牙周炎与焦虑抑郁双向关联的研究进展
Research Progress on the Bidirectional Association between Periodontitis and Anxiety/Depression
DOI: 10.12677/acm.2026.1651977, PDF,   
作者: 林哲豪, 任昀坚, 朱赴东*：浙江大学医学院附属口腔医院，浙江大学口腔医学院，浙江省口腔疾病临床医学研究中心，全省口腔生物医学重点实验室，浙江 杭州
关键词: 牙周炎；焦虑；抑郁；双向关联；机制；Periodontitis； Anxiety； Depression； Bidirectional Association； Mechanism
摘要: 牙周炎是由牙菌斑生物膜介导的慢性感染性炎症性疾病，焦虑和抑郁是全球患病率最高的两种精神障碍。近年来越来越多的证据表明，牙周炎与焦虑抑郁之间存在双向关联。流行病学研究显示，焦虑抑郁人群患慢性牙周炎的风险升高约54%，而牙周炎患者后续发生抑郁的风险比可达1.73。这种双向作用的机制涉及行为途径(如口腔卫生忽视、不良生活习惯)、神经内分泌途径(HPA轴激活、皮质醇升高)、免疫炎症途径(促炎因子水平升高、中枢神经炎症)以及口腔微生物–脑轴途径。临床实践中，应重视对两类疾病的联合筛查和多学科协作，同时控制两类疾病可改善双方的治疗结局。本文系统综述了牙周炎与焦虑抑郁双向关联的流行病学证据、潜在机制及临床启示，为整合医疗模式提供参考。
Abstract: Periodontitis is a chronic infectious inflammatory disease mediated by dental plaque biofilm, while anxiety and depression are the two most prevalent mental disorders worldwide. Accumulating evidence in recent years suggests a bidirectional association between periodontitis and anxiety/depression. Epidemiological studies have shown that individuals with anxiety and depression have an approximately 54% increased risk of developing chronic periodontitis, while patients with periodontitis have a subsequent hazard ratio of 1.73 for depression. The mechanisms underlying this bidirectional interaction involve behavioral pathways (e.g., neglect of oral hygiene, unhealthy lifestyle habits), neuroendocrine pathways (HPA axis activation, elevated cortisol), immuno-inflammatory pathways (increased pro-inflammatory cytokine levels, central neuroinflammation), and the oral microbiota-brain axis. In clinical practice, joint screening for both conditions and multidisciplinary collaboration should be emphasized, and concurrent management of both disorders can improve treatment outcomes for each. This article systematically reviews the epidemiological evidence, potential mechanisms, and clinical implications of the bidirectional association between periodontitis and anxiety/depression, providing a reference for integrated medical models.
文章引用：林哲豪, 任昀坚, 朱赴东. 牙周炎与焦虑抑郁双向关联的研究进展[J]. 临床医学进展, 2026, 16(5): 1741-1750. https://doi.org/10.12677/acm.2026.1651977

参考文献

[1] Warren, K.R., Postolache, T.T., Groer, M.E., Pinjari, O., Kelly, D.L. and Reynolds, M.A. (2013) Role of Chronic Stress and Depression in Periodontal Diseases. Periodontology 2000, 64, 127-138. [Google Scholar] [CrossRef] [PubMed]
[2] Martínez, M., Postolache, T.T., García-Bueno, B., Leza, J.C., Figuero, E., Lowry, C.A., et al. (2022) The Role of the Oral Microbiota Related to Periodontal Diseases in Anxiety, Mood and Trauma-And Stress-Related Disorders. Frontiers in Psychiatry, 12, Article ID: 814177. [Google Scholar] [CrossRef] [PubMed]
[3] Ganesan, A., Kumar, G., Gauthaman, J., Lakshmi, K.C. and Kumbalaparambil, Y.A. (2024) Exploring the Relationship between Psychoneuroimmunology and Oral Diseases: A Comprehensive Review and Analysis. Journal of Lifestyle Medicine, 14, 13-19. [Google Scholar] [CrossRef] [PubMed]
[4] Torabi-Gaarden, R., et al. (2004) Negative Life Events, Anxiety, Depression and Coping Ability (Stress) as Related to Chronic Periodontitis. Periodontal Practice Today, 1, 35-42.
[5] Liu, F., Wen, Y., Zhou, Y., Lei, G., Guo, Q. and Dang, Y. (2018) A Meta-Analysis of Emotional Disorders as Possible Risk Factors for Chronic Periodontitis. Medicine, 97, e11434. [Google Scholar] [CrossRef] [PubMed]
[6] Naveed, N. and Ramesh, A. (2017) Assessment of the Relationship between Anxiety, Depression with the Periodontal Status in Pregnant Indian Women—A Cross Sectional Study. International Journal of Multidisciplinary Research and Modern Education, 3, 405-409.
[7] Walther, C., Lieske, B., Borof, K., Kühn, S., Härter, M., Löwe, B., et al. (2023) Association between Periodontitis and Depression Severity—A Cross-Sectional Study of the Older Population in Hamburg. Brain, Behavior, & Immunity—Health, 34, Article ID: 100689. [Google Scholar] [CrossRef] [PubMed]
[8] Nascimento, G.G., Gastal, M.T., Leite, F.R.M., Quevedo, L.A., Peres, K.G., Peres, M.A., et al. (2019) Is There an Association between Depression and Periodontitis? a Birth Cohort Study. Journal of Clinical Periodontology, 46, 31-39. [Google Scholar] [CrossRef] [PubMed]
[9] Persson, G.R., Persson, R.E., MacEntee, C.I., Wyatt, C.C.I.I., Hollender, L.G. and Kiyak, H.A. (2003) Periodontitis and Perceived Risk for Periodontitis in Elders with Evidence of Depression. Journal of Clinical Periodontology, 30, 691-696. [Google Scholar] [CrossRef] [PubMed]
[10] Nolde, M., Holtfreter, B., Kocher, T., Alayash, Z., Reckelkamm, S.L., Ehmke, B., et al. (2022) No Bidirectional Relationship between Depression and Periodontitis: A Genetic Correlation and Mendelian Randomization Study. Frontiers in Immunology, 13, Article ID: 918404. [Google Scholar] [CrossRef] [PubMed]
[11] Hsu, C., Hsu, Y., Chen, H., Lin, C., Chang, K., Lee, C., et al. (2015) Association of Periodontitis and Subsequent Depression. Medicine, 94, e2347. [Google Scholar] [CrossRef] [PubMed]
[12] Tsai, K., Tsai, S., Lin, K., Chang, Y., Lin, Y. and Lin, G. (2022) Associations of Decayed Teeth and Localized Periodontitis with Mental Stress in Young Adults: CHIEF Oral Health Study. Scientific Reports, 12, Article No. 19139. [Google Scholar] [CrossRef] [PubMed]
[13] Al-Ani, A.S.R. and Faisal, G.G. (2017) Assessment of Depression, Anxiety and Stress Symptoms among Patients with Periodontal Disease.
http://irep.iium.edu.my/58091/
[14] Faisal, G.G. and Al-Ani, A.S.R. (2017) Depression, Anxiety and Stress among Diabetic and Non-Diabetic Patients with Periodontitis. Journal of International Dental and Medical Research, 10, 248-252.
[15] Shappell, A.V. and Cartier, P.M. (2023) Understanding the Mental-Dental Health Connection Said to Be Integral to Patient Care. Psychiatric News, 58. [Google Scholar] [CrossRef] 
[16] Fereidooni, M., Nouri, P., Faramarzi, M., et al. (2021) Evaluation of Association between Perceived Stress, Anxiety, Depression, Salivary Alpha-Amylase and Salivary Cortisol with Chronic Periodontitis. Journal of Dentistry & Oral Disorders, 7, Article No. 1152.
[17] Duseja, S., Parikh, H.A. and Duseja, S. (2025) Evaluating the Clinico-Biochemical Association between Stress and Chronic Periodontitis by Estimation of Serum Cortisol and Serum Chromogranin A Levels. Advances in Human Biology, 15, 73-80. [Google Scholar] [CrossRef] 
[18] Spector, A.M., Postolache, T.T., Akram, F., Scott, A.J., Wadhawan, A. and Reynolds, M.A. (2020) Psychological Stress: A Predisposing and Exacerbating Factor in Periodontitis. Current Oral Health Reports, 7, 208-215. [Google Scholar] [CrossRef] 
[19] Breivik, T., Gundersen, Y., Myhrer, T., Fonnum, F., Osmundsen, H., Murison, R., et al. (2006) Enhanced Susceptibility to Periodontitis in an Animal Model of Depression: Reversed by Chronic Treatment with the Anti‐Depressant Tianeptine. Journal of Clinical Periodontology, 33, 469-477. [Google Scholar] [CrossRef] [PubMed]
[20] Johannsen, A., Rydmark, I., Söder, B. and Åsberg, M. (2007) Gingival Inflammation, Increased Periodontal Pocket Depth and Elevated Interleukin‐6 in Gingival Crevicular Fluid of Depressed Women on Long‐Term Sick Leave. Journal of Periodontal Research, 42, 546-552. [Google Scholar] [CrossRef] [PubMed]
[21] Li, Q., Yang, J.X., Mo, Z.Y., Tang, X.H., Ma, G.W. and Yang, Y. (2012) Relationship between the IL-6 in the Gingival Crevicular Fluid of the Chronic Periodontitis and the Depression-Anxiety Psychological Factor. China Modern Medicine，No. 5, 34-35.
[22] Costa, J.E., Gomes, C.C., Cota, L.O.M., Pataro, A.L., Silva, J.F.C., Gomez, R.S., et al. (2008) Polymorphism in the Promoter Region of the Gene for 5-HTT in Individuals with Aggressive Periodontitis. Journal of Oral Science, 50, 193-198. [Google Scholar] [CrossRef] [PubMed]
[23] Hashioka, S., Inoue, K., Hayashida, M., Wake, R., Oh-Nishi, A. and Miyaoka, T. (2018) Implications of Systemic Inflammation and Periodontitis for Major Depression. Frontiers in Neuroscience, 12, 483-483. [Google Scholar] [CrossRef] [PubMed]
[24] Hashioka, S., Inoue, K., Miyaoka, T., Hayashida, M., Wake, R., Oh-Nishi, A., et al. (2019) The Possible Causal Link of Periodontitis to Neuropsychiatric Disorders: More than Psychosocial Mechanisms. International Journal of Molecular Sciences, 20, Article No. 3723. [Google Scholar] [CrossRef] [PubMed]
[25] Malan-Müller, S., Vidal, R., O’Shea, E., Montero, E., Figuero, E., Zorrilla, I., et al. (2024) Probing the Oral-Brain Connection: Oral Microbiome Patterns in a Large Community Cohort with Anxiety, Depression, and Trauma Symptoms, and Periodontal Outcomes. Translational Psychiatry, 14, Article No. 419. [Google Scholar] [CrossRef] [PubMed]
[26] Cao, T., Tian, D., Wang, S., Pan, Y., Xia, Z., Chen, W., et al. (2024) Microglial DBP Signaling Mediates Behavioral Abnormality Induced by Chronic Periodontitis in Mice. Advanced Science, 11, e2406269. [Google Scholar] [CrossRef] [PubMed]
[27] Li, Y., Guan, X., He, Y., Jia, X., Pan, L., Wang, Y., et al. (2023) ProBDNF Signaling Is Involved in Periodontitis-Induced Depression-Like Behavior in Mouse Hippocampus. International Immunopharmacology, 116, Article ID: 109767. [Google Scholar] [CrossRef] [PubMed]
[28] Mei, F., Xie, M., Huang, X., Long, Y., Lu, X., Wang, X., et al. (2020) Porphyromonas Gingivalis and Its Systemic Impact: Current Status. Pathogens, 9, Article No. 944. [Google Scholar] [CrossRef] [PubMed]
[29] Singh Solorzano, C., De Cillis, F., Mombelli, E., Saleri, S., Marizzoni, M. and Cattaneo, A. (2025) From Gums to Moods: Exploring the Impact of the Oral Microbiota on Depression. Brain, Behavior, & Immunity-Health, 48, Article 101057. [Google Scholar] [CrossRef] [PubMed]
[30] Qian, J., Lu, J., Cheng, S., Zou, X., Tao, Q., Wang, M., et al. (2023) Periodontitis Salivary Microbiota Exacerbates Colitis-Induced Anxiety-Like Behavior via Gut Microbiota. NPJ Biofilms and Microbiomes, 9, Article No. 93. [Google Scholar] [CrossRef] [PubMed]
[31] Goh, V., Hassan, F.W., Baharin, B. and Rosli, T.I. (2022) Impact of Psychological States on Periodontitis Severity and Oral Health-Related Quality of Life. Journal of Oral Science, 64, 1-5. [Google Scholar] [CrossRef] [PubMed]
[32] Kong, Y. (2024) Analysis of Influencing Factors of Anxiety and Depression in Patients with Periodontitis. World Journal of Psychiatry, 14, 141-147. [Google Scholar] [CrossRef] [PubMed]
[33] D’Ambrosio, F., Caggiano, M., Schiavo, L., Savarese, G., Carpinelli, L., Amato, A., et al. (2022) Chronic Stress and Depression in Periodontitis and Peri-Implantitis: A Narrative Review on Neurobiological, Neurobehavioral and Immune-Microbiome Interplays and Clinical Management Implications. Dentistry Journal, 10, Article No. 49. [Google Scholar] [CrossRef] [PubMed]
[34] Petit, C., Anadon-Rosinach, V., Tuzin, N., Davideau, J. and Huck, O. (2021) Influence of Depression and Anxiety on Non-Surgical Periodontal Treatment Outcomes: A 6-Month Prospective Study. International Journal of Environmental Research and Public Health, 18, Article No. 9394. [Google Scholar] [CrossRef] [PubMed]
[35] Katuri, K., Dasari, A., Kurapati, S., Vinnakota, N., Bollepalli, A. and Dhulipalla, R. (2016) Association of Yoga Practice and Serum Cortisol Levels in Chronic Periodontitis Patients with Stress-Related Anxiety and Depression. Journal of International Society of Preventive and Community Dentistry, 6, Article No. 7. [Google Scholar] [CrossRef] [PubMed]
[36] Andrade, E.F., Orlando, D.R., Gomes, J.A.S., Foureaux, R.d.C., Costa, R.C., Varaschin, M.S., et al. (2017) Exercise Attenuates Alveolar Bone Loss and Anxiety‐Like Behaviour in Rats with Periodontitis. Journal of Clinical Periodontology, 44, 1153-1163. [Google Scholar] [CrossRef] [PubMed]
[37] Gokturk, O., Inanir, S., Yuce, H., Demir, O. and Turkal, H. (2021) The Effect of Periodontal Treatment on Depression, Body Image, Self Esteem and Anxiety in Individuals: A Randomized Controlled Clinical Trial. Annals of Medical Research, 28, Article No. 1155. [Google Scholar] [CrossRef] 
[38] Kim, S.W., Shrestha, S.K., Chuluunbaatar, B. and Soh, Y. (2024) Combination of Cannabidiol with Taurine Synergistically Treated Periodontitis in Rats. Biomolecules & Therapeutics, 33, 203-209. [Google Scholar] [CrossRef] [PubMed]
[39] Sayedyousef, H., Yilmaz, O., Ozturk, C., Demir, B., Toygar, H.U. and Balci, N. (2025) Taurine, Sirtuin-1 and TNF-α Levels in Different Aged Adults with Periodontitis: A Pilot Study. BMC Oral Health, 25, Article No. 1354. [Google Scholar] [CrossRef] [PubMed]
[40] Levis, B., Sun, Y., He, C., Wu, Y., Krishnan, A., Bhandari, P.M., et al. (2020) Accuracy of the PHQ-2 Alone and in Combination with the PHQ-9 for Screening to Detect Major Depression: Systematic Review and Meta-Analysis. JAMA, 323, Article No. 2290. [Google Scholar] [CrossRef] [PubMed]
[41] Kroenke, K., Spitzer, R.L. and Williams, J.B.W. (2001) The PHQ-9: Validity of a Brief Depression Severity Measure. Journal of General Internal Medicine, 16, 606-613. [Google Scholar] [CrossRef] [PubMed]
[42] Luo, Z., Li, Y., Hou, Y., Zhang, H., Liu, X., Qian, X., et al. (2019) Adaptation of the Two-Item Generalized Anxiety Disorder Scale (GAD-2) to Chinese Rural Population: A Validation Study and Meta-Analysis. General Hospital Psychiatry, 60, 50-56. [Google Scholar] [CrossRef] [PubMed]
[43] Toussaint, A., Hüsing, P., Gumz, A., Wingenfeld, K., Härter, M., Schramm, E., et al. (2020) Sensitivity to Change and Minimal Clinically Important Difference of the 7-Item Generalized Anxiety Disorder Questionnaire (GAD-7). Journal of Affective Disorders, 265, 395-401. [Google Scholar] [CrossRef] [PubMed]
[44] Smith, T.B., Berryhill, M.B., Culmer, N., McBurnie, M.A., Kopycka-Kedzierawski, D., Gilbert, G.H., et al. (2024) Mental Health Screenings in Dental Settings: Feasibility and Outcomes from a Study by the National Dental Practice-Based Research Network. The Journal of the American Dental Association, 155, 963-971. [Google Scholar] [CrossRef] [PubMed]

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