Abstract
Background
Psychological stress is linked to elevated salivary cortisol levels, potentially worsening periodontitis by exacerbating inflammation. This study examines the impact of stress on cortisol levels in periodontitis patients, aiming to explore salivary cortisol as a biomarker for disease severity and its role in improving management strategies.
Methods
This case-control study, conducted at Dow University of Health Sciences in Karachi from January to December 2022, involved 120 dental clinic patients aged 30–60. Participants were selected based on the presence (cases) or absence (controls) of periodontitis, excluding those with systemic diseases, taking hydrocortisone, immunosuppressives, antidepressants, systemic antibiotics, having oral ulcers and pregnancy or lactation. Periodontal parameters, stress levels (using the Perceived Stress Scale), and morning salivary cortisol (measured via ELISA) were assessed. Statistical analyses were performed using SPSS version 23, including descriptive statistics, independent t-tests, ANOVA, and odds ratio calculations with a 95% confidence interval at 0.05.
Results
The study cohort comprised 120 subjects, equally divided between periodontitis patients and healthy controls. Predominantly male (63%) with a mean age of 41.75 years, participants were subjected to comprehensive evaluations. Oral health indices (Gingival index, Plaque index, Clinical attachment loss, Periodontal probing depth, Tooth mobility) and stress markers (Perceived Stress Score, Salivary cortisol levels [SCLs]) were significantly higher in cases compared to controls (p < 0.001). Majority of cases (58.3%) had stage II periodontitis. Notably, cases exhibited significantly higher stress levels (2.05 ± 0.59 vs. 1.38 ± 0.52; p < 0.001) and elevated salivary cortisol levels (6.67 ± 1.64 vs. 2.54 ± 0.88; p < 0.001) compared to controls. The odds ratio (OR) of 3.73 (95% CI [1.75, 7.93], p = 0.0006) indicated that periodontitis patients were over 3.5 times more likely to have elevated SCLs. Stress prevalence was 42.5% in periodontitis patients compared to 18.33% in controls.
Conclusions
This study highlights a potential link between stress, cortisol levels, and periodontitis, suggesting that salivary cortisol could be a valuable biomarker. Incorporating cortisol measurements into routine dental evaluations may enable personalized treatment plans, addressing both biological and psychological contributors to periodontitis. Further research is needed to explore the long-term effects of stress on cortisol levels and periodontal disease progression, as well as the role of stress management in managing periodontitis.
Keywords: Stress, Cortisol, Periodontitis, Saliva, Case-control studies
Background
Severe periodontitis affects almost 10% of the global population, indicating a significant prevalence of the condition [1]. According to a survey by the World Health Organization (W.H.O.), 18% of the population in Pakistan is affected by periodontal disorders, with 31% of these cases being specifically diagnosed as periodontitis [2]. Recent research has confirmed a strong link between periodontitis and cardiovascular diseases (CVD), including stroke. Chronic inflammation from periodontitis is believed to contribute to atherosclerosis, a key factor in CVD development. Oral bacteria and inflammatory mediators from periodontal pockets can spread systemically, causing endothelial dysfunction and increasing the risk of heart attacks and strokes [3]. Some studies suggest that effective periodontal therapy may reduce systemic inflammation and improve cardiovascular outcomes. Recent research has demonstrated that minimally invasive non-surgical treatment effectively reduced periodontal parameters and key inflammatory markers, including C-reactive protein and lipoprotein-associated phospholipase A2, which are linked to systemic inflammation in individuals with periodontitis [4]. Implants can be used as an alternative treatment for some patients with periodontitis, instead of the conventional periodontal treatment [5]. Smoking, individuals with diabetes or other systemic disorders, and environmental variables exacerbate the issue, rendering periodontitis significantly more prevalent and difficult to treat [6, 7].
Research has additionally established a connection between the development of periodontitis and feelings of anxiety and stress [8]. Stress is an unavoidable aspect of life, but it is beneficial to maintain a level that can be effectively handled. Stress, despite its negative connotations, really confers health advantages due to its essential role in ensuring existence. A minimal level of anxiety is necessary for the body’s regular homeostatic system, but an over reaction can disrupt the homeostatic equilibrium and promote the development of disease.
Prolonged psychological distress can inhibit the body’s inherent immunological response. This intricate network of bidirectional impulses facilitates the integration of neurological, hormonal, and immunological activities, enabling communication between the brain system and immune cells. Stress disrupts the balance of this circuit, potentially affecting the immune system’s reaction [9, 10].
Stress plays a role in chronic periodontitis through two mechanisms: it stimulates sympathetic nerves to release catecholamines, which cause blood vessels to contract, so limiting the influx of inflammatory cells to the site of infection. Stress triggers the activation of the hypothalamic-pituitary-adrenal axis, leading to the release of cortisol. Cortisol exerts its anti-inflammatory effects primarily by stabilizing lysosomal membranes, so preventing the development of inflammation. Additionally, it reduces the migration of leukocytes to the inflamed area and inhibits phagocytosis. Measuring cortisol levels helps detect illness and track its course [11, 12].
Salivary cortisol concentration serves as a physiologic indicator of stress. Saliva sampling is preferred by individuals due to its simplicity, minimal discomfort, and lack of need for specialist equipment. Testing cortisol levels in blood is not only costlier than testing saliva, but it also yields a falsely elevated cortisol result due to the activation of the Hypothalamic-Pituitary-Adrenal (HPA) axis during blood collection [13]. Research has shown that salivary cortisol level (SCL) accurately represents the amount of free, active cortisol in the body and is not affected by the overall rate of saliva production [14].
The concept and novelty of this study lie in the examination of periodontitis, mediators, and systemic outcomes. These aspects have been validated in medicine, but further research on this topic could introduce innovative perspectives and spark creative debates in the literature by contributing new information. The aim of this study is to investigate the relationship between psychological stress and periodontitis by assessing salivary cortisol levels as a marker of stress. This study seeks to explore how elevated cortisol levels, influenced by stress, may contribute to the severity and progression of periodontal disease. Additionally, given the high prevalence of periodontitis in Pakistan and its association with systemic conditions, the research will examine whether stress management interventions could potentially reduce cortisol levels and improve periodontal outcomes, offering insights into the treatment implications.
Methods
Study design
The scope of our case-control study encompassed all individuals aged 30 to 60 who sought medical attention at the Periodontology Clinic at the Dow University of Health Sciences (DUHS) in Karachi, Pakistan, during the period from January 2022 to July 2022.
Inclusion and exclusion criteria
The study comprised a cohort of sixty persons diagnosed with periodontitis, and a control group of sixty healthy individuals who visited the dental clinic for a routine check-up. The analysis comprised 120 participants.
Inclusion criteria
1. Periodontitis cases:
Periodontitis classified according to the 2017 criteria from the new classification system.
Aged 30–60 years.
Able to provide informed consent.
2. Healthy controls:
No history of periodontal disease.
Aged 30–60 years.
Able to provide informed consent.
Exclusion criteria for cases and controls
1. Systemic and medication-related exclusions:
History of or current use of systemic corticosteroids (e.g., prednisone, hydrocortisone) or other immunosuppressive medications.
Use of anti-psychotic, anti-depressant, anti-inflammatory drugs, or systemic antibiotics within the past 3 months.
Current or recent use of medications affecting cortisol levels (e.g., oral contraceptives, hormonal therapies).
2. Oral health conditions:
Presence of oral inflammatory lesions that could affect saliva composition (e.g., ulcers, lesions).
Periodontitis involving wisdom teeth.
3. Other conditions:
History of or current xerostomia (dry mouth).
Recent periodontal therapy (within the past 6 months).
Any other conditions or factors that could significantly influence cortisol levels or periodontal health (e.g., severe psychiatric disorders).
4. Pregnancy and nursing:
Pregnant or nursing women due to potential hormonal changes affecting cortisol levels.
Participant recruitment and informed consent
The study was approved by the Institutional Review Board at DUHS on February 22, 2022, with a decision number of 2022/758. Following the provision of written and oral information regarding the objectives, procedures, and implications of the study, every participant provided their signature on a consent form.
Sample size calculation
OpenEpi, version 3 was utilized in order to make an estimation of the study’s sample size. The sample size calculation was based on a similar study conducted in India in 2018, which reported a significant association between psychological stress and periodontitis using comparable methodology. To ensure the study’s ability to detect a meaningful effect size with sufficient precision, we selected a final total of 60 cases and 60 controls. The confidence interval of 95% was chosen to provide a balance between statistical precision and generalizability of the findings, while the test power of 80% was deemed appropriate to detect a clinically relevant difference with a reasonable degree of certainty [15].
However, it’s important to acknowledge that sample size calculations are based on several assumptions, including the anticipated effect size, variability of the outcome, and the chosen significance level and power. While efforts were made to select parameters that align with the study objectives and available resources, there may be inherent limitations and uncertainties associated with these assumptions. Additionally, to account for potential dropout or non-response rates, a conservative estimate of 10% was added to the calculated sample size for both cases and controls.
Diagnostic criteria for periodontitis
We conducted an oral examination following the criteria established by the American Academy of Periodontology (AAP) and the European Federation of Periodontology (EFP) in 2017 to assess the presence of periodontitis [16]. The primary diagnostic criteria were Clinical Attachment Loss (CAL) and radiographic evidence of bone loss. Based on this classification, periodontitis was categorized into four stages, ranging from Stage I (mild) to Stage IV (severe). The specific criteria for each oral health index are detailed below.
Oral examination
Prior to the oral examination, we obtained the patient’s saliva for cortisol analysis.
During the oral examination for periodontitis, we thoroughly assessed the gingival, plaque, calculus, and mobility indices (Table 1), along with the Periodontal Probing Depth (PPD) and Clinical Attachment Loss (CAL). The examination steps included:
Table 1.
Indices of Periodontitis
| Index | Category | Description |
|---|---|---|
| Plaque Index – Loe & Silness Index [17] | ||
| 0 | Normal | No plaque next to the gingiva |
| 1 | Mild | There is a thin film of plaque present on the gingival margin |
| 2 | Moderate | Moderate amount of plaque present on the gingival margin/tooth/pocket |
| 3 | Severe | Increased amount of plaque present on the gingival margin/tooth/pocket |
| Calculus Index- Green and Vermilion Index [18] | ||
| 0 | Normal | No calculus |
| 1 | Mild | Up to one third of the tooth surface covered in supragingival calculus |
| 2 | Moderate | Supragingival calculus up to two thirds of the tooth or the observation of isolated particles of subgingival calculus around the cervical portion of the tooth. |
| 3 | Severe | Supragingival calculus greater than two thirds of the tooth or a continuous dense deposit of subgingival calculus encircling the cervical portion of the tooth. |
| Gingival Index- Loe and Silness Index [17] | ||
| 0 | Normal | Normal gingiva |
| 1 | Mild | Mild changes in color and size of gingiva, no bleeding on probing |
| 2 | Moderate | Gingiva is red, swollen, and has a glossy appearance. Bleeding on probing |
| 3 | Severe | The gingiva is red, swollen, and has ulcers. Spontaneous bleeding |
| Mobility Index – Miller’s Index [19] | ||
| Grade 0 | Physiologic movement when force is applied | |
| Grade 1 | Slight movement of < 1 mm in horizontal direction | |
| Grade 2 | Movement of > 1 mm but < 2 mm in horizontal direction | |
| Grade 3 | Movement of > 1 mm in horizontal and vertical direction | |
Medical and dental history review: Identified risk factors like smoking and diabetes.
Clinical examination:
Visual inspection of gums for inflammation, redness, swelling, and recession.
Other periodontal health indicators were assessed as follows:
-
3.
Missing teeth (due to periodontitis): (Stage I & II ◊ No tooth loss; Stage III ◊ ≤ 4 teeth; Stage IV ◊ ≥ 5 teeth)
-
4.
Periodontal probing depth: Measured the depth of periodontal pockets using a probe. (Stage I ◊ ≤ 4 mm; Stage II ◊ ≤ 5 mm; Stage III ◊ ≥ 6 mm; Stage IV ◊ ≥ 6 mm)
-
5.
Clinical attachment loss: Evaluated the extent of attachment loss. (Stage I ◊ 1–2 mm; Stage II ◊ 3–4 mm; Stage III ◊ ≥ 5 mm; Stage IV ◊ ≥ 5 mm)
-
6.
Radiographic examination: Conducted a bitewing radiograph to visualize bone levels and detect bone loss. (Stage I ◊ Coronal third < 15%; Stage II ◊ Coronal third 15–33%; Stage III & IV ◊ Extending to middle 1/3rd of root & beyond)
Fig. 1.

Periodontal probing depth and radiographic evidence of bone loss
The perceived stress scale
Each participant was instructed to fill out the Perceived Stress Scale (PSS) [20], which is a commonly used tool for measuring psychological stress. It quantifies the level of stress in one’s life. The items assessed the unpredictability, uncontrollability, and overload of the respondents’ lifestyles. The measure also inquires explicitly about stress levels.
Scores on the PSS vary from 0 to 40, with elevated scores indicating increased perceived stress levels.
Ratings between 0 and 13 denote low stress.
Ratings between 14 and 26 indicate moderate stress.
Ratings between 27 and 40 signify high perceived stress.
The PSS was primarily designed for community samples consisting of individuals with a junior high school education. The items and answer possibilities are clear and unambiguous. The questions also do not contain content that is distinctive to subpopulations. The PSS inquires about one’s most recent emotional state. The researchers inquired about the frequency with which the respondents encountered each emotion. Researchers in Pakistan have employed the PSS due to its availability in both English and Urdu, the native language of Pakistan.
Salivary sample collection
Saliva samples were obtained within the time frame of 9 to 11 am to assess cortisol levels in the morning and minimize the impact of circadian rhythm. The “cortisol awakening reaction” (CAR) refers to the phenomenon where cortisol levels peak in the morning and to their lowest point at night. Prior to the salivary cortisol test, subjects were required to observe a waiting period of 30–60 min after consuming food, beverages, chewing gum, or brushing their teeth. Saliva samples were collected by allowing the flow of saliva into sterile Eppendorf tubes for a duration of three minutes. Subsequently, we collected the saliva samples and stored them in tubes, preserving them at a temperature of -20 degrees Celsius till we analysed them using the ELISA technique within a period of one month.
Statistical analyses
The data analysis was conducted using statistical tools, such as SPSS version 23.0. The descriptive statistics included a summary of several participant characteristics, including age and gender. Additionally, it included oral health indicators such as the gingival index and plaque index, as well as information on periodontal status, including periodontitis, CAL (clinical attachment loss), and PPD (probing pocket depth). Furthermore, the study also examined stress scores using the Perceived Stress Scale and salivary cortisol levels. We employed the odds ratio (OR) chi-squared test to evaluate the uniformity of SCL values across different groups, specifically investigating whether the cortisol levels were similar between patients with and without periodontitis. Independent-samples t-tests were employed to examine continuous variables such as age and cortisol levels between the healthy controls and the periodontitis group. To examine the relationship between salivary cortisol and the severity of periodontitis (mild, moderate, severe), we used a one-way ANOVA to determine any overall differences. If the ANOVA result was significant, we next conducted Tukey’s post-hoc test to compare the severity groups pairwise. The stress scores, as measured by the Perceived Stress Scale, were compared between the healthy group and the periodontitis group using independent-samples t-tests. A significance level of p < 0.05 was consistently used for the analysis.
Results
Participant characteristics
This study included 120 subjects: 60 with periodontitis and 60 healthy controls. Participants included 76 men (63%) and 44 women (37%). Both cases and controls had a mean age of 41.75 years and a standard deviation of 8.53 years, which was not statistically significant.
Group comparisons
Independent Samples T Test was used to find whether the means between cases and controls was statistically significant. The oral health indices measured were Gingival index, Plaque index, Calculus index, Mobility index, Missing teeth, Periodontitis, CAL, and PPD. Stress was measured by a questionnaire PSS and SCLs (nmol/L). The difference between the two groups in terms of oral health indices and stress markers were significantly greater in cases (all P trend < 0.001). The SCLs (mean ± SD) of cases and controls were 6.67 ± 1.64 and 2.54 ± 0.88, respectively (Table 2).
Table 2.
Comparison between cases and controls
| Cases (n = 60) Mean ± SD |
Controls (n = 60) Mean ± SD |
p value | |
|---|---|---|---|
| Oral Health Indices | |||
| Gingival Index | 1.98 ± 0.50 | 0.90 ± 0.75 | < 0.001 |
| Plaque Index | 1.80 ± 0.51 | 1.16 ± 0.84 | < 0.001 |
| Calculus Index | 1.53 ± 0.53 | 0.78 ± 0.71 | < 0.001 |
| Mobility Index | 1.96 ± 0.71 | 0.00 ± 0.00 | < 0.001 |
| Periodontitis | 2.12 ± 0.55 | 0.00 ± 0.00 | < 0.001 |
| Clinical Attachment loss, mm | 3.11 ± 1.12 | 0.00 ± 0.00 | < 0.001 |
| Periodontal Pocket Depth, mm | 2.28 ± 0.66 | 1.46 ± 0.62 | < 0.001 |
| Markers of Stress | |||
| Perceived Stress Scale | 2.05 ± 0.59 | 1.38 ± 0.52 | < 0.001 |
| Salivary Cortisol, nmol/L | 5.82 ± 2.42 | 2.54 ± 0.88 | < 0.001 |
Note: Independent Samples T Test was used to find whether the means between cases and controls was statistically significant; <0.001 = Extremely significant. Abbreviations: SD, standard deviation.
In periodontitis patients, radiographic bone loss (RBL) was observed in 26.6% of those with Stage I periodontitis, 53.3% in Stage II, and 20% in Stages III and IV combined.
Association between stress and periodontitis
Given the strong association between stress and salivary cortisol levels, we used the SCLs of individuals experiencing mild, everyday stress as the cutoff value. Salivary cortisol levels were classified as either within the normal range (1.33 to 3.00 nmol/L) or above the usual range (> 3.00 nmol/L). The odds ratio (OR) for the association between periodontitis and levels of salivary cortisol was 3.73 (95% CI [1.75, 7.93], p = 0.0006), indicating that individuals with periodontitis were over 3.5 times more likely to have higher salivary cortisol levels.
According to the classification of periodontitis, 21.6% had stage I, 58.3% had stage II, and 20% had stages III & IV combined. One-way Anova was performed to determine how the levels of salivary cortisol (nmol/L) and PSS affected the severity of periodontitis (Table 3). The findings demonstrated that the mean PSS had a statistically significant increase in correlation with the degree of periodontitis, F (2, 57) = 11.19, p < 0.001. The severity of periodontitis was also significantly correlated with significant increases in the mean levels of salivary cortisol, F (2, 57) = 33.58, p < 0.001. The means ± SD for PSS and salivary cortisol according to the severity of periodontitis are also given in the Table 3.
Table 3.
Comparison of PSS and Salivary Cortisol levels with the severity of Periodontitis (n = 60)
| Periodontitis | ||||
|---|---|---|---|---|
| Stage I (n = 13) | Stage II (n = 35) | Stage III & IV (n = 12) | P | |
| Perceived Stress Scale | 1.53 ± 0.51 | 2.08 ± 0.50 | 2.50 ± 0.52 | < 0.001 |
|
Salivary Cortisol nmol/L |
3.95 ± 2.03 | 5.37 ± 1.75 | 9.17 ± 0.65 | < 0.001 |
One-Way ANOVA was used to compare means between cases. * p < 0.05 = significant.
Distribution of participants based on psychological stress and Periodontitis
Psychological stress was potentially measured through validated stress questionnaire, the PSS.
As previously mentioned in methodology, the PSS assigns scores ranging from 0 to 40, with higher scores reflecting greater perceived stress. Here’s a breakdown of what the scores indicate:
0–13: Low stress.
14–26: Moderate stress.
27–40: High perceived stress.
We considered the cut-off value of being in stress as 14 or above, as mild stress is essential part of life. Cases and controls with and without stress were significantly different, as seen in Table 4. Seventy-three of the individuals who filled out the PSS questionnaire and participated in this study were found to be stressed. While 42.5% were classified as cases, just 18.33% were designated controls, even though they too had experienced stress but were clear of periodontitis. Stress-free people accounted for 31.6% of the healthy population and 7.5% of the periodontitis patients.
Table 4.
The distribution of participants based on stress and periodontitis
| Stress | |||
|---|---|---|---|
| Cases | Controls | Total | |
| With | 51 (42.5%) | 22 (18.33%) | 73 (60.83%) |
| Without | 9 (7.5%) | 38 (31.66%) | 47 (39.16%) |
| Total | 60 (50%) | 60 (50%) | 120 (100%) |
Discussion
This case-control study explores the intricate relationship between stress, salivary cortisol levels, and periodontitis. Our findings corroborate existing research, indicating a significant correlation between elevated salivary cortisol levels and increased severity of periodontitis. Patients with periodontitis not only exhibited markedly higher cortisol levels and perceived stress scores compared to healthy controls but also demonstrated a strong association between stress and periodontal disease severity, reinforcing the impact of stress on periodontal health and supporting the potential use of salivary cortisol as a biomarker for disease progression, underscoring the potential influence of psychoneuroimmunologic factors on periodontal health [21].
The decision to focus on individuals aged 30 to 60 stems from their heightened susceptibility to stressors like financial strain, work pressure, and personal crises, all of which can elevate cortisol levels and predispose individuals to periodontal diseases. Epidemiological evidence supports this assertion, with studies by Genco et al. (1998) and Tanveer et al. (2021) providing additional support for the link between stress and periodontitis [22, 23].
Moreover, our study underscores the bidirectional nature of the relationship between stress and periodontal disease, implicating immune dysregulation and oral microbiome dysbiosis as key mediators [24]. By integrating perceived stress scores and salivary cortisol levels, we offer a comprehensive assessment of stress’s impact on periodontal health, with higher stress levels correlating with elevated cortisol levels and increased severity of periodontal disease. Periopathogenic bacteria trigger inflammation, but the severity of the disease is influenced by immune responses. Cortisol, a stress hormone, has a negative effect on immunity during chronic stress [25].
Periodontitis increases reactive oxygen species in periodontal lesions, leading to higher levels of oxidized LDL and oxidative stress in the blood. Treatment, including improved oral hygiene and non-surgical periodontal care, effectively reduces these oxidative markers, demonstrating the impact of managing periodontitis on lowering oxidative stress [26].
Our study demonstrated a significant association between periodontitis and elevated SCLs, with an OR of 3.73 (95% CI [1.75, 7.93], p = 0.0006), suggesting a strong link between periodontitis and increased psychological stress. In contrast, a study on maternal psychological distress found no significant correlation between distress and cortisol levels (OR 1.4, 95% CI [0.9–2.0]). The discrepancy may stem from differences in the nature of the stressors, as periodontitis involves persistent inflammation directly impacting physiological stress pathways, whereas psychological distress may not consistently translate to measurable cortisol changes. Another study indicated a direct relationship between the levels of cortisol in saliva and the presence of dental biofilm during the 33rd week of pregnancy. These findings highlight the distinct ways chronic inflammatory conditions and psychological factors can affect the HPA axis, suggesting a need for further research into these complex interactions [27, 28].
According to our current study, even individuals without periodontal disease exhibit cortisol presence in their saliva, albeit at significantly lower levels compared to those with the condition. Cortisol potentially affects immune-regulating chemotaxis in clinically healthy tissues. Within a healthy oral cavity, various microorganisms reside, potentially triggering low-grade periodontal inflammation. Notably, the relationship between periodontal disease and SCL severity remains understudied. However, a study in 2020 highlighted that elevated cortisol levels exacerbate periodontitis, revealing a diversity of severity in salivary cortisol level-associated periodontal disease [29].
In our study, we observed a notable trend: stress levels appeared to increase in conjunction with PPD. Additionally, we identified a positive correlation between SCLs and stress, indicating that elevated stress levels coincide with higher cortisol levels. Notably, researchers have uncovered a similar positive correlation between salivary cortisol and PPD, particularly noting that higher cortisol levels are linked to an increased number of PPD locations falling within the 5–7 mm range. These findings are consistent with several other studies in the field [30, 31].
Nouri et al. (2021) underscored that periodontitis not only manifests in deteriorating oral health but also correlates with heightened levels of tension, anxiety, and depression, alongside notable alterations in biochemical markers such as alpha-amylase and salivary cortisol. Their findings illuminate a complex interplay between psychological factors and periodontal health. Intriguingly, the study suggests that anxiety and depression may serve as more reliable predictors of periodontitis compared to acute stress and cortisol levels alone, shedding light on the nuanced relationship between mental well-being and oral health outcomes [32]. A recent study found a strong correlation between periodontitis and elevated levels of stress, anxiety, and depression among a sample of 50 undergraduate students [33]. Typically, the diagnosis of these psychiatric diseases necessitates the careful observation of the patient and conducting interviews with both the patient and their family. Nevertheless, a single study has assessed putative salivary biomarkers, including cortisol, lysozyme, Immunoglobulin A, alpha-amylase, fibroblast growth factor and chromogranin A, which may offer more definitive evidence of these disorders. Moreover, these biomarkers can assist in distinguishing between the illnesses [34].
Moreover, a study conducted in Pakistan corroborated these findings by revealing a significant association between severe depression and elevated salivary cortisol levels. This suggests a bidirectional relationship wherein psychological distress may not only predispose individuals to periodontal disease but also contribute to dysregulation in stress hormone levels, potentially exacerbating the progression of periodontitis. These insights highlight the importance of considering mental health factors in the comprehensive management and understanding of periodontal conditions [35].
Tanveer et al. (2021) conducted a study to investigate the impact of psychological stress on women’s periodontal health. Their research focused on a sample of approximately 385 individuals from shelters. Assessments of community periodontal health and stress levels were conducted utilizing the community periodontal index and perceived stress scale, respectively. The findings elucidated that woman facing socioeconomic disadvantages are disproportionately affected by mental stress stemming from periodontal disease. These insights underscore the importance of considering social determinants of health in understanding the multifaceted nature of periodontal conditions and their impact on vulnerable populations [23].
Obulareddy et al. (2018) conducted a study in India to investigate the correlation between psychological stress and periodontitis. The study involved a total of 92 participants. The results indicated that individuals experiencing both stress and periodontitis exhibited a notably high mean SCL. Salivary cortisol was found to be associated with both periodontitis and psychological stress, suggesting a potential link between stress response mechanisms and periodontal health outcomes [36].
Another study found a strong relationship between emotional stress, smoking, and periodontitis. Smokers with periodontitis have higher salivary cortisol levels than serum cortisol levels, and higher salivary IL-1β levels compared to non-smokers with periodontitis. Smokers also exhibit higher stress levels, which correlate positively with salivary cortisol in both smokers and non-smokers. Further long-term studies and interventional periodontal therapy evaluations are needed for definitive conclusions [37].
It is imperative not to discount the influence of stress on periodontal health, given the substantial body of evidence supporting its involvement in this oral health concern. Therefore, there is a critical need for further research involving diverse population groups to thoroughly investigate the impact of stress on periodontal disease and elucidate the precise nature of the relationship between them.
Limitations of the study
While our study sheds light on the relationship between stress, cortisol, and periodontitis, it has limitations. The cross-sectional design precludes establishing causality. We cannot definitively conclude that stress causes increased cortisol levels, which then lead to periodontitis. Longitudinal studies are crucial to confirm a cause-and-effect relationship, tracking cortisol levels and periodontal health over time [38].
Furthermore, our study’s relatively small sample size might limit the generalizability of our findings to larger populations. Future research with more diverse and geographically representative cohorts is necessary to strengthen the generalizability of this association [39].
Finally, relying solely on self-reported stress through questionnaires might introduce bias. Participants might underreport or overreport stress levels based on social desirability or difficulty recalling past experiences. Incorporating objective stress measures, such as heart rate variability or salivary alpha-amylase levels, could enhance the study’s reliability [40].
Future research
Subsequent research should examine the efficacy of stress management interventions, such as mindfulness-based or cognitive-behavioural therapies, on periodontal health and supporting structures, and investigate the connection between stress, cortisol and periodontal disease in particular groups, such as pregnant women or individuals with chronic illnesses. Longitudinal studies are necessary to investigate the influence of chronic stress on the advancement of periodontal disease and determine whether salivary cortisol levels can be used as biomarkers for the early identification and prevention of the disease. Incorporating stress evaluation and control measures into regular dental treatment, creating stress assessment instruments that can be used during dental procedures, and examining the impact of stress reduction approaches on periodontal outcomes could yield significant knowledge on the relationship between psychological and oral health aspects.
Conclusion
In conclusion, our study strengthens the evidence for a potential link between stress, cortisol levels, and periodontitis. The presence of reactive oxygen species in periodontal lesions further highlights the biological impact of periodontitis, leading to increased oxidative stress. Treatment, including improved oral hygiene and non-surgical periodontal care, effectively reduces oxidative stress markers, emphasizing the importance of managing periodontitis for better systemic health. Salivary cortisol assessment shows promise as a biomarker for psychosocial factors influencing periodontal health.
However, further research is needed to explore the longitudinal effects of stress on cortisol levels and periodontal disease progression in larger and more diverse populations. Integrating salivary cortisol measurements into routine dental evaluations could offer valuable insights for personalized treatment plans. By addressing both biological and psychological factors that contribute to periodontitis, clinicians can potentially optimize treatment outcomes and promote better periodontal health for patients. Additionally, future research should explore the potential of stress management interventions as an adjunct therapy for managing periodontitis, particularly in individuals with high levels of perceived stress.
Acknowledgements
Not applicable.
Abbreviations
- CAL
Clinical Attachment Loss
- CAR
Cortisol Awakening Reaction
- DUHS
Dow University of Health Sciences
- GI
Gingival Index
- HPA
Hypothalamic-Pituitary-Adrenal
- IL-1
Interleukin-1
- IL-6
Interleukin-6
- MI
Mobility Index
- OR
Odds Ratio
- PI
Plaque Index
- PPD
Periodontal Probing Depth
- PSS
Perceived Stress Scale
- SCL
Salivary cortisol level
Author contributions
MRH: Conceptualization, formal analysis, interpretation of data for the work, and revising it critically for important intellectual content, review and final approval of manuscript. MO: Data curation, writing original draft. SS: Review and final approval of manuscript. SN: Methodology and writing – review and editing. YSA: Data curation and formal analysis. All authors read and approved the final version of the manuscript.
Funding
We did not receive any funding for this work.
Data availability
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Declarations
Ethics approval and consent to participate
Ethical approval of this study was obtained from the Institutional Review Board (IRB) committee of Dow University of Health Sciences, Karachi. (Ref: IRB-2382/DUHS/Approval/2022/758, dated 22nd February, 2022). All participants gave written informed consent.
Consent for publication
Not applicable.
Competing interests
The authors declare no competing interests.
Disclosure
This article was written from Physiology Thesis of MPhil Scholar Muhammad Owais.
Footnotes
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
References
- 1.Frencken JE, Sharma P, Stenhouse L, Green D, Laverty D, Dietrich T. Global epidemiology of dental caries and severe periodontitis - a comprehensive review. J Clin Periodontol. 2017;44(Suppl 18):S94–105. 10.1111/jcpe.12677. Article PubMed Google Scholar. [DOI] [PubMed] [Google Scholar]
- 2.Bibi T, Arshad Hassan DR, Kumar C, Naz A, Tanwir F, Qadir F, Mazhar S. Prevalence of periodontitis based on ethnic disparity in Karachi, Pakistan. J Xi’an Shiyou Univ. Nat Sci Ed. 2023;19(3):970–87. Research Gate Google Scholar. [Google Scholar]
- 3.Naderi S, Merchant AT. The Association between Periodontitis and Cardiovascular Disease: an update. Curr Atheroscler Rep. 2020;22:52. 10.1007/s11883-020-00878-0. Article PubMed Google Scholar. [DOI] [PubMed] [Google Scholar]
- 4.Isola G, Pesce P, Polizzi A, Lo Giudice A, Cicciù M, Scannapieco FA. Effects of minimally invasive non-surgical therapy on C-reactive protein, lipoprotein-associated phospholipase A2, and clinical outcomes in periodontitis patients: A 1-year randomized, controlled clinical trial. J Periodontol. 2024 May 2. doi: 10.1002/JPER.23-0518. Epub ahead of print. PMID: 38696664. Article PubMed Google Scholar. [DOI] [PubMed]
- 5.Matarese G, Ramaglia L, Fiorillo L, Cervino G, Lauritano F, Isola G. Implantology and Periodontal Disease: the panacea to Problem solving? Open Dent J. 2017;11:460–5. doi: 10.2174/1874210601711010460. PMID: 28979575; PMCID: PMC5611775. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Hajishengallis G. Interconnection of periodontal disease and comorbidities: evidence, mechanisms, and implications. Periodontol 2000. 2022;89(1):9–18. 10.1111/prd.12430. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Gayatri RW, Tama TD, Alma LR, Yun LW, Savira L, Kuroidah A. Behavioral risk factors and periodontal disease in Malang. Indonesia Gac Sanit. 2021;35(Suppl 2):S438–40. 10.1016/j.gaceta.2021.10.071. Article PubMed Google Scholar. [DOI] [PubMed] [Google Scholar]
- 8.Yaribeygi H, Panahi Y, Sahraei H, Johnston TP, Sahebkar A. The impact of stress on body function: a review. EXCLI J. 2017;16:1057–72. 10.17179/excli2017-480. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Haykin H, Rolls A. The neuroimmune response during stress: a physiological perspective. Immunity. 2021;54(9):1933–47. 10.1016/j.immuni.2021.08.023. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10.Macrì M, D’Albis G, D’Albis V, Antonacci A, Abbinante A, Stefanelli R, Pegreffi F, Festa F. Periodontal Health and Its Relationship with Psychological Stress: A Cross-Sectional Study. J Clin Med. 2024;13(10):2942. 10.3390/jcm13102942. Article Research Gate Google Scholar. [DOI] [PMC free article] [PubMed]
- 11.Greaney JL, Surachman A, Saunders EF, Alexander LM, Almeida DM. Greater daily psychosocial stress exposure is associated with increased norepinephrine-induced vasoconstriction in young adults. J Am Heart Assoc. 2020;9(9):e015697. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Kazakou P, Nicolaides NC, Chrousos GP. Basic concepts and hormonal regulators of the stress system. Horm Res Paediatr. 2023;96(1):8–16. 10.3390/healthcare11101516. Article PubMed Google Scholar. [DOI] [PubMed] [Google Scholar]
- 13.Vage A, McCarron E, Hamilton PK. Biological testing during acute psychological stress: a hindrance or an opportunity? Clin Biochem. 2023;114:11–7. 10.1016/j.clinbiochem.2023.01.005. Article PubMed Research Gate Google Scholar. [DOI] [PubMed] [Google Scholar]
- 14.López-Jornet P, Hynninen JN, Parra-Perez F, Peres-Rubio C, Pons-Fuster E, Tvarijonaviciute A. The Role of Salivary Biomarkers in Monitoring Oral Health in Patients with Implants and Periodontitis. Appl Sci. 2024;14(2):927. 10.3390/app14020927. Article Research Gate Google Scholar.
- 15.Obulareddy VT, Chava VK, Nagarakanti S. Association of Stress, salivary cortisol, and chronic periodontitis: a clinico-biochemical study. Contemp Clin Dent. 2018;9(Suppl 2):S299–304. 10.4103/ccd.ccd_289_18. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 16.Papapanou PN, Sanz M, Buduneli N, Dietrich T, Feres M, Fine DH, et al. Periodontitis: Consensus report of workgroup 2 of the 2017 World workshop on the classification of Periodontal and Peri-implant diseases and conditions. J Periodontol. 2018;89(S1):73–82. Article PubMed Google Scholar. [DOI] [PubMed] [Google Scholar]
- 17.Ayan G, Dayi B. Evaluation of plaque index, gingival index and oral health-related quality of life in obese patients. Odovtos-International J Dent Sci. 2023;25(1):166–78. 10.15517/ijds.2022.52533. Article Google Scholar. [Google Scholar]
- 18.Greene JC, Vermillion JR. The oral hygiene index: a method for classifying oral hygiene status. The J Am Dent Assoc. 1960;61(2):172–179. 10.14219/jada.archive.1960.01. Article.
- 19.Azodo CC, Umoh AO. Tooth mobility among rural dwellers in midwestern area of Nigeria. Savannah J Med Res Pract. 2014;3(2):64 – 9. 10.4314/sjmrp.v3i2.3. Article Google Scholar.
- 20.Cohen S, Kamarck T, Mermelstein R. A global measure of perceived stress. J Health Soc Behav. 1983;24:386–96. Article PubMed. [PubMed] [Google Scholar]
- 21.Corridore D, Saccucci M, Zumbo G, Fontana E, Lamazza L, Stamegna C et al. Impact of Stress on Periodontal Health: Literature Revision. Healthcare (Basel). 2023;22;11(10):1516. 10.3390/healthcare11101516. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed]
- 22.Genco RJ, Ho AW, Kopman J, Grossi SG, Dunford RG, Tedesco LA. Models to evaluate the role of stress in periodontal disease. Ann Periodontol. 1998;3(1):288–302. Article PubMed Google Scholar. [DOI] [PubMed] [Google Scholar]
- 23.Tanveer SA, Afaq A, Alqutub MN, Aldahiyan N, AlMubarak AM, Shaikh AC, et al. Association of self-perceived psychological stress with the periodontal health of socially deprived women in shelter homes. Int J Env Res Pub He. 2021;18(10):e5160. 10.3390/ijerph18105160. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 24.Spector AM, Postolache TT, Akram F, Scott AJ, Wadhawan A, Reynolds MA. Psychological stress: a predisposing and exacerbating factor in periodontitis. Curr Oral Health Rep. 2020;7:208 – 15. 10.1007/s40496-020-00282-2. Article Research Gate Google Scholar.
- 25.Knezevic E, Nenic K, Milanovic V, Knezevic NN. The role of cortisol in chronic stress, neurodegenerative diseases, and Psychological disorders. Cells. 2023;12(23):2726. 10.3390/cells12232726. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Tamaki N, Tomofuji T, Ekuni D, et al. Periodontal treatment decreases plasma oxidized LDL level and oxidative stress. Clin Oral Invest. 2011;15:953–8. 10.1007/s00784-010-0458-y. Article PubMed Google Scholar. [DOI] [PubMed] [Google Scholar]
- 27.Vlenterie R, Geuijen PM, van Gelder MMHJ, Roeleveld N. Questionnaires and salivary cortisol to measure stress and depression in mid-pregnancy. PLoS ONE. 2021;16(4):e0250459. 10.1371/journal.pone.0250459. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 28.Tiznobaik A, Taheri S, Torkzaban P, Ghaleiha A, SOLTANİAN AR, Omrani R, et al. Relationship between dental plaque formation and salivary cortisol level in pregnant women. Eur Oral Res. 2019;53(2):62–6. 10.26650/eor.20192484. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 29.Develioglu H, Korkmaz S, Dundar S, Schlagenhauf U. Investigation of the levels of different salivary stress markers in chronic periodontitis patients. J Oral Biol Craniofac Res. 2020;10(4):514–8. 10.1016/j.jobcr.2020.07.020. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Zhang J, Lin S, Luo L, Zhang Q, Jiao Y, Liu W. Psychological stress: neuroimmune roles in periodontal disease. Odontology. 2023;111(3):554–64. 10.1007/s10266-022-00768-8. Article PubMed Google Scholar. [DOI] [PubMed] [Google Scholar]
- 31.Helmy SM, Nassar HA, Ahmed OE. The effect of psychological stress on Periodontal Disease during COVID-19 virus threat: relation to salivary prostaglandin (PGE2). Al-Azhar Dent J Girls. 2023;10(1):139–50. Article Google Scholar. [Google Scholar]
- 32.Nouri P, Fereidooni M, Faramarzi M, Sadeghi S, Qujeq D, Neamati N. Evaluation of Association between Perceived stress, anxiety, Depression, Salivary Alpha-Amylase and Salivary Cortisol with Chronic Periodontitis. J Dent Oral Disord. 2021;7(1):1152. Research Gate Google Scholar. [Google Scholar]
- 33.Mankar K, Bawankar P, Chavan P, Borkar S. Association of Stress, Depression and anxiety with Periodontal Health indicators among Professional Students. Int J Behav Healthc Res. 2021;6(2):82–7. 10.52403/ijshr.20210416. Article Google Scholar. [Google Scholar]
- 34.Chojnowska S, Ptaszyńska-Sarosiek I, Kępka A, Knaś M, Waszkiewicz N. Salivary biomarkers of stress, anxiety and depression. J Clin Med. 2021;10(3):517. 10.3390/jcm10030517. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Khan QU. Relationship of salivary cortisol level with severe depression and family history. Cureus. 2020;12(11):e11548. 10.7759/cureus.11548. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Obulareddy VT, Chava VK, Nagarakanti S. Association of stress, salivary cortisol, and chronic periodontitis: a clinico-biochemical study. Contemp Clin Dent. 2018;9(Suppl 2):S299. 10.4103/ccd.ccd_289_18. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 37.Bawankar PV, Kolte AP, Kolte RA. Evaluation of stress, serum and salivary cortisol, and interleukin-1β levels in smokers and non‐smokers with chronic periodontitis. J Periodontol. 2018;89(9):1061–8. 10.1002/JPER.18-0028. Article PubMed Google Scholar. [DOI] [PubMed] [Google Scholar]
- 38.Mikkelsen S, Forman JL, Fink S, Vammen MA, Thomsen JF, Grynderup MB, et al. Prolonged perceived stress and saliva cortisol in a large cohort of Danish public service employees: cross-sectional and longitudinal associations. Int Arch Occup Environ Health. 2017;90(8):835–48. 10.1007/s00420-017-1241-z. Article PubMed PubMed Central Google Scholar. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 39.Tipton E, Hallberg K, Hedges LV, Chan W. Implications of small samples for generalization: adjustments and rules of Thumb. Eval Rev. 2017;41(5):472–505. Article PubMed Google Scholar. [DOI] [PubMed] [Google Scholar]
- 40.Ali N, Nater UM. Salivary alpha-amylase as a biomarker of stress in behavioral medicine. Int J Behav Med. 2020;27(3):337–42. 10.1007/s12529-019-09843-x. [DOI] [PMC free article] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Data Availability Statement
The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
