Jianke Wang, Mingxiao Li, Ze Zhang, Yu Duan, Ziyi Zhang, Hanlin Liu, Ke Yang, Jiang Liu
{"title":"精神障碍与三叉神经痛的关系:一项队列研究和孟德尔随机化分析。","authors":"Jianke Wang, Mingxiao Li, Ze Zhang, Yu Duan, Ziyi Zhang, Hanlin Liu, Ke Yang, Jiang Liu","doi":"10.1186/s10194-025-02026-y","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Clinical observational evidence suggests a close association between Trigeminal Neuralgia (TN) and Mental disorders (MDs). However, the causal relationship between the two remains unclear. This study aims to observe and analyse the associations between depression, anxiety, insomnia, and TN through clinical research. It also employs Mendelian randomization (MR) analysis to verify the potential genetic correlation between TN and various mental disorders. offering new insights for the diagnosis, prevention, and intervention strategies for TN.</p><p><strong>Methods: </strong>In the cohort study section, clinical data were collected from 154 patients with TN, all of whom were excluded from preoperative use of psychotropic drugs such as carbamazepine. The PHQ-9, GAD-7, and ISI scales were used to assess preoperative symptoms of depression, anxiety, and insomnia. Multivariable linear regression models were used to identify factors associated with questionnaire scores, with model performance evaluated by adjusted R², AIC, BIC, and p-values. Patients with significant positive symptoms preoperatively were followed up one-year after surgery, and non-parametric tests were employed to examine changes in mental disorder symptoms after pain relief. In MR analysis section, the main MR analysis methods include Inverse Variance Weighted (IVW), MR Egger, Weighted Median, Simple Mode, and Weighted Mode. The Benjamini-Hochberg (BH) method was used to adjust the p -values and control the false discovery rate (FDR). Subsequent sensitivity analyses involved Cochran's Q test, MR-Egger regression intercept, MR-pleiotropy residual sum and outlier test (MR-PRESSO).</p><p><strong>Results: </strong>Multiple linear regression analyses revealed that longer disease duration and greater involvement of trigeminal branches were consistently associated with higher PHQ-9, GAD-7, and ISI scores, while demographic factors and baseline BNI scores showed no significant predictive value. MR analysis indicated that autism (OR = 0.697, 95% CI [0.494-0.982], P = 0.039), schizophrenia (OR = 0.910, 95% CI [0.831-0.997], P = 0.042), and ADHD combined with OCD (OR = 0.175, 95% CI [0.044-0.693], P = 0.013) reduced the risk of TN. Conversely, bipolar disorder (OR = 1.249, 95% CI [1.016-1.535], P = 0.034), depression (OR = 2.375, 95% CI [1.043-5.409], P = 0.039), anxiety (OR = 1.174, 95% CI [1.008-1.368], P = 0.039), and insomnia (OR = 2.036, 95% CI [1.074-3.861], P = 0.029)increased the risk of TN. TN also elevated the risk of anxiety (OR = 1.43, 95% CI [1.04-1.96], P = 0.034), depression (OR = 1.00305, 95% CI [1.00036-1.00549], P = 0.013), and insomnia (OR = 1.00918, 95% CI [1.00236-1.01605], P = 0.008).</p><p><strong>Conclusions: </strong>Longer disease duration and broader trigeminal nerve involvement were independently associated with increased severity of depressive, anxiety, and insomnia symptoms, highlighting the importance of early clinical intervention in patients with TN. And results of MR analysis provide evidence supporting a causal relationship between MDs and TN. In contrast to the traditional view that pain causes mood changes such as anxiety and depression, a variety of MDs such as anxiety, depression, and insomnia also alter the risk of developing TN.</p>","PeriodicalId":16013,"journal":{"name":"Journal of Headache and Pain","volume":"26 1","pages":"74"},"PeriodicalIF":7.3000,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992777/pdf/","citationCount":"0","resultStr":"{\"title\":\"Association between mental disorders and trigeminal neuralgia: a cohort study and Mendelian randomization analysis.\",\"authors\":\"Jianke Wang, Mingxiao Li, Ze Zhang, Yu Duan, Ziyi Zhang, Hanlin Liu, Ke Yang, Jiang Liu\",\"doi\":\"10.1186/s10194-025-02026-y\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Clinical observational evidence suggests a close association between Trigeminal Neuralgia (TN) and Mental disorders (MDs). However, the causal relationship between the two remains unclear. This study aims to observe and analyse the associations between depression, anxiety, insomnia, and TN through clinical research. It also employs Mendelian randomization (MR) analysis to verify the potential genetic correlation between TN and various mental disorders. offering new insights for the diagnosis, prevention, and intervention strategies for TN.</p><p><strong>Methods: </strong>In the cohort study section, clinical data were collected from 154 patients with TN, all of whom were excluded from preoperative use of psychotropic drugs such as carbamazepine. The PHQ-9, GAD-7, and ISI scales were used to assess preoperative symptoms of depression, anxiety, and insomnia. Multivariable linear regression models were used to identify factors associated with questionnaire scores, with model performance evaluated by adjusted R², AIC, BIC, and p-values. Patients with significant positive symptoms preoperatively were followed up one-year after surgery, and non-parametric tests were employed to examine changes in mental disorder symptoms after pain relief. In MR analysis section, the main MR analysis methods include Inverse Variance Weighted (IVW), MR Egger, Weighted Median, Simple Mode, and Weighted Mode. The Benjamini-Hochberg (BH) method was used to adjust the p -values and control the false discovery rate (FDR). Subsequent sensitivity analyses involved Cochran's Q test, MR-Egger regression intercept, MR-pleiotropy residual sum and outlier test (MR-PRESSO).</p><p><strong>Results: </strong>Multiple linear regression analyses revealed that longer disease duration and greater involvement of trigeminal branches were consistently associated with higher PHQ-9, GAD-7, and ISI scores, while demographic factors and baseline BNI scores showed no significant predictive value. MR analysis indicated that autism (OR = 0.697, 95% CI [0.494-0.982], P = 0.039), schizophrenia (OR = 0.910, 95% CI [0.831-0.997], P = 0.042), and ADHD combined with OCD (OR = 0.175, 95% CI [0.044-0.693], P = 0.013) reduced the risk of TN. Conversely, bipolar disorder (OR = 1.249, 95% CI [1.016-1.535], P = 0.034), depression (OR = 2.375, 95% CI [1.043-5.409], P = 0.039), anxiety (OR = 1.174, 95% CI [1.008-1.368], P = 0.039), and insomnia (OR = 2.036, 95% CI [1.074-3.861], P = 0.029)increased the risk of TN. TN also elevated the risk of anxiety (OR = 1.43, 95% CI [1.04-1.96], P = 0.034), depression (OR = 1.00305, 95% CI [1.00036-1.00549], P = 0.013), and insomnia (OR = 1.00918, 95% CI [1.00236-1.01605], P = 0.008).</p><p><strong>Conclusions: </strong>Longer disease duration and broader trigeminal nerve involvement were independently associated with increased severity of depressive, anxiety, and insomnia symptoms, highlighting the importance of early clinical intervention in patients with TN. And results of MR analysis provide evidence supporting a causal relationship between MDs and TN. In contrast to the traditional view that pain causes mood changes such as anxiety and depression, a variety of MDs such as anxiety, depression, and insomnia also alter the risk of developing TN.</p>\",\"PeriodicalId\":16013,\"journal\":{\"name\":\"Journal of Headache and Pain\",\"volume\":\"26 1\",\"pages\":\"74\"},\"PeriodicalIF\":7.3000,\"publicationDate\":\"2025-04-11\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11992777/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Headache and Pain\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1186/s10194-025-02026-y\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Headache and Pain","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s10194-025-02026-y","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
引用次数: 0
摘要
背景:临床观察证据提示三叉神经痛(TN)与精神障碍(MDs)密切相关。然而,两者之间的因果关系尚不清楚。本研究旨在通过临床研究,观察和分析抑郁、焦虑、失眠与TN之间的关系。并采用孟德尔随机化(Mendelian randomization, MR)分析来验证TN与各种精神障碍之间潜在的遗传相关性。方法:在队列研究部分,收集154例TN患者的临床资料,所有患者术前均不使用卡马西平等精神药物。采用PHQ-9、GAD-7和ISI量表评估术前抑郁、焦虑和失眠症状。采用多变量线性回归模型来确定与问卷得分相关的因素,并通过调整后的R²、AIC、BIC和p值来评估模型的性能。术前有明显阳性症状的患者术后随访1年,采用非参数检验检查疼痛缓解后精神障碍症状的变化。在MR分析部分,主要的MR分析方法有逆方差加权(IVW)、MR Egger、加权中位数、简单模态和加权模态。采用Benjamini-Hochberg (BH)方法调整p值,控制错误发现率(FDR)。随后的敏感性分析包括科克伦Q检验、MR-Egger回归截距、mr -多效性残差和和异常值检验(MR-PRESSO)。结果:多元线性回归分析显示,病程越长、三叉分支受累量越大,PHQ-9、GAD-7和ISI评分越高,而人口统计学因素和基线BNI评分没有显著的预测价值。先生分析表明自闭症(OR = 0.697, 95% CI [0.494 - -0.982], P = 0.039),精神分裂症(OR = 0.910, 95% CI [0.831 - -0.997], P = 0.042),和多动症加上强迫症(OR = 0.175, 95% CI [0.044 - -0.693], P = 0.013)减少TN的风险。相反地,双相情感障碍(OR = 1.249, 95% CI [1.016 - -1.535], P = 0.034),抑郁(OR = 2.375, 95% CI [1.043 - -5.409], P = 0.039),焦虑(OR = 1.174, 95% CI [1.008 - -1.368], P = 0.039),和失眠(OR = 2.036, 95% CI (1.074 - -3.861),P = 0.029)增加了TN的风险,TN也增加了焦虑(OR = 1.43, 95% CI [1.04-1.96], P = 0.034)、抑郁(OR = 1.00305, 95% CI [1.00036-1.00549], P = 0.013)和失眠(OR = 1.00918, 95% CI [1.00236-1.01605], P = 0.008)的风险。结论:更长的病程和更广泛的三叉神经受累与抑郁、焦虑和失眠症状的严重程度增加独立相关,突出了TN患者早期临床干预的重要性。MR分析结果提供了支持MDs与TN之间因果关系的证据。与传统观点相反,疼痛导致焦虑和抑郁等情绪变化,焦虑、抑郁、失眠也会改变患TN的风险。
Association between mental disorders and trigeminal neuralgia: a cohort study and Mendelian randomization analysis.
Background: Clinical observational evidence suggests a close association between Trigeminal Neuralgia (TN) and Mental disorders (MDs). However, the causal relationship between the two remains unclear. This study aims to observe and analyse the associations between depression, anxiety, insomnia, and TN through clinical research. It also employs Mendelian randomization (MR) analysis to verify the potential genetic correlation between TN and various mental disorders. offering new insights for the diagnosis, prevention, and intervention strategies for TN.
Methods: In the cohort study section, clinical data were collected from 154 patients with TN, all of whom were excluded from preoperative use of psychotropic drugs such as carbamazepine. The PHQ-9, GAD-7, and ISI scales were used to assess preoperative symptoms of depression, anxiety, and insomnia. Multivariable linear regression models were used to identify factors associated with questionnaire scores, with model performance evaluated by adjusted R², AIC, BIC, and p-values. Patients with significant positive symptoms preoperatively were followed up one-year after surgery, and non-parametric tests were employed to examine changes in mental disorder symptoms after pain relief. In MR analysis section, the main MR analysis methods include Inverse Variance Weighted (IVW), MR Egger, Weighted Median, Simple Mode, and Weighted Mode. The Benjamini-Hochberg (BH) method was used to adjust the p -values and control the false discovery rate (FDR). Subsequent sensitivity analyses involved Cochran's Q test, MR-Egger regression intercept, MR-pleiotropy residual sum and outlier test (MR-PRESSO).
Results: Multiple linear regression analyses revealed that longer disease duration and greater involvement of trigeminal branches were consistently associated with higher PHQ-9, GAD-7, and ISI scores, while demographic factors and baseline BNI scores showed no significant predictive value. MR analysis indicated that autism (OR = 0.697, 95% CI [0.494-0.982], P = 0.039), schizophrenia (OR = 0.910, 95% CI [0.831-0.997], P = 0.042), and ADHD combined with OCD (OR = 0.175, 95% CI [0.044-0.693], P = 0.013) reduced the risk of TN. Conversely, bipolar disorder (OR = 1.249, 95% CI [1.016-1.535], P = 0.034), depression (OR = 2.375, 95% CI [1.043-5.409], P = 0.039), anxiety (OR = 1.174, 95% CI [1.008-1.368], P = 0.039), and insomnia (OR = 2.036, 95% CI [1.074-3.861], P = 0.029)increased the risk of TN. TN also elevated the risk of anxiety (OR = 1.43, 95% CI [1.04-1.96], P = 0.034), depression (OR = 1.00305, 95% CI [1.00036-1.00549], P = 0.013), and insomnia (OR = 1.00918, 95% CI [1.00236-1.01605], P = 0.008).
Conclusions: Longer disease duration and broader trigeminal nerve involvement were independently associated with increased severity of depressive, anxiety, and insomnia symptoms, highlighting the importance of early clinical intervention in patients with TN. And results of MR analysis provide evidence supporting a causal relationship between MDs and TN. In contrast to the traditional view that pain causes mood changes such as anxiety and depression, a variety of MDs such as anxiety, depression, and insomnia also alter the risk of developing TN.
期刊介绍:
The Journal of Headache and Pain, a peer-reviewed open-access journal published under the BMC brand, a part of Springer Nature, is dedicated to researchers engaged in all facets of headache and related pain syndromes. It encompasses epidemiology, public health, basic science, translational medicine, clinical trials, and real-world data.
With a multidisciplinary approach, The Journal of Headache and Pain addresses headache medicine and related pain syndromes across all medical disciplines. It particularly encourages submissions in clinical, translational, and basic science fields, focusing on pain management, genetics, neurology, and internal medicine. The journal publishes research articles, reviews, letters to the Editor, as well as consensus articles and guidelines, aimed at promoting best practices in managing patients with headaches and related pain.