Neupane Sudan Prasad, Virtej Anca, Myhren Lene Elisabeth, Bull Vibeke Hervik
National Centre for Suicide Research and Prevention, Institute of Clinical Medicine, University of Oslo, Norway.
Oral Health Centre of Expertise in Rogaland, Stavanger, Norway.
Brain Behav Immun Health. 2022 Mar 14;21:100450. doi: 10.1016/j.bbih.2022.100450. eCollection 2022 May.
Dysregulated immune response arising in the periphery can induce depressive symptoms through neuroimmune interactions. Inflammatory oral pathology can be a potent inducer of chronic neuroimmune response relevant to depression. We aimed to synthesize available evidence for the association between inflammatory periodontal diseases (IPD) and major depression (MD) in relation to a broad range of biomarkers.
Medline, Embase, PsycInfo, Cochrane Library, Web of Science and Scopus databases were searched from inception until January 27, 2022. Search terms included subject headings and synonyms for inflammatory periodontal disease and depression. Studies that reported data on both depression and inflammatory periodontal disease as categories along with measurement of a biomarker were considered. Two reviewers independently selected the articles for inclusion, extracted data and assessed the quality of each study. The protocol for this study was registered with PROSPERO, CRD42021215524.
Twenty-eight studies were included in the final review-eleven cross-sectional studies, seven case-control studies, and six prospective cohort studies conducted in humans; the remaining four were experimental animal studies. Eighteen studies including all animal studies reported a positive association between depression and periodontal disease; one study reported a negative association and another nine studies found no such associations. Twenty studies reported mixed associations between IPD and biomarkers (i.e, salivary, serum, urine or gingival crevicular fluid cortisol, C reactive protein, cytokines, etc.). Biomarkers related to depression were gingival crevicular fluid cortisol, interleukin 6 (IL-6), Il-1β, immunoglobulin G against Bacterioides forsythus; root canal lipopolysaccharides; blood IL-6, IL-1β, cortisol, advanced oxidation protein products, nitric oxide metabolites, lipid hydroperoxides and trapping antioxidant parameter; whereas five studies found no associations between depression and a biomarker. Although animal studies showed interaction of immune, inflammatory and neurotrophic biomarkers in the relationship between depression and periodontal disease, human studies showed mixed findings. In most studies, there were risks of bias due to the sample selection and assessment protocol. Study heterogeneity and limited number of comparable studies reporting on shared biomarkers precluded a meta-analysis.
Immune-inflammatory contribution to depression was evident in the context of inflammatory periodontal diseases, but whether biomarkers mediate the associations between IPD and MD needs to be tested through methodologically rigorous studies aiming specifically at this hypothesis.
外周免疫反应失调可通过神经免疫相互作用诱发抑郁症状。炎症性口腔病变可能是与抑郁症相关的慢性神经免疫反应的有力诱导因素。我们旨在综合现有证据，探讨炎症性牙周疾病（IPD）与重度抑郁症（MD）之间的关联以及一系列生物标志物。
检索了Medline、Embase、PsycInfo、Cochrane图书馆、Web of Science和Scopus数据库，检索时间从建库至2022年1月27日。检索词包括炎症性牙周疾病和抑郁症的主题词及同义词。纳入报告了抑郁症和炎症性牙周疾病分类数据以及生物标志物测量值的研究。两名评审员独立选择纳入的文章，提取数据并评估每项研究的质量。本研究方案已在PROSPERO注册，注册号为CRD42021215524。
最终综述纳入了28项研究——11项横断面研究、7项病例对照研究和6项针对人类的前瞻性队列研究；其余4项为实验动物研究。包括所有动物研究在内的18项研究报告抑郁症与牙周疾病之间存在正相关；1项研究报告为负相关，另外9项研究未发现此类关联。20项研究报告了IPD与生物标志物（即唾液、血清、尿液或龈沟液中的皮质醇、C反应蛋白、细胞因子等）之间的混合关联。与抑郁症相关的生物标志物有龈沟液皮质醇、白细胞介素6（IL-6）、IL-1β、抗福赛坦氏菌的免疫球蛋白G；根管脂多糖；血液中的IL-6、IL-1β、皮质醇、晚期氧化蛋白产物、一氧化氮代谢物、脂质氢过氧化物和捕获抗氧化参数；而5项研究未发现抑郁症与生物标志物之间存在关联。尽管动物研究显示免疫、炎症和神经营养生物标志物在抑郁症与牙周疾病的关系中存在相互作用，但人类研究结果不一。在大多数研究中，由于样本选择和评估方案存在偏倚风险。研究异质性以及报告共享生物标志物的可比研究数量有限，无法进行荟萃分析。
在炎症性牙周疾病的背景下，免疫炎症对抑郁症的影响是明显的，但生物标志物是否介导IPD与MD之间的关联，需要通过专门针对这一假设的方法严谨的研究来检验。
