DOI: 10.1111/prd.

12238

REVIEW ARTICLE

Stress, allostatic load, and periodontal diseases

Wael Sabbah1 | Noha Gomaa2 | Aswathikutty Gireesh3

1
Division of Population and Patient Health, Dental Institute, King’s College London, London, UK
2
Faculty of Dentistry, University of Toronto, Toronto, ON, Canada
3
Institute of Child Health, University College London, London, UK

Correspondence
Wael Sabbah
Email: [email protected]

1 | INTRODUCTION disease.18,19 Fewer reviews have addressed the role of stress and
psychological wellbeing on periodontal disease.10,11 Studies have
Psychological stress has been postulated as a risk factor for a num- also examined the mediating role of stress between socioeconomic
ber of chronic health conditions, such as cardiovascular diseases, dia- position and periodontal diseases.10,14 While clarification of the rela-
1-4
betes, and obesity, among others. Stresses induced by poverty, tionship between stress and periodontal diseases might help to iden-
unemployment, job insecurity, highly demanding routine jobs, and tify those at high risk, its main importance lies in highlighting the
lack of control at the workplace and at home have been linked to role of environmental and social factors that could only be addressed
cardiovascular diseases, obesity, diabetes, physical limitations, and at a higher level.
cancer.5,6 The vicious cycle between socioeconomic factors, stress, Given the increasing global burden of periodontal diseases, and
and health has perhaps been best described by Evans & Kim7 as the importance of stress as a modifiable risk factor for periodontal
“poverty gets under the skin”. Stress affects health through different diseases along with other chronic conditions, we conducted this nar-
pathways, resulting in biological impact on the autoimmune and rative review pertaining to the role of stress in periodontal diseases
endocrine systems, and on metabolism.8 Stress can also affect health and the different mechanisms through which stress impacts peri-
through inducing change in behaviors. Individuals may adopt some odontal diseases.
unhealthy behaviors, such as smoking, excessive consumption of
alcohol, and use of illicit drugs, to cope with stressful situations.9
There is also evidence that stress affects oral health.10 Using 2 | THE ROLE OF STRESS IN THE
unhealthy behaviors (such as smoking, drinking alcohol, and comfort COMPLEX DETERMINANTS OF
eating) as coping mechanisms for stress increases risk for periodontal PERIODONTAL DISEASE
diseases, dental caries, and oral cancer.10 Additionally, biological
changes associated with stresses are depicted as risk factors for oral Periodontal disease is a socially patterned condition with a strong
diseases.11 There is also evidence that stresses are linked to salivary behavioral component. Smoking and poor oral hygiene, associated
changes which result in increased susceptibility to dental caries.12 with inadequate personal and professional tooth cleaning, are among
On the other hand, the biological pathways between stresses and the top behavioral risk factors for periodontal disease.18,19 There is
periodontal diseases appear to be more evident and have been also a strong genetic component that increases susceptibility to peri-
addressed in several studies.11,13,14 Chronic and repeated exposure odontal disease.20 Certain systemic conditions are implicated in pre-
to stressors affect periodontal tissues in the same manner that they disposing individuals to periodontitis; these include diabetes,
14
affect other body systems. leukemia, and acquired neutropenia, among others.19 Psychological
Recent studies on the global burden of oral health suggest that stressors have been repeatedly shown to play an important role in
the prevalence of periodontal diseases is increasing,15 in contrast to periodontitis because they are able to influence the behavioral risk
a previous review.16 Furthermore, periodontal diseases appear to factors for periodontitis and/or affect periodontal tissues directly.
result in an increase in disability-adjusted life years (ie, the number Studies have shown that individuals under stresses are more likely
of years lost due to ill-health, disability, or early death).17 Several to smoke, less likely to brush their teeth, and less likely to visit a
reviews have addressed proximal risk factors for periodontal dentist,9,21 all-important behavioral determinants of periodontal dis-
diseases, highlighting opportunities to tackle the burden of the eases. On the other hand, stressors have been shown to have an

154 | © 2018 John Wiley & Sons A/S. wileyonlinelibrary.com/journal/prd Periodontology 2000. 2018;78:154–161.
Published by John Wiley & Sons Ltd
SABBAH ET AL. | 155

impact on the body, increasing susceptibility to inflammation and 4 | STRESS ASSESSMENT

affecting the host immune response and endocrine systems.8,22,23
Such reactions to chronic stressors affect different tissues through- There are several subjective, objective, and physiological/biomedical
out the body, including the periodontium. Unsurprisingly, the com- measures to measure stress responses. In the absence of a gold stan-
mon effect of stressors on different body organs is implicated in the dard for measurement of stress, selection of tool depends on the stres-
relationship between systemic conditions and periodontal dis- sor (acute or chronic) that is presented to the study subjects, the
eases.13,14 Finally, examining the contextual determinants of health methodological constraints of the study design, and the research ques-
and related behaviors will enable identification of socioeconomic and tion.29 Questionnaires and interviews are the main measurement tools
environmental factors that impact on both stress and behaviors both used to assess environmental and self-perceived stress, while biomark-
directly, by limiting an individual’s ability to engage in healthy behav- ers or endocrine measures help to quantify physiological or chronic
iors and avoid unhealthy ones, and indirectly, through psychological stress.23 In this section, the most widely used measures of stress will
pathways, which include stress.8 be discussed.

4.1 | Self-reported measures

3 | TYPES OF PSYCHOSOCIAL STRESSES
4.1.1 | Perceived stress scale
Psychosocial stress can be defined as the physiological and psy-
chological changes that occur in the body when an external The Perceived Stress Scale is the most validated tool among self-
demand or stressor taxes an individual’s adaptive capacity.24 Based reported measures and has strong psychometric properties. It com-
on the duration of exposure, stress can be broadly classified into prises 14 items that rate stress based on the frequency of difficult
chronic or acute forms; however, there is no universally accepted events in a period of 1 month. There are 2 short versions of the
definition or established temporal cut-off period for acute and Perceived Stress Scale: Perceived Stress Scale-4; and Perceived
chronic stress. Stress Scale-10. As perceived stress has a large impact on cortisol
Stressors are external stimuli that cause stress in an individual level, Perceived Stress Scale scores tend to be positively correlated
and they are categorized into 3 groups: with biomarkers of stress.30

• Disasters or crises. An unpredictable event which is completely

4.1.2 | Stress appraisal measure
out of the control of the individual. For instance, devastating nat-
ural disasters, such as major floods or earthquakes, or wars. This pooled inventory of 28 items is developed based on the differ-
• Major life events. These are rare events that can be either posi- ent aspects of 6 dimensions of primary (threat, challenge, and cen-
tive or negative and include marital separation, imprisonment, trality) and secondary (controllable-by-self, controllable-by-others,
death of a close family member, dismissal from work, and per- uncontrollable-by-anyone) appraisal of stress. Each item is rated on a
sonal injury. 4-point scale and an overall mean rating is obtained.31
• Micro stressors. Accumulation of micro stressors or daily hassles
can have the same negative impact on our health as experiencing
4.1.3 | Impact of event scale
a major stressful event. They occur in every individual’s life; how-
ever, they are different for each individual, as not everyone per- The Impact of Event Scale-R consists of 22 items and assesses
ceives a certain event as stressful.25 the degree to which a distressful traumatic event impacts an indi-
vidual. An individual is required to identify a difficult situation in
Acute stressors are most commonly referred to as short-term the past week and indicate the difficulty score on a 5-point scale,
and time-limited events, whereas chronic stressors denote conditions ranging from ‘not at all’ to ‘extremely’, yielding a total score of up
that are longer lasting and may not be attributed to a discrete to 88.32
26
event.
The organizational model of the stress process that explains how
4.1.4 | Life experiences survey
chronic stress leads to deleterious health outcomes can be catego-
rized into 3 broad stages: exposure to environmental demands or The Life Experiences Survey is a 60-item self-reported structured
negative life events or stressors; self-evaluation and appraisal of the interview which includes events that typically would be perceived as
stressors, which could elicit negative responses in the absence of negative or positive. If individuals had experienced the event, they
coping skills; and activation of the biological system in response to were asked to indicate, on a 7-point scale, the extent to which it
27,28
environmental and psychological demand. This conceptualization had an impact. Typically, the range spans scores from extremely neg-
of stress serves as a resource for developing stress assessment tools ative, to no influence, to extremely positive.33
to aid researchers to select an appropriate measure to use in differ- In addition to these measures, there are many other self-report
ent studies. instruments and structured interviews (Table 1). The appropriate
156 | SABBAH ET AL.

T A B L E 1 Self-reported and structured interviews used to assess stress in relation to periodontal disease
Assessment
Study ID Instrument method Components Measurement focus
Green et al Life Experiences Normative - Section 1 (47 items) explores life changes in a wide Major life events in the past
(1986)65 Survey33 structured variety of situations year
interview Section 2 (10 items) is used among students
Genco et al (a) Life Event Scale - Subjective - Personal relationships (7 items), childbirth (8 items), Life events, including their
(1999)66 adaptation from Psychiatric questionnaire work (9 items), finances (8 items), health and illness perceived controllability and
Epidemiology Research (7 items), crime and legal matters (8 items), impact
Interview67 residential and household events (7 items), and
education (5 items) for 102 life events
(b) Measures of chronic Subjective - Coping response items in marriage, parenting, Coping responses in different
stress (daily strains)68 questionnaire household economics, and occupation (84 items) role areas: spouse, parent,
worker, and financial manager
Hilgert et al Lipp’s Stress Symptoms Subjective - Three sections dealing with the 4 phases of stress: Identify the phase of the stress
(2006)55 Inventory for Adults69 questionnaire section 1, alarm; section 2, resistance & near- process and physical/
exhaustion; section 3, exhaustion psychological dimension of
stress
Park et al The Center for Subjective - A 20-item measure that asks caregivers to rate Perceived stress and pregnancy
(2016)70 Epidemiological Studies- questionnaire affective, cognitive, behavioral, and somatic stress
Depression Scale71 symptoms within the previous 7 days
Fenol et al Depression, Anxiety, and Subjective - A 21-item scale with 7 points per item measuring Emphasizes the links between
(2017)72 Stress Scale73 questionnaire negative emotional states of depression, anxiety the relatively enduring state of
and tension/stress anxiety/stress and the acute
response of fear
Rosania et al Derogatis Stress Profile75 Normative 77 items, comprising 7 items for each of the Stimulus, response, and
(2009)74 11 primary dimensions including ‘vocational interactional elements of
environment, domestic environment, health stress
environment, time pressure, driven behavior,
attitude posture, relaxation potential, role
definition, hostility, anxiety, and depression’
Solis et al Life Events Scale modified Subjective List of 43 life-events related to “work” lack of Life events in the past year
(2004)76 by Savoia et al77,78 social support, family, environmental changes,
personal difficulties, and financial strain

assessment of stress is critical for understanding the potential conse- outcomes, cortisol captures the status of the hypothalamic-
quences of these disorders, as well as for the development of appro- pituitary-adrenal axis function. The immediate sources of cortisol
priate behavioral and pharmacological treatments. The reliability and are blood (plasma or serum) and saliva. Dehydroepiandrosterone
validity of screening instruments must be carefully evaluated before is also a marker of chronic stress and functions as a hypo-
they are used. thalamic-pituitary-adrenal axis antagonist. Dehydroepiandrosterone
measurements directly capture the status of hypothalamic-
pituitary-adrenal axis functioning. However, because of the large
4.2 | Clinical-biochemical measures
diurnal variation in cortisol or dehydroepiandrosterone levels,
which makes it difficult to ascertain the levels from a single mea-
4.2.1 | Neuroendocrine biomarkers
surement, these are not generally effective as biomarkers for
Whenever a stressor induces chronic physiological stress, there are chronic stress.
some systemic level alterations, as well as an increase in energy pro- In recent years, researchers have also become increasingly inter-
duction to maintain homeostasis. The neuroendocrine system is ested in hair samples as another potentially practical mode of assess-
the first to be triggered and this will initiate the release of endo- ing the cumulative exposure to stress. Unlike other, less reliable
crine markers which can be detected effectively. The various neu- measures, the noninvasive sampling of hair has several advantages in
roendocrine biomarkers of chronic stress currently in use include terms of collection, storage, and transportation.34,35 Furthermore,
cortisol, dehydroepiandrosterone, epinephrine, norepinephrine, and the level of cortisol in hair can also reflect both acute and chronic
dopamine. stress.

Cortisol and dehydroepiandrosterone Epinephrine, dopamine, aldosterone, and norepinephrine

The cortisol level is one of the measures most frequently used to The levels of these biomarkers consistently show an increase in
quantify physiological stress. As a mediator of many secondary response to stress, regardless of whether the stress it is perceived
SABBAH ET AL. | 157

as a threat or an opportunity for gain. Hence, these measures

4.2.4 | Allostatic load
may not necessarily be static measures of stress.36,37 Nevertheless,
when used in conjunction with other markers of chronic stress in No single metric can accurately measure chronic stress, and this
an allostatic load model, norepinephrine and dopamine can be use- shortcoming is managed by using a compendium of biomarkers,
ful pointers of sympathetic nervous system and cardiovascular released from different body systems, known as allostatic load,
functioning, respectively. Aldosterone can be a useful measure of which is generally defined as the ‘the price the body pays for being
the function of the adrenal gland when used in conjunction with forced to adapt to adverse psychological or physical situations, and
38
other biomarkers of allostatic load. Importantly, it is the fre- it represents either the presence of too much stress, or the ineffi-
quency of acute stressors that are detrimental to health. cient operation of the stress hormone response system’.22
Allostasis is an active physiological or biochemical adaptation
that helps the body to reestablish homeostasis after exposure to a
4.2.2 | Immunological biomarkers
stressor. While the acute stress response is critical for survival,
Other commonly used biomarkers of chronic stress are the circulat- repeated or chronic exposure to stressors can have deleterious
ing levels of interleukin-6, tumor necrosis factor-alpha, C-reactive effects on the nervous and endocrine systems and on immune func-
protein, and insulin-like growth factor.39,40 The secretion of immuno- tions. When individuals are repeatedly exposed to chronic stressors,
logical biomarkers may be altered by chronic exposure to stress. biological responses are induced to cope with these stressors, lead-
Interleukin-6, a proinflammatory cytokine that functions synergisti- ing to wear and tear on the immune, cardiovascular, metabolic, and
cally with tumor necrosis factor-alpha and interleukin-1, can indi- nervous systems and this is primarily marked by elevated epinephr-
rectly capture the dysfunction of the hypothalamic-pituitary-adrenal ine and cortisol levels in the body, a phenomenon known as allo-
axis mediated by glucocorticoid signaling. The level of C-reactive static load.22,23,42,43
protein has been used in many studies as one of the inflammatory As chronic exposure to stress hinders the normal functioning of
responses to chronic stress.41 the physiological regulatory system, the status of the biological sys-
These biomarkers, however, are markers of inflammation, and tem should be considered for allostatic load measurement. The first
are not used as primary markers of stress. They are rather indica- study to validate these interlinking. The cascading relationships were
tors of how stress can affect the immune system. Although these validated initially by the McArthur studies of successful aging.8,23
biomarkers are used with other primary markers (such as epinephr- The study contains information about the 10 parameters which
ine and cortisol) to test the relationship between stress and cardio- determine the physiological status of the hypothalamic-pituitary-
vascular and periodontal diseases,8,14,23,42 they can also be found adrenal axis, sympathetic nervous system, metabolic processes, and
in the body system as markers of inflammation in the absence of cardiovascular system. The first four primary mediators (dehy-
stress. droepiandrosterone, cortisol, epinephrine, and norepinephrine) per-
taining to stress response were identified. Other mediators were
indices of outcomes: metabolic (eg, insulin, glucose, total cholesterol,
4.2.3 | Metabolic biomarkers
high density lipoprotein, cholesterol, triglycerides, visceral fat
Changes in metabolism have been used as secondary and tertiary depositing), cardiovascular (eg, systolic and diastolic blood pressure),
markers of stress.22,23,43 Studies have used biomarkers such as and immune (eg, fibrinogen, C-reactive protein; Table 2). Most of the
cholesterol levels, albumin, waist-hip ratio, and glycosylated hemo- biomarkers measured to derive the allostatic load score are biologi-
4,8,22,23
globin in combination with other biomarkers discussed above. cally interconnected. Although allostatic load reflects cumulative
Such biomarkers are, however, majorly confounded by many vari- exposures to stress over many years, most allostatic load studies are
ables which makes them less reliable and less valid measures in epi- of cross-sectional nature. Longitudinal measurement of allostatic load
demiological studies. can provide information about the allostatic profile of an individual

T A B L E 2 Primary and secondary markers of allostatic load

Stress biomarkers System Biomarker
Primary markers Neuroendocrine Epinephrine, norepinephrine, dopamine, salivary cortisol, hair cortisol, norepinephrine,
dehydroepiandrosterone, aldosterone
Secondary Immunological Interleukin-6, tumor necrosis factor-alpha, C-reactive protein, fibrinogen, insulin-like growth factor-1
outcomes biomarkers
Metabolic biomarkers High-density lipoprotein and low-density lipoprotein cholesterol, triglycerides, glycosylated hemoglobin,
plasma glucose, glucose insulin, albumin, creatinine, homocysteine
Cardiovascular and Systolic blood pressure, diastolic blood pressure, peak expiratory flow, heart rate/pulse
respiratory
Anthropometric Waist-to-hip ratio, waist circumference, body mass index
158 | SABBAH ET AL.

at various stages of development of stress-related health outcomes. conditions generating psychosocial stressors and material constraints
This can shed some insight into the pathways of pathophysiology determine whether individuals take up unhealthy behaviors and
leading to the development of disease.8,43,44 whether they possess the necessary resources and motivation to
care for their oral and overall health. Related to this is the link
between the social environment and self-perceived health and health
5 | STRESS PATHWAYS TO PERIODONTAL
locus of control, which in turn affects one’ s ability to change harm-
DISEASES
ful behaviors.48,49
Furthermore, as the association between stress and periodontal
5.1 | Biological changes
disease needs to be clarified, prospective studies should take health
In response to chronic stressors, a cascade of reactions occurs. behaviors into consideration to determine their contribution to the
First, the hypothalamus releases corticotropin-releasing hormone stress-periodontal disease relationship.50
from the periventricular nucleus, initiating the hypothalamic-pitui-
tary-adrenal pathway, which in turn stimulates the pituitary gland to
release adrenocorticotropic hormone. Because of the stimulating 6 | ALLOSTATIC LOAD AND
effect of circulating adrenocorticotropic hormone, glucocorticoids, PERIODONTAL DISEASES
such as cortisol (primary stress hormone), are produced by the
cortex of the adrenal glands. Dehydroepiandrosterone, an endoge- A number of studies have examined the association between allo-
nous, cortisol regulatory hormone, is also released. Another parallel static load and specific biological markers of stress, on the one hand,
pathway, the sympatho-adrenal medullary axis, also operates at the and periodontal diseases on the other hand. Bakri et al,51 using longi-
same time in the medullary cortex of the adrenal gland, resulting in tudinal data, found that patients with stress indicated by a high level
the release of epinephrine and norepinephrine (together called of C-reactive protein and a high Perceived Stress Scale at baseline
catecholamines).45,46 had worse periodontal outcomes than those with lower levels of
Glucocorticoids, including cortisol, exert major suppressive stress. The study was hindered by having a small sample size.
effects, through highly specific mechanisms, at different levels. At Another study used a longitudinal design to examine the relationship
the molecular level, they inhibit vital functions of inflammatory cells, among socioeconomic position, C-reactive protein (as a marker of
such as macrophages, neutrophils, eosinophils, and mast cells, in stress), and periodontitis. However, both C-reactive protein and peri-
functions such as chemotaxis, secretion, and degranulation. The odontitis were assessed at the same time point.52 Almost all other
immunological function can be independently altered by release of studies used either case-control or cross-sectional data. An associa-
all of these biochemical mediators into the system. Cortisol is an tion between salivary cortisol, interleukin-1beta, interleukin-6, and
immunosuppressant, and its major effects are on T-helper cell periodontitis was demonstrated in a number of studies.12,53-57 It is
responses: it suppresses the production of interleukin-12, the major worth noting here that salivary cortisol is a marker of acute stress,
inducer of T-helper type 1 cells; and it enhances the production of and hence it is difficult to verify a potential causal relationship with
T-helper type 2 cytokines (interleukins 4, 10, and 13), which in turn periodontal disease. Two known studies used a combined variable of
boosts T-helper type 2 cell functions.47 Consequently, cortisol inhi- different biological markers as indicators of allostatic load, using data
bits the presentation of macrophage antigen, and lymphocyte prolif- from different waves of the National Health and Examination Survey.
eration and differentiation, and overall dysregulation of the immune Sabbah et al14 used an aggregate variable of 7 biomarkers of allo-
system occurs. Prolonged stress-related stimulation of the hypothala- static load, namely C-reactive protein, fibrinogen, high blood pres-
mic-pituitary-adrenal axis suppresses both immune and inflammatory sure, waist circumference, triglycerides, plasma glucose, and high-
responses, and biological adjustments occur.8 density lipoprotein-cholesterol to assess whether stress indicated by
allostatic load mediates the relationship between socioeconomic con-
ditions and each of periodontal and ischemic heart diseases. The
5.2 | Behavioral changes
authors found an association between allostatic load and each of the
Allostatic load reflects the influence of social circumstances and conditions and argued that biological markers of stress possibly medi-
stressful life experiences, as well as behaviors such as smoking, diet, ate the association between socioeconomic position and these health
exercise, and alcohol consumption, which have been shown to con- outcomes. Similarly, Borrell & Crawford13 argued that a combined
tribute, in large part, to the allostatic load. Indeed, health behaviors variable of allostatic load, which included blood pressure, body mass
are well-known risk factors for periodontal disease and several other index, glycated hemoglobin, triglycerides level, C-reactive protein,
health conditions. However, while stress has been shown to corre- homocysteine level, total cholesterol level, albumin, and creatinine,
late with poor health behaviors, some would argue that the role of explains ethnic inequalities in periodontal diseases. Although these 2
behavior in disease has been overemphasized, and that health studies used objective indicators of stress (allostatic load) and large,
behaviors are mediators of the psychosocial environment in which nationally representative, samples of the US population, their conclu-
people live, rather than causals themselves. Social and living sions do not support temporality.
SABBAH ET AL. | 159

7 | THE ROLE OF STRESS REACTIVITY AND options available. However, considering the potential benefit of estab-
COPING lishing allostatic load as a causal risk factor for periodontitis, research-
ers and funding agencies should work on developing longitudinal and
It is not surprising that different studies have used allostatic load to intervention studies with adequate sample size to establish or refute a
explain socioeconomic and ethnic inequalities in periodontal dis- relationship between allostatic load and periodontal diseases.
eases. Indeed, studies on stress reactivity suggest that there are vari-
ations in response to acute and chronic stressors which are mostly
influenced by employment status, education, social isolation, loneli- 10 | CONCLUSIONS
ness, effort-reward imbalance, and belonging to ethnic minor-
ity.10,58,59 Individuals at the top of the social hierarchy are more In this narrative review, the results of several studies that examined
likely to cope with a stressful situation as they have more control the relationship between stress (as assessed by subjective instru-
over their lives and have the opportunity to engage in leisure activi- ments and by biological markers of stress, particularly allostatic load)
ties to cope with daily stressors. On the other hand, those at the and periodontal diseases, were reported. Despite the methodological
lower end of the social hierarchy are subjected to more frequent limitations of the studies that addressed this important relationship,
stressful situations and have fewer opportunities to engage in there is a clear and plausible indication of a strong role for stress in
healthy activities that would help cope with stress; by contrast, they the manifestation of periodontal diseases. The reviewed studies also
are more likely to engage in unhealthy behaviors, such as smoking, highlight a number of biological indicators of allostatic load that have
binge drinking, and comfort eating, as a coping mechanism. been collectively associated with periodontal disease. Furthermore,
this review demonstrates a link among socioeconomic position
stress/allostatic load and periodontal diseases, highlighting a possible
8 | PERSONALIZED PERIODONTICS AND mediating role of stress in oral health inequalities. Finally, identifying
ALLOSTATIC LOAD biomarkers of stress could add an important dimension to the
emerging field of personalized periodontics.
Categorizing the patients into specific risk groups has been adopted
in medicine and dentistry for years. However, with advances in med-
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