焦虑与抑郁症状对牙周炎影响的孟德尔随机化研究

doi:10.19439/j.sjos.2025.04.013

摘要/Abstract

摘要： 目的：采用孟德尔随机化（Mendelian randomization,MR）方法评估焦虑、抑郁状态对牙周炎发病风险的影响,分析牙周炎患者中焦虑、抑郁症状的流行情况及其影响因素,为临床预防和治疗提供依据。方法：收集2022年8月—2024年8月在长沙市第四医院就诊的70例牙周炎患者及35例健康对照者数据,采用汉密尔顿焦虑量表（Hamilton Anxiety Rating Scale,HAMA）和汉密尔顿抑郁量表（Hamilton Depression Rating Scale,HAMD）分别评估焦虑和抑郁症状,并通过logistic回归分析潜在危险因素。从全基因组关联研究（Genome-Wide Association Study,GWAS）数据库筛选单核苷酸多态性（single nucleotide polymorphisms,SNP）作为工具变量,依据P值阈值（P=5e-05）及连锁不平衡聚类方法（窗口大小为10 000 kb,r²阈值为0.001）筛选独立SNP,并进行数据协调。利用逆方差加权（inverse variance weighted, IVW）等5种MR方法分析焦虑和抑郁与急性及慢性牙周炎的因果关系。结果：在临床病例对照研究中,牙周炎病例组HAMA和HAMD评分显著高于对照组（HAMA: P=0.006;HAMD: P=0.007）。病例组焦虑状态发生率显著高于对照组（P=0.008）,抑郁状态发生率显著高于对照组（P=0.006）。Logistic回归分析发现,焦虑、抑郁及年龄≥60岁是牙周炎的独立危险因素（P<0.05）。MR分析显示,焦虑与急性牙周炎呈显著正相关（IVW法,P=0.037）,抑郁与急性牙周炎呈显著正相关（IVW法,P=0.043）,但两者与慢性牙周炎无显著关联（P>0.05）。多效性和异质性检验表明,分析结果可靠（IVW法和MR Egger法,P均>0.05）。结论：焦虑与抑郁症状与牙周炎之间存在显著关联,建议临床上处理牙周炎时综合考虑心理因素的影响。

关键词: 牙周炎, 心理健康, 焦虑, 抑郁, 孟德尔随机化, 单核苷酸多态性

Abstract: PURPOSE: To evaluate the effects of anxiety and depression on the risk of periodontitis using Mendelian randomization (MR) method, and to analyze the prevalence and influencing factors of anxiety and depression symptoms in patients with periodontitis, so as to provide evidence for clinical prevention and treatment. METHODS: The data of 70 patients with periodontitis and 35 healthy controls who were treated in the Fourth Hospital of Changsha from August 2022 to August 2024 were collected.Hamilton Anxiety Rating Scale (HAMA) was used to assess the anxiety of the subjects. Hamilton Depression Rating Scale (HAMD) was used to assess symptoms of depression of the subjects, and potential risk factors were analyzed by logistic regression. Single nucleotide polymorphisms (SNP) were screened from the Genome-Wide Association Study (GWAS) database as instrumental variables. The independent SNP were screened according to the P-value threshold (P=5e-05) and the linkage unbalanced clustering method (window size 10 000 kb, r² threshold 0.001), and the data were coordinated. Five MR methods, including inverse variance weighted (IVW), were used to analyze the causal relationship between anxiety and depression on acute and chronic periodontitis. RESULTS: In the clinical case-control study, HAMA and HAMD scores of the periodontitis group were significantly higher than those of the control group (HAMA: P=0.006; HAMD: P=0.007). The incidence of anxiety in the periodontitis group was significantly higher than that in the control group (P=0.008), and the incidence of depression was also significantly higher (P=0.006). Logistic regression analysis revealed that anxiety, depression, and age ≥ 60 years were independent risk factors for periodontitis (P<0.05). MR analysis showed that anxiety was significantly positively correlated with acute periodontitis (IVW method, P =0.037), and depression was significantly positively correlated with acute periodontitis (IVW method, P=0.043), but neither was significantly associated with chronic periodontitis (P>0.05). The tests for pleiotropy and heterogeneity indicated that the analysis results were reliable (IVW method and MR Egger method, P>0.05 for both). CONCLUSIONS: There is significant correlation between anxiety and depression symptoms and periodontitis. It is recommended to consider the influence of psychological factors in clinical treatment of periodontitis.

Key words: Periodontitis, Mental health, Anxiety, Depression, Mendelian randomization, Single nucleotide polymorphism

中图分类号:

R781.4

雷邓, 周英斌, 黄思慧, 李玉峰. 焦虑与抑郁症状对牙周炎影响的孟德尔随机化研究[J]. 上海口腔医学, 2025, 34(4): 414-421.

Lei Deng, Zhou Yingbin, Huang Sihui, Li Yufeng. Effect of anxiety and depression symptoms on periodontitis based on Mendelian randomization study[J]. Shanghai Journal of Stomatology, 2025, 34(4): 414-421.

参考文献

[1] Sanz M, Marco del Castillo A, Jepsen S, et al. Periodontitis and cardiovascular diseases: consensus report[J]. J Clin Periodontol, 2020, 47(3): 268-288.
[2] Kwon TH, Lamster IB, Levin L.Current concepts in the management of periodontitis[J]. Int Dent J, 2021, 71(6): 462-476.
[3] Slots J.Primer on etiology and treatment of progressive/severe periodontitis: a systemic health perspective[J]. Periodontol 2000, 2020, 83(1): 272-276.
[4] Lorenzo-Erro SM, Andrade E, Massa F, et al.Periodontitis prevalence and associated factors: a comparison of two examination protocols[J]. Acta Odontol Latinoam, 2022, 35(3): 178-187.
[5] Nwizu N, Wactawski-Wende J, Genco RJ.Periodontal disease and cancer: epidemiologic studies and possible mechanisms[J]. Periodontol 2000, 2020, 83(1): 213-233.
[6] Heitz-Mayfield LJA.Conventional diagnostic criteria for periodontal diseases (plaque‐induced gingivitis and periodontitis)[J]. Periodontol 2000, 2024, 95(1): 10-19.
[7] Walther C, Wenzel JP, Schnabel RB, et al.Association between periodontitis and heart failure in the general population[J]. ESC Heart Fail, 2022, 9(6): 4189-4197.
[8] Zhang Z, Zhao D, Lin M, et al.Application of health quotient to enhance chronic periodontitis treatments[J]. Patient Prefer Adherence, 2018, 12: 359-362.
[9] Ball J, Darby I.Mental health and periodontal and peri-implant diseases[J]. Periodontol 2000, 2022, 90(1): 106-124.
[10] Dhingra K.Is periodontal disease a risk factor for oral cancer?[J]. Evid Based Dent, 2022, 23(1): 20-21.
[11] Matsuda S, Yoshimura H.Impact of oral health management on mental health and psychological disease: a scoping review[J]. J Int Med Res, 2023, 51(1): 3000605221147186.
[12] Birney E.Mendelian randomization[J]. Cold Spring Harb Perspect Med, 2022, 12(4): a041302.
[13] Wang J, Wang Y, Li H, et al.Associations between oral health and depression and anxiety: a cross-sectional and prospective cohort study from the UK Biobank[J]. J Clin Periodontol, 2024, 51(11): 1466-1477.
[14] He J, Gai J.Genome-wide association studies (GWAS)[J]. Methods Mol Biol, 2023, 2638: 123-146.
[15] Hamilton M.The assessment of anxiety states by rating[J]. Br J Med Psychol, 1959, 32(1): 50-55.
[16] Hamilton M.A rating scale for depression[J]. J Neurol Neurosurg Psychiatry, 1960, 23(1): 56-62.
[17] 中华口腔医学会牙周病学专业委员会.重度牙周炎诊断标准及特殊人群牙周病治疗原则的中国专家共识[J].中华口腔医学杂志, 2017, 52(2): 67-71.
[18] Aragão WAB, Souza-Monteiro D, Frazão DR, et al.Is there any association between chronic periodontitis and anxiety in adults? a systematic review[J]. Front Psychiatry, 2021, 12: 710606.
[19] Chatzopoulos GS, Koidou VP, Wolff LF.Expression of Wnt signaling agonists and antagonists in periodontitis and healthy subjects, before and after non-surgical periodontal treatment: a systematic review[J]. J Periodontal Res, 2022, 57(4): 698-710.
[20] Kim TS, Silva LM, Theofilou VI, et al.Neutrophil extracellular traps and extracellular histones potentiate IL-17 inflammation in periodontitis[J]. J Exp Med, 2023, 220(9): e20221751.
[21] 欧明倩, 邢莹, 孙晓亮, 等. 口腔幽门螺杆菌感染患者血清GSH-Px、TNF-α、TGF-β1的变化及与牙周病危险因素分析[J]. 中华医院感染学杂志, 2020, 30(16): 2434-2438.
[22] Martínez M, Postolache TT, García-Bueno B, et al.The role of the oral microbiota related to periodontal diseases in anxiety, mood and trauma- and stress-related disorders[J]. Front Psychiatry, 2022, 12: 814177.
[23] Goh V, Hassan FW, Baharin B, et al.Impact of psychological states on periodontitis severity and oral health-related quality of life[J]. J Oral Sci, 2022, 64(1): 1-5.
[24] Cataldo D, Mourão LC, Gonçalves LS, et al.Association of anxiety, age and oral health-related quality of life with periodontitis: a case-control study[J]. Int J Dent Hyg, 2024, 22(3): 540-546.
[25] Lio F, Ottria L, Mazzetti V, et al.The effectiveness of subgingival irrigant ozone-based as adjuvant for non-surgical periodontal therapy in the treatment of chronic periodontitis: a review[J]. J Biol Regul Homeost Agents, 2020, 34(3 Suppl. 1): 27-34.
[26] Dibello V, Custodero C, Cavalcanti R, et al.Impact of periodontal disease on cognitive disorders, dementia, and depression: a systematic review and meta-analysis[J]. Geroscience, 2024, 46(5): 5133-5169.
[27] Walther C, Lieske B, Borof K, et al.Association between periodontitis and depression severity - a cross-sectional study of the older population in Hamburg[J]. Brain Behav Immun Health, 2023, 34: 100689.
[28] Deng Y, He S, Wang J.Validation of the Hospital Anxiety and Depression Scale and the Perceived Stress Scale and psychological features in patients with periodontitis[J]. J Periodontol, 2021, 92(11): 1601-1612.
[29] Li Y, Guan X, He Y, et al.ProBDNF signaling is involved in periodontitis-induced depression-like behavior in mouse hippocampus[J]. Int Immunopharmacol, 2023, 116: 109767.
[30] Aldosari M, Helmi M, Kennedy EN, et al.Depression, periodontitis, caries and missing teeth in the USA, NHANES 2009-2014[J]. Fam Med Community Health, 2020, 8(4): e000583.
[31] Robledo-Montaña J, Díaz-García C, Martínez M, et al.Microglial morphological/inflammatory phenotypes and endocannabinoid signaling in a preclinical model of periodontitis and depression[J]. J Neuroinflammation, 2024, 21(1): 219.
[32] Sun C, Han J, Bai Y, et al.Neuropeptides as the shared genetic crosstalks linking periodontitis and major depression disorder[J]. Dis Markers, 2021: 3683189.
[33] 惠月, 马梦如, 宋红权, 等. 骨密度对牙周炎发生的因果关联:一项两样本孟德尔随机化研究[J]. 现代口腔医学杂志, 2024, 38(2): 88-93.
[34] 孙晓瑜, 胡佳敏, 赵静心, 等. 牙周炎与妊娠期糖尿病因果关系的孟德尔随机化研究[J]. 安徽医学, 2024, 45(6): 725-731.