0,"name":"Na Zhang","email":"","orcid":"","institution":"Bengbu Medical University","correspondingAuthor":false,"prefix":"","firstName":"Na","middleName":"","lastName":"Zhang","suffix":""},{"id":623053010,"identity":"6647f6a0-0070-4417-b3ce-4dfea346ec14","order_by":1,"name":"Yuanyuan Dai","email":"","orcid":"","institution":"Shandong Mental Health Center","correspondingAuthor":false,"prefix":"","firstName":"Yuanyuan","middleName":"","lastName":"Dai","suffix":""},{"id":623053011,"identity":"bac23499-1343-41a7-9a17-4998a4292692","order_by":2,"name":"lin Zhao","email":"","orcid":"","institution":"Shandong Mental Health Center","correspondingAuthor":false,"prefix":"","firstName":"lin","middleName":"","lastName":"Zhao","suffix":""},{"id":623053012,"identity":"55b07e44-f210-475f-bb7d-07f06d60f12f","order_by":3,"name":"Chengcong Wu","email":"","orcid":"","institution":"Bengbu Medical University","correspondingAuthor":false,"prefix":"","firstName":"Chengcong","middleName":"","lastName":"Wu","suffix":""},{"id":623053013,"identity":"ee9b151d-7506-4ae0-95dd-7534252fa11b","order_by":4,"name":"Zhihai Zhou","email":"","orcid":"","institution":"Wuhu Hospital of Anding Hospital (Wuhu Fourth People's Hospital)","correspondingAuthor":false,"prefix":"","firstName":"Zhihai","middleName":"","lastName":"Zhou","suffix":""},{"id":623053014,"identity":"1ea3c1d9-076d-4b5a-b008-05e4cb7713e2","order_by":5,"name":"Cheng Yang","email":"","orcid":"","institution":"Wuhu Hospital of Anding Hospital (Wuhu Fourth People's Hospital)","correspondingAuthor":false,"prefix":"","firstName":"Cheng","middleName":"","lastName":"Yang","suffix":""},{"id":623053015,"identity":"772c4fc2-6ef6-422e-9c52-915f7022f6a4","order_by":6,"name":"Hongxian Shen","email":"","orcid":"","institution":"National Clinical Research Center for Mental Disorders, The Second Xiangya Hospital of Central South University","correspondingAuthor":false,"prefix":"","firstName":"Hongxian","middleName":"","lastName":"Shen","suffix":""},{"id":623053016,"identity":"d1d211a3-d74c-4f34-acef-a5536656276e","order_by":7,"name":"Kan Zhang","email":"","orcid":"","institution":"Anhui Medical University","correspondingAuthor":false,"prefix":"","firstName":"Kan","middleName":"","lastName":"Zhang","suffix":""},{"id":623053017,"identity":"cf3f3c01-8130-4895-9505-bf7de49db6a0","order_by":8,"name":"Shucai Huang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA4ElEQVRIiWNgGAWjYFACHgjJz9588EFChQ3xWmQke44lGzw4k0a8FhuDGzlqkg/bDhHWIN9+9pjEzx21PAZnzrBVJLAdYOBv707Aq8XgTF6aZO+Z4zySx3uP3UjgucMgcebsBvxaJHjMJHjbjvHwnTmXdiNB4hlQJBe/FvkZPGaSf4FaGG7kmBUkGBwmrIXhBo+ZNG9bDY8AUAtDQgIRWgzO5Bhby7Yd4AEFskTCgTQegn6Rbz9jePNtW509KCo//vxnI8ff3kvAYRBwGM7iIUY5CNQRq3AUjIJRMApGIgAABFdMBaPP+wMAAAAASUVORK5CYII=","orcid":"","institution":"Shandong Mental Health Center","correspondingAuthor":true,"prefix":"","firstName":"Shucai","middleName":"","lastName":"Huang","suffix":""}],"badges":[],"createdAt":"2026-03-16 14:54:42","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-9139380/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-9139380/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":107255868,"identity":"37351d9b-651f-48ed-97de-859cae5033df","added_by":"auto","created_at":"2026-04-19 12:12:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":97846,"visible":true,"origin":"","legend":"\u003cp\u003eComparison of hormone levels between adolescents with and without NSSI in the BD and major MDD groups.\u003c/p\u003e\n\u003cp\u003eBar charts illustrate differences in serum testosterone, TSH, FT3, and FT4 levels between adolescents with NSSI and those without NSSI in the BD group (left panel) and the MDD group (right panel). Data are presented as mean ± standard deviation. Statistical significance between groups is indicated as follows: *\u003cem\u003ep\u003c/em\u003e\u0026lt; 0.05, **\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.01, ***\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001; ns, not significant. BD, bipolar disorder; MDD, major depressive disorder; NSSI, non-suicidal self-injury; T, testosterone; TSH, thyroid-stimulating hormone; FT3, free triiodothyronine; FT4, free thyroxine.\u003c/p\u003e","description":"","filename":"OnlineFigure1.png","url":"https://assets-eu.researchsquare.com/files/rs-9139380/v1/a525f684507bf4a7a6c9752d.png"},{"id":107483099,"identity":"15083ed5-9daa-4768-a8df-5078711a11d4","added_by":"auto","created_at":"2026-04-22 02:26:19","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":804030,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-9139380/v1/db9dfabe-3582-4b6a-a4db-366d32609c11.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Characteristics of Self-Injury Behavior and Its Associations with Thyroid and Sex Hormones in Major Depressive Disorder and Bipolar Disorder","fulltext":[{"header":"1. Background","content":"\u003cp\u003eNon-suicidal self-injury (NSSI) is defined as the deliberate, repetitive destruction of one\u0026apos;s own body tissue without suicidal intent, such as cutting, scratching, or hitting oneself (Kruzan et al., 2025). This behavior is particularly prevalent among adolescents and has increased globally in recent years. The lifetime prevalence among adolescents is approximately 22.0%, with a recurrence rate of up to 20.3% (Xiao et al., 2022). In China, prevalence is higher, reaching 24.7%; children and adolescents show higher rates than university students(Qu et al., 2023), highlighting the need for prompt identification and intervention. NSSI is associated with an elevated risk of subsequent suicidal behaviors(Muehlenkamp et al., 2019), is especially common among individuals with mood disorders, and correlates with emotional dysregulation, impulse control difficulties, and other psychiatric conditions (He et al., 2023; McHugh et al., 2019).\u003c/p\u003e\n\u003cp\u003eNumerous studies have focused on psychosocial factors contributing to NSSI. These include childhood trauma, school bullying, and family dysfunction(Zhang et al., 2025). However, systematic research on the biological mechanisms of NSSI remains limited. Recent neurobiological and endocrine studies suggest that the endocrine system\u0026mdash;particularly the hypothalamic\u0026ndash;pituitary\u0026ndash;thyroid (HPT) axis and hypothalamic\u0026ndash;pituitary\u0026ndash;gonadal (HPG) axis, which are closely involved in emotional regulation\u0026mdash;may play a critical role in the pathogenesis of NSSI (Peng et al., 2024).\u003c/p\u003e\n\u003cp\u003eThyroid hormones, the end products of the HPT axis, regulate metabolic functions and play key roles in neuronal differentiation, synaptogenesis, and neurotransmitter metabolism(Bernal, 2007). Hormones such as thyroid-stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) have been implicated in depression and suicidal behaviors (Ma et al., 2022). Duval (2017)proposed that a blunted TSH response to thyrotropin-releasing hormone (TRH) may represent a risk factor for suicide. One study found FT4 levels were significantly lower in individuals who attempted suicide compared with non-attempters, while differences in TSH and FT3 were inconsistent(Peng et al., 2018). Other studies have reported elevated TSH levels in patients with mood disorders(Toloza et al., 2021). This suggests that thyroid function may influence self-injurious impulses through complex mechanisms. However, heterogeneity in study samples, including medication use and comorbidities, has limited the consistency of findings.\u003c/p\u003e\n\u003cp\u003ePuberty is a critical period for rapid brain remodeling. During this time, emotional regulation and impulse control are not yet fully mature. This increases the risk of impulsive behaviors such as self-injury and suicide(Johnston et al., 2017). Testosterone levels rise significantly in puberty and are considered an important factor influencing central nervous system development and behavioral changes in adolescents(Varlinskaya et al., 2013). Testosterone is the end product of the HPG axis. It is closely linked to risk-taking behaviors, impulse control, and emotional regulation(Terburg et al., 2009; Rice \u0026amp; Sher, 2015). Testosterone can cross the blood\u0026ndash;brain barrier and modulate neurotransmitter systems, including dopamine, GABA, and serotonin. These actions influence emotional and behavioral responses(McHenry et al., 2014). Some studies have reported that adolescents with depression who engage in self-injury may have higher testosterone levels than their non-injurious peers(Ma et al., 2022). However, contradictory findings have also been reported(Sher, 2023).\u003c/p\u003e\n\u003cp\u003ePrevious studies have preliminarily examined abnormalities in thyroid and sex hormones in patients with mood disorders. They have looked at how these hormones may be linked to NSSI. However, systematic investigations of the relationship between these hormones and self-injurious behaviors across mood disorder subtypes remain scarce. MDD and BD are both mood disorders. However, they differ significantly in pathophysiological mechanisms, neuroendocrine profiles, and emotional regulation strategies. Some studies suggest that individuals with BD may exhibit distinct neuroendocrine characteristics compared with those with MDD. This may influence patterns of self-injurious behavior(Wei et al., 2025). Changes in specific biological markers have also been proposed as early indicators of suicide risk. These indicators could provide clinicians with potential tools for identifying high-risk individuals(Johnston et al., 2022). Investigating the associations between these hormones and NSSI, especially differences across mood disorder subtypes, holds important theoretical and clinical significance.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.1 Participants\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis retrospective cross-sectional study included adolescent inpatients with mood disorders. These patients were hospitalized at the Fourth People\u0026rsquo;s Hospital of Wuhu, Anhui Province, China, between January 2020 and December 2021. A total of 484 patients were enrolled: 311 with MDD and 173 with BD.\u003c/p\u003e\n\u003cp\u003eThe inclusion criteria were as follows:\u003cbr\u003e\u0026nbsp;(1) a diagnosis of MDD or BD according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). The diagnosis was confirmed jointly by experienced attending psychiatrists and senior physicians;\u003cbr\u003e\u0026nbsp;(2) age between 10 and 19 years;\u003cbr\u003e\u0026nbsp;(3) complete, reliable medical records.\u003c/p\u003e\n\u003cp\u003eThe exclusion criteria were as follows:\u003cbr\u003e\u0026nbsp;(1) comorbid psychiatric disorders (e.g., schizophrenia spectrum disorders or pervasive developmental disorders) or serious neurological conditions;\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e(2) history of or current endocrine, andrological, or gynecological disorders; thyroid dysfunction; metabolic syndrome; gout; hypertension; long-term liver or kidney problems; asthma; or any other major physical illness;\u003cbr\u003e\u0026nbsp;(3) pregnancy or lactation at the time of hospitalization;\u003cbr\u003e\u0026nbsp;(4) recent (within three months) use of medications that could affect hormones, such as hormone medicines, oral contraceptives, or any kind of corticosteroids;\u003cbr\u003e\u0026nbsp;(5) substance or alcohol abuse or dependence, confirmed by urine screening;\u003cbr\u003e\u0026nbsp;(6) evident intellectual disability.\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Ethics Committee of Wuhu Fourth People\u0026rsquo;s Hospital (approval number: [2021]-KY-06). Due to the retrospective nature of the study, the ethics committee waived the requirement for informed consent. All patient data were anonymized during analysis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.2 Clinical data collection\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAll demographic and clinical data were obtained from the electronic medical record system and standardized assessment forms of Wuhu Fourth People\u0026rsquo;s Hospital. Two trained researchers independently extracted and entered the data, which were cross-checked by a third researcher for accuracy and completeness. Demographic variables included sex, age, place of residence, only-child status, and family structure. Clinical variables included somatic symptoms and positive psychotic symptoms. NSSI was assessed independently by two psychiatrists using medical history, examination records, and psychiatric evaluations, with consensus required for a DSM-5 diagnosis.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.3 Hormone assays\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eSerum levels of thyroid and sex hormones were measured using fasting venous blood samples collected between 6:30 and 7:00 a.m. on the morning following hospital admission. All samples were delivered to the laboratory within 30 minutes of collection and analyzed immediately. Sex hormone levels were measured using the Atellica Solution analyzer (Siemens Healthineers, Germany) with a chemiluminescent immunoassay. Thyroid function indices were assessed with the Roche Cobas e601 electrochemiluminescence immunoassay system (Shanghai Lanwei Clinical Testing Co., Ltd.). All assays were performed by laboratory physicians who had completed standardized training and followed established procedures.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e2.4 Statistical analysis\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStatistical analyses were performed using IBM SPSS Statistics version 26.0. Demographic characteristics and hormone levels were compared within each diagnostic group using independent-samples t tests for continuous variables and chi-square tests for categorical variables. To examine the predictive effects of hormone levels on NSSI risk while controlling for sex-related confounding, sex-stratified binary logistic regression analyses were conducted within each group, with hormone variables entered using the enter method. All statistical tests were two-tailed, and a p \u0026lt; 0.05 was considered statistically significant.\u003c/p\u003e"},{"header":"3. Results","content":"\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.1 Statistical analyses in patients with BD\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.1.1 Demographic characteristics of patients with BD\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 1 presents the demographic characteristics of adolescents with BD with and without NSSI. Compared with those without NSSI, adolescents with NSSI were more likely to be female (\u003cem\u003e\u0026chi;\u0026sup2;\u0026nbsp;\u003c/em\u003e= 21.546，\u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u0026lt; 0 .001)、had an earlier age at onset (\u003cem\u003et =\u0026nbsp;\u003c/em\u003e2.86，\u003cem\u003ep =\u0026nbsp;\u003c/em\u003e0.005) , and exhibited more positive psychotic symptoms (\u003cem\u003e\u0026chi;\u0026sup2;\u0026nbsp;\u003c/em\u003e= 4.067，\u003cem\u003ep =\u0026nbsp;\u003c/em\u003e0.044). The proportion of only children was also lower in the NSSI group (\u003cem\u003e\u0026chi;\u0026sup2;\u0026nbsp;\u003c/em\u003e=5.700，\u003cem\u003ep =\u0026nbsp;\u003c/em\u003e0.017) . No significant differences were found in age, place of residence, family structure, or somatic symptoms (\u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"623\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 623px;\"\u003e\n \u003cp\u003eTable 1. Comparison of demographic characteristics between adolescents with and without NSSI in the BD group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003eNSSI group (n=98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003eNon-NSSI group \u0026nbsp;(n=75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u0026sup2;/t\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eFemale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e89（65.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e46（34.1%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e21.546\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e0.001\u003csup\u003e***\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eAge, years, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e15.92\u0026plusmn;1.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e16.03\u0026plusmn;1.34\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e1.03\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e0.612\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eAge at onset, years, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e13.97\u0026plusmn;1.80\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e13.03\u0026plusmn;1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e2.86\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e0.005\u003csup\u003e**\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eUrban residence, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e42（42.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e30（40.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.143\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e0.706\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eOnly-child status, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e37（56.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e42（53.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e5.700\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e0.017\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eNuclear family, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e73（74.5%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e59（78.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.410\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e0.522\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eSomatic symptoms, n (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e22（22.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e16（21.3%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.031\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e0.861\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003ePositive psychotic symptoms, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e49（50.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e26（34.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e4.067\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 63px;\"\u003e\n \u003cp\u003e0.044\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.1.2 Relationship between testosterone, thyroid hormones, and non-suicidal self-injury in adolescents with BD\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Figure 1, compared with adolescents with BD without NSSI, those with NSSI had significantly lower levels of Testosterone\u0026nbsp;(\u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001) and FT4 (\u003cem\u003ep\u003c/em\u003e = 0.03). No significant differences were observed in FT3 (\u003cem\u003ep\u003c/em\u003e = 0.09) or TSH (\u003cem\u003ep\u003c/em\u003e = 0.06) between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.1.3 Binary logistic regression analysis of hormone levels and NSSI in patients with BD\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo further clarify the role of hormone levels in predicting the risk of NSSI, binary logistic regression analyses were conducted in patients with BD. Previous analyses revealed a significant difference in sex distribution between the NSSI and non-NSSI groups. Considering the potential confounding effect of sex on hormonal associations, sex-stratified analyses were therefore performed.\u003c/p\u003e\n\u003cp\u003eAs shown in Table 2, TSH was a significant negative predictor of NSSI risk in female patients (\u003cem\u003eOR\u003c/em\u003e = 0.777, \u003cem\u003ep\u003c/em\u003e = 0.024). FT4 also showed a significant negative association with NSSI risk (\u003cem\u003eOR\u003c/em\u003e = 0.784, \u003cem\u003ep\u003c/em\u003e = 0.028), indicating that lower levels of TSH and FT4 were associated with an increased risk of NSSI. In contrast, neither TSH nor FT4 significantly predicted NSSI risk in male patients (\u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05). In addition, testosterone and FT3 were not significant predictors of NSSI in either sex (\u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05).\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"726\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" style=\"width: 726px;\"\u003e\n \u003cp\u003eTable 2. Sex-stratified binary logistic regression analyses of factors associated with NSSI in patients with BD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 167px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 256px;\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 302px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003eTestosterone,ng/mL,M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.118\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e1.125\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.997-1.269\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.586\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.796\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.805-4.008\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.153\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003eTSH, mIU/L, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e-0.102\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.903\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.523-1.558\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.714\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e-0.252\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.777\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.624-0.968\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.024\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003eFT3, pmol/L, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e1.024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.440-2.384\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.956\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e-0.135\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.874\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.512-1.491\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.621\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003eFT4, pmol/L, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e-0.037\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.964\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.753-1.233\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.770\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e-0.243\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.784\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.632-0.974\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.028\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eNote: TSH: Thyroid-stimulating hormone;\u0026nbsp;FT3: Free triiodothyronine;\u0026nbsp;FT4: Free thyroxine.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.2 Statistical analyses in patients with MDD\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.2.1 Demographic characteristics of patients with MDD\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTable 3 presents the demographic characteristics of adolescents with MDD with and without NSSI.The NSSI group showed significantly higher proportions of females (\u003cem\u003e\u0026chi;\u003c/em\u003e\u0026sup2; = 44.412, \u003cem\u003ep\u003c/em\u003e \u0026lt; 0.001), only-child status (\u003cem\u003e\u0026chi;\u003c/em\u003e\u0026sup2; = 4.514, \u003cem\u003ep\u003c/em\u003e = 0.034), and positive psychotic symptoms (\u003cem\u003e\u0026chi;\u003c/em\u003e\u0026sup2; = 5.166, \u003cem\u003ep\u003c/em\u003e = 0.023). In contrast, age (\u003cem\u003et\u003c/em\u003e = 3.539, \u003cem\u003ep\u003c/em\u003e = 0.047) and age at onset (\u003cem\u003et\u003c/em\u003e = 5.84, \u003cem\u003ep\u003c/em\u003e = 0.001) were significantly lower in the NSSI group. No significant differences were found in place of residence, family structure, or somatic symptoms (\u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05).\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"637\"\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 637px;\"\u003e\n \u003cp\u003eTable 3. Comparison of demographic characteristics between adolescents with and without NSSI in the MDD group\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003eNSSI group (n=98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003eNon-NSSI group \u0026nbsp;(n=75)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u0026sup2;/t\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eFemale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e190（92.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e66（62.3%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e44.412\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e0.001\u003csup\u003e***\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eAge, years, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e15.90\u0026plusmn;1.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e16.24\u0026plusmn;13.3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e3.539\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e0.047\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eAge at onset, years, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e12.75\u0026plusmn;1.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e14.01\u0026plusmn;1.96\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e5.84\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e\u0026lt;0.001\u003csup\u003e***\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eUrban residence, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e94（45.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e45（42.5%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.327\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e0.567\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eOnly-child status, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e90（43.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e60（56.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e4.514\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e0.034\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eNuclear family, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e155（75.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e90（84.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e3.612\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e0.057\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003eSomatic symptoms, n (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e39（19.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e24（22.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e0.566\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e0.452\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 207px;\"\u003e\n \u003cp\u003ePositive psychotic symptoms, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 129px;\"\u003e\n \u003cp\u003e87（42.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 166px;\"\u003e\n \u003cp\u003e31（29.2%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 58px;\"\u003e\n \u003cp\u003e5.166\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 77px;\"\u003e\n \u003cp\u003e0.023\u003csup\u003e*\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.2.2 Relationship between testosterone, thyroid hormones, and non-suicidal self-injury in adolescents with MDD\u0026nbsp;\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAs shown in Figure1,\u0026nbsp;compared with adolescents with MDD without NSSI, those with NSSI had significantly lower testosterone levels than those without NSSI (p \u0026lt; 0.001). No significant differences were observed in TSH (p = 0.56), FT3 (p = 0.92), and FT4 (p = 0.11)between the two groups.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.2.3 Binary logistic regression analysis of hormone levels and NSSI in patients with MDD\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eTo further examine the predictive effects of hormone levels on the risk of NSSI while controlling for potential sex-related confounding, gender-stratified binary logistic regression analyses were conducted in patients with MDD. As shown in Table 4, none of the hormone variables significantly predicted NSSI risk in either male or female patients (\u003cem\u003ep\u0026nbsp;\u003c/em\u003e\u0026gt; 0.05).\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"726\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"9\" style=\"width: 726px;\"\u003e\n \u003cp\u003eTable 4. Sex-stratified binary logistic regression analyses of factors associated with NSSI in patients with BD\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd rowspan=\"2\" style=\"width: 167px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 256px;\"\u003e\n \u003cp\u003emale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd colspan=\"4\" style=\"width: 302px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003eB\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003eOR\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e95% CI\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003eTestosterone,ng/mL,M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e1.014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.940-1.093\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.723\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e-0.061\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.941\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.562-1.576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.817\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003eTSH, mIU/L, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e-0.110\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.330\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.102-1.063\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.063\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.209\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.232\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.946-1.605\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.121\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003eFT3, pmol/L, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e-0.325\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e0.723\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.222-2.353\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.590\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.240\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e1.271\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.821-1.966\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.282\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 167px;\"\u003e\n \u003cp\u003eFT4, pmol/L, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 57px;\"\u003e\n \u003cp\u003e0.088\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 48px;\"\u003e\n \u003cp\u003e1.092\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 84px;\"\u003e\n \u003cp\u003e0.699-1.708\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 67px;\"\u003e\n \u003cp\u003e0.699\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e-0.095\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 76px;\"\u003e\n \u003cp\u003e0.909\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 85px;\"\u003e\n \u003cp\u003e0.758-1.090\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 66px;\"\u003e\n \u003cp\u003e0.303\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eNote: TSH: Thyroid-stimulating hormone;\u0026nbsp;FT3: Free triiodothyronine;\u0026nbsp;FT4: Free thyroxine.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003e\u003cem\u003e3.3 Comparison between BD and MDD groups with NSSI\u003c/em\u003e\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAmong adolescents with NSSI, no significant differences were observed between the BD and MDD groups with respect to sex, age, place of residence, only-child status, family structure, somatic symptoms, positive psychotic symptoms, or hormone levels (\u003cem\u003ep\u003c/em\u003e \u0026gt; 0.05; see Table 5).\u003c/p\u003e\n \u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" align=\"\" width=\"629\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\" style=\"width: 629px;\"\u003e\n \u003cp\u003eTable 5. Comparison of Demographics and Hormone Levels Between Adolescents With NSSI in the BD and MDD Groups (M\u0026nbsp;\u0026plusmn;\u0026nbsp;SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003eBD group (n=98)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003eMDD group (n=205)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e\u003cem\u003e\u0026chi;\u0026sup2;/t\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e\u003cem\u003ep\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eFemale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e89（90.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e190（92.7%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.317\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.574\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eAge, years, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e15.92\u0026plusmn;1.43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e15.90\u0026plusmn;1.46\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.576\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.907\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eAge at onset, years, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e13.03\u0026plusmn;1.99\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e12.75\u0026plusmn;1.71\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e1.26\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.209\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eUrban residence, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e42（42.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e94（45.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.241\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.624\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eOnly-child status, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e37（37.8%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e90（43.9%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e1.029\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.310\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eNuclear family, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e73（74.5%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e155（75.6%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.833\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eSomatic symptoms, n (%)\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e22（22.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e39（19.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.484\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.487\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003ePositive psychotic symptoms, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e49（50.0%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e87（42.4%）\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e1.532\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.216\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eTestosterone,ng/mL,M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e3.204\u0026plusmn;6.993\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e2.805\u0026plusmn;6.296\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e-1.098\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.273\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eTSH, mIU/L, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e2.092\u0026plusmn;1.604\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e1.821\u0026plusmn;1.276\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e-0.142\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.887\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eFT3, pmol/L, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e4.344\u0026plusmn;0.669\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e4.439\u0026plusmn;0.720\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e0.496\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.620\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd style=\"width: 214px;\"\u003e\n \u003cp\u003eFT4, pmol/L, M(SD)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 121px;\"\u003e\n \u003cp\u003e11.767\u0026plusmn;1.968\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 150px;\"\u003e\n \u003cp\u003e11.800\u0026plusmn;1.873\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 72px;\"\u003e\n \u003cp\u003e1.585\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd style=\"width: 73px;\"\u003e\n \u003cp\u003e0.114\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eNote: TSH: Thyroid-stimulating hormone; FT3: Free triiodothyronine; FT4: Free thyroxine.\u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis study examined the associations between thyroid hormones, sex hormones, and NSSI in adolescents with MDD and BD. To our knowledge, research focusing on the endocrine correlates of NSSI in these clinical populations remains limited. In the present sample, the prevalence of NSSI was 56.6% among adolescents with BD and 65.9% among those with MDD. In both diagnostic groups, female adolescents showed a significantly higher prevalence of NSSI than males. Further analyses indicated that, among female adolescents with BD, TSH and FT4 levels significantly predicted NSSI risk. These findings suggest that thyroid hormone levels, particularly TSH and FT4, may be associated with NSSI risk in female adolescents with BD.\u003c/p\u003e \u003cdiv id=\"Sec18\" class=\"Section2\"\u003e \u003ch2\u003e4.1 Association between hormone levels and NSSI in patients with BD\u003c/h2\u003e \u003cp\u003eAmong adolescents with BD, this study found that NSSI was significantly associated with lower levels of testosterone and FT4, suggesting that reduced T and FT4 levels may increase vulnerability to NSSI. Building on this, Sex-stratified logistic regression analyses further showed that only TSH and FT4 levels significantly predicted NSSI risk in female patients, whereas no hormone showed a significant association with NSSI in male patients. Together, these findings suggest that the influence of thyroid axis dysfunction on NSSI in BD may differ by sex.\u003c/p\u003e \u003cp\u003eSome previous studies have reported fluctuations in testosterone levels in adolescents with BD during depressive episodes and remission, with notable sex differences in the direction of these changes (Yin et al., \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e2025\u003c/span\u003e; Wooderson et al., \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e2015\u003c/span\u003e). In the present study, group-level analyses showed that BD patients with NSSI had significantly lower testosterone levels than those without NSSI. However, in sex-stratified logistic regression analyses, testosterone did not emerge as an independent predictor of NSSI.These findings suggest that testosterone may not be directly associated with NSSI through a simple causal pathway in adolescents with BD. Consistent with previous research on emotion regulation and neural functioning, the influence of testosterone on NSSI risk may operate through indirect mechanisms. Evidence indicates that testosterone exerts neuroprotective and anti-inflammatory effects and may influence emotional regulation by modulating GABAergic and glutamatergic neurotransmission(Radaghdam et al., \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e2021\u003c/span\u003e).Moreover, McHenry(2014) reported that testosterone may buffer anxiety and depressive symptoms and contribute to the regulation of impulsive behavior through its effects on limbic neurotransmission and neural plasticity. Taken together, these mechanisms suggest that testosterone may indirectly influence NSSI risk under certain conditions. Nevertheless, this association appears to be complex, and further studies with larger samples and longitudinal designs are required to clarify the role of testosterone across different pathological states.\u003c/p\u003e \u003cp\u003eIn addition to sex hormones, thyroid hormones also appear to play an important role in adolescents with BD. Previous studies have suggested that reduced levels of FT4 may be associated with impaired plasticity in the prefrontal cortex and hippocampus, which could weaken stress-coping capacity and increase vulnerability to NSSI(Norman et al., \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e2024\u003c/span\u003e). Moreover, even mild reductions in thyroid hormone levels may be linked to disruptions in hippocampal and prefrontal functioning, potentially contributing to greater emotional instability and a higher propensity for impulsive behaviors (Zhong et al., \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e2019\u003c/span\u003e). Accordingly, in adolescents with BD, lower levels of FT4 and TSH may jointly represent an endocrine basis for NSSI, offering potential biological markers for identifying individuals at elevated risk. Importantly, sex differences may moderate this association. In the present study, reductions in both TSH and FT4 were significantly associated with increased NSSI risk among female adolescents with BD, whereas no significant associations between thyroid hormones and NSSI were observed in male patients. One possible explanation is that thyroid hormone\u0026ndash;related emotion regulation pathways may function differently across sexes. Previous research has shown that estrogen can influence deiodinase activity, modulate TSH feedback sensitivity, and increase the expression of thyroid hormone\u0026ndash;binding proteins, thereby rendering females more sensitive to fluctuations in thyroid function. In contrast, males may show noticeable emotional or behavioral changes only under conditions of more pronounced thyroid dysfunction(Poppe \u0026amp; Velkeniers, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e2003\u003c/span\u003e; Santin \u0026amp; Furlanetto, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e2011\u003c/span\u003e). Another possible explanation is that the relatively smaller male BD sample in the present study may have limited statistical power, potentially obscuring weaker associations. Future studies with larger, sex-stratified samples are therefore needed to further clarify the endocrine mechanisms underlying NSSI risk.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section2\"\u003e \u003ch2\u003e4.2 Association between hormone levels and NSSI in patients with MDD\u003c/h2\u003e \u003cp\u003eIn adolescents with MDD, we observed that those engaging in NSSI exhibited significantly lower testosterone levels compared with their counterparts without NSSI. However, in subsequent sex-stratified logistic regression analyses, testosterone did not emerge as an independent predictor of NSSI. Additionally, no significant group differences or predictive effects were found for TSH, FT3, or FT4. Thus, hormone level variations in adolescents with MDD may reflect depressive state rather than NSSI risk.\u003c/p\u003e \u003cp\u003ePrevious studies have indicated that patients with depression often exhibit HPA axis dysfunction and heightened inflammatory responses. These factors may modulate the risk of NSSI and obscure the independent predictive effects of testosterone and thyroid hormones(Leistner \u0026amp; Menke, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e2020\u003c/span\u003e). Moreover, sex hormone levels in depressed populations are influenced by many physiological and environmental factors. These include age, disease status, medication use, and psychological stress(Zarrouf et al., \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e2009\u003c/span\u003e). Testosterone shows considerable variability among adolescents with MDD, which limits its stability as a predictor of NSSI. In addition, hormone levels display pronounced diurnal and cyclical fluctuations. Single measurements, therefore, are insufficient to reflect long-term status. There may also be lagged effects between hormonal changes and NSSI behaviors. Cross-sectional or single-time-point designs are thus inadequate to capture their dynamic associations.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section2\"\u003e \u003ch2\u003e4.3 Comparison between BD and MDD groups with NSSI\u003c/h2\u003e \u003cp\u003eAmong adolescents with NSSI, there were no significant differences between the BD and MDD groups in hormone levels or demographic characteristics. Taken together, these findings suggest that while TSH and FT4 independently predicted NSSI risk among female adolescents with BD, demographic variables and single-time-point hormone measures were insufficient to distinguish BD from MDD after the onset of NSSI. This pattern suggests that thyroid function may serve better as a biological marker of risk during the vulnerability stage, rather than as a marker for diagnostic differentiation after NSSI has begun. Clinically, these findings underscore the importance of considering both diagnostic subtype and sex when identifying adolescents at high risk for NSSI. In particular, assessment and ongoing monitoring of thyroid function may be especially relevant in female adolescents with BD.\u003c/p\u003e \u003cp\u003eIn summary, the present study found that FT4 and TSH levels were predictive of NSSI among female adolescents with BD. In adolescents with MDD, however, testosterone levels were significantly reduced but did not independently predict NSSI. These findings indicate that identifying adolescents at high risk for NSSI should take into account both diagnostic subtypes and sex differences. In particular, thyroid function assessment may be especially relevant in female adolescents with BD. Building on these findings, this study provides preliminary evidence linking endocrine indicators to NSSI across different adolescent mood disorder subtypes, offering potential biological clues for early identification and individualized intervention. Nevertheless, several limitations should be noted. First, the cross-sectional design and reliance on a single morning hormone measurement limited the ability to assess dynamic hormonal changes. The sample size was also relatively small. Therefore, future studies should use longitudinal designs with repeated hormone measurements to validate these findings and further explore the endocrine mechanisms underlying NSSI in various mood disorder subtypes. Ultimately, these findings may help inform individualized intervention strategies.\u003c/p\u003e \u003c/div\u003e"},{"header":"5. Conclusions","content":"\u003cp\u003eAmong female adolescents with BD, FT4 and TSH levels independently predicted the risk of NSSI, whereas testosterone was not an independent predictor in adolescents with MDD. These findings suggest that reduced thyroid function may increase vulnerability to NSSI in female adolescents with BD. Monitoring thyroid function in this group may help identify individuals at higher risk for NSSI. Larger longitudinal studies are needed to confirm these findings.\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 conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Ethics Committee of Wuhu Fourth People\u0026rsquo;s Hospital (approval number: [2021]-KY-06). Due to the retrospective nature of the study, the ethics committee waived the requirement for informed consent. All patient data were anonymized during analysis.\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 used and/or analysed during the current study 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 work was supported by the Shandong Provincial Medical and Health Science and Technology Program (Youth Fund) [202303090348]; the National Key Research and Development Program of China[SQ2023YFC3300058].\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eHSC, ZN, and DYY designed the study. ZL, YC, ZZH, and WCC analyzed the data. ZN and DYY wrote the first draft of the manuscript. HSC, ZL, SHX, and ZK provided supervision, resources, and critical review and editing. All authors contributed to the interpretation of the data, critically revised the manuscript for important intellectual content, approved the final version to be published, and agreed to be accountable for all aspects of the work.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003cstrong\u003e：\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe would like to express our sincere gratitude to all the researchers who contributed to completion of the work and the execution of the experiment, as well as to all participants for their invaluable assistance in this study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eBernal J. Thyroid hormone receptors in brain development and function. 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Neuroendocrinology. 2019;108:232\u0026ndash;43. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://doi.org/10.1159/000497182\u003c/span\u003e\u003cspan address=\"10.1159/000497182\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"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":"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":"Major depressive disorder, Bipolar disorder, Testosterone, Thyroid hormones, Non-suicidal self-injury","lastPublishedDoi":"10.21203/rs.3.rs-9139380/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-9139380/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eNon-suicidal self-injury (NSSI) is prevalent among adolescents with mood disorders. However, differences in NSSI characteristics between major depressive disorder (MDD) and bipolar disorder (BD), and their endocrine correlates, remain insufficiently explored. This study examined NSSI characteristics and their associations with thyroid and sex hormones in adolescents with MDD and BD.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eThis retrospective study included 484 adolescents diagnosed with MDD or BD. Demographic characteristics and hormone levels were compared within each diagnostic group. Sex-stratified binary logistic regression analyses were conducted to identify factors associated with NSSI. Additionally, adolescents with NSSI were compared between the MDD and BD groups.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eNSSI prevalence was 56.6% in BD and 65.9% in MDD. Females were significantly more frequent than males in both groups. In BD, adolescents with NSSI had lower testosterone and free thyroxine (FT4) than those without NSSI. Sex-stratified logistic regression showed that, in females, thyroid-stimulating hormone (TSH) and FT4independently predicted NSSI. There were no significant predictors in males. In MDD, adolescents with NSSI had lower testosterone, but no hormones significantly predicted NSSI by sex. Among adolescents with NSSI, there were no demographic or hormonal differences between the BD and MDD groups.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eThyroid hormones predicted NSSI mainly in females with BD. After NSSI, hormone levels and demographic characteristics did not differ significantly between BD and MDD patients, suggesting hormones levels have limited value for distinguishing diagnostic subtypes. Identification of high-risk individuals should consider both diagnoses and sex, with close attention to thyroid function in females with BD.\u003c/p\u003e","manuscriptTitle":"Characteristics of Self-Injury Behavior and Its Associations with Thyroid and Sex Hormones in Major Depressive Disorder and Bipolar Disorder","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-04-19 12:12:33","doi":"10.21203/rs.3.rs-9139380/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-17T05:00:26+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-16T16:56:23+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-11T20:37:05+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"189301571402169006911462408824408496515","date":"2026-04-23T14:01:00+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"69077961744115180736394392701732225336","date":"2026-04-22T15:01:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"255288613168052937979225959080729081944","date":"2026-04-20T15:48:17+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"152244950304822013288806958884114033806","date":"2026-04-20T15:20:36+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-04-09T14:05:41+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2026-03-26T18:09:44+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-03-24T06:42:18+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-03-24T06:41:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Psychiatry","date":"2026-03-16T14:44:54+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":"582079b9-b1e9-4c2b-98bd-20375157939c","owner":[],"postedDate":"April 19th, 2026","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-17T05:00:26+00:00","index":50,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-16T16:56:23+00:00","index":49,"fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-05-11T20:37:05+00:00","index":48,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2026-04-19T12:12:34+00:00","versionOfRecord":[],"versionCreatedAt":"2026-04-19 12:12:33","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-9139380","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-9139380","identity":"rs-9139380","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}