Occlusal problems, mental health issues and non-carious cervical lesions

Abstract

Non-carious cervical lesions (NCCLs) are characterized by a loss of hard dental tissue near the cement–enamel junction with multifactorial etiology. The aim of this study was to demonstrate that occlusal factors as attrition, malocclusion, and bruxism, and mental disorders as depression, stress, and anxiety are involved in the etiology of NCCLs. Salivary samples and clinical data of 340 individuals selected from 6,112 participants were obtained from the University of Pittsburgh School of Dental Medicine Dental Registry and DNA Repository project. The affected group was formed by individuals with NCCL (34 females, 34 males, mean age 55.34 years). In addition, the comparison group was formed by individuals without NCCL (136 females, 136 males, mean age 55.14 years). Eleven single-nucleotide polymorphisms (SNPs) previously associated with mental disorders were genotyped and tested for association with NCCLs. When all occlusal factors were combined there was found a significant association with NCCL (p = 0.000001/adjusted OR 4.38, 95% CI 2.50–7.69). Attrition (OR 3.56, 95% CI 2.00–6.32) and malocclusion (OR 5.09, 95% CI 1.65–15.68) as separate variables showed statistically significant associations with NCCL. There was a significant difference in stress history between the two groups (OR 2.17, 95% CI 1.08–4.39). No associations between NCCLs and the SNPs selected were found. However, when the occlusal factors were analyzed as covariates, associations were found between bruxism and seven of the selected SNPs. Our results suggest that occlusal factors might be associated with NCCLs.

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Odontology
https://doi.org/10.1007/s10266-021-00658-5
ORIGINAL ARTICLE
Occlusal problems, mental health issues andnon‑carious cervical
lesions
BrunaL.Nascimento1· AlexandreR.Vieira2· MarianaBezamat2· SergioA.Ignácio1· EveliseM.Souza1
Received: 26 May 2021 / Accepted: 13 September 2021
© The Society of The Nippon Dental University 2021
Abstract
Non-carious cervical lesions (NCCLs) are characterized by a loss of hard dental tissue near the cement–enamel junction
with multifactorial etiology. The aim of this study was to demonstrate that occlusal factors as attrition, malocclusion, and
bruxism, and mental disorders as depression, stress, and anxiety are involved in the etiology of NCCLs. Salivary samples and
clinical data of 340 individuals selected from 6,112 participants were obtained from the University of Pittsburgh School of
Dental Medicine Dental Registry and DNA Repository project. The affected group was formed by individuals with NCCL
(34 females, 34 males, mean age 55.34years). In addition, the comparison group was formed by individuals without NCCL
(136 females, 136 males, mean age 55.14years). Eleven single-nucleotide polymorphisms (SNPs) previously associated with
mental disorders were genotyped and tested for association with NCCLs. When all occlusal factors were combined there
was found a significant association with NCCL (p = 0.000001/adjusted OR 4.38, 95% CI 2.50–7.69). Attrition (OR 3.56,
95% CI 2.00–6.32) and malocclusion (OR 5.09, 95% CI 1.65–15.68) as separate variables showed statistically significant
associations with NCCL. There was a significant difference in stress history between the two groups (OR 2.17, 95% CI
1.08–4.39). No associations between NCCLs and the SNPs selected were found. However, when the occlusal factors were
analyzed as covariates, associations were found between bruxism and seven of the selected SNPs. Our results suggest that
occlusal factors might be associated with NCCLs.
Keywords Dental occlusion· Bruxism· Depression· Anxiety· Polymorphism genetic
Background
Non-carious cervical lesions (NCCLs) are characterized by
a loss of hard dental tissue near the cement–enamel junc-
tion and are commonly found in dental practice [1]. The
incidence of this condition has increased due to population
longer life expectancy and the longevity of permanent denti-
tion during individual’s lifespan [2]. Recent studies reported
prevalence data of these lesions ranging from 9% [3], to
35% [4] to 77% [5]. The reasons for such disparities can be
justified by differences in study design (sample size, sub-
jects’ age, and diet habits), distinct geographic locations of
the cohorts evaluated, as well as differences in diagnostic
criteria [6–10].
We suggested that the etiology of NCCLs is multifacto-
rial, where genetics and environmental factors are involved
in the disease progression. The interaction of several mecha-
nisms, such as biocorrosion of tooth enamel due to chemical,
biochemical and electrochemical degradation, stress leading
to mechanical loss of tooth structure (abfraction), and abra-
sion (wear caused by friction) result in the appearance of this
specific phenotype [11]. Determining the precise etiology of
NCCLs is important to prevent further loss of tooth struc-
ture, designate the best treatment, and prevent new lesions.
In the case of abfraction, excessive non-axial forces cause
stress that concentrates in the cervical region of the tooth,
and as a result, the crystals of hydroxyapatite of the enamel
near the gingival margin are lost, leading to microfractures,
enamel chipping, and loss of dental structure [12]. Etio-
logical factors responsible for abfraction can be divided in
endogenous and exogenous. Endogenous factors may be
related to parafunctional habits such as bruxism and dental
* Evelise M. Souza
evelise.souza@pucpr.br
1 Graduate Program inDentistry, School ofLife Sciences,
Pontifícia Universidade Católica doParaná, R. Imaculada
Conceição, 1155, Curitiba, PR80215-901, Brazil
2 Department ofOral Biology, University ofPittsburgh,
Pittsburgh, Pennsylvania, USA

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clenching, malocclusion, the presence of occlusal interfer-
ences, or eccentric loads and swallowing. Exogenous factors
may involve chewing hard and resistant foods, deleterious
habits such as biting nails or objects and dental appliances
such as orthodontic and removable partial prosthesis clasps
[13].
Epidemiologic studies have shown that approximately
one in 10 adult individuals may suffer from bruxism [14].
As for the etiology of bruxism, over the years many theories
have been proposed. New evidence suggests that biological,
psychological and exogenous factors have greater involve-
ment than morphological factors in the etiology of bruxism
[15]. Different approaches have been proposed to define,
diagnose, evaluate the impact and consequences, under-
stand the pathophysiology, and treat or control bruxism and
other occlusal parafunctions [16]. Data from a large clinical
study with 1342 volunteers showed a significant associa-
tion between the presence of non-carious cervical lesion and
dental clenching, as well as a relationship with the diagnosis
of temporomandibular dysfunction (TMD) [17]. Therefore,
parafunctional habits such as bruxism and clenching, and the
presence of TMD should be considered in the diagnosis and
treatment plan of non-carious cervical lesions.
Studies also suggest that bruxism may be the result of
psychological factors such as anxiety and emotional or
physical stress [14, 18–20]. Furthermore, individual genetic
load has been more closely studied in relation to bruxism.
Different single-nucleotide polymorphisms (SNPs) in genes
codifying for components of dopaminergic pathways have
been suggested to play a role in the etiology of bruxism [21].
Dopaminergic pathways are neural pathways important for
functions such as motivation, arousal and reward and have
been associated with emotional behavior and consequently
depression. However, to the best of our knowledge, associa-
tion studies seeking for a relationship between genes that
influence mental health and NCCLs in the same individuals
have never been performed. Therefore, the determination of
whether there is a relationship between occlusal parafunc-
tion, mental disorders, and the prevalence of non-carious
cervical lesions being that due to a genetic effect or not,
remains a significant gap in this area, despite all research
efforts made to this day. Therefore, the aim of this study was
to evaluate the association between occlusal factors and his-
tory of mental disorders within the patients diagnosed with
non-carious cervical lesions. Additional genotypic analy-
ses, utilizing SNPs associated with mental disorders, were
performed with the rationale that the genes nearby those
polymorphisms will have an influence in the development
of NCCLs.
Methods
Sample selection
Participants’ data and DNA samples were obtained from
existing records of the University of Pittsburgh School of
Dental Medicine, Dental Registry and DNA Repository
project. Sixty-eight subjects diagnosed with at least one
non-carious cervical lesion were selected from the 6112
records from the registry. Awake and sleep bruxism were
detected by extra-intra-oral examination, anamnesis and
a questionnaire based on the patients’ habits. Attrition
was diagnosed considering general wear of incisal and
occlusal surfaces of teeth, and malocclusion was defined
as an incorrect relation between teeth of the upper and
lower dental arches. Bruxism, attrition, and malocclu-
sion were diagnosed by students supervised by faculty.
Depression, stress, and anxiety were self-reported. Partici-
pants with any dental element affected with NCCLs were
included. NCCL was considered as wedge- or V-shaped
cervical lesions with clearly defined internal and external
margins. The sample of affected individuals consisted of
34 females, 34 males, mean age of 55.34years ranging
from 21.5 to 80years. A comparison group was comprised
of individuals that had absence of NCCL (N = 272, 136
females, 136 males, mean age of 55.14years) and were
matched to the affected individuals by age and sex, reach-
ing a 1:4 affected–unaffected ratio to improve statistical
power [22]. The clinical characteristics of interest for the
study were occlusal risk factors, such as self-reported
bruxism, attrition, and malocclusion, and history of mental
disorders, namely depression, stress, and anxiety.
Genotyping
Genomic DNA was extracted from whole saliva using
established protocols [23]. Eleven polymorphisms in
genes associated with mental disorders were analyzed in
the sample described above (Table1). PCR reactions were
carried out using Taqman chemistry [24] in volumes of
3.0μl in an ABI PRISM QuantStudio 6 Flex Real-Time
PCR System (Applied Biosystems, Foster City, CA, USA).
The genotyping results were analyzed using SDS software
version 1.7 (Applied Biosystems). PCR reactions were
repeated twice when necessary and allele frequencies and
Hardy–Weinberg equilibrium were calculated. The margin
of error for genotyping calls in our laboratory was previ-
ously assessed in a large project and it was established to
be less than 1%, and therefore, negligible [25]. Associa-
tion analyses were performed comparing genotypes to phe-
notype between affected individuals and their respective

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comparison group as implemented in the PLINK software
[26].
Statistical analysis
All data were categorized into dichotomized variables,
except for age. Student’s t test was used to compare age and
sex differences between the groups. ANOVA was used to
test differences of age between the two groups considering
sex. 2X2 tables were constructed for each of the study vari-
ables and the Pearson’s Chi-square test was used to compare
the distribution of occlusal and mental factors within and
between the groups. All variables with p values < 0.20 for
these bivariate relationships were identified and a signifi-
cant relationship between attrition and occlusal factors was
found. A backwards logistic regression selection procedure
was then applied to the models generated in the sixth step,
with the results considered to be the final unadjusted main
effects model. All study variables were analyzed in both
univariate and multivariate logistic regression analyses.
Odds ratios [21] and 95% confidence intervals [1] were cal-
culated and the significance levels for all the comparisons
were set at 0.05. Statistical analysis was carried out using
the software SPSS (Statistical Package for Social Science,
V.25, IBM, USA).
Results
Table2 shows the distribution of affected and unaffected
individuals according to bruxism, attrition, malocclusion,
depression, stress, and anxiety and the results of the univari-
ate logistic regression analysis. From all variables related
to occlusal factors, attrition and malocclusion showed sig-
nificantly more chance of causing NCCLs, with OR values
of 3.56 (95% confidence interval 2.00–6.32) and 5.09 (95%
confidence interval 1.65–15.68), respectively. Regarding
the frequency of mental disorders, there was a difference
Table 1 Details of the SNPs
investigated in this study Chromosome Gene SNP marker Base position Location Consequence Base change
20 MMP9 rs13925 46,016,326 Intron Synonymous variant G > A
16 MMP2 rs243832 55,505,279 Intron Intron Variant C > G
6ESR1 rs4870053 151,771,614 Intron Intron variant G > A
6ESR1 rs12154178 151,929,945 Intron Intron variant C > A
6ESR1 rs7774230 151,843,104 Intron Intron variant C > T
6ESR1 rs851977 151,708,473 Intron Intron variant T > C
5HTR1A rs1364043 63,955,024 Intron None T > G
5HTR1A rs13361335 63,970,064 Intron None T > G
16 TSC2 rs1051771 2,088,583 Intron Synonymous variant G > C
16 TSC2 rs2073636 2,055,054 Intron Intron variant A > G
16 TSC2 rs2516735 2,053,004 Intron Intron variant C > T
Table 2 Univariate logistic
regression analysis and
distribution of affected and
unaffected individuals according
to occlusal factors and mental
disorders
*Univariate logistic regression, with confidence level of 0.05
OR Odds Ratio, CI Confidence Interval,
Bold indicates presence of association
Variables Occlusal Case n (%) Control n (%) p value* OR (CI)
Bruxism Present 3 (4.4) 4 (1.5) 0.1266 3.09 (0.67–14.15)
Absent 65 (95.6) 268 (98.5) Reference –
Attrition Present 29 (42.6) 47 (17.3) 0.0000 3.56 (2.00–6.32)
Absent 39 (57.4) 255 (82.7) Reference –
Malocclusion Present 7 (10.3) 6 (2.2) 0.0019 5.09 (1.65–15.68)
Absent 61 (89.7) 266 (97.8) Reference –
Depression Present 11 (16.2) 45 (16.5) 0.9417 0.97 (0.47–2.00)
Absent 57 (83.8) 227 (83.5) Reference –
Stress Present 14 (20.6) 29 (10.7) 0.0276 2.17 (1.08–4.39)
Absent 54 (79.4) 243 (89.3) Reference –
Anxiety Present 13 (19.1) 31 (11.4) 0.0898 1.84 (0.90–3.74)
Absent 55 (80.9) 241 (88.6) Reference –

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in stress history between the two groups, with an OR of
2.17 (95% confidence interval 1.08–4.39). Data from the
multivariate logistic analysis (Table3) showed significant
association between occlusal factors (combined) and NCCLs
[p = 0.000001/adjusted OR: 4.38 (95% confidence interval
2.50–7.69)], meaning that for each 100 individuals in the
unaffected group, presenting at least one of the occlusal fac-
tors evaluated, there will be 438 individuals in the affected
group. After Bonferroni correction, the p < 0.0045 was con-
sidered significant (0.05/11 SNPs).
The genotypic analysis did not show any associations
between the SNPs of interest and the non-carious cervi-
cal lesions; however, further analyses utilizing the occlusal
risk factors as covariates showed an association between
NCCLs and seven SNPs (Table4) when bruxism was used
as a covariate.
Discussion
In this study, we examined whether occlusal factors and
history of mental disorders were associated with NCCLs
by clinical data and genotypical analyses. The main finding
was a significant association between the combined occlusal
factors and NCCLs.
The association between bruxism, attrition and malocclu-
sion with NCCL can be explained by the excess of occlusal
forces in the cement–enamel junction, leading to displace-
ments of enamel prisms in the cervical region, where the
structural weakness of the enamel layer is at its thinnest [27].
However, within the studied occlusal risk factors, we only
found significant association between attrition and malocclu-
sion with NCCL. Chemical factors, such as endogenous and
exogenous acids, and proteolytic agents act upon the organic
matrix of dentin, causing or accelerating the development of
NCCLs [9]. A limitation of this study was the lack of dietary
or gastro-esophageal problems data in the existing records.
Although dental attrition is manifested clinically, it is
considered a physiological phenomenon as opposed to the
pathological abrasive wear caused by bruxism, jaw grinding,
pipe-clenching and the use of teeth for gripping objects [28].
Probably, the frequency of attrition found in our data might
be related to the age of the individuals with NCCL (mean
age 55.34years) and was found in 42.6% of the individuals
in the affected group. Since elderly people are more prone
to attrition [29], the dental wear found in these individuals
could have been diagnosed solely as attrition instead of a
clinical sign of bruxism.
According to a systematic review, frequent bruxism is
expected to be present in 8% of the population and awake
bruxism, on the other hand, can be as prevalent as 22% [30].
Questionnaires are commonly used for the diagnosis of brux-
ism, but their subjective nature risks over- or underscoring
the condition. Clinical examinations are also frequently used
but could be mistaken with multiple differential diagnoses.
Instrumental diagnosis by electromyography/electrocardi-
ography (EMG/ECG) or polysomnography is considered
standard of reference but of limited availability and high
cost [30]. Findings from a clinical assessment demonstrated
that clinical signs/symptoms are not well correlated with
bruxism diagnosis performed with a portable EMG/ECG
recorder [31] and suggested that clinical diagnosis is able
to detect, at best, a ‘probable’ bruxism [32]. In the present
study, bruxism diagnosis was based on self-reported data
and clinical inspection which could have accounted for the
low prevalence of this condition in our registry.
The association between NCCL and bruxism is still con-
troversial. Although the results comparing self-reported
bruxism with NCCL did not show significant differences
between affected and unaffected individuals, other studies
indicate bruxism as a risk factor for NCCL [33–36]. A pre-
vious study demonstrated significant association between
Table 3 Multivariate logistic analysis
*Multivariate logistic regression, with confidence level of 0.05
ORa Odds Ratio adjusted
Bold indicates presence of association
Variables p value* ORa
Occlusal factors Present 0.000 4.38 (2.50–7.69)
Absent Reference –
Mental disorders Present 0.316 1.33 (0.76–2.34)
Absent Reference
Table 4 Significant results of
bruxism analyzed as covariate Chromosome Gene SNP Test Odds ratio STAT p value
5HTR1A rs1364043 Covariate 9.17 2.513 0.01
5HTR1A rs13361335 Covariate 5.683 2.236 0.02
6ESR1 rs851977 Covariate 5.784 2.241 0.02
6ESR1 rs12154178 Covariate 5.733 2.247 0.02
16 TSC2 rs1051771 Covariate 5.445 2.178 0.03
16 MMP2 rs243832 Covariate 7.452 2.162 0.03
20 MMP9 rs13925 Covariate 9.074 2.499 0.01

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self-reported bruxism with posterior or anterior dental attri-
tion and abfractions in adult Greek subjects with a mean age
of 44.6years [37]. Several patients with related bruxism also
show incisal/occlusal surface wear [2] which coincides with
the clinical presentation of attrition. This type of tooth wear
is easier to detect because it features matched, sharp and
clearly demarcated wear facets between opposing teeth [37].
Bruxism alone may not be the sole cause of such faceting
and is more likely the result of a combination of different
wear-promoting causative factors [38, 39]. The interpre-
tation of these results might suggest that when combined
NCCLs and bruxism are present in the same individuals, a
more homogeneous group is tested, and genetic associations
are more easily detected.
Psychological factors, such as personality and stress,
could modulate the occurrence and severity of such par-
afunctional behavior. In terms of personality, bruxers were
observed to tend to score higher in somatic anxiety and mus-
cular tension and lower in socialization [40]. Depression,
stress and anxiety were investigated as clinical character-
istics of interest for the study and grouped as mental disor-
ders. There were significant associations between NCCL and
stress and NCCL and several SNPs studied when bruxism
was analyzed as a covariate.
There is evidence in the literature that HTR1A [41], ESR1
[42], TSC2 [43], MMP2 [44], and MMP9 [45] are associ-
ated with mental health issues. It was not a surprise that
markers in all five genes we tested showed an association
with mental health conditions when bruxism was analyzed
as a covariate. Although there was evidence that the SNPs
tested were neutral, we did not test if they have potential
functional roles. Functional SNPs are found in the promot-
ers of protein-coding and non-coding RNA genes, or on
the structure of the precursor mRNAs (exons and introns),
mature mRNA (5' untranslated region, coding sequence, and
3' untranslated region), and can affect the splicing, the trans-
lation, stability, amino acid sequence, structure, and function
of proteins and interaction between mRNA and microRNAs
[46]. Considering bruxism in the analysis may mean that a
less heterogeneous group is being evaluated, which allowed
for the detection of associations. This result is relevant and
may motivate the design of future studies to consider the
inclusion of a measure of tooth grinding as a tool to increase
homogeneity and allow for the detection of causal and/or
risk factors that may have smaller effect sizes.
Conclusion
Our results suggest that occlusal factors, such as malocclu-
sion and attrition, might be associated with the incidence
NCCLs.
Author contributions BLN: Research conception and design, acquisi-
tion of data, analysis and interpretation of data, drafting the manuscript.
ARV: Manuscript review, agreed to be accountable for all aspects of
the work in ensuring that questions related to the accuracy or integrity
of any part of the work are appropriately investigated and resolved.
MB: Contributions to conception and design, acquisition, analysis and
interpretation of genetic data. SAI: Analysis and interpretation of data.
EMS: Research conception and design, drafting the manuscript, final
approval of the version to be published.
Funding This study was financed in part by the Coordenação de Aper-
feiçoamento de Pessoal de Nível Superior—Brasil (CAPES)—Finance
Code 001.
Declarations
Conflict of interest The authors declare that they have no conflict of
interest.
Ethical approval Data for the study were obtained from the University
of Pittsburgh School of Dental Medicine Dental Registry and DNA
repository project. The study protocol was approved by the University
of Pittsburgh Institutional Review Board.
Informed consent Informed consent was obtained from all individual
participants included in the study.
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