The effect of stress on periodontitis: A clinicobiochemical study.

BACKGROUND: Clinical and epidemiological data suggest that negative life experience events, like depression, may contribute to an increased susceptibility to periodontal disease. AIM: To study the association between psychological stress and chronic periodontitis.
MATERIALS AND METHODS: One hundred and eleven dentate individuals, of age 40 years and above, were selected. The clinical examination included, the number of teeth present, plaque index, Probing Pocket Depth, and Clinical Attachment Level. Assessment of Psychological stress levels were done by a questionnaire and were correlated with salivary cortisol levels, which were estimated biochemically by using the Enzyme-Linked Immunosorbent Assay (ELISA) method.
RESULTS: Statistical analysis was done by using the student 't' test and Mann Whitney test. According to our observation, chronic periodontitis showed a significant correlation with hypercortisolemia (P<0.0001), work tension (P=0.04), economic problems (P<0.0001), clinical stress syndrome (P<0.0001), plaque index (P<0.0001), and unsecured job (P=0.003).
CONCLUSION: Stress may be considered as an important risk factor for periodontal disease. Routine salivary cortisol assessment may be an economical and useful diagnostic marker to rule out stress in periodontitis patients.

INTRODUCTION

Negative life events manifested as psychological stress and depression are common in day-to-day life, emphasizing the relationship between the person and environment.[1]

Stress is said to influence the host defenses, exerting an immunosuppressive effect, increasing one's vulnerability to disease.[2-4] Cytokines and other humoral mediators of inflammation are potent activators of the central stress response, and the glucocorticoids released via this mechanism might regulate the recruitment of immune cells into inflamed tissues, in order to cope with the psychological stress and depression.[56] When the inflammatory action is sufficiently long and profound, the systemic manifestations of the disease may become evident, as could happen with periodontitis.

The relationship between periodontal illness and the psychological predisposing factors is well-established in specific conditions, like, Acute Necrotizing Ulcerative Gingivitis (ANUG) is identified to be significantly associated with high levels of trait anxiety, depression, and other emotional disturbances.[78]

Few studies have demonstrated the importance of subjective factors in oral infections and stress.[9-11] Prospective investigations have also demonstrated the importance of psychological disturbances on the progression of periodontitis[1213] and its response to treatment.[14]

Studies also explain this relationship by the modulation of the immune system, through neuroendocrinal interactions and alterations in oral health behavior.[15] Therefore, factors related to the social and environment may provoke changes in the host defenses and modify health behavior. However, why and how these factors are associated with an increase in periodontal disease susceptibility are poorly understood at this stage. Even though investigators have studied the impact of the immune response and of psychological components on the extent and severity of periodontitis, very few studies exist that demonstrate the impact of stress on the status of the well-being of the immune system and health of the periodontium.

Hence, an attempt was made in this present study to evaluate the effects of psychological stress and salivary cortisol on chronic periodontitis.

MATERIALS AND METHODS

A cross-sectional study was conducted by the Department of Periodontics, Narayana Dental College and Hospital, Nellore, involving a sample size of 111 patients, to evaluate the psychological stress and salivary cortisol levels and their effect on chronic periodontitis.

The patients with an age group of 40 years and above, with at least 20 teeth in the mouth, were selected and recruited for the study.

Excluding criteria included:

Patients who were using corticosteroid drugs chronically

Patients who were using immunosuppressive drugs

Immunosuppressed persons

Patients who had undergone periodontal treatment six months before examination.

The nature of the study was explained to all the participants and consent was obtained prior to the commencement of the study. A detailed Institutional Ethical Committee Approval was taken before the start of the study.

All participants answered a questionnaire on the demographic variables and socioeconomic level, smoking, health history, and health problems.

Psychological evaluation

Lipp's Stress Symptoms for Adults Inventory,[16] a psychological evaluation tool developed and validated, was applied by psychology students, under the guidance of a psychologist, to detect whether a patient presented a clinical stress syndrome. After completion of the inventory, the participants received the materials for saliva collection, and the date for the clinical examination was set.

Study Method: Two independent examiners performed the clinical examinations. Probing Pocket Depth and Clinical Attachment Level were measured and recorded to the nearest millimeter, at six sites per tooth, using the William's periodontal probe§ . Individuals with a probing depth ≥ 4 mm and CAL ≥ 3 mm at the same site, in at least four teeth, were considered to have chronic localized periodontitis.[17] The plaque was assessed by using the Sillness and Loe plaque index (1964).[18]

A ‘pre-study’ reliability test was conducted by performing duplicate dental examinations in ten participants, selected at the Department of Periodontics, Narayana Dental College and Hospital. The re-examinations to evaluate reproducibility ′during the study′ were performed two hours after the end of the initial examination in the participants.

After the clinical examinations all the subjects were asked to report the next day between 8 AM and 10 AM for collection of saliva samples. Whole saliva was collected by means of sterilized cotton rolls. Individuals were asked to keep a cotton roll in the mouth sublingually for three minutes. It was transferred into containers and stored at -20°C in the freezer. Samples were analyzed for cortisol by using the ELISAFNx01 method, within 24 hours of collection. Conjugate of 200 μl was added to 20 μl of saliva in polystyrene wells. After incubating for one hour the solution in the polystyrene wells was washed with a buffer solution. Then 100 μl of substrate was added to the same polystyrene well. After 15 minutes, 100 μl of Stoppers solution was added and placed in the ELISA reader for electronic readings.

RESULTS

Descriptive statistical analyses and univariate / multivariate logistic regression analyses were done with the SPSS system. Unadjusted and adjusted risk ratios were calculated with 95% confidence intervals. Statistical significance was defined as P<0.05.

When a comparison of means and standard deviations of different subjective variables between groups was done, the plaque index showed high significance at 1% level, whereas, the others did not show any significance, as shown in Table 1.

Table 1

Comparison of means and standard deviations of different subjective variables in group 1 and group 2

High significance was observed when the clinical stress syndrome (P<0.0001), cortisol levels (P<0.0001), employment status (P=0.003), work tension (P=0.04), and death of relatives (P=0.04) were compared between the groups, as shown in Table 2.

Table 2

Comparison of means and standard deviations of different variables in group 1 and group 2

Results of the logistic regression analysis are shown in terms of crude and adjusted OR's and corresponding 95% CI [Tables 3 and 4]. Hypercortisolemia (P<0.0001), Plaque index scores (P=0.003), economic status (P<0.0001), and employment status (P = 0.009) were significant variables in the univariate analysis, as shown in the Table 3.

Table 3

Results of univariate logistic regression analysis

Table 4

Results of multiple logistic regression analysis

Hypercortisolemia (P<0.0001), economic status (P=0.02), and work tension (P=0.004) were significant at a 1% level, when a multiple logistic regression analysis was done, as shown in Table 4.

DISCUSSION

The results of this clinicobiochemical study involving 111 subjects have shown an association between elevated levels of cortisol in subjects, aged 40 years and above, with periodontitis. This age group was selected, because patients above 40 years of age would come across many negative life events such as financial problems, overload at work, death of partner / close relative / close friend, divorce, major personal illness, and retirement, which cause an increase in the salivary cortisol level persistently, for a long time, causing stress and ultimately leading to various systemic diseases, including periodontal disease, and most of the epidemiological studies have indicated that both the severity[19] and prevalence[20] of chronic periodontitis are higher at this age.

The present study showed significant association between the cortisol level and psychological stress levels recorded by demographic and subjective variables in the proforma. This could be due to deregulation of the immune system, mediated through the hypothalamic-pituitary-adrenal and sympathetic-adrenal medullary axis[21]. The activation of this by means of stress might result in the release of an increased concentration of the corticotropin-releasing hormone from the hypothalamus, which in turn, may act on the anterior pituitary, resulting in the release of the adrenocorticotropic hormone (corticotropin). The corticotropin may then act on the adrenal cortex enhancing the production and release of cortisol into the circulation, leading to unwanted effects throughout the body, such as suppression of the inflammatory response, modifying cytokine profiles, elevation of blood glucose levels, and alteration of certain growth factor levels.[2223] Breivik.[24] have shown stressful stimuli and extreme genetic differences in the hypothalamus-pituitary-adrenal axis structure in rats and their susceptibility to periodontal disease. These differences between individuals with high- and low-responding hypothalamus-pituitary-adrenal axis could be modulated by environmental factors.[4] This is in disagreement with Mengel.[25] and Vedhara,[26] who did not find any association between cortisol and psychological stress. This may be related to the individual's response toward stress and limited sample size.

Our study showed a highly significant association between the mean cortisol levels and periodontal disease, this is in accordance with studies conducted by Genco.,[27] in a subsample of individuals with and without periodontitis. This could be attributed to the inhibition of T-cell immune responses mediated by glucocorticoids, leading to a change toward antibody-mediated immunity (Th2-mediated response), enhancing the growth of pathogenic microorganisms that can activate a cellular response.[28]

A significant association was established between work tension (P=0.04), economic problems (P<0.0001), insecure job (P=0.003) and chronic periodontitis. This is in accordance with the studies conducted by Monteiro da Silva.[10] and Moss.[13]

The other non-significant parameters in this study could be attributed to the female participants who were non-smokers and non-alcoholics.

This is one of the few human studies to evaluate the important role of psychological stress and hyperactivation of the hypothalamus-pituitary-adrenal axis, assessed by salivary levels of cortisol, on chronic periodontitis. According to our results, psychological stress and high salivary cortisol levels are associated with chronic periodontitis in the age group of 40 years and above, establishing a risk profile. Therefore, patients who are under stress should be provided more periodontal care to avoid initiation of periodontal disease or to avoid a more severe form of periodontal disease if the disease already exists, along with the treatment to reduce the stress.

However, to confirm this hypothesis longitudinal studies are necessary in order to evaluate the role of social support and stress-coping strategies, together with psychosocial / physiological stress, and progression of periodontitis.