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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 32  |  Issue : 4  |  Page : 354-359

Salivary cortisol could be a promising tool in the diagnosis of temporomandibular disorders associated with psychological factors


1 Department of Oral Medicine and Radiology, Genesis Institute of Dental Sciences and Research, Ferozepur, Punjab, India
2 Department of Oral Medicine and Radiology, M. M. College of Dental Sciences and Research, Mullana, Ambala, Haryana; Department of Oral Medicine and Radiology, Bapuji Dental College and Hospital, Davengere, Karnataka, India

Date of Submission05-May-2020
Date of Decision19-Oct-2020
Date of Acceptance23-Oct-2020
Date of Web Publication28-Dec-2020

Correspondence Address:
Dr. Gaurav Goyal
Department of Oral Medicine and Radiology, Genesis Institute of Dental Sciences and Research, Ferozepur, Punjab
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jiaomr.jiaomr_83_20

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   Abstract 


Background: Biopsychosocial models emphasize the multifactorial nature of temporomandibular disorders (TMDs). The role of cognitive, social, and biological factors in the etiology of TMDs has been reported. Aim: To test the salivary cortisol levels in young adults with the temporomandibular joint disorder and having positive depression level and with TMD but with negative depression level and compared with the control group. The correlation between cortisol levels and depression levels according to axis-II of Research Diagnostic Criteria (RDC) was assessed. Settings and Design: The study was a randomized, prospective, and double-blinded study. Materials and Method: The total sample comprised 60 subjects. The study comprised 20 subjects with TMD and depression, 20 subjects with TMDs and without depression, and 20 subjects were taken as the control group. To measure these variables, research diagnostic criteria (RDC/TMJ) were used for the study. Salivary cortisol levels were determined by Enzyme-linked immunosorbent assay (ELISA). Statistical Analysis: A paired t-test, ANOVA, and linear multi regression tests applied to compare the TMD groups with the control group. Results: The results showed that there was a positive correlation between morning and evening salivary cortisol levels in all the groups and the correlation coefficient was 0.729. There was a significantly higher value of salivary cortisol in TMD patients with depression than TMD patients without depression and the control group. Conclusion: Salivary cortisol could be a promising tool in identifying underlying psychological factors that could be associated with TMD.

Keywords: Psychological factors, research diagnostic criteria, salivary cortisol, TMD


How to cite this article:
Goyal G, Gupta D, Pallagatti S. Salivary cortisol could be a promising tool in the diagnosis of temporomandibular disorders associated with psychological factors. J Indian Acad Oral Med Radiol 2020;32:354-9

How to cite this URL:
Goyal G, Gupta D, Pallagatti S. Salivary cortisol could be a promising tool in the diagnosis of temporomandibular disorders associated with psychological factors. J Indian Acad Oral Med Radiol [serial online] 2020 [cited 2021 Jan 20];32:354-9. Available from: https://www.jiaomr.in/text.asp?2020/32/4/354/305279




   Introduction Top


Biopsychosocial models emphasize the multifactorial nature of the temporomandibular disorder (TMD). The role of cognitive, social, and biological factors in the etiology of TMDs has been reported.[1],[2] Future research on TMD etiology should emphasize both physiological and psychological factors and the relationship between them.[3],[4] There have been several previous attempts to link depression with the hypothalamic-pituitary-adrenal (HPA) axis response in TMD patients.[5],[6] Raised elevator tonus leads to increased intra-articular pressure in the temporomandibular joint (TMJ) and alteration in the normal biomechanics, resulting in micro traumatic damage to the joint capsules and disk attachment.[7],[8]

Depression has been shown to influence the expression of TMD signs and symptoms, but the relationship between these psychological variables and physiological parameters, such as cortisol levels, was not established in TMD patients.[9] With this in mind, the aim and objective of the study were to evaluate the salivary cortisol levels in young adults with temporomandibular joint disorder and positive depression levels.


   Material and Method Top


The total sample size comprised 60 subjects between the ages of 18 and 30 years. The sample size was divided into 30 males and 30 females. Out of 60 subjects, 20 subjects had TMDs and positive depression levels, 20 subjects had TMDs with no depression, and 20 subjects who were taken as the control group had no TMDs and depression. The control subjects were randomly selected who were coming to the department for any dental treatment. Only those controls were enrolled in the study who revealed a negative history of any systemic diseases and on questionnaire categorized under negative depression. The study was taken as a double-blinded protocol, as the lab investigator and patients were unaware of the groups which they had been allotted.

The sample size calculation was based on a reliable regression model, which suggested at least 10 samples per parameter. Assuming that a 10% dropout rate might occur, it was calculated that 11 patients would need to be enrolled in each group (i.e., 33 patients total). However, taking 5% CI and a maximum drop out of 30%, we have considered that 20 patients will give statistically sound results, so 60 patients had been taken.

Parallel random assignment to treatment arms was performed and simple type randomization was used with no restriction. An automated computerized system has been used for the random allocation sequence.

Ethical approval had been taken from the ethical cum research committee of the M. M. University regarding this study under the vide letter no. MMU/2010-321 dated Nov 2010 and a written informed consent form had been obtained from all the participants of the study. Not a single patient refused to take part in the study. The design of the study was prospective and double-blinded. The duration of the study was 2 years and 6 months. The study was conducted in accordance with the Declaration of Helsinki (1964) and Good Clinical Practice (GCP) guidelines.

Any systemic disease and ingestion of any other medication, which can increase the level of salivary/blood cortisol such as hyperpituitarism (overactive pituitary gland), benign and malignant pituitary tumors including adenomas, benign and malignant adrenal gland tumors, Cushing syndrome, Long term and a high dose of corticosteroid medications used to treat asthma, arthritis, certain cancers, pregnancy was used as exclusion criteria for all the groups.

For the TMD group with and without depression, the inclusion criterion was pain in the TMJ region for at least 3 months and conforming to the RDC/TMD criteria.

RDC/TMD Criteria[8]

a. AXIS-1 (Physical Conditions)

Group 1-with myofascial pain

  • Group 1a-with limited opening
  • Group 1b-without limited opening


Group 2-with disc displacement

  • Group 2a-with reduction
  • Group 2b-without reduction and with limited mouth opening
  • Group 2c-without reduction and without limited opening


Group 3-with arthralgia or arthritis

The subjects of the control group were selected only if they did not fulfill any of the Axis –I RDC/TMD criteria.

b. Axis -2 (Psychological Factors)

All subjects were subjected to the RDC/TMD AXIS-2 self-report measurement. These included the graded chronic pain scale (GCPS) and depression measurements as recommended by RDC/TMD.

All the subjects were asked to fill another questionnaire regarding the Graded Chronic Pain Scale and Depression, so they could be subjectively assessed for the severity of disease and depression. The depression was assessed by the standard questionnaire used for depression. The SCL-90 developed by Derogatis is a self-report instrument containing 90 items and designed to measure nine current psychiatric symptoms, and psychological depression.[10]

Saliva collection

The subjects were provided with plain plastic tubes to collect the saliva samples at home, twice a day, between 7:00 and 8:00 hrs on awakening and then again between 20:00 to 22:00 hrs because of the circadian rhythm of cortisol. The subjects were asked to abstain from eating and drinking one hour before the collection of saliva. However, water consumption was allowed before the collection of the saliva. They were also asked not to smoke, exercise, and brush their teeth before the collection of saliva. The morning post- awakening salivary cortisol samples were immediately handed to the laboratory, whereas for evening samples, the samples were kept in a refrigerator overnight and handed to the laboratory the next day.

Upon receipt at the laboratory, saliva samples were centrifuged and the clear fluid was stored at 70°C until analysis. Cortisol biochemical parameters were analyzed by commercially available reagent kits. The cortisol saliva enzyme-linked immunosorbent assay (ELISA) kit was supplied by Diagnostic Biochem (Canada). All saliva samples were analyzed at the Biochemistry Laboratory of M.M. College of Medical Sciences and Research, Mullana, Haryana, India. All the samples were analyzed by the expert faculty of the biochemistry department.

Statistical analysis

The collected data was put to statistical analysis using Statistical Package for Social Sciences software (SPSS inc., Chicago, IL, version 23.0 for Windows). Mean, median, range, and standard deviation (SD) for all variables in all the groups were calculated. A paired t-test was used to calculate the value of the difference in ratio between the TMD group and the control group. The Pearson correlation was performed to see the relationship between the mean value of cortisol in the morning and the evening. ANOVA was used to assess the means of salivary cortisol level of TMD patients without depression, TMD patients with depression, and the control group. A Wilcoxon signed-rank test was used to calculate between the TMD group and the control group. Linear multi regression between and psychosocial factors in both groups was performed and a linear correlation with associated values between cortisol levels and psychosocial factors. The P value < 0.05 was considered significant. Measurements were recorded by a single examiner. All patients completed the study and fully complied with the recall program.


   Results Top


The study has shown that for the TMD patients without depression, the minimum age of the subjects was 25 years and the maximum was 30 years. The mean age was 26.95 years with a standard deviation of 1.57. For the TMD patients with depression, the minimum age of the subjects was 23 years, and the maximum was 30 years. The mean age was 24.05 years with a standard deviation of 2.3. For the control group, the minimum age of the subjects was 22 years and the maximum age was 28 years. The mean age was 23.65 with a standard deviation of 1.59 [Table 1].
Table 1: Age Groups

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The Pearson correlation was performed to see the relationship between the mean value of cortisol in the morning and the evening. The result obtained showed that there was a positive correlation between the morning and evening salivary cortisol levels. The correlation coefficient was 0.90. The correlation was highly significant in the groups, with a P- value less than 0.0001. Thus, it shows that the salivary cortisol level is higher in the morning than in the evening [Table 2]a and [Table 2]b. The highest mean value was observed in TMD patients with depression in the morning group with a statistically significant P value of less than 0.05 [Table 3].


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Table 3: Mean Values of Morning and Evening Salivary Cortisol in TMD Patients Without Depression, TMD Patients with Depression and in Control Group

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According to the ANOVA test, when the means of morning salivary cortisol level in TMD patients without depression, TMD patients with depression, and with the control group were correlated, the results obtained showed that there was a statistically significantly higher value of salivary cortisol in TMD patients with depression than that of TMD patients without depression with a P value of 0.0001 and a mean difference of 32.2. There was also statistically significantly higher value of cortisol in TMD patients with depression than that of the control group with a P value less than 0.0001 and a mean difference of 39.6. However, when the comparison of salivary cortisol levels was done between the TMD without depression and the control group, the result showed a nonsignificant P value of 0.157 with a mean difference of 7.49 [Table 4]
Table 4: ANOVA Test - Correlation of the salivary cortisol level in TMD patients without depression, TMD patients with depression, and with control group

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The means of evening salivary cortisol level in TMD patients without depression, TMD patients with depression, and with the control group were correlated, the results obtained showed that there was a statistically significantly higher value of salivary cortisol in TMD patients with depression than that of TMD patients without depression with a P value of less than 0.0001 with a mean difference of 15.8. There was also a statistically significantly higher value of cortisol in TMD patients with depression than that of the control group with a P value less than 0.0001 with a mean difference of 19.6. However, when the comparison of salivary cortisol levels was done between the TMD without depression and the control group, the result showed a nonsignificant P value of 0.258 with a mean difference of 3.84 [Table 4].

[Table 5], showing gender variation in the mean of salivary cortisol level among TMD patients without depression, TMD patients with depression, and with the control group.
Table 5: Gender variation in mean of salivary cortisol level between TMD patients without depression, TMD patients with depression, and with the control group

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The student t-test was performed to see the relationship between salivary cortisol levels in males and females in all three groups. The result obtained showed that there was a positive correlation between males and females regarding the salivary cortisol level. In TMD patients without depression, females have higher morning and evening salivary cortisol levels than males with a significant P value < 0.0001. Similarly, in TMD patients with depression, females have a higher morning salivary cortisol level than males with a significant P value of 0.025 and high evening salivary cortisol level than males with a significant P value of 0.035. In the control group, females have a higher evening salivary cortisol level than males with a significant P value of < 0.0001. However, in the morning, females have a higher salivary cortisol level than males, but it is not statistically significant. This table signifies that females have a higher mean value of salivary cortisol level as compared to males in their respective groups. The highest mean value of salivary cortisol is found in the female TMD patients with depression in the morning [Table 6].
Table 6: t-test for the statistical analysis between the genders

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Linear Regression analysis was applied to depression, gender, TMD, chronic pain scale, disability score, and disability point with cortisol as a dependent variable. It was observed that the main predictor variable was positive depression level, gender, and TMD with a statically significant P value of <0.0001. Other variables like chronic pain scale, disability point, and disability score came out to be nonsignificant with cortisol as a dependent variable [Table 7].
Table 7: Regression Coefficient

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   Discussion Top


Although the underlying cause of TMD remains poorly understood, it is widely recognized to be multifactorial involving physiological, behavioral, psychological, and environmental factors.[6] In dental research, dental occlusion and parafunctional activities were the two etiologic factors that have received the most attention in epidemiological studies.

In our study, all the patients were young adults between the ages of 18 and 30 years with the mean age being 24.88 years. LeResche et al. in 1997[11] also reviewed that TMD is primarily a condition of young and middle-aged adults, rather than that of the elderly, and that it is approximately twice as common in women as in men. This prevalence pattern suggested that etiologic investigations should be directed at biological and psychosocial factors that are more common in women than in men.

The authors believe that both physical and psychological factors contribute to the onset and maintenance of TMD. Psychometric tests, and endocrine measurements, have been used to test some psychological factors. Any differences in these respects between diagnostic categories of TMDs might have implications for the understanding and treatment of the condition.[12]

Growing evidence implicates the role of the hypothalamic-pituitary-adrenal (HPA) axis in the pathophysiologic development of TMDs.[13],[10] The HPA axis system is the primary endocrine depression axis in humans. When stimulated, the hypothalamus secretes corticotrophin-releasing hormone (CRH) in response to which the pituitary gland secretes adrenocorticotropic hormone (ACTH). This stimulates the secretion of cortisol from the cortex of the adrenal glands. Facial pain may represent a greater stimulus to HPA-axis activation than pain elsewhere in the body.[13],[10]

In our study, the results show that in all three groups namely, TMD patients with depression, TMD patients without depression, and the control group, cortisol levels were significantly higher in the morning as compared with the evening, with a P value < 0.0001. The results were consistent with the study conducted by Wilhelm et al. in 2007.[14] They stated that there is a distinct rise in cortisol levels, in both plasma and saliva, that occurs after awakening in the morning. This can be increasingly used as an indicator of adrenocortical activity.[14]

The outcome of our study showed that TMD patients with depression presented higher cortisol levels in the morning and the evening than TMD patients without depression and the control group, with a significant P value of < 0.0001. However, salivary cortisol levels in TMD patients without depression when compared with the salivary cortisol levels in the control group, showed a nonsignificant P value of 0.154. The results were like the study conducted by Jones DA et al.[15] They assessed salivary cortisol response to psychological depression and its relationship to psychological variables. They subjected a changed version of the Trier Social Stress Test to all patients, which lasted for 20 min. The TMD group showed a significantly higher cortisol response to experimental depression than the control group.[15]

In our study, in TMD patients without depression, the females had higher morning and evening salivary cortisol levels than the males, with a significant P value < 0.0001. Similarly, in TMD patients with depression, the females had higher morning salivary cortisol levels than the males, with a significant P value of 0.025, and high evening salivary cortisol levels than the males, with a significant P value of 0.035.

On further evaluation, among the females when the means of salivary cortisol level in TMD patients without depression, TMD patients with depression, and the control group were correlated, the results obtained showed that there was a significantly high value of morning and evening salivary cortisol value in TMD female patients with depression when compared with TMD female patients without depression and the control group, with a significant P value <0.0001. However, no significant correlation was found between TMD female patients without depression and control.

The highest mean value of salivary cortisol was found in the female TMD patients with depression in the morning. The experience of depressive life events is a major risk factor for depression, and understanding vulnerability to depression is the key to understanding depression. The results of the current study showed that the Graded Chronic Pain Scale was higher in TMD patients who had a higher depression score as compared to TMD patients without depression. Thus, it was considered possible that the pain interference in daily, recreational/social/family and work-related activities could account for the higher cortisol levels seen in TMD patients with depression.

Gameiro GH et al suggested that the influence of depression on TMD is not as simple as suggested according to Laskin's theory, in which it is theorized that depression evokes chronic recurrent muscular hyperactivity that progressively damages the joint, which in time becomes symptomatic.[7] Many authors have concluded that the biological processes can translate psychological depression into the sensation of pain and can contribute to the development of TMD.[16],[17]

In TMDs, treatment is directed to the elimination of the pain and/or dysfunction such as limitation. Medicines such as analgesics and anti-inflammatory drugs, psychological consultation, different intraoral appliances and splints, and arthrocentesis (hydraulic distension) have been used for the elimination of the etiologic factor (s) of the complaints. Besides the traditional psychotropic drugs (tricyclic antidepressants), the introduction of psychological intervention, stress management, and change of habits as a part of the integral treatment of TMD patients with depression can be effective in the reduction of painful conditions and tension in various types of patients suffering from TMD.[18]

Limitations and Future Prospects

Larger sample size and a long-term assessment in the form of a longitudinal study are needed to further corroborate the findings of the present study.


   Conclusion Top


Considering that the diagnosis, assessment, and management of TMDs must include both physical and psychological factors, salivary cortisol could be a promising tool in identifying underlying psychological factors that could be associated with TMDs. If TMD is present in a patient and there are no obvious identifiable etiologic factors, evaluation of salivary cortisol level may point towards psychological etiologic factors that may be responsible for TMD. More studies are needed to test the correlation between TMD patients with positive depression levels and the salivary cortisol level in them.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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Jones DA, Rollman GB, Brooke RI. The cortisol response to psychological stress in temporomandibular dysfunction. Pain 1997;72:171-82.  Back to cited text no. 15
    
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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]



 

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