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RESEARCH REPORT
Use of Saliva for Assessment of Stress and Its Effect
on the Immune System Prior to Gross Anatomy
Practical Examinations
S. Reid Lester,1 Jason R. Brown,1 Jeffrey E. Aycock,1 S. Lee Grubbs,1 Roger B. Johnson1,2*
1
Department of Periodontics and Preventive Sciences, School of Dentistry, University of Mississippi Medical
Center, Jackson, Mississippi
2
Department of Anatomy, School of Medicine, University of Mississippi Medical Center, Jackson, Mississippi
The objective of this study was to determine the longitudinal effects of a series of stressful gross
anatomy tests on the immune system. Thirty-six freshman occupational therapy students completed a written stress evaluation survey, and saliva samples were obtained at baseline and prior
to each of three timed-practical gross anatomy tests. Cortisol, secretory IgA (sIgA), and IL-12
concentrations were measured within the salivary samples by enzyme-linked immunosorbent
assay. The total scores from the stress surveys were used as markers for environmental stress.
Data were compiled for each student at baseline and prior to each examination and were compared by repeated-measures MANOVA and Pearson’s correlation test. Following normalization
for protein concentration and flow rate, the concentrations of IL-2, IL-6, IL-12, and sIgA progressively increased from baseline to the third test. Cortisol concentrations, following normalization for flow rate, were highest prior to the first test and became significantly reduced prior to
second and third test. Prior to second and third test, salivary concentrations of IL-6, IL-2, IL-12,
and sIgA were significantly correlated (P < 0.05). In contrast, prior to third test, there was a negative correlation between salivary concentrations of cortisol and IL-12 (P < 0.05). Progressive
increases in salivary sIgA, IL-6, IL-2, and IL-12 concentrations from the first to the third test
coincident to decreased salivary cortisol suggest that the initial examination stressors precede
significant effects on the immune system. These data suggest that there may be latent effects of
examination stress on the immune system and that saliva can be used to predict these effects.
Anat Sci Educ 3:160–167, 2010. © 2010 American Association of Anatomists.
Key words: gross anatomy; examination stress; immunology; occupation therapy
students; saliva; laboratory examination
INTRODUCTION
Stress is defined as a series of events composed of a stimulus
(stressor), which initiates a reaction in the brain (stress perception); the latter activating a stress response (Dhabhar and
*Correspondence to: Dr. Roger B. Johnson, Department of
Periodontics and Preventive Sciences, School of Dentistry, University
of Mississippi Medical Center, 2500 North State Street, Jackson, MS
39216-4505, USA. E-mail: [email protected]
Grant sponsor: University of Mississippi Intramural Grant
Received 23 November 2009; Revised 11 May 2010; Accepted 20
May 2010.
Published online 6 July 2010 in Wiley
interscience.wiley.com). DOI 10.1002/ase.161
© 2010 American Association of Anatomists
Anat Sci Educ 3:160–167 (2010)
InterScience
(www.
McEwen, 1997). Stress can be either challenging (positive) or
threatening (negative) and may be either adaptive or debilitating (Sanders and Lushington, 2002). It can either be a creative force to increase drive and energy or can have negative
results when excessive or prolonged (Dhabhar and McEwen,
1997).
The academic stress model has been frequently used to
investigate the effects of psychological stress on immune function (Kiecolt-Glaser et al., 1984, 1986). Acute stress can lead
to increases in several measures of immunity (Carroll et al.,
1996; Ring et al., 1999, 2000; Willemsen et al., 2000; Winzer
et al., 2000; Benham, 2007).
Examinations are considered to be one of the most significant
acute stressors experienced by students (Jemmott and Magloire,
1988; Maes et al., 1997; Spangler, 1997; Maes et al., 1998a,b;
Deinzer et al., 2000; Lacey et al., 2000; Lowe et al., 2000).
Substantial research regarding student stress has centered on
JULY/AUGUST 2010
Anatomical Sciences Education
examination stress (Grandy et al., 1989), as students often experience high levels of stress associated with either written or
oral examinations. There have been numerous cross-sectional
studies of the effects of examination stress on healthy medical
(Kiecolt-Glaser et al., 1984, 1986; Glaser et al., 1987; Dobbin
et al., 1991; Glaser et al., 1993, 1994; Marshall et al., 1998;
Deinzer et al., 2000; Uchakin et al., 2001; Otsuki et al., 2004;
Segal et al., 2006), dental (Ng et al., 2003), physiotherapy (Sarid
et al., 2004), and nursing students (Takatsuji et al., 2008).
Students enrolled in occupational therapy programs have not
been studied. There is little longitudinal data about the cumulative effects of examination stress on the immune system coincident to gross anatomy courses in any of these student groups.
Effects of Academic Stress on
Cortisol Secretion
Previous studies have used oral presentations and written examinations as acute stress situations (Maes et al., 1997; Deinzer
et al., 2000; Lacey et al., 2000; Ng et al., 2003). The intensity
and nature of the stress has been reported to be different for
each type of examination (Ng et al., 2003). Acute stress has
been reported to increase the activity of the hypothalamus-pituitary-adrenal (HPA) axis, which results in elevated serum cortisol
concentrations (Ng et al., 2003). Because they are soluble in lipids, steroid hormones can also be detected in saliva, and salivary
cortisol concentrations have been reported to be highly correlated with the serum concentrations (Peters et al., 1982; Vining
et al., 1983; Kirschbaum and Hellhammer, 1994). Salivary cortisol concentrations have been reported to be higher prior to a
written examination, with anticipation of the examination as
the stressor (Peters et al., 1982; Vining et al., 1983; Kirschbaum
and Hellhammer, 1994). However, several other studies have
reported decreased cortisol expression after a stressful examination (Ng et al., 2003; Loft et al., 2007; Takatsuji et al., 2008).
Cytokine expression, including IL-6 and IL-12, has been
reported to be inhibited by cortisol (Weigers and Reul, 1998;
Richards et al., 2001; Sapolsky et al., 2001). The inhibition of
IL-12 expression affects the TH1/TH2 balance, suppressing the
cell-mediated response and favoring an immunosuppressive TH2
response (Elenkov and Chrousos, 2002). IL-2 is produced by
activated CD41 cells and is responsible for expansion of the
CD41 and CD81 cell populations. This cytokine has recently
been reported to function as a stimulating factor for differentiation of TH2 cells and in maintaining the expression of TH2-committed cells by activation of STAT5 (Liao et al., 2006).
Effects of Academic Stress on Salivary
Secretory IgA Concentrations
Salivary secretory IgA (sIgA) is the main defense against
pathogens within the oral cavity. The regulation of the secretion of sIgA is dependent on prior antigenic stimulation and
HPA axis activity (Teeuw et al., 2004). Salivary concentrations of sIgA have been reported to be either correlated (Jemmott et al., 1983; Jemmott and Magloire, 1988; Deinzer and
Schuller, 1998; Uchakin et al., 2001; Otsuki et al., 2004;
Takatsuji et al., 2008) or not correlated with academic stress
(McClelland et al., 1985; Evans et al., 1994; Bosch et al.,
1996; Ng et al., 2003) in previous studies.
Individuals experiencing acute stressors such as oral presentations (Evans et al., 1994), public speaking (Bristow
et al., 1997), and active mental stress tasks (Ring et al.,
Anatomical Sciences Education
JULY/AUGUST 2010
2002) were reported to have significantly higher concentrations of salivary sIgA after performing those tasks.
As different types of situations induce different intensities
of stress to individuals, changes in the salivary slgA concentrations could be a sensitive marker for the intensity of the
stressor. There are reports of increased symptoms of upper respiratory infections coincident to decreased concentrations of
slgA in students experiencing academic stress (Deinzer and
Schuller, 1998), suggesting a mechanism for the association
between the effects of academic stress and disease.
Effects of Academic Stress on the
Immune System
The interaction between the central nervous, endocrine, and
immune systems has recently been reviewed (Calcagni and Elenkov, 2006), which indicates that psychological stressors are capable of suppression of the immune response. Release of cytokines,
including IL-6 and IL-12, results in activation of the stress system
(Calcagni and Elenkov, 2006), and stress hormones inhibit
expression of several cytokines, including IL-2 (Elenkov, 2006).
The human immune response is composed of a cell-mediated (TH1) and an immunosuppressive (TH2) component,
which usually exist in equilibrium. Psychological stress alters
TH1 responses and psychologically stressful situations shift
the TH1/TH2 cytokine balance toward TH2 (Elenkov, 2006).
Academic stress and stress-induced anxiety increase serum
concentrations of TH1 cytokines, such as TNF-a, IFN-g, and
IL-6, and decreased concentrations of TH2 cytokines, such as
IL-10 and IL-4 (Maes et al., 1998a).
Acute psychological stress has been associated with elevated serum interferon (IFN)-y, interleukin (IL)-1-b and IL-2
concentrations, and reduced IL-4 and IL-10 concentrations,
suggesting activation of the TH1 immune pathway by stress
(Maes et al., 1998a; Heinz et al., 2003). Psychologically
stressful situations shift the TH1/TH2 cytokine balance toward a predominance of TH2 cytokines, resulting in immunodysregulation, which may explain the increased incidence of
viral infections, latent viral expression, allergic/asthmatic conditions, and autoimmunity reported during periods of high
stress (Marshall et al., 1998; Kang and Fox, 2001).
There is little information available concerning the longitudinal effects of stress associated with timed-practical examinations, which are frequently administered to students pursuing health care careers. A common experience for these students is the gross anatomy practical examination, which is
often the source of significant stress (Johnson and Bernanke,
2000). This type of examination contains both content and
time stressors, which makes it unique among the types of
examinations available for evaluation of stress. A study of
reactions to a series of examinations suggests that the initial
examination is the most stressful, with decreased stress experienced with subsequent examinations (Sarid et al., 2004).
Stress and glucocorticoids may impair memory and cognitive
function (de Quervain et al., 1998; al’Absi et al., 2002) and
are associated with poor grades (Ng et al., 2003). Thus, it is
important to identify students experiencing excessive stress
early in a course. In addition, it is valuable to differentiate
between the students that would benefit from stress reduction
therapy and those which only require help with course content. Thus, salivary biomarkers could be useful for identification of students who are severely stressed prior to examinations and who may perform poorly because of their inability
to cope with stressors. These students might benefit from
161
stress awareness education and learning effective coping strategies for preparation and taking of examinations.
METHODS
Salivary protein and sIgA concentrations were also normalized for flow rate (mL/min), and the normalized concentrations/minute were included as outcome variables. In addition, the place of the examination in the course (baseline,
Examination 1, etc.), survey scores, gender, race, and age
were additional outcome variables.
Student Population
This study was approved by the Institutional Review Board of
the University of Mississippi Medical Center. Thirty-six freshman occupational therapy students were studied during their
gross anatomy course. Students were accepted for the study if
they were enrolled in the course and were able to give informed
consent. They were excluded if they were pregnant.
Saliva Collection
We collected whole, unstimulated saliva between 12:30 and
1:00 p.m., just prior to the gross anatomy practical examination
using the techniques based on those of Navazesh (Navazesh,
1993), which have been commonly used in our laboratory for
previous studies (Streckfus et al., 1997; Johnson et al., 2002;
McGehee and Johnson, 2004; Johnson, 2005). The students had
nothing to eat or drink one hour prior to the saliva collection.
Each student was asked to spit into a 50-mL centrifuge tube for
five minutes. The final volume and flow rate of the collected
saliva was then determined gravimetrically (Navazesh, 1993).
In the laboratory, the samples were centrifuged at 3,000
rpm for 20 min in a refrigerated centrifuge. Following centrifugation, the supernatant was separated from the pelleted cells
and the volume was measured. A protease inhibitor (CompleteTM, Sigma-Aldrich, St. Louis, MO) was added to the supernatant, which was then frozen at 2808C.
Saliva was collected at a baseline time point (two weeks before
the first test) and prior to each gross anatomy practical examination. Prior to the baseline collection, each participant completed a
survey to measure environmental stress [‘‘Perceived Stress Scale’’
(Cohen et al., 1983)]. On the day of the examination, the participants also completed a short survey ‘‘Symptoms of Test Anxiety’’
measuring their perceived stress at that time (ULC, 2001).
Saliva Analysis
The total protein was measured in triplicate samples of each salivary aliquot using a colorimetric test (MicroBCA Protein Assay;
Pierce Chemical Company, Rockford, IL). The final concentrations were determined by comparison to standards supplied with
each kit, using a microplate spectrophotometer at 570 nm. The
mean concentrations of each triplicate sample were expressed as
mg protein/mL saliva. Cortisol and slgA were measured in triplicate samples of each salivary aliquot by enzyme-linked immunosorbent assay (ELISA) using a commercial kit (ALPCO Diagnostics, Salem, NH). The final concentrations were determined using
a microplate spectrophotometer at 450 nm. Mean concentrations
of each triplicate sample were expressed as mg or ng/mL saliva.
IL-12 concentrations were measured in triplicate samples of each
salivary aliquot by ELISA using commercial kits (R&D Systems,
Minneapolis, MN). The final concentrations were determined by
comparison to standards supplied with each kit, using a microplate spectrophotometer at 450 nm. The mean concentration of
each triplicate sample was expressed as pg IL-12/mL saliva. The
mean concentrations from each cortisol, IL-2, IL-6, IL-12, and
sIgA assay were normalized for salivary protein and were
expressed as ng, mg, or pg/mg protein.
162
Statistical Analysis
A power test using the variability from a previous study of
medical students (baseline vs. pre-examination periods; Johnson
and Bernanke, 2000) suggested that significant differences
(P < 0.05) could be determined between concentrations of the
salivary biomarkers if n 5 12 for each group (UnifyPow, SAS
Systems, Cary, NC). Repeated-measures MANOVA and the
Pearson’s correlation test were used to examine the relationships
between the groups, using SPSS ver. 16.0 software (SPSS Inc.,
Chicago, IL). The data were adjusted for salivary flow rate; gender; race; and age, as these are known confounders (Streckfus
et al., 1997; McGehee and Johnson, 2004; Johnson, 2005). Outcome data were not uniformly distributed and were transformed
to log10 prior to statistical analyses. The groups for analysis
were (1) all students from each pretest collection period (Test 1,
Test 2, and Test 3) versus baseline data (each pretest collection
was compared to baseline) and (2) each pretest collection compared with other test periods. The salivary volume, specific gravity, and flow rate, normalized (to either protein or flow rate)
concentrations of cortisol, slgA, IL-2, IL-6, IL-12, normalized
protein and sIgA; and pre-examination survey scores or baseline
survey scores were compared between these groups.
RESULTS
Our study population was freshman occupational therapy
students, 34 female (age 20–35 years) and 2 male (age 21–22
years); 32 Caucasian and four African-American. Thus, this
represented a nearly homogeneous population with minimal
confounders for the salivary data. When normalized for protein concentration and flow rate, salivary cortisol concentrations were highest prior the first test and were significantly
lower prior to Tests 2 and 3 (P < 0.05; Fig. 1).
When normalized for protein concentration and flow rate,
the salivary concentrations of IL-12 (Fig. 2), sIgA (Fig. 3),
and IL-6 and IL-2 (Fig. 4) progressively increased from baseline to the third test (P < 0.05).
Scores from the written stress evaluation were not significantly different between tests (Test 1 5 9.14 6 0.57; Test 2 5
9.60 6 0.54; Test 3 5 9.17 6 0.54). In general, individual student salivary parameters and stress surveys reflected the mean
values for background and for each examination (Table 1).
Pearson’s correlation data indicated significantly positive
correlations between salivary concentrations of IL-12, IL-6,
IL-2, and sIgA prior to Tests 2 and 3 (P < 0.05) and a negative correlation between salivary cortisol and IL-12 concentrations prior to Test 3 (P < 0.05) (Table 2).
DISCUSSION
Our data suggest that this population of occupational therapy
students accommodated to physiological stress (as measured
by salivary concentration of cortisol) during a series of gross
anatomy tests. However, there were adverse changes to the
immune system following resolution of the physiological
Lester et al.
Figure 1.
Figure 3.
Saliva samples that had been obtained from students either two weeks (Baseline) or within one hour of a gross anatomy practical examination were frozen
and then processed as explained in the ‘‘Methods’’ section. The cortisol concentrations were obtained by ELISA and normalized to total protein concentration
and salivary flow rate. Means (6SEM) are reported in this chart. The examinations were approximately three weeks apart. aSignificantly different from Baseline, P < 0.05. bSignificantly different from Test 1, P < 0.05.
Saliva samples that had been obtained from students either two weeks (Baseline) or within one hour of a gross anatomy practical examination were frozen
and then processed as explained in the ‘‘Methods’’ section. The sIgA concentrations were obtained by ELISA and normalized to total protein concentration
and salivary flow rate. Means (6SEM) are reported in this chart. The examinations were approximately three weeks apart. aSignificantly different from Baseline and Test 1, P < 0.05. bSignificantly different from Test 2, P < 0.05.
stress. These students had higher concentrations of salivary
cortisol concentrations prior to the first test (compared to
baseline), followed by progressively lower concentrations
prior to subsequent tests. It is possible that this decrease was
a result of acclimation to stress by the students, as students
are often maximally stressed for the first examination in a
course. Salivary cortisol concentrations did not correlate with
the scores from the stress survey, which were not significantly
different during the course. These data extend previous studies that evaluate stress relative to a single examination or a
pair of examinations, by reporting the accommodation of
physiological stress during an entire gross anatomy course.
There has been some disagreement concerning whether academic stress increases or decreases salivary sIgA concentrations. Several studies report lower than normal concentrations
(Jemmott et al., 1983; Jemmott and Magloire, 1988; Deinzer
and Schuller, 1998; Takatsuji et al., 2008) while others report
higher than normal concentrations (McClelland et al., 1985;
Evans et al., 1994; Bosch et al., 1996) coincident to academic
stress. In addition, both stress-reducing and stress-inducing
tasks have been reported to increase sIgA concentrations within
saliva (Benham et al., 2009). Our data do not agree with those
studies reporting decreased salivary sIgA concentrations
Figure 2.
Figure 4.
Saliva samples that had been obtained from students either two weeks (Baseline) or within one hour of a gross anatomy practical examination were frozen
and then processed as previously described. The IL-12 concentrations were
obtained by ELISA and normalized to total protein concentration and salivary
flow rate. Means (6SEM) are reported in this chart. The examinations were
approximately three weeks apart. aSignificantly different from Baseline and
Test 1, P < 0.05.
Saliva samples that had been obtained from students either two weeks (Baseline) or within one hour of a gross anatomy practical examination were frozen
and then processed as explained in the ‘‘Methods’’ section. The IL-6 and IL-2
concentrations were obtained by ELISA and normalized to total protein concentration and salivary flow rate. Means (6SEM) are reported in this chart.
The examinations were approximately three weeks apart. aSignificantly different from Baseline and Test 1, P < 0.05.
Anatomical Sciences Education
JULY/AUGUST 2010
163
Table 1.
Saliva Samples Obtained from Students Either Two Weeks (Baseline) or Within One Hour of a Gross Anatomy Practical Examination
Change from baseline to
Variable
Examination 1
Examination 2
Examination 3
Cortisol
10 (), 26 (>)
35 (), 1 (>)
36 (), 0 (>)
IL-12
15 (), 21 (>)
8 (), 28 (>)
8 (), 28 (>)
IL-6
0 (), 36 (>)
1 (), 35 (>)
3 (), 33 (>)
IL-2
1 (), 35 (>)
2 (), 34 (>)
2 (), 34 (>)
sIgA
21 (), 15 (>)
8 (), 28 (>)
9 (), 27 (>)
Survey
10 (), 26 (>)
19 (), 17 (>)
21 (), 15 (>)
Change from Examination 1 to
Examination 2
Examination 3
Cortisol
36 (), 0(>)
36 (), 0 (>)
IL-12
31 (), 5 (>)
31 (), 5 (>)
IL-6
2 (), 34 (>)
0 (), 36 (>)
IL-2
2 (), 34 (>)
0 (), 36 (>)
sIgA
29 (), 7 (>)
30 (), 6 (>)
Survey
20 (), 16 (>)
22 (), 14 (>)
Change from Examination 2 to Examination 3
Cortisol
26 (), 10 (>)
IL-12
25 (), 11 (>)
IL-6
2 (), 34 (>)
IL-2
1 (), 35 (>)
sIgA
22 (), 14 (>)
Survey
24 (), 12 (>)
The number of students with a change in biomarker concentration between either the baseline period or the individual examinations is
recorded in the table. The symbols in parentheses indicate the direction of the change from the collection period related to baseline levels. For example, there were 36 students in each group, and looking at cortisol levels before Examinationination 1, 10 students had levels that were less than or equal to baseline levels and 26 students had levels that were greater than baseline levels.
following examinations, as sIgA progressively increased from
Test 1 to Test 3 in our population (Deinzer and Schuller, 1998;
Deinzer et al., 2000). These increases could indicate the response
of the immune system to pathogens, which affect sIgA concentrations following the original infection. Thus, it is possible that
our methods missed the initial reduction in sIgA following Test
1, but revealed an immune response to bacteria invading the
oral cavity during this period of immunosuppression.
Coincident to this decrease, salivary sIgA, IL-2, IL-6, and
IL-12 concentrations increased. Increased salivary concentration of IL-2 and IL-6 was expected, as these markers have
been elevated in previous studies (Calcagni and Elenkov,
164
2006). The stressors present at the initial examination precede significant adverse effects on the immune system. SIgA is
considered to be a major defense against diseases produced
by microorganisms (Tomasi and Grey, 1972). The concentrations of sIgA within saliva have been reported to correlate
with resistance to certain viruses (Murphy et al., 1982).
Thus, sIgA, in itself, does not seem to be a good marker for
measuring the intensity of academic stress.
Our study is the first to report increased salivary concentration of IL-12 coincident to academic stress. IL-12 regulates the
expression of a TH1 immunological profile, and its elevated
concentrations could indicate either an existing or pending
Lester et al.
Table 2.
The Concentrations of the Biomarkers Compared by Pearson’s Correlation Test to Determine Statistical Correlations Between
the Variables
Test 1
sIgA Test 1
Test 2
Test 3
0.031: IL-12
0.121: IL-6
0.093: IL-2
0.438a: IL-12
sIgA Test 2
0.239: IL-6
0.213: IL-2
0.587a: IL-12
sIgA Test 3
0.612a: IL-6
0.413a: IL-2
Cortisol Test 1
0.042: IL-12
0.113: IL-6
0.121: IL-2
20.066: IL-12
Cortisol Test 2
20.131: IL-6
20.173: IL-2
20.422a: IL-12
Cortisol Test 3
20.579a: IL-6
20.431: IL-2
The correlation coefficients between salivary concentrations of sIgA, cortisol, and IL-12 are presented in the table. The data were
adjusted for total protein, salivary flow rate, gender, race, and age.
a
Significant correlation, P < 0.05.
cell-mediated response. Previous studies suggest that stress produces an immune dysregulation rather than overall immunosuppression (Marshall et al., 1998; Kang and Fox, 2001). Our study
extends those data by indicating that part of the immune dysregulation is likely IL-12, which increased during the series of tests.
Thus, salivary IL-12 concentrations could be a sensitive marker
of immune dysregulation during a series of examinations.
Psychological stress impacts immune function and health. This
type of stress can impair B- and T-cell-mediated immune responses,
which has been reported to increase both the severity and duration
of infectious disease (Godbout and Glaser, 2006). Psychological
stressors are also associated with increased frequency of lesions in
women infected with HSV-1 or HSV-2 and in the duration and
recurrence of HSV-1 and EBV (Cohen et al., 1999).
As there was a significant positive correlation between salivary sIgA, IL-6, IL-2, and IL-12 concentrations, taken together, assays featuring combinations of these cytokines could
be a valid marker for effects of examination stress on the
immune system. Our data suggest that these effects continue
Anatomical Sciences Education
JULY/AUGUST 2010
after the examination stress becomes normal, suggesting that
students could develop an immune dysregulation during a
course, even if they do not perceive significant stress. Thus,
stress accommodation does not ablate the changes in the
immune system. These data partially explain the increased
incidence of cell-mediated diseases of bacterial origin during
gross anatomy courses, as IL-12 is the key cytokine driving
the expression of a Type I immunological profile and IL-2 is
an important cytokine for maintaining the TH1 profile (Liao
et al., 2006). Because cytokine and sIgA expression in saliva
are downstream from the primary infection, their increased
concentrations in saliva could signal the presence of a subclinical Type 1-related disease (Calcagni and Elenkov, 2006).
LIMITATIONS
There are a number of limitations of this study. Its major limitation
is lack of access to student grades. While we know that all students
165
passed the course, we do not know their individual grades. We also
do not have access to the academic background of the students,
which might have influenced their pre-examination stress. It would
have been interesting to compare the student’s grades to how they
responded in the pre-examination survey, but this was not possible.
Also, we could not access the medical records of the students following the conclusion of the course. These records would have indicated whether a student was receiving medication for stress during
the examination period, which might have affected our results.
NOTES ON CONTRIBUTORS
S. REID LESTER, B.A., D.M.D., is currently a postgraduate
resident in periodontics at the Louisiana State University,
New Orleans, Louisiana. He was a senior dental student
while the study was performed. He was the research lead,
collected the salivary samples, administered the survey, and
supervised analysis of the salivary samples and assisted in
writing all sections of the article.
JASON R. BROWN, P.T., D.M.D., is currently a postgraduate resident in general dentistry at the University of
Mississippi Medical Center, Jackson, Mississippi. He was a
senior dental student while the study was performed. He
assisted in sample collection and analysis and assisted in writing the Methods section of the article.
JEFFREY E. AYCOCK, B.S., D.M.D., is currently a general practice resident in the United States Army, Fort Morgan,
Georgia. He was a senior dental student while the study was
performed. He assisted in sample collection and analysis and
assisted in writing the methods section of the article.
S. LEE GRUBBS, B.S., D.M.D., is currently a postgraduate
resident in general dentistry at the University of Mississippi,
School of Dentistry, Jackson, Mississippi. He was a senior
dental student while the study was performed. He assisted in
sample collection and analysis and assisted in writing the
Methods section of the article.
ROGER B. JOHNSON, D.D.S., Ph.D., is a professor of
anatomy and course coordinator for the gross anatomy
course for dental students at the University of Mississippi
Medical Center, Jackson, Mississippi. He designed the study,
supervised the research team, and performed the statistical
analysis of the data.
LITERATURE CITED
al’Absi M, Hugdahl K, Lovallo WR. 2002. Adrenocortical stress responses and
altered working memory performance. Psychophysiology 39:95–99.
Benham G. 2007. The shape of stress: The use of frequent sampling to measure
temporal variation in sIgA levels during acute stress. Stress Health 23:295–301.
Benham G, Nash MR, Baldwin DR. 2009. A comparison of changes in secretory immunoglobulin A following a stress-inducing and stress-reducing task.
Stress Health 25:81–90.
Bosch JA, Brand HS, Ligtenberg TJ, Bermond B, Hoogstraten J, Nieuw Amerongen AV. 1996. Psychological stress as a determinant of protein levels and salivary-induced aggregation of Streptococcus gordonii in human whole saliva.
Psychosom Med 58:374–382.
Bristow M, Hucklebridge F, Clow A, Evans P. 1997. Modulation of secretory
immunoglobulin A in saliva in relation to an acute episode of stress and
arousal. J Psychophysiol 11:248–255.
Calcagni E, Elenkov I. 2006. Stress system activity, innate and T helper cytokines, and susceptibility to immune-related diseases. N Y Acad Sci 1069:62–76.
Carroll D, Ring C, Shrimpton J, Evans P, Willemsen G, Hucklebridge F. 1996.
Secretory immunoglobulin A and cardiovascular responses to acute psychological challenge. Int J Behav Med 3:266–279.
Cohen S, Kamarck T, Mermelstein R. 1983. A global measure of perceived
stress. J Health Soc Behav 24:385–396.
Cohen S, Doyle WJ, Skoner DP. 1999. Psychological stress, cytokine production, and severity of upper respiratory illness. Psychosom Med 61:175–180.
166
de Quervain DJ, Roozendaal B, McGaugh JL. 1998. Stress and glucocorticoids
impair retrieval of long-term spatial memory. Nature 394:787–790.
Deinzer R, Schuller N. 1998. Dynamics of stress-related decrease of salivary
immunoglobulin A (sIgA): Relationship to symptoms of the common cold and
studying behavior. Behav Med 23:161–169.
Deinzer R, Kleineidam C, Stiller-Winkler R, Idel H, Bachg D. 2000. Prolonged
reduction of salivary immunoglobulin A (sIgA) after a major academic exam.
Int J Psychophysiol 37:219–232.
Dhabhar FS, McEwen BS. 1997. Acute stress enhances while chronic stress
suppresses cell-mediated immunity in vivo: A potential role for leukocyte trafficking. Brain Behav Immun 11:286–306.
Dobbin JP, Harth M, McCain G, Martin RA, Cousin K. 1991. Cytokine production and lymphocyte transformation during stress. Brain Behav Immun 5:339–348.
Elenkov IJ. 2006. Glucocorticoids and the Th1/Th2 balance. Ann N Y Acad
Sci 1024:138–146.
Elenkov IJ, Chrousos GP. 2002. Stress hormones, proinflammatory, and antiinflammatory cytokines and autoimmunity. Ann NY Acad Sci 96:290–303.
Evans P, Bristow M, Hucklebridge F, Clow A, Pang FY. 1994. Stress, arousal,
cortisol and secretory immunoglobulin A in students undergoing assessment. Br
J Clin Psychol 33:575–576.
Glaser R, Rice J, Sheridan J, Fertel R, Stout J, Speicher C, Pinsky D, Kotur M,
Post A, Beck M, Kiecolt-Glaser JK. 1987. Stress-related immune suppression:
Health implications. Brain Behav Immun 1:7–20.
Glaser R, Pearson GR, Bonneau RH, Esterling BA, Atkinson C, Kiecolt-Glaser
JK. 1993. Stress and the memory T-cell response to the Epstein-Barr virus in
healthy medical students. Health Psychol 12:435–442.
Glaser R, Pearl DK, Kiecolt-Glaser JK, Malarkey WB. 1994. Plasma cortisol
levels and reactivation of latent Epstein-Barr virus in response to academic
stress. Psychoneuroendocrinology 19:765–772.
Godbout JP, Glaser R. 2006. Stress-induced immune dysregulation: Implications for wound healing, infectious disease and cancer. J Neuroimmun Pharm
1:421–427.
Grandy TG, Westerman GH, Combs CE, Turner CH. 1989. Perceptions of
stress among third-year dental students. J Dent Educ 53:718–721.
Heinz A, Hermann D, Smolka MN, Rieks M, Graf KJ, Pohlau D, Kuhn W,
Bauer M. 2003. Effects of acute psychological stress on adhesion molecules,
interleukins and sex hormones: Implication for coronary heart disease. Psychopharmacology 165:111–117.
Jemmott JB, Magloire K. 1988. Academic stress, social support, and secretory
immunoglobulin A. J Pers Soc Psychol 55:803–810.
Jemmott JB III, Borysenko JZ, Borysenko M, McClelland DC, Chapman R,
Meyer D, Benson H. 1983. Academic stress, power motivation, and decrease
in secretion rate of salivary secretory immunoglobulin A. Lancet 1:1400–1402.
Johnson RB. 2005. Racial differences in salivary sIgA concentrations in postmenopausal women. Spec Care Dentist 25:145–149.
Johnson RB, Bernanke DH. 2000. Effects of academic stress on salivary sIgA
concentrations. J Dent Educ 64:177.
Johnson RB, Gilbert JA, Cooper RC, Parsell DE, Stewart BA, Dai X, Nick TG,
Streckfus CF, Butler RA, Boring JG. 2002. Effect of estrogen deficiency on skeletal and alveolar bone density in sheep. J Periodontol 73:383–391.
Kang DH, Fox C. 2001. Th1 and Th2 cytokine responses to academic stress.
Res Nurs Health 24:245–257.
Kiecolt-Glaser JK, Garner W, Speicher C, Penn G, Holliday J, Glaser R. 1984.
Psychological modifiers of immunocompetence in medical students. Psychosom
Med 46:7–14.
Kiecolt-Glaser JK, Glaser R, Strain EC, Stout JC, Tarr KL, Holliday JE,
Speicher CE. 1986. Modulation of cellular immunity in medical students. J
Behav Med 9:5–21.
Kirschbaum C, Hellhammer DH. 1994. Salivary cortisol in psychoneuroendocrine research: Recent developments and applications. Psychoneuroendocrinology 194:313–333.
Lacey K, Zaharia MD, Griffiths J, Ravindran AV, Merali Z, Anisman H. 2000.
A prospective study of neuroendocrine and immune alterations associated with
the stress of an oral academic examination among graduate students. Psychoneuroendocrinology 25:339–356.
Liao W, Schones DE, Oh J, Cui Y, Cui K, Tae-Young R, Zhao K, Leonard WJ.
2006. Priming for T helper type 2 differentiation by interleukin 2-mediated
induction of IL-4 receptor alpha chain expression. Nat Immunol 9:1288–1296.
Loft P, Thomas MG, Petrie KJ, Booth RJ, Miles J, Vedhara K. 2007. Examination stress results in altered cardiovascular responses to acute challenge and
lower cortisol. Psychoneuroendocrinology 32:367–375.
Lowe G, Urquhart J, Greenman J, Lowe G. 2000. Academic stress and secretory immunoglobulin A. Psychol Rep 87:721–722.
Maes M, Song C, Lin A, De Jongh R, Van Gastel A, Kenis G, Bosmans E, De
Meester I, Benoy I, Neels H, Demedts P, Janca A, Scharpé S, Smith RS. 1998a.
The effects of psychological stress on humans: Increased production of proinflammatory cytokines and a Th-1-like response in stress-induced anxiety.
Cytokine 10:313–318.
Maes M, Van der Planken M, Van Gastel A, Bruyland K, VanHuncel F, Neels
H, Hendricks D. 1998b. Influence of academic examination stress on hemato-
Lester et al.
logical measurements in subjectively healthy volunteers. Psychiatry Res
80:201–212.
Maes M, Hendriks D, Van Gastel A, Demedts P, Wauters A, Neels H, Janca A,
Scharpe S. 1997. Effects of psychological stress on serum immunoglobulin,
complement and acute phase protein concentrations in normal volunteers. Psychoneuroendocrinology 22:397–409.
Marshall GD, Agarwal SK, Lloyd C, Cohen L, Henninger EM, Morris GJ.
1998. Cytokine dysregulation associated with exam stress in healthy medical
students. Brain Behav Immun 12:297–307.
McClelland DC, Ross G, Patel V. 1985. The effect of an academic examination
on salivary norepinephrine and immunoglobulin levels. J Human Stress 11:52–
59.
McGehee JW, Johnson RB. 2004. Biomarkers of bone turnover can be assayed
from human saliva. J Gerontol A Biol Sci Med Sci 59:B196–B200.
Murphy BR, Nelson DL, Wright PF, Tierney EL, Phelan MA, Chanock
RM. 1982. Secretory and systemic immunological response in children
infected with live attenuated influenza A virus vaccines. Infect Immun
36:1102–1108.
Navazesh M. 1993. Methods for collecting saliva. Ann N Y Acad Sci
694:72–77.
Ng V, Koh D, Mok BY, Chia SE, Lim LP. 2003. Salivary biomarkers associated
with academic assessment stress among dental undergraduates. J Dent Educ
67:1091–1094.
Otsuki T, Sakaguchi H, Hatayama T, Takata A, Hyodoh F, Tsuita S, Ueki A,
Morimoto K. 2004. Secretory IgA in saliva and academic stress. Int J Immunopathol Pharmacol 17(2 Suppl):45–48.
Peters JR, Walker RF, Riad-Fahmy D, Hall R. 1982. Salivary cortisol assays
for assessing pituitary-adrenal reserve. Clin Endocrinol 17:583–592.
Richards DF, Fernandez M, Caulfield J, Hawrylowicz CM. 2001. Glucocorticoids
drive human CD8(1) T cell differentiation towards a phenotype with high IL-10
and reduced IL-4, IL-5 and IL-13 production. Eur J Immunol 30:2344–2354.
Ring C, Carroll D, Willemsen G, Cooke J, Ferraro A, Drayson M. 1999. Secretory immunoglubulin A and cardiovascular activity during mental arithmetic
and paced breathing. Psychophysiology 36:602–609.
Ring C, Harrison LK, Winzer A, Carroll D, Drayson M, Kendall M. 2000. Secretory immunoglobulin A and cardiovascular reactions to mental arithmetic,
cold pressor, and exercise: Effects of alpha-adrenergic blockade. Psychophysiology 37:634–643.
Ring C, Drayson M, Walkey DG, Dale S, Carroll D. 2002. Secretory immunoglobulin A reactions to prolonged mental arithmetric stress: Inter-session and
intra-session reliability. Biol Psychol 59:1–13.
Sanders AE, Lushington K. 2002. Effect of perceived stress on student performance in dental school. J Dent Educ 66:75–81.
Anatomical Sciences Education
JULY/AUGUST 2010
Sapolsky RM, Romero LM, Munck AU. 2001. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and
preparative actions. Endocrine Rev 21:55–89.
Sarid O, Anson O, Yaari A, Margalith M. 2004. Academic stress, immunological reaction, and academic performance among students of nursing and physiotherapy. Res Nurs Health 27:370–377.
Segal AB, Bruno S, Forte WC. 2006. Immune function in acute stress. Allergol
Immunopathol (Madr) 34:136–140.
Spangler G. 1997. Psychological and physiological responses during an exam
and their relation to personality characteristics. Psychoneuroendochrinology
22:423–441.
Streckfus CF, Johnson RB, Nick T, Tsao A, Tucci M. 1997. Comparison of alveolar bone loss, alveolar bone density and second metacarpal bone density,
salivary and gingival crevicular fluid interleukin-6 concentrations in healthy
premenopausal and postmenopausal women on estrogen therapy. J Gerontol A
Biol Sci Med Sci 52:M343–M351.
Takatsuji K, Sugimoto Y, Ishizaki S, Ozaki Y, Matsuyama E, Yamaguchi
Y. 2008. The effects of examination stress on salivary cortisol, immunoglobulin A, and chromogranin A in nursing students. Biomed Res 29:221–
224.
Teeuw W, Bosch JA, Veerman EC, Amerongen AVN. 2004. Neuroendocrine
regulation of salivary sIgA synthesis and secretion: Implications for oral health.
Biol Chem 385:1137–1146.
Tomasi TB, Grey HM. 1972. Structure and function of immunoglubulin A.
Prog Allergy 16:81–213.
Uchakin PN, Tobin B, Cubbage M, Marshall G Jr, Sams C. 2001. Immune
responsiveness following academic stress in first-year medical students. J Interferon Cytokine Res 21:687–694.
ULC. 2001. University Learning Centers. Symptoms of Text Anxiety. University
Park, PA: Penn State University. URL: http://www.ulc.psu.edu/studyskills/test_
taking.html#symptoms. [accessed 12 April 2010].
Vining RF, McGinley RA, Maksvytis JJ, Ho KY. 1983. Salivary cortisol: A better measure of adrenal cortical function than serum cortisol. Ann Clin Biochem
20:329–335.
Weigers GJ, Reul JM. 1998. Induction of cytokine receptors by glucocorticoids: Functional and pathological significance. Trends Pharmacol 19:317–321.
Willemsen G, Ring C, McKeever S, Carroll D. 2000. Secretory immunoglobulin A and cardiovascular activity during mental arithmetic: Effects of task difficulty and task order. Biol Psychol 52:127–141.
Winzer A, Ring C, Carroll D, Willemsen G, Drayson M, Kendall M. 2000. Secretory immunoglubulin A and cardiovascular reactions to mental arithmetic,
cold pressor and exercise: Effects of beta-adrenergic blockade. Psychophysiology 36:591–601.
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