Stress-Induced Increase in Morning Cortisol Variance

127Copyright 2004 John Wiley & Sons, Ltd.

S t r e s s - i n d u c e d i n c r e a s e i nm o r n i n g c o r t i s o l v a r i a n c e

Frank A. Kaspers and O. Berndt Scholz

Department of Clinical and Applied Psychology, University of Bonn, Germany

*Correspondence to: Dr Frank Kaspers, Abteilung frKlinische und Angewandte Psychologie, UniversittBonn, Rmerstr. 164, D-53117 Bonn, Germany. E-mail: [email protected]

S t r e s s a n d H e a l t hStress and Health 20: 127139 (2004)

Published online 25 May 2004 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/smi.1004

Received 13 August 2003Accepted 27 January 2004

on only one of these possibilities: i.e. rising cor-tisol in the tradition of Selyes general adapta-tion syndrome (Selye, 1950), and reduced cortisol levels as examined in more recent studies (Heim,Ehlert, & Hellhammer, 2000). Comprehensivepsychophysiological models which explain both,hyper- and hypocortisolism in chronic stress, or which can be falsified by the third possibleoutcome (no change at all) are rare.

Henry (1986, 1993; Henry & Stephens, 1977)designed a psychophysiological stress theory,which ascribes physiological processes to specificreactions to stress. Helplessness under stress isassumed to go along with HPA activation whilefight-flight behavior results in neurosympatheticadrenomedullary activation. In subsequent for-

SummaryEmpirical evidence for the role of the hypothalamo-pituitary-adrenal axis in chronic stress is con-tradictory. Findings of enhanced cortisol concentrations conflict with hypocortisolism in chronicstress. Both, high and low cortisol levels, have been reported to go along with psychological andsomatic complaints. To integrate conflicting empirical results and theoretical assumptions it ishypothesized, that (1) the cortisol distribution becomes broader under the influence of persistingstress. Because of the association between extreme cortisol values and stress related complaints itis supposed, that (2) stress related complaints will increase in prevalence in chronic stress. A highlevel of chronic stress was assured by recruiting a sample of nursing staff; a waiting list controlledcognitive-behavioral stress management intervention was implemented to vary stress systemati-cally. As expected a high level of stress was accompanied by a broader morning cortisol distrib-ution. After the intervention the distribution was less broad and corresponded with representativenormative values. However, subjects grouped on basis of (extreme) cortisol values did not differin the amount of stress, coping or psychophysiological complaints. The results suggest a stress-induced variation of basal cortisol concentrations. The assumption of specific complaints depend-ing on cortisol status could not be confirmed. Copyright 2004 John Wiley & Sons, Ltd.

Key Wordschronic stress; saliva cortisol; humans; cognitive-behavioral stress management; distribution characteristics

Introduction

An investigation of cortisol levels under chronicstress conditions would be expected to returnthree possible results: no change in, enhanced,and reduced concentrations of cortisol. Empiricalevidence supports each of those outcomes (Ockenfels, 1995). Theories examining the role ofchronic stress on the hypothalamic-pituitary-adrenal (HPA) axis (dys)regulation usually focus

mulations of this model Henry integrated aspectsof alexithymia and hemispheric lateralization. Heassumed that the cortisol reaction is particularlyguided righthemispheric. A combination of psy-chological and physiological models of stress wasproposed by Ursin (1980, 1987, 1998; Levine & Ursin, 1991). Two basic principles underpinthis approach: (i) activation, and (ii) expectancy.Activation, the outcome in cases of homeostaticimbalance, is understood as a process which tendsto re-establish balance by initiating a series ofcentral nervous-, vegetative-, skeletomuscular-,endocrine- and immune-system changes. Activa-tion is therefore an adaptive principle, because itsfunction is to prepare the organism to respond to a stressor. Ursin, in agreement with Henry, postulates a psychoneuroendocrine reactionspecificity, that distinguishes between active (catecholaminergic), and passive (cortisol),defense. The connecting link between stressor and activation is expectancy. Expectancy includesstimulus-expectancy and outcome-expectancy,both of which are differentiated by the possibleinfluence of coping. There are some meaningfulparallels in Ursins model: stimulus-expectancyand outcome-expectancy can easily be identifiedas Lazarus primary and secondary appraisal(Lazarus & Folkman, 1984). The concept of activation reflects Selyes physiological view of the stress process without his problematicalassumption of unspecificity (Mason, 1968). Thecybernetic view of the organism suits modern psychosomatic thinking (Weiner, 1998).

At first sight, these theoretical assumptions satisfactorily explain hypercortisolism but nothypocortisolism: hypercortisolism occurs whenchronic stress or sustained activation meets help-lessness, or passive coping. However, it is alsopossible to explain hypocortisolism using thismodel as being merely necessary to differentiateat least two ways of passive coping: e.g. helpless-ness, and denial, to do so. Helplessness, or hope-lessness, arises from a behavioral (withdrawal)and physiological (higher cortisol) activationwhich differs in kind from that found in denial orrefusal to believe stress (Henry, 1993). In thelatter case neither coping, nor elevated cortisol,would be expected. Extraordinarily intense levelsof stress may however, evoke activation whichdue to this coping-dependent reduced reagibilityof the HPA-axisoccurs more pronouncedly inthe later activation systems, for example in ahigher reagibility of the immune system (Buske-Kirschbaum, Jobst, & Hellhammer, 1998). This

becomes even more likely, when a physiologicaldiathesis in the form of a dispositional reagibilityof the HPA-axis is presupposed. In the light ofgenetic influences on cortisol (Kirschbaum, Wst,Faig, & Hellhammer, 1992) which in interactionwith lower birth weight (Wst, Wolf, Hellhammer, & Kirschbaum, 1999) or earlystress experiences (King & Edwards, 1999) cancontribute to such a dispositional hypoactivitythis supposition seems appropriate.

The following conclusions can be drawn up tothis point: chronic psychosocial stress results inactivation as described by Ursin. This activationtriggers the described physiological and behav-ioral dispositions. Under their impact the fre-quencies of high and low cortisol levels rise andthe distribution of cortisol becomes broader. (Cortisol is assumed to be normally distributed.Empirical evidence for this supposition is rare,occasional veterinary studies (Popot et al., 1997)as well as singular human publications (Smyth et al., 1996) favor a decadic logarithmic normaldistribution).

Extreme cortisol-concentrations are assumedto be physiologically disadvantageous since theyhave been linked to diverse psychophysiologicalcomplaints: extremely high cortisol in depression(e.g. Carroll, Curtis, & Mendels, 1976) and infec-tious diseases (Dillman & Ostroumova, 1984),extremely low cortisol in somatoform (Ehlert,Gaab, & Heinrichs, 2001) and atopic diseases(Buske-Kirschbaum et al., 1998) or in burnoutsyndrome (Prner, 1998; overview in Heim etal., 2000). The frequency of these complaints isconsidered to increase in step with stress-inducedchanges in cortisol distribution.

The question of if and how chronic stress maycause long-term HPA-axis dysregulation, may beanswered, if at all, by controlled prospective lon-gitudinal studies. At the same time however, inview of the many likely determinants of HPA-axisactivity such as genetic makeup (Kirschbaum et al., 1992), age (Heuser et al., 1994), sex (Reinberg et al., 1996), smoking (Kirschbaum,Strasburger, & Scherer, 1994), nyctohemeralchanges (Hakola, Hrm, & Laitinen, 1996),physical activity (Opstad, 1991), physical illness(Geiss, Varadi, Steinbach, Bauer, & Anton, 1997),psychopathology (Caroll et al., 1976) or acutestress (Kirschbaum et al., 1991), it is questionablewhether all potential influences may be able to becontrolled. An alternative strategy and one whichplaces lower demands upon the experimenter, ispresented in this article, i.e. the acquisition of

F. A. Kaspers and O. B. Scholz

Copyright 2004 John Wiley & Sons, Ltd. Stress and Health 20: 127139 (2004)128

subjects from a population with high pre-existingstress levels. A systematic variation of the hypoth-esized influence factor, stress, was then applied.Nursing staff have been identified in many studiesas a profession with high levels of chronic jobstress (Addey, 1987; Cherniss, 1980; Gentry,Forster, & Froehling, 1982; Maslach, 1978).Hence, for this study subjects were recruited fromnursing staff.

The aims of this study may be summarized asfollows:

(a) sustained psychophysiological activation and (habitual) dysfunctional coping interactin such a way as to make constitutionallyextreme cortisol levels become even moreextreme in response to chronic stress. Conse-quently, populations who suffer from chronicstress should show a greater cortisol variationand an increased frequency of extreme corti-sol values.

(b) Extreme cortisol values are assumed to be dis-advantagous, having been shown to co-occurwith diverse psychophysiological complaints.Hence, it is expected that along with changesin cortisol distribution such complaintsshould increase in frequency.

(c) A cognitive behavioral stress management(CBSM) intervention would be expected toimprove coping and reduce stress, as well asnormalize HPA-axis functioning and decreasethe frequency of stress/cortisol-related complaints.

Materials and methods

Subjects

Thirty-six hospital nurses were recruited fromlocal hospitals in Bonn, Germany. Eleven of themwere excluded from the study for a number ofreasons: four dropped out of the intervention,four were unable to deliver the post-interventionmeasurement though taking part in the interven-tion regularly, two moved out of Bonn, onesubjects set of saliva-samples contained no saliva.The final sample comprised 25 subjects (23female, 2 male). The mean age was 39.1 8.2years (2354 years). Subjects who received med-ication that could affect HPA-axis activity wereexcluded from analysis. The participants hadworked as nurses for 127 years (mean and standard deviation: 13.6 8.3). Most worked in

orthopedic (seven) or psychiatric wards (eight),four worked in neurosurgery, three in oncologyand the remainder in various other wards. Onlysix subjects were on shift work (two early, fourlate, no night shift workers). Nearly 73% workedfull-time (38.5 hours per week) whilst the remain-der worked part-time on a 5075 per cent timeschedule. Those subjects who were working part-time did not have any other jobs. Subjects wererecruited by offering the nursing services theopportunity for their staff to take part in a free-of-charge stress management intervention. Thenursing services were contacted via mail, tele-phone and personal contact. Three hospitals par-ticipated in the study. The present sample is notrepresentative and was not intended to be so,since the primary aim was to select a populationrepresentative of high stress levels.

To evaluate the efficacy of the CBSM two versions of the interventiona full and a blockedversion (described later in this article)werecompared with a waiting-list control group. Sub-jects were not randomly allocated to the experi-mental conditions because the primary aim wasto have three equivalent experimental groups ofsimilar size comprised of individuals with similarstress levels. However, this strategy failed due tothe dropout rate. Subjects were allocated to theexperimental conditions as follows: full version,n = 10; blocked version, n = 7; waiting-list, n =8.

Saliva sampling and cortisol analysis

For later cortisol analysis four saliva sampleswere obtained at home from each subject at 20-minute intervals after awakening by means of the Salivette device (Sarstedt, Rommelsdorf,Germany). Recent studies suggest that multiplemorning cortisol measures to be a more reliablemarker for basal HPA-axis activity than singleassessments at fixed times, e.g. at 8 a.m. (Prneret al., 1997). Subjects were instructed neither tobrush their teeth in the sampling period nor to eator drink coffee, tea or carbonated soft drinks. Allsaliva samples were stored at -20C until bio-chemical analysis. For analysis of change in HPA-axis activity, cortisol was measured before (t1)and after (t2) the stress management intervention.For controls the second measurement was takenat the same time as that for the interventiongroups. While subjects were told not to disrupttheir awakening routines at t1 they were

Stress-induced increase in morning cortisol variance

Copyright 2004 John Wiley & Sons, Ltd. Stress and Health 20: 127139 (2004) 129

instructed to wake up at the same time on t2. Salivary cortisol analysis was performed usingfluorescence immunoassay according toDressendrfer, Kirschbaum, Rohde, Stahl, &Strasburger (1992). Intra- and inter-assay vari-ability of the assays was less than 10 and 12 percent, respectively. The analysis was carried out atthe biochemical laboratory of the Center for Psy-chobiological and Psychosomatic Research at theUniversity of Trier, Germany. Two strategies wereused to analyze divergence in the distribution ofcortisol in this chronically stressed sample: thecount of extreme values, and a comparison ofvariances. In both cases the sample values werealso compared with the normative values fromWst et al. (2000) (n = 509).

Psychological variables

Three features of perceived stress were examined:chronic stress, nursing-stress, and everyday stress.Chronic stress was assessed using the TrierInventory for the Assessment of Chronic Stress(TICS; Schulz & Schlotz, 1999). This Inventoryaims especially to assess the impact of stress uponhealth. The TICS consists of 39 items whichrecord retrospective stress experiences over a 1year period, using a five-step frequency rating.The test items constitute six scales: work over-load, work discontent, social stress, lack ofsocial recognition, worries and intrusive mem-ories. Internal consistency (Cronbachs a) rangesbetween 0.76 and 0.91, split-half-reliability(Guttman) between 0.79 and 0.90. Individualtest-scores were aggregated to a sum score ofchronic stress. Nursing stress was assessed usingthe Nursing Stress Questionnaire (KP-SF;Widmer, 1988). This test was developed in aSwiss study and assesses seven dimensions of jobstress in nursing: workload, relationship to thesuperior, insecurity, patient & ethics, lack ofindependence, staff conflicts and relationshipto the doctor. These scales comprise 50 itemsdescribing job stress situations which can be ratedwith respect to the extent of perceived stress ona five-stage Likert scale. Internal consistencyranges between 0.68 and 0.84 (Cronbachs a).Individual test-scores were aggregated to a sumscore of nursing stress. To control the influence of acute stress, daily hassles were measured byusing the Hassles and Uplifts Scale (DeLongis,Folkman, & Lazarus, 1988) in an own translatedversion which was also modified for German

conditions. It was employed on three consecutivedays at t1 and two days at t2.

Coping was assessed by the Coping with StressQuestionnaire (SVF 120-S, Janke & Erdmann,1997). The SVF 120-S constitutes 20 subscaleswhich measure individual coping preferences. Asituation-specific version of the questionnaire wasused to examine coping under job-stress condi-tions. Two kinds of passive coping were identifiedby combining subscales and secondary scales:passive coping due to helplessness/hopelessnessappeared to be linked with the subscales: flight,social withdrawal, cognitive rumination, res-ignation, self-pity and self-blame; avoid-ance/denial of stress appeared to be linked withthe strategies of minimization, playing downand blame-defence.

Several aspects of strain in terms of complaintswere considered: burnout, depression and bodilycomplaints. Burnout was measured using theMaslach Burnout Inventory (MBI; Maslach &Jackson, 1986) in a German version (Barth, 1992;Bssing & Perrar, 1992). The AllgemeineDepressions Skala (ADS; Hautzinger & Bailer,1993) is a screening instrument for depressionbased on the Center for Epidemiological StudiesDepression Scale (CES-D; Radloff, 1977). Bodilycomplaints were assessed by means of self reportusing the Freiburg Complaint List (FBL-W;Fahrenberg, 1986). Forty items, grouped into five scalesgeneral condition, cardiovascular,gastrointestinal, tenseness and painwhosescores can be combined to give a total score.

Cognitive-behavioral stress management(CBSM) intervention

The specific content of the training is describedelsewhere in more detail (Kaspers, 2001). Thetreatment consisted of a standardized grouptraining program, based on the intervention byKaluza (1996). The aim of this health interven-tion program is to teach participants more flexi-ble ways of coping with individual stress. Theintervention consists of training in progressivemuscle relaxation, problem solving, and pleasure-enhancement. The originally nonspecific pre-ventive intervention was adapted so as to better address nursing stress, and to facilitate thereduction of stress-specific complaints. This wasachieved by tailoring the therapeutic materials(e.g. in psychoeducation) to nursing-stressdemands, and by adding a number of other spe-



cific elements to the intervention (e.g. the demon-stration of psychophysiological interconnec-tions in stress and relaxation, via biofeedback(Dimsdale, Stern, & Dillon, 1988)). Table I liststhe original and additional elements of the intervention.

The CBSM intervention was drawn up as aseries of 12 weekly meetings of 120 minutes.Because of shift work it was anticipated that par-ticipants may not be able to regularly visit everysession. Hence, a second version was provided, toavoid this problem by combining the meetingsinto four weekly blocks of 360 minutes (plusbreak-time).

Statistical analysis

According to Curio (1989) two procedures wereused to calculate indices of morning cortisol:deviation from the normative progression, andcalculation of the area under the curve (AUC).The normative data of Wst et al. (2000) wereused to construct a model curve of morning cor-tisol progression. This model makes it possible toidentify deviations from the norm. Albeit thevalues from Wst et al. were gathered at differ-ent time intervals (+0, +30, +45 and +60 minutesafter awakening) they can easily be extrapolated(mathematically or graphically) for the time inter-vals of the present study (+0, +20, +40 and +60minutes after awakening). The AUC values werecalculated according to Prner (1998) with thefollowing formula for identical time intervals:AUC = C1 + C2 + C3 + (C4 - C1)/2 (with Ci forthe single measures).

The statistical comparison of sample meanswith normative values was made using t-values,differences between the sample variances at t1with those at t2 were tested with F-tests, differ-

ences between sample variances with normativevariances with c2 tests. The latter were also usedto compare expected and observed frequencies.Because of the rather small group sizes, group differences were tested with KruskalWallis testand MannWhitney-U-test to account for possi-bly violated test conditions regarding analysis of variance. The data analysis was performed on a personal computer using Statistica forWindows.

Results

Stress: plausibility check and manipulation check

The selection of subjects from nursing staffshould have served to provide a sample withabove-average stress levels. Table II contains thecomparisons of the sample means in the twostress questionnaires (TICS, KP-SF) with the normative values of the test-scales.

With the exception of the subscales work discontent and intrusive memories all aspects ofchronic stress as measured with the TICS aremore strongly delineated in the present sample,with work overload and lack of social recogni-tion reaching statistical significance. The extentof nursing stress does not differ from the expectedvalues in Widmer (1988) though workload iseven higher in the present sample. These findingsconfirm that, as previously hypothesized, thissample of nursing staff does indeed experiencestress at a high level.

The purpose of the CBSM intervention was tosystematically vary the level of subjective stress.Compared to t1 it was expected that at t2 subjectswould show improved coping and reduced levelsof perceived stress. While the KruskalWallis test



Table I. Specification of the intervention components under aspects of bodily complaint reduction.

Problem solving Relaxation Pleasure enhancement

Focusing on bodily effects of Progressive muscle relaxation Promotion of exercise andstress in the modules education, as a method which sensitizes activitybehavior analysis and coping for psychosomatic

interconnections in Additional module: tension/relaxation

demonstration ofpsychophysiological processes Additional modules:via biofeedback (Dimsdale et al., imaginative strategies of1988) pain management

was unable to detect significant time or groupeffects in coping effectiveness (apart from a ten-dency to relax more under stress in the two inter-vention groups at t2) there was a significant timeeffect in stress over all three groups, which wasdue to reductions in nursing stress but not inchronic stress. Table III shows the result of thestatistical analysis.

The data suggest that stress is reduced at t2, andthat the hypothesized changes in cortisol con-centrations may be expected under all threeexperimental conditions. While the data fail todemonstrate a significant treatment effect whichexceeds the effect of the waiting control condi-tion, they prove a significant stress reduction intreatment and control subjects. Due to the under-lying group differences in regard to stress levels it seemed advisable to subject these differences to further analysis, for example by using changemeasures unaffected by the initial values.

Cortisol

Analysis of morning cortisol shows the typicalrise immediately after awakening. Table IV illus-

trates the cortisol concentrations before and afterthe CBSM intervention.

The comparison of means (analysis of variance,two factors, repeated measurement on both)show a significant main effect within (F = 21.01,df = 3, p = 0.000), not between the days (F = 0.00,df = 1, p = 0.953), the interaction effect is alsonot significant (F = 0.28, df = 3, p = 0.840). Pair-wise comparisons of means (t-tests) show signifi-cant (p < 0.05) differences between the first andthe third and the fourth value. The characteristicpattern of rising morning cortisol was shown by18 (72 per cent) subjects, which is little less thanthe responder rate (77 per cent) found by Wstet al. (2000). Correlations (product-moment)between the morning cortisol concentrations ontwo consecutive days range between 0.61 to 0.83with a correlation for AUC of 0.70 (all correla-tions statistically significant with p < 0.001). Thisis a stronger relationship than that found fornormal values over two consecutive days reportedby Wst et al.

Firstly the variances at t1 were compared withthose at t2. It was expected that the higher stresslevels at t1 would go along with higher variances,while the variances should be smaller at t2 when



Table II. Plausibility check: comparison of the sample means at t1 with the normative values in the two stressquestionnaires concerning chronic stress (TICS, normative values according to Schulz & Schlotz, 1999) andnursing stress (KP-SF, normative values according to Widmer, 1988). As expected, nurses show higher levels ofchronic stress; nursing stress is comparable to values reported in literature (variables with values which weresignificantly different are marked with an asterisk).

Subscale Normative Standard Sample tempir. tcrit.,a=5 per centvalue deviation mean

Work overload (TICS)* 21.0 5.33 24.88 3.64 1.71Social stress (TICS) 14.9 4.69 16.12 1.30 1.71Worries (TICS) 16.7 3.19 17.52 1.29 1.71Work discontent (TICS) 12.7 4.09 12.52 -0.22 1.71Lack of social 16.9 3.30 18.28 2.09 1.71

recognition (TICS)*Intrusive memories 16.1 4.40 15.80 -0.34 1.71

(TICS)

Relationship to the 2.46 0.93 2.63 0.91 2.06superior (KP-SF)

Workload (KP-SF)* 2.78 0.70 3.04 4.14 2.06Insecurity (KP-SF) 2.96 0.75 2.87 -0.60 2.06Patient & ethics (KP-SF) 3.65 0.66 3.45 -1.52 2.06Lack of independence 2.51 0.85 2.66 0.88 2.06

(KP-SF)Staff conflicts (KP-SF) 3.09 0.82 3.22 0.79 2.06Relationship to the 2.38 0.90 2.57 1.06 2.06

doctor (KP-SF)Total score (KP-SF) 2.88 0.56 2.96 0.71 2.06

stress was found to be reduced. As Table IVshows, three of the four variances are significantlysmaller at t2.

Secondly, the sample variances of the fourmorning cortisol measures were compared with

the normal values. Table V shows the result of this analysis. At t1, the variance for all fourmorning cortisol measures in the present sampleis greater than the critical variances reported byWst et al., whereas only one of the variances in



Table III. Manipulation check: pre-post-comparison of means (MN) in thestress measures (chronic stress reflects a weighted mean from the TICSsubscales as a total score; nursing stress reflects the total score of the KP-SF). Changes are analyzed separately for the two training groups (full, fullversion; block, blocked version) and control group. The analysis ofvariance (two factorized MANOVA with repeated measurement on thetime factor) only results in a significant time effect (F2,21 = 5.625, p =0.001).

Trainingfull,n=10 Trainingblock,n=7 Controlsn=8

MNPre MNPost MNPre MNPost MNPre MNPost

Chronic stress 2.595 2.552 2.438 2.586 3.029 3.030Nursing stress 2.964 2.868 2.609 2.329 3.268 3.003

Table IV. Morning cortisol concentration means (MN, nmol/l) andvariances (s2) before (t1) and after (t2) the CBSM intervention. Thevariances are compared using F-tests. Except for the fourth value (+60minutes) all variances at t2 are significantly smaller than the correspondingones at t1.

MNt1 MNt2 s2t1

s2t2 F-value p-value

+0 minutes* 15.083 14.237 98.823 23.602 4.187 0.001+20 minutes 20.995 19.237 149.170 56.103 2.659 0.010+40 minutes 24.461 24.527 201.419 92.432 2.179 0.031+60 minutes 21.652 22.283 127.657 116.609 1.095 0.413

*Because of missing data in two cases (the awakening saliva sample at t2 containedno saliva) the sample size differs in the awakening condition (n = 23).

Table V. Comparison of variances of the present sample (empir. s2) withthose according to Wst et al. (2000, crit. s2) before (t1) and after (t2) theCBSM intervention. At t1 all variances differ significantly from thenormative distribution. While the fourth value (+60 minutes) at t1 and t2reaches significance at 5 per cent-level (respectively 2.5 per cent, bilateraltest), the first three values also stand the test, when a = 0.001.

empir. s2 crit. s2 empir. c2 crit. c2a=2.5 per cent

+0 minutes t1 98.82 39.06 55.66 (p = 0.000) 36.78*t2 23.60 13.29 (p = 0.925)

+20 minutes t1 149.17 65.61 54.57 (p = 0.000) 39.36t2 56.10 20.52 (p = 0.667)

+40 minutes t1 201.42 88.36 54.71 (p = 0.000) 39.36t2 92.43 25.11 (p = 0.400)

+60 minutes t1 127.66 68.06 45.02 (p = 0.006) 39.36t2 116.16 41.12 (p = 0.016)

*Because of missing data in two cases (the awakening saliva sample at t2 containedno saliva) the expected value differs in the awakening condition.

condition t2 showed a significant difference fromthe normative variance.

Thirdly, extreme values were counted. Valueswere judged as extreme when they differed bymore than one standard deviation from thesample mean. In a normal distribution 68.26 percent of all values lie inside, and 31.74 per centoutside, the interval of one standard deviation onboth sides of the distribution mean. It is thereforepossible to postulate the expected frequency ofvalues for given sample sizes. These expected fre-quencies can then be compared with the observedcount before (t1) and after (t2) treatment. Table VIshows the results of these calculations.

At t1 three of the four frequencies of observedextreme values exceed the expected frequencies.For the third value (+40 minutes) even an inver-sion of expected frequencies can be shown with56 per cent of the observed values lying outsidethe aforementioned one-standard-deviation inter-val. At t2 none of the comparisons betweenobserved and expected frequencies show any sig-nificant difference.

To test the second hypothesis, that extreme cor-tisol concentrations occur together with diversecomplaints (results of this hypothesis testing arepresented later), subjects were divided into threegroups, representing the two extremes and theundeviating values in the middle of the distribu-tion. In order to get comparable sample sizes, aweaker criterion for classifying values as extremewas applied here. By using the normative data ofWst et al. mean values 2/3 standard deviationwere set as the cut-off criteria. In a normal dis-tribution this should divide the distribution into

two nearly equal parts (hither versus beyond themean range). Values were labelled as hypo-cortisolism if at least three of the four morningcortisol values lay below the criterion of mean -2/3 standard deviation; they were labelled ashyper-cortisolism when they lay above mean+2/3 standard deviation. Applying these criteria,21 of the data sets at t2 could unambiguously beclassified as hypo- (n = 7), hyper- (n = 6) ornormo-cortisolism (n = 8), while the curves ofthe remainder were nontypical. When these crite-ria were applied to t2 a different picture emerged:only one data set could be classified as hypo-and only four as hyper-cortisolism whilst thelarger proportion of curve shapes (16) werewithin the normal range. Figure 1 shows themovements of group memberships from t1 to t2.

To further illustrate the breadth of morningcortisol distribution in t1 and the changes in t2,equidistant categories of AUCs were established.Then the category frequencies for the AUCs werecomputed. The results are presented in Figure 2.It shows that at t1 only 13 subjects (56.5 per cent)lay within the range of mean 1 standard devia-tion. At t2 this number rises up to 17 subjects (74per cent).

Strain

As mentioned earlier, subjects were divided intothree groups, classifying them as hyper-, hypo-and normo-cortisolism group in order to test the second hypothesis. This hypothesis assumes a higher frequency of psychophysiological com-



Table VI. Comparison of expected and observed frequencies of extremecortisol values before (t1) and after (t2) the CBSM intervention (valuesoutside mean 1 standard deviation; expected frequencies were calculatedaccording to the normative values of Wst et al. (2000) (n = 509). Threeof the four values differ from the expected frequencies at t1, none at t2(c2crit.,a=5 per cent = 2.71, c2crit.,a=1 per cent = 6.63).

Expected value Observed value c2empir.

+0 minutes 7.3* t1 10 1.46 (p = 0.114)t2 6 0.34 (p = 0.280)

+20 minutes 7.9 t1 12 3.10 (p = 0.039)t2 7 0.16 (p = 0.345)

+40 minutes 7.9 t1 14 6.87 (p = 0.004)t2 8 0.00 (p > 0.90)

+60 minutes 7.9 t1 13 4.80 (p = 0.014)t2 9 0.21 (p = 0.325)

*Because of missing data in two cases (the awakening saliva sample at t2 containedno saliva) the expected value differs in the awakening condition.

plaints or strain in the extreme groups. Groupmembership was allocated using the mean values2/3 standard deviationcriterion as describedearlier. Because of reduced number of extremevalues at t2 a statistical comparison is only possi-ble for t1. The means of the strain variables arepresented in Table VII.

With group membership at t1 as the indepen-dent variable, no identifiable differences were seeneither between extreme groups and the normo-cortisolism group, or between the hypo- and hyper-cortisolism group in any of the self report measures (F14,22 = 1.092, p = 0.415).This meant that the groups did not differ in theamount of stress, coping quality (helplessness/hopelessness versus avoidance/denial) or quan-tity (extent of ineffective coping), in strain quality (depression versus burnout) or quantity, or in the amount or profile of physical complaints.

Discussion

A high level of stress at t1 and a reduced stresslevel at t2 were the conditions to test causalhypotheses about the role of chronic stress in thechosen quasi-experimental design. The first ques-tion was whether chronic stress caused a broaderdistribution of basal cortisol levels. This could be shown for the concentrations at t1, comparedto those at t2, indicated by sample variances andextreme values count. As construct validity is critical in quasi-experimental designs, someefforts can be made in order to enhance it andbroaden the basis of data generalization (Cook &



Hypo Hyper

42 1

11 40 2 8 24 25 5

9 28 4 34

6 1214

Normo 20 26 2739

43

Figure 1. Movements in group-membership regardinghypocortisolism or hypercortisolism respectively normocortisolism from t1 to t2. Subjects were classifiedas extreme, when at least three of the four morning cor-tisol levels lay outside mean 2/3 standard deviation.Movements are illustrated by arrows.

m-2s m-s m m+s m+2s m-2s m-s m m+s m+2s

0

1

2

3

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5

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7

8

0-12

12-2

424

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36-4

848

-60

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272

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84-9

696

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>108

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1

2

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5

6

7

8

0-12

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424

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848

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>108

Figure 2. Distribution of morning cortisol areas under the curve (AUC) at t1 (left) and t2 (right). The abscissa con-tains 10 equidistant categories of AUCs, represented by the category borders. The ordinate shows the categorialfrequencies. Vertical dotted lines indicate means (m) and standard deviations (s) as benchmarks of the distributionof the normative control sample. They were computed from the data reported by Wst et al. (2000). Because of missing data in two cases (the awakening saliva sample at t2 contained no saliva) the comparison was only performed for complete samples (n = 23).

Campbell, 1979). This was intended when thedata obtained from subjects in this study werecompared with normative data. In the presentsample morning cortisol concentrations showed abroader distribution than predicted by studieswhich provided normative values for morningcortisol (Wst et al., 2000). This broader distrib-ution was found in all morning cortisol measures,with each group of four showing greater vari-ability and with three measures out of the fourhaving more extreme values. Only the measuretaken on awakening value the comparisonbetween observed and expected frequenciesmissed statistical significance. One possible con-clusion may be that interindividual differences in morning cortisol are primarily differences ofincrease rather than differences in baseline level.This is consistent with the results of Buske-Kirschbaum et al. (1998) who reported thatattenuated cortisol concentrations in atopic der-matitis were found for the HPA-axis reactiviy, butnot for the baselines. The finding of a broader dis-tribution of cortisol in chronic stress integratescontrary findings of rising versus falling cortisollevels (Ockenfels, 1995).

Subjects with extreme morning cortisol con-centrations did not differ in self-report measures,whether with respect to each or with respect to agroup whose levels of cortisol were in the averagerange. The second hypothesis, which postulateddifferences in psychophysiological complaints,burnout and depression was not confirmed. Thegroups did not differ in the amount of perceivedstress or in their locus of control. Nor could dif-ferences in coping styles be confirmed by the data.It was postulated that denial of stress would leadto hypocortisolism, passive coping to hypercorti-solism. The use of a questionnaire, to measureavoidance/denial, may be problematic and a

possible reason for this unexpected result. As this method requires the primary appraisal of animagined situation as stressful (as the Copingwith Stress Questionnaire does), future exami-nation might more appropriately use behavioralobservation.

How may a stress induced increase in morningcortisol variation be explained? Stress models are usually defined as diathesis-stress-models. InUrsins activation theory diatheses could belocated in the habitually-preferred method ofinformation processing, physiological reaction, orcoping style. The nature of the information processing in Ursins theory is a state or conditionof expectancy. His neuropsychological model ofexpectancy resembles the assumptions of Graystheory of emotion (1987, 1990). According toLeplow and Ferstl (1998) Grays theory is likelyto modulate the diathesis in diathesis-stress-concepts. For psychophysiological disorders theypostulate a hyperactivity in the behavioral inhi-bition system (BIS), which Gray locates in thesepto-hippocampal region of the brain. Hyperac-tivity of the BIS results in a behavior blockade(passive, or no coping), which leads to an empha-sized HPA-activation under stressful conditionsand an accentuated production of cortisol. Fromthis, three diatheses can be assumed whichatfirstare quite independent of each other:

(a) Cortisol diathesisgenetics (Kirschbaum et al., 1992) as well as early stress experiences(King & Edwards, 1999) or other factors maycontribute to a dispositional HPA-axis levelof activity.

(b) Expectancy diathesisthe denial to believestress represents dysfunctional primaryappraisal of objectively sustaining stressors.Activation skips the HPA-axis and occurs



Table VII. Extreme group (cortisol) comparison of means in the strain measures at t1 (chronic stress reflects aweighted mean from the TICS subscales as a total score; nursing stress reflects the total score of the KP-SF).Subjects were classified as extreme, when at least three of the four morning cortisol levels lay outside mean 2/3standard deviation.

Hypocortisolismn=7 Normocortisolismn=8 Hypercortisolismn=6

Chronic stress 2.793 2.504 3.019Nursing stress 2.857 2.889 3.200Helplessness 10.095 9.286 13.083Avoidance/denial 12.095 11.048 8.833Depression 50.143 43.571 48.333Burnout 2.456 2.360 2.625Physical complaints 81.429 76.429 87.667

more pronouncedly in the later activationsystems while the protective effects of cortisol fail (e.g. the mobilization of energyreserves (Demitrack et al., 1991); or regula-tion of the immune system (Munck, Guyre,& Holbrook, 1984)). It may be that thisdiathesis emerges more from social learningprocesses such as modeling, or the social reinforcement of toughness (Dienstbier,1989). From a neurophysiological perspectiveit could be speculated that the expectancydiathesis is accompanied by a hyporeactiveBIS. Empirical evidence for lower cortisol inimpulsivity (King, Jones, Scheuer, Curtis, &Zarcone, 1990; Moss, Vanyukov, & Martin,1995) or extraversion (Dabbs & Hopper,1990; Prner, 1994) supports this speculation.

(c) Activation diathesisthis diathesis representsthose theoretical assumptions of Henry andUrsin, which view high cortisol concentra-tions as a result of passive, helpless coping. Inlater formulations Henry (1993) integratedalexithymia and righthemispheric dominancein his concept. In doing this he strongly sug-gested that this reaction specifity is a traitor a diathesis. As described earlier, thisdiathesis is accompanied by a hyperreactiveBIS.

The three diatheses interact in a dysfunctionalway which results in a broader cortisol distribu-tion, as already described. This study, however,shows that this process is a reversible one. CBSMcan sensitize participants to perceive stress situa-tions; this improves the adequacy of expectancy.Training in problem solving enhances activecoping. Both are conditions that operate in a waythat better adapt coping to situational demands.

As expected, the present sample of nursing staffshowed an attenuated level of chronic stress, particularly in work overload and lack of socialrecognition. Job-specific workload was evenhigher than in comparable nursing staff studies(Widmer, 1988). This warrants the assumptionthat the choice of subjects did establish a highlevel of stress in the present sample. After theCBSM intervention not only the two experimen-tal groups but also the waiting-list control groupshowed lower levels of stress. The reasons for thisunintended effect are unclear nor is it the purposeof this present study to seek an explanation forsuch an outcome. To fulfill the aims of this studyit was necessary to reduce stress at t2; that this

effect occurred in the control group as well maybe seen as beneficial. It may be that the fact oftaking part in a scientific program which includedprocedures aimed at stress reduction (eventhough after a time interval) produced a thera-peutic effect on the control group. This effectcould be described in terms of reframing, whichcan be seen as an aspect of cognitive coping. Asanother explanation, being allocated to thewaiting-list could have had a positive effect onmotivation in sense of a Now more than ever!kind of reaction. This would result in a mobi-lization of coping resources.

Shift work can alter circadian rhythms; alteredcircadian rhythms can affect morning cortisolconcentrations (Hakola et al., 1996; Motohashi,1992). It could be argued, that abnormal morningcortisol concentrations in nurses are rather theresult of shift work than of anything else. Onlysix subjects were on shift work during the periodof investigation. So it seems unlikely that shiftwork is responsible for changes in cortisol concentrations which affect the whole sample. Analternative theory could explain reduced vari-ances at t2 as an effect of learned behavior: itmight be that the actual stress of collecting cortisol affected the concentrations observed.However, studies could show, that this is usuallynot the case (Prner, 1998; Prner et al., 1997;Wst et al., 2000).

There are, of course, several limitations in thepresent studyone being the small sample size,another that this was a highly selected non-representative samplethat call for caution indiscussing the data. Further research would berequired to provide a broader basis for the drawnconclusions.

Acknowledgment

Very special thanks to: Prof. Dr Dirk H. Hellhammerfor his support.

References

Addey, C. (1987). Who cares? Nursing Times, 83, 5253.Barth, A.-R. (1992). Burnout bei Lehrern. Gttingen:

Hogrefe.Bssing, A., & Perrar, K.-M. (1992). Die Messung von

Burnout. Untersuchung einer deutschen Fassung desMaslach Burnout Inventory (MBI-D). Diagnostica, 38(4),328353.

Buske-Kirschbaum, A., Jobst, S., & Hellhammer, D.H.(1998). Altered reactivity of the hypothalamus-pituitary-adrenal axis in patients with atopic dermatitis: pathologic



factor or symptom? Annals of the New York Academy ofScience, 840, 747754.

Carroll, B.J., Curtis, G.C., & Mendels, J. (1976). Neuro-endocrine regulation in depression. I. Limbic system-adrenocortical dysfunction. Archives of General Psychiatry,33, 10391044.

Cherniss, C. (1980). Professional burnout in human serviceorganizations. New York: Praeger.

Cook, T.D., & Campbell, D.T. (1979). Quasi experimenta-tion: Design and analysis issues for field settings. Chicago,IL: Rand McNally.

Curio, I. (1989). Einzelfall- und Zeitreihenanalyse biochemis-cher Indikatoren. In F. Petermann (Ed.), Einzelfallanalyse.2., vllig berarbeitete Auflage (pp. 307315). Munich:Oldenbourg.

Dabbs, J.M., & Hopper, C.H. (1990). Cortisol, arousal, andpersonality in two groups of normal men. Personality andIndividual Differences, 11(9), 931935.

DeLongis, A., Folkman, S., & Lazarus, R.S. (1988). Theimpact of daily stress on health and mood: Psychologicaland social resources as mediators. Journal of Personalityand Social Psychology, 54(3), 486495.

Demitrack, M.A., Dale, J., Straus, S.E., Laue, L., Listwak, S.J.,Kruesi, M.J.P., Chrousos, G.P., & Gold, P.W. (1991). Evidence for impaired activation of the hypothalamic-pituitary-adrenal axis in patients with chronic fatigue syndrome. Journal of Clinical Endocrinology and Metabo-lism, 73, 12241234.

Dienstbier, R.A. (1989). Arousal and physiological toughness:Implications for mental and physical health. PsychologicalReviews, 96, 84100.

Dillman, V.M., & Ostroumova, M.N. (1984). Hypothalamic,metabolic, and immune mechanisms of the influence ofstress. In B.H. Fox, & B.H. Newberry (Eds), Impact of psy-choendocrine systems in cancer and immunity (pp. 5885).New York: Hogrefe.

Dimsdale, J.E., Stern, M.J., & Dillon, E. (1988). The stressinterview as a tool for examining physiological reactivity.Psychosomatic Medicine, 50, 6471.

Dressendrfer, R.A., Kirschbaum, C., Rohde, W., Stahl, F., &Strasburger, C.J. (1992). Synthesis of a cortisol-biotin con-jugate and evaluation as a tracer in immunoassay for sali-vary cortisol measurement. Journal of Steroid Biochemistryand Molecular Biology, 43, 683692.

Ehlert, U., Gaab, J., & Heinrichs, M. (2001). Psychoneu-roendocrinological contributions to the etiology of depres-sion, posttraumatic stress disorder and stress-related bodilydisorders: The role of the hypothalamus-pituitary-adrenalaxis. Biological Psychology 57, 141152.

Fahrenberg, J. (1986). Die Freiburger Beschwerdenliste FBL.Diagnostica, 20, 7996.

Geiss, A., Varadi, E., Steinbach, K., Bauer, H.W., & Anton, F.(1997). Psychoneuro-immunological correlates of persistingsciatic pain in patients who underwent discectomy. Neuro-science Letters, 237, 6568.

Gentry, W.D., Forster, S.B., & Froehling, S. (1982). Psycho-logic response to situational stress in intensive and nonin-tensive nursing. In E.A. McConnell (Ed.), Burnout in thenursing profession (pp. 262266). St. Louis: Mosby.

Gray, J.A. (1987). The neuropsychology of anxiety. Oxford:Clarendon Press.

Gray, J. (1990). Brain systems that mediate both emotions andcognition. In J. Gray (Ed.), Psychobiological aspects of rela-tionships between emotion and cognition (pp. 269288).East Sussex: Erlbaum.

Hakola, T., Hrm, M.I., & Laitinen, J.T. (1996). Circadianadjustment of men and women to night work.

Scandinavian Journal of Work and Environmental Health,22, 133138.

Hautzinger, M., & Bailer, M. (1993). ADS, AllgemeineDepressions Skala, manual. Weinheim: Beltz.

Heim, C., Ehlert, U., & Hellhammer, D.H. (2000). The poten-tial role of hypocortisolism in the pathophysiology of stressrelated bodily disorders. Psychoneuroendocrinology, 25,135.

Henry, J.P. (1986). Neuroendocrine patterns of emotionalresponse. In R. Plutchik, & H. Kellerman (Eds), Emotion:Theory, research and experiences, vol 3 (pp. 3760). SanDiego, CA: Academic Press.

Henry, J.P. (1993). Psychological and physiological responsesto stress: The right hemisphere and the hypothalamo-pituitary-adrenal axis. An inquiry into problems of humanbondings. Integrative Physiological and Behavioral Science,28, 368387.

Henry, J.P., & Stephens, P.M. (1977). Stress, health and thesocial environment: A sociobiologic approach to medicine.New York: Springer.

Heuser, I.J., Gotthardt, U., Schweiger, U., Schmider, J.,Lammers, C.H., Dettling, M., & Holsboer, F. (1994). Age-associated changes of pituitary-adrenocortical hormoneregulation in humans: Importance of gender. Neurobiologyof Aging, 15, 227231.

Janke, W., & Erdmann, G. (1997). Streverarbeitungsbogen(SVF120) nach W. Janke, G. Erdmann, K.W. Kallus und W.Boucsein. Kurzbeschreibung und grundlegende Kennwerte.Gttingen: Hogrefe.

Kaluza, G. (1996). Gelassen und sicher im Stre; psycholo-gisches Programm zur Gesund-heitsfrderung. Berlin:Springer.

Kaspers, F.A. (2001). Endokrinologische Korrelate krper-licher Beschwerden bei chronischem Stre. Gttingen:Cuvillier.

King, J.A., & Edwards, E. (1999). Early stress and geneticinfluences on hypothalamic-pituitary-adrenal axis function-ing in adulthood. Hormones and Behavior, 36, 7985.

King, R.J., Jones, J., Scheuer, J.W., Curtis, D., & Zarcone, V.P.(1990). Plasma cortisol correlates of impulsivity and sub-stance abuse. Personality and Individual Differences, 11(3),287291.

Kirschbaum, C., Strasburger, C.J., & Scherer, G. (1994). Pitu-itary and adrenal hormone responses to pharmacological,physical and psychological stimulation in habitual smokersand nonsmokers. Clinical Investigation, 72, 804810.

Kirschbaum, C., Wst, S., Faig, H.G., & Hellhammer, D.H.(1992). Heritability of cortisol responses to h-CRH, ergom-etry and psychosocial stress in humans. Journal of ClinicalEndocrinology and Metabolism, 75, 15261530.

Kirschbaum, C., Steyer, R., Eid, M., Patalla, U.,Schwenkmezger, P., & Hellhammer, D.H. (1991). Cortisoland behavior. 2. Application of a latent state-trait model to salivary cortisol. Psychoneuroendocrinology, 15(4),297307.

Lazarus, R.S., & Folkman, S. (1984). Stress, appraisal andcoping. New York: Springer.

Leplow, B., & Ferstl, R. (1998). Psychophysiologische Strun-gen [Psychophysiological disorders]. In H. Reinecker (Ed.),Lehrbuch der Klinischen Psychologie. 3., berarbeitete underweiterte Auflage (pp. 539562). Gttingen: Hogrefe.

Levine, S., & Ursin, H. (1991). What is stress? In M.R.Brown, C. Rivier, & H. Koob (Eds), Neurobiology and neu-roendocrinology of stress (pp. 321). New York: MarcelDecker.

Maslach, C. (1978). The client role in staff burn-out. Journalof Social Issues, 34(4), 111124.



Maslach, C., & Jackson, S.E. (1986). Maslach Burnout Inven-tory (2nd ed.). Palo Alto: Consulting Psychologists Press,Inc.

Mason, J.W. (1968). A review of psychoendocrine research onthe pituitary-adrenal cortical system. Psychosomatic Medi-cine, 30, 576607.

Moss, H.B., Vanyukov, M.M., & Martin, C.S. (1995). Sali-vary cortisol responses and the risk for substance abuse inprepubertal boys. Biological Psychiatry, 38(8), 546555.

Motohashi, Y. (1992). Alterations of circadian rhythm inshift-working ambulance personnel. Monitoring of salivarycortisol rhythm. Ergonomics, 35(11), 11311340.

Munck, A., Guyre, P.M., & Holbrook, N.M. (1984). Physio-logical functions of glucocorti-coids. Endocrine Reviews, 5,2544.

Ockenfels, M. (1995). Der Einflu von chronischem Stre aufdie Cortisolkonzentration im Speichel: Gesamtkonzentra-tion, Tagesprofil und Cortisolreaktivitt auf alltglicheStressoren. Munich/New York: Waxmann.

Opstad, P.K. (1991). Androgenic hormones during prolongedphysical stress, sleep, and energy deficiency. Journal of Clinical Endocrinology and Metabolism, 74, 11761183.

Popot, M.A., Houghton, E., Ginn, A., Jones, M., Teale, P.,Samuels, T., Lassourd, V., Dunnett, N., Cowan, D.A., Bonnaire, Y., & Toutain, P.L. (1997). Cortisol concentra-tions in post competition horse urine: A French and Britishsurvey. Equine Veterinary Journal, 29(3), 226229.

Prner, J. (1994). Effekte wiederholter psychischer Belastungauf die Cortisolspiegel unter Bercksichtigung von Persn-lichkeitsvariablen. Unpublished diploma thesis, Universityof Trier, Germany.

Prner, J.C. (1998). Freie Cortisolspiegel am Morgen: Unter-suchungen zu Anstieg, Stabilitt, soziodemographischenund psychologischen Variablen. Gttingen: Cuvillier.

Prner, J.C., Wolf, O.T., Hellhammer, D.H., Buske-Kirschbaum, A., Auer, K., von, Jobst, S., Kaspers, F., &Kirschbaum, C. (1997). Free cortisol levels after awaken-ing: A reliable marker for the assessment of adrenocorticalactivity. Life Sciences, 61(26), 25392549.

Radloff, L.S. (1977). The CES-D scale: A self-report depres-sion scale for research in the general population. AppliedPsychological Measurement, 1(3), 385401.

Reinberg, A.E., Touitou, Y., Soudant, E., Bernard, D., Bazin,R., & Mechkouri, M. (1996). Oral contraceptives alter circadian rhythm parameters of cortisol, melatonin, bloodpressure, heart rate, skin blood flow, transepidermal waterloss and skin amino acids of healthy young women.Chronobiology International, 13(3), 199211.

Schulz, P., & Schlotz, W. (1999). Trierer Inventar zur Erfas-sung von chronischem Stre (TICS): Skalenkonstruktion,teststatistische berprfung und Validierung der SkalaArbeitsberlastung. Diagnostica, 45(1), 819.

Selye, H. (1950). Stress. (The physiology and pathology ofexposure to stress). Montreal: Acta, Inc.

Smyth, J.M., Ockenfels, M.C., Gorin, A.A., Catley, D., Porter,L.S., Kirschbaum, C., Hellhammer, D.H., & Stone, A.A.(1996). Individual differences in the diurnal cycle of corti-sol. Psychoneuroendocrinology, 22(2), 89105.

Ursin, H. (1980). Personality, activation and somatic health.In S. Levine, & H. Ursin (Eds), Coping and health (pp.259280). New York: Plenum Press.

Ursin, H. (1987). Expectancy and activation: An attempt tosystematize stress theory. In D.H. Hellhammer, I. Florin, &H. Weiner (Eds), Neurobiological Approaches to HumanDisease (pp. 313343). Bern: Huber.

Ursin, H. (1998). The psychology in psychoneuroendocrinol-ogy. Psychoneuroendocrinology, 23(6), 555570.

Weiner, H. (1998). Notes on an evolutionary medicine. Psychosomatic Medicine, 60, 510520.

Widmer, M. (1988). Stress, Stressbewltigung und Arbeit-szufriedenheit beim Krankenpflegepersonal. Aarau:Schweizerisches Institut fr Gesundheits- undKrankheitswesen SKI.

Wst, S., Wolf, J.M., Hellhammer, D.H., & Kirschbaum, C.(1999). Salivary cortisol levels after awakening as a newindex for adrenocortical activity: Normal values and recentfindings. Poster presented at the XXXth annual ISPNE Con-gress, July 30August 3, 1999, Orlando, Florida.

Wst, S., Wolf, J.M., Hellhammer, D.H., Federenko, I.,Schommer, N., & Kirschbaum, C. (2000). The cortisolawakening responsenormal values and confounds. Noise& Health, 7, 7988.



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Stress-Induced Increase in Morning Cortisol Variance