Salivary cortisol, dehydroepiandrosterone, and chromogranin A levels in patients with gingivitis and periodontitis and a novel biomarker for psychological stress

Introduction: This study aimed to investigate the neuroendocrine responses based on cortisol, dehydroepiandrosterone (DHEA), cortisol/DHEA ratio, and chromogranin A levels, which reflect the activity of the hypothalamic-pituitary-adrenal axis, according to the presence or absence of psychological stress in patients with gingivitis and periodontitis compared to that in healthy controls. Methods: In total, 117 patients (60 women, mean age: 36.29 ± 19.03 years) participated in this case-control study, comprising 32 healthy controls, 49 patients with gingivitis, and 36 patients with periodontitis. We investigated the presence of psychological stress and salivary characteristics, and analyzed the stress-related biomarkers of cortisol, DHEA, cortisol/DHEA ratio, and chromogranin A in the stimulated saliva. Results: Salivary cortisol and chromogranin A levels increased with the severity of periodontal disease; their levels were the highest in the periodontitis group and were significantly higher in the following descending order: periodontitis, gingivitis, and healthy control groups (all values of p < 0.001). Additionally, the DHEA levels and cortisol/DHEA ratio were higher in the periodontitis group than those in the healthy control group (all values of p < 0.001). A multivariate logistic regression analysis revealed that the factors predicting above-average cortisol levels were periodontitis (odds ratio [OR] = 256.829; p < 0.001), women (OR = 6.365; p = 0.004), and psychological stress (OR = 6.036; p = 0.007); those predicting above-average cortisol/DHEA ratios were periodontitis (OR = 11.436; p < 0.001), psychological stress (OR = 3.977; p = 0.003), and women (OR = 2.890; p = 0.026). Thus, periodontitis and psychological stress were significant and strong predictors of above-average cortisol levels and cortisol/DHEA ratios. In the gingivitis group, salivary cortisol levels (r = 0.381, p = 0.007) and cortisol/DHEA ratios (r = 0.479, p < 0.001) were correlated with the presence of psychological stress. In the periodontitis group, increased cortisol/DHEA ratios (r = 0.412, p = 0.013) and lowered salivary buffer capacities (r = -0.334, p = 0.047) were correlated with the presence of psychological stress. Conclusion: Periodontitis is a multifactorial disease resulting in inflammatory tissue destruction, which differs from gingivitis and a healthy state. Differences in stress-related neuroendocrine markers were revealed based on the severity of periodontal disease. The biomarkers that could be classified according to disease severity were salivary cortisol and chromogranin A levels. Above-average cortisol levels and cortisol/DHEA ratios are significant predictors of psychological stress in patients with gingivitis and periodontitis.