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ORIGINAL ARTICLE
Year : 2015  |  Volume : 19  |  Issue : 5  |  Page : 507-511  

Association of periodontal health indicators and major depressive disorder in hospital outpatients


Department of Periodontology, Navodaya Dental College, Raichur, Karnataka, India

Date of Web Publication13-Oct-2015

Correspondence Address:
Amit Kumar
Department of Periodontology, Navodaya Dental College, Mantralayam Road, Raichur - 584 103, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0972-124X.167161

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   Abstract 

Background: Major depressive disorder (MDD) has been associated with changes in behavioral, neurophysiological, and neuroendocrinological factors and thought to be one of the leading causes of disability worldwide. There are various evidences that depression and periodontitis may also be related.Aim: The aim was to evaluate the association between MDD and periodontitis in a convenience sample of hospital outpatients. Materials and Methods: Sixty individuals (30 subjects with MDD and 30 subjects without MDD) of age 26–67 years were included in the study. Depression was assessed by means of structured clinical interview for diagnostic and statistical manual of mental disorders. The periodontal clinical examination included the number of missing teeth, plaque index, gingival index (GI), probing pocket depth, and clinical attachment level (CAL). Results: Mean number of missing teeth per patient was 1.14 (±1.2 standard deviation [SD]) in the control group and 2.58 (±1.64 SD) in case group (P < 0.001). The amount of plaque was significantly higher in cases compared with control (P = 0.001). The patients had an average GI of 1.82 (±0.65 SD) compared to 1.14 (±0.81 SD) for the controls (P < 0.001). Mean probing depth and CAL were 4.67 (±0.8 SD) mm and 4.96 (±0.2 SD) mm in the case group and 2.6 (±2.2 SD) mm and 2.7 (±0.43 SD) mm in the control group, respectively (P < 0.05). Conclusion: Our study confirms the significant association between depression and periodontitis and depression can be considered one of the important risk factors for periodontal diseases.

Keywords: Clinical attachment level, major depressive disorder, probing pocket depth, structured clinical interview


How to cite this article:
Kumar A, Kardkal A, Debnath S, Lakshminarayan J. Association of periodontal health indicators and major depressive disorder in hospital outpatients. J Indian Soc Periodontol 2015;19:507-11

How to cite this URL:
Kumar A, Kardkal A, Debnath S, Lakshminarayan J. Association of periodontal health indicators and major depressive disorder in hospital outpatients. J Indian Soc Periodontol [serial online] 2015 [cited 2020 Apr 10];19:507-11. Available from: http://www.jisponline.com/text.asp?2015/19/5/507/167161




   Introduction Top


The contribution of psychological factors to the development and progression of the periodontal disease has recently become an area of increased research activity. Studies indicated that there might be strong relationships between stress, depression, and periodontal disease demonstrating convincing linkages between depression and elevated cortisol levels, negligence of oral hygiene, pocket depth, attachment loss, and tooth loss.[1]

Bipolar disorder and major depressive disorder (MDD) are two major psychiatric disorders classified as mood disorders in the diagnostic and statistical manual of mental disorders (DSM-IV).Bipolar disorder is a mental illness characterized by periods of elevated mood and periods of depression. The elevated mood is significant and is known as mania or hypomania depending on the severity. Whereas, MDD is characterized by the presence of one or more major depressive episodes and no manic or hypomanic episodes. A depressive episode is defined as depressed mood or loss of interest accompanied by at least four additional symptoms of depression (significant weight change without being on a diet, insomnia or hypersomnia, agitation or psychomotor retardation, fatigue or loss of energy, feelings of uselessness or guilt, reduced ability to think or concentrate, and recurrent thoughts about death) for at least 2 weeks. According to these criteria, the symptoms may not be attributed to a general medical condition.[2]

Some authors considered depression to be one of the important risk factors for the development of periodontitis,[3],[4] while others did not find an association between them.[5],[6] There are a variety of hypotheses proposed to show the association between depression and periodontitis. An explanation on the behavioral level might be that depressed patients adopt habits which are harmful to periodontal health, such as negligent oral hygiene, intensification of smoking, changes in eating habits; and neglect regular dental check-ups as a result of reduced drive, mood, affectivity, and interest.[7] On the neuroendocrinological level, the relation between depressive mood and periodontitis has been attributed to an impaired immune response caused by a disturbance in the hypothalamo-pituitary-adrenocortical (HPA) system.[8],[9],[10],[11] Although decreased immune activity has been observed in patients with depression, the clinical implications of these findings for diseases such as cancer and infectious diseases are still controversial. Moreover, the clinical relevance of these immunological alterations in the course of infectious diseases, especially periodontal disease, has not been well established.[12]

Taking antidepressant drugs has negative effects on periodontal health. Reduced saliva secretion as a consequence of antidepressant medication is one of the main reasons which make the oral environment susceptible to periodontal diseases.[13],[14] According to Friedlander and Norman,[15] depression is also related to increase anticholinergic activity. There are several studies regarding depression and decreased salivary flow. Strongin and Hinsie [16] compared parotid gland flow in six manic-depressive patients with flow rates in normal control subjects and found that manic group flow rates fell within the normal range, whereas in the depressed subjects flow rates were below the lowest rate of the normal group.

There is a need for more research to establish the relationship between periodontal disease and depression. Therefore, the objective of the present study was to compare periodontal clinical parameters between patients with MDD and healthy controls without diagnosed depression.


   Materials and Methods Top


Study sample

Prior to the start of the study ethical clearance of the protocol was obtained from Ethical Committee of the Institutional Review Board (Navodaya Dental College and Hospital). This study was conducted in the Department of Periodontology at Navodaya Dental College and Hospital, Raichur. The sample consisted of 60 physically healthy subjects, recruited from Navodaya Medical College and Hospital. All subjects signed an informed consent before taking part in the study and were assured that all information gathered in the course of study will be kept confidential. All participants were assessed using the Structured Clinical Interview for DSM IV (SCID).[17] Current severity of depression was evaluated with the Hamilton Depression Scale (HAM-D-31).[18]

Subjects in the age group of 26–67 and having at least 20 teeth in the mouth were included in the study. Subjects with uncontrolled diabetes, HIV infection, cardiovascular disease, psychiatric Axis I disorders (delirium, dementia, schizophrenia, eating disorders, organic mental disorder, type 1 or 2 bipolar disorder, psychotic depression, and schizoaffective disorder), undergone periodontal treatment 6 months before examination, alcohol or drug dependence within 6 months before the study and having history of epilepsy, infectious or autoimmune disease were excluded from the study.

The case group subjects were randomly selected from a larger group of available hospital outpatients from the Department of Psychiatry, Navodaya Medical College. They were having one or more recurrent depressive episodes and a score of at least 15 points on the HAM-D-31. The control group comprised of same number of subjects, having age (±3 years) and as much as possible other demographic variables-matched. They were recruited from hospital staff and volunteers by means of simple random sampling and were not having MDD. From both patients and controls, socioeconomic data's, as well as information pertaining to smoking habits were obtained. Subjects were identified as nonsmokers if they had never smoked, current smokers if they had a current smoking habit, and former smokers if they reported that they had quit smoking.

Psychometric instruments

A diagnostic instrument and observer rating scales were used for this assessment. SCID version 2.0 based on DSM-IV criteria was used for psychiatric diagnosis.[17] Interviews were conducted by trained interviewer. The Hamilton Depression Rating Scale version 31 was used to assess the depression severity.[18] These assessments were done according to intensity and frequency within a specific period. The depressive syndrome was defined as chronic when symptoms were present for at least 2 years without remission lasting 2 months or longer.

Procedure

All participants underwent a standard physical examination and their medical history was recorded. Clinical diagnoses were made by one experienced psychiatrist using the SCID. Patients with depression met the DSM-IV criteria for MDD. All participants were physically healthy. The participants were invited for periodontal clinical examination. The periodontal clinical examinations were carried out using a sterile dental mouth mirror and Periodontal probe (Hu Friedy, Chicago, IL, USA). The presence of plaque was recorded using the plaque index (PI)[19] and the gingival condition using the gingival index (GI).[19],[20] The clinical attachment level (CAL) and the probing depth (PD) were measured at six sites per tooth. The frequency of missing teeth was also reported. All clinical data were collected by a single examiner, who had been calibrated prior to the commencement of the study until the examiner could maintain >90% agreement on repeated measures of all examination protocols. The intra-examiner agreements were evaluated by means of repeated measurements with a 7-day interval from the first examination.

Statistical analysis

The mean values for the PI, the GI, the PD, the CAL, and the frequency of missing teeth were calculated for each subject and compared for each group. Nonparametric test (Chi-square test, Fisher's exact test and Mann–Whitney test), and parametric test (unpaired t-test) were used to compare different variables used in this study. Data were stored in a database and was or were analyzed using Statistical Package for Social Sciences (SPSS) for Windows version 16th (SPSS version 16, Chicago, Illinois).


   Results Top


Initially, 66 subjects according to the inclusion criteria were recruited for the study. After SCID 6 subjects were excluded from the study because four subjects refused the periodontal examinations and two of them showed the bipolar disorder. The final sample size was comprised of 60 subjects (30 MDD outpatients and 30 healthy controls). Clinical periodontal examination and psychiatric interview were done for these subjects.

[Table 1] shows the demographic and socioeconomic data of 60 subjects. Employment status (P < 0.001) and household income (P = 0.006) between groups were statistically significant. About 56.67% subjects in the case group were unemployed whereas only 6.67% subjects in the control group were unemployed. Household income of 96.67% subjects in the case group and 63.33% subjects in the control group were less than Rs. 6000/month. [Table 2] shows the mean scores of clinical parameters between the groups. There was a statistically significant difference between groups in all clinical parameters evaluated (P < 0.05). The PI, the GI and the frequency of missing teeth were 1.56 ± 0.5, 1.82 ± 0.65, and 2.3 ± 1.6 for case group and 1.12 ± 0.38, 1.14 ± 0.81, and 1.13 ± 1.28 for control group, respectively. The mean probing pocket depth was 4.67 ± 0.8 mm for the case group and 2.6 ± 2.2 mm for control group whereas mean CAL for case was 4.96 ± 0.2 mm and for control was 2.7 ± 0.43 mm. [Table 3] represents MDD and Hamilton scores. About 83.33% subjects under case group had more than one episodes of depression. Most of depression had melancholic features (86.67%) and about 76.67% were classified as severe. The HAM-D-31 mean values were statistically significant. [Table 4] shows the statistically significant mean scores of probing pocket depth, CAL and missing teeth between smokers and nonsmokers (P < 0.05).
Table 1: Demographic and socioeconomic variables of the groups

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Table 2: Clinical parameters in case and control groups (mean±SD)

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Table 3: Depression characteristics of the groups

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Table 4: Periodontal clinical characteristics of the nonsmoking and smoking groups

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   Discussion Top


The connection between the body and mind is a topic of much controversy. For many years studies have been performed to show the relationship between psychosocial factors and periodontal status. This study is one of them in order to show an association between depression and periodontitis. For this study, we selected MDD patients because psychoneuroimmunology studies have shown that immunological and endocrinological alterations in patients with MDD differ from those of subjects with posttraumatic stress disorder, personality disorder and/or a history of early adverse stressful events.[16],[21] We used observer rating scale (HAM-D-31) and a diagnostic instrument (structured clinical interview) for psychiatric evaluation because self-report scales do not allow an assessment of the subjective and behavioral aspects of individuals and when this type of instrument is used in research, one should bear in mind that the informers may supply incorrect information due to misunderstanding of the questions. Structured clinical interview is the gold standard for classification of major psychiatric and personality disorders. In this study, patients with periodontitis showed significantly higher observer-rated score, similar results were observed in the study performed by Saletu et al.[4]

Subjects with MDD and control group had a similar distribution for most of the demographic and clinical variables such as age, gender, educational level, marital status, and smoking status. Socioeconomic level is a good marker of various risk factors for periodontitis such as oral hygiene, provision of dental care, and behaviors. Previous studies have documented differences in periodontal health based on socioeconomic status (SES) factors, such as income and education, showing that lower SES was associated with increased risk to periodontitis.[22] In this study, patients with depression had a lower household income, probably because of the larger number of unemployed individuals (56.67%) in this group. This finding is consistent with studies that have shown a higher prevalence of depression among unemployed compared to employed individuals and can be explained by the debilitating nature of MDD.[23] This shows that unemployed status and low household income were prime risk factors for MDD, which affected behavioral and neuroendocrinological changes that leads to severe clinical attachment loss and PD. In our study, greater proportion of females, among depression patients with the female/male ratio of about 2:1, is found which suggests higher prevalence of MDD in females, this is in accordance with an epidemiological study conducted by Bromet et al.[24]

In this study, the amount of plaque was significantly higher in cases compared with control (P = 0.001). The patients had a statistically significant mean GI when compared to that of controls (P < 0.001), this is in accordance with studies conducted by Genco et al.,[25] and Ng and Leung.[26] Our study showed a statistically significant association between periodontal clinical parameters like mean PD and CAL between the case group and the control group, respectively (P < 0.05). This high level of clinical attachment loss and PD may be due to fact that depression enhances the production of pro-inflammatory cytokines, including Interleukin (IL)-6.[12] In a more extensive study, Alesci and colleagues found that IL-6 levels were increased in MDD patients throughout the circadian cycle. There was a 12 h shift in the circadian rhythm of IL-6 plasma levels and its complexity was reduced.[27] Johannsen et al.,[28] compared oral health status, proinflammatory markers, and cortisol in gingival crevicular fluid (GCF) and saliva in patients with stress-related mental depression and controls to investigate the importance of stress for the development of periodontitis. They found that the levels of cortisol and IL-6 in GCF were significantly higher in patients than in controls. Significantly, both depressive symptoms and syndromal depression are associated with heightened plasma IL-6 levels. Overproduction of proinflammatory cytokines may lead to maladaptive immune and endocrine changes subsequently. IL-6 is a potent stimulator of corticotrophin releasing hormone production, a mechanism that leads to heightened HPA activity, including elevated levels of plasma adrenocorticotropic hormone (ACTH), followed by increased cortisol levels:[29] Elevation in ACTH and cortisol can provoke multiple adverse immunological changes.

Our study indicated an adverse effect of MDD on oral hygiene. The depressed patients had significantly higher plaque accumulation (P = 0.001) and gingival inflammation (P < 0.001), this was in agreement with the findings of Johanssen et al.,[30] The depressed patients neglect oral hygiene and professional regular dental care due to reduced motivation and interest.[31] In this study, significant relationship was found between smoking, CAL (P = 0.001), probing pocket depth (P = 0.002), and missing teeth (P < 0.001) This was in accordance to longitudinal study conducted by Jasmin M Albandar et al.,[32] Our study consisted of equal distribution of smokers between MDD patients and controls, and there was no significant difference of Gl and PI between smokers and nonsmokers. Many studies have found that GI is lower in smokers [33],[34] and smoking is more prevalent in depression patients.[35],[36]

Discrepancies in results between our study and others may be due to differences in the controlled variables: Depression level, sampling strategies, study design and age range. Various studies used self-report scales as instruments to measure psychological variables. These differences may limit the comparisons between the investigations. Discrepancies in the results found in the literature may also be explained by differences in sample sizes of the studies. We recognize the limitations of the small, homogeneous sample that limited the generalizability, and power to detect some associations.


   Conclusion Top


The results of our study suggest that MDD may influence periodontal disease due to its impact on psychoneuroimmunology, endocrinology and also on human behavior. Hence, it is important to understand patients' physical and psychological state both to help in maintaining a healthy periodontium. Further studies are required to investigate the association of periodontal disease and MDD using structured interviews on groups with operational diagnosis, by means of instruments like DSM-IV. Thus, sources of error can be minimized and the influence of depression on periodontal status can be evaluated with greater precision.


   Acknowledgement Top


The authors would like to thank faculties of the Department of Psychiatry, Navodaya Medical College and Hospital, Raichur for their cooperation and help in providing subjects during the course of the study.

 
   References Top

1.
Rosania AE, Low KG, McCormick CM, Rosania DA. Stress, depression, cortisol, and periodontal disease. J Periodontol 2009;80:260-6.  Back to cited text no. 1
    
2.
American Psychiatric Association (APA), Task Force on DSM-IV, First MB, editors. Diagnostic and Statistical Manual of Mental Disorders: DSM-IV. 4th ed. Washington (DC): American Psychiatric Press, Inc.; 1994. p. 886.  Back to cited text no. 2
    
3.
Da Silva AM, Newman HN, Oakley DA. Psychosocial factors in inflammatory periodontal diseases. A review. J Clin Periodontol 1995;22:516-26.  Back to cited text no. 3
    
4.
Saletu A, Pirker-Frühauf H, Saletu F, Linzmayer L, Anderer P, Matejka M. Controlled clinical and psychometric studies on the relation between periodontitis and depressive mood. J Clin Periodontol 2005;32:1219-25.  Back to cited text no. 4
    
5.
Persson GR, Persson RE, MacEntee CI, Wyatt CC, Hollender LG, Kiyak HA. Periodontitis and perceived risk for periodontitis in elders with evidence of depression. J Clin Periodontol 2003;30:691-6.  Back to cited text no. 5
    
6.
Solis AC, Lotufo RF, Pannuti CM, Brunheiro EC, Marques AH, Lotufo-Neto F. Association of periodontal disease to anxiety and depression symptoms, and psychosocial stress factors. J Clin Periodontol 2004;31:633-8.  Back to cited text no. 6
    
7.
Monteiro da Silva AM, Oakley DA, Newman HN, Nohl FS, Lloyd HM. Psychosocial factors and adult onset rapidly progressive periodontitis. J Clin Periodontol 1996;23:789-94.  Back to cited text no. 7
    
8.
Marques-Deak A, Cizza G, Sternberg E. Brain-immune interactions and disease susceptibility. Mol Psychiatry 2005;10:239-50.  Back to cited text no. 8
    
9.
Blume J, Douglas SD, Evans DL. Immune suppression and immune activation in depression. Brain Behav Immun 2011;25:221-9.  Back to cited text no. 9
    
10.
Miller AH, Maletic V, Raison CL. Inflammation and its discontents: The role of cytokines in the pathophysiology of major depression. Biol Psychiatry 2009;65:732-41.  Back to cited text no. 10
    
11.
Raison CL, Miller AH. Is depression an inflammatory disorder? Curr Psychiatry Rep 2011;13:467-75.  Back to cited text no. 11
    
12.
Zorrilla EP, Luborsky L, McKay JR, Rosenthal R, Houldin A, Tax A, et al. The relationship of depression and stressors to immunological assays: A meta-analytic review. Brain Behav Immun 2001;15:199-226.  Back to cited text no. 12
    
13.
Hunter KD, Wilson WS. The effects of antidepressant drugs on salivary flow and content of sodium and potassium ions in human parotid saliva. Arch Oral Biol 1995;40:983-9.  Back to cited text no. 13
    
14.
Scully C. Drug effects on salivary glands: Dry mouth. Oral Dis 2003;9:165-76.  Back to cited text no. 14
    
15.
Friedlander AH, Norman DC. Late-life depression: Psychopathology, medical interventions, and dental implications. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94:404-12.  Back to cited text no. 15
    
16.
Strongin EI, Hinsie LE. Parotid gland Secretions in manic-depressive patients. Am J Psychiatry 1938;94:1459-66.  Back to cited text no. 16
    
17.
Spitzer RL, Williams JB, Gibbon M, First MB. The Structured Clinical Interview for DSM-III-R (SCID). I: History, rationale, and description. Arch Gen Psychiatry 1992;49:624-9.  Back to cited text no. 17
    
18.
Hamilton M. A rating scale for depression. J Neurol Neurosurg Psychiatry 1960;23:56-62.  Back to cited text no. 18
[PUBMED]    
19.
Silness J, Loe H. Periodontal disease in pregnancy. II. correlation between oral hygiene and periodontal condtion. Acta Odontol Scand 1964;22:121-35.  Back to cited text no. 19
    
20.
Loe H. The gingival index, the plaque index and the retention index systems. J Periodontol 1967;38 Suppl: 610-6.  Back to cited text no. 20
    
21.
Yehuda R. Disease markers: Molecular biology of PTSD. Dis Markers 2011;30:61-5.  Back to cited text no. 21
    
22.
Hamasha AA, Alomari QD. Prevalence of dens invaginatus in Jordanian adults. Int Endod J 2004;37:307-10.  Back to cited text no. 22
    
23.
Greenberg PE, Kessler RC, Birnbaum HG, Leong SA, Lowe SW, Berglund PA, et al. The economic burden of depression in the United States: How did it change between 1990 and 2000? J Clin Psychiatry 2003;64:1465-75.  Back to cited text no. 23
    
24.
Bromet E, Andrade LH, Hwang I. Cross-national epidemiology of DSM-IV major depressive episode. BMC Med 2011;9:90.  Back to cited text no. 24
    
25.
Genco RJ, Ho AW, Grossi SG, Dunford RG, Tedesco LA. Relationship of stress, distress and inadequate coping behaviors to periodontal disease. J Periodontol 1999;70:711-23.  Back to cited text no. 25
    
26.
Ng SK, Keung Leung W. A community study on the relationship between stress, coping, affective dispositions and periodontal attachment loss. Community Dent Oral Epidemiol 2006;34:252-66.  Back to cited text no. 26
    
27.
Alesci S, Martinez PE, Kelkar S, Ilias I, Ronsaville DS, Listwak SJ, et al. Major depression is associated with significant diurnal elevations in plasma interleukin-6 levels, a shift of its circadian rhythm, and loss of physiological complexity in its secretion: Clinical implications. J Clin Endocrinol Metab 2005;90:2522-30.  Back to cited text no. 27
    
28.
Johannsen A, Rylander G, Söder B, Asberg M. Dental plaque, gingival inflammation, and elevated levels of interleukin-6 and cortisol in gingival crevicular fluid from women with stress-related depression and exhaustion. J Periodontol 2006;77:1403-9.  Back to cited text no. 28
    
29.
Dentino AN, Pieper CF, Rao MK, Currie MS, Harris T, Blazer DG, et al. Association of interleukin-6 and other biologic variables with depression in older people living in the community. J Am Geriatr Soc 1999;47:6-11.  Back to cited text no. 29
    
30.
Johannsen A, Asberg M, Söder PO, Söder B. Anxiety, gingival inflammation and periodontal disease in non-smokers and smokers-an epidemiological study. J Clin Periodontol 2005;32:488-91.  Back to cited text no. 30
    
31.
Kurer JR, Watts TL, Weinman J, Gower DB. Psychological mood of regular dental attenders in relation to oral hygiene behaviour and gingival health. J Clin Periodontol 1995;22:52-5.  Back to cited text no. 31
    
32.
Albandar JM, Streckfus CF, Adesanya MR, Winn DM. Cigar, pipe, and cigarette smoking as risk factors for periodontal disease and tooth loss. J Periodontol 2000;71:1874-81.  Back to cited text no. 32
    
33.
Preber H, Bergström J. Occurrence of gingival bleeding in smoker and non-smoker patients. Acta Odontol Scand 1985;43:315-20.  Back to cited text no. 33
    
34.
Dietrich T, Bernimoulin JP, Glynn RJ. The effect of cigarette smoking on gingival bleeding. J Periodontol 2004;75:16-22.  Back to cited text no. 34
    
35.
Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH. Smoking and mental illness: A population-based prevalence study. JAMA 2000;284:2606-10.  Back to cited text no. 35
    
36.
McClave AK, McKnight-Eily LR, Davis SP, Dube SR. Smoking characteristics of adults with selected lifetime mental illnesses: Results from the 2007 National Health Interview Survey. Am J Public Health 2010;100:2464-72.  Back to cited text no. 36
    



 
 
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  [Table 1], [Table 2], [Table 3], [Table 4]



 

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