Suppressing the endocrine and autonomic stress systems does not impact the emotional stress experience after psychosocial stress
Nida Ali
a,∗, Jonas P. Nitschke
a, Cory Cooperman
a, Jens C. Pruessner
a,b,c,daDepartmentofPsychology,McGillUniversity,1205Dr.PenfieldAvenue,Montreal,QC,Canada
bMcGillCentreforStudiesinAging,FacultyofMedicine,McGillUniversity,Montreal,QCCanada
cDouglasHospitalResearchCentre,DepartmentofPsychiatry,FacultyofMedicine,McGillUniversity,Montreal,QCCanada
dUniversityofConstance,DepartmentofPsychology,Constance,Germany
a b s t r a c t
Acutepsychosocialstressactivatesthephysiologicalandendocrinestresssystemsandincreasesthe subjectiveemotionalexperienceofstress.Whileconsiderableeffortshavebeenmadetolinkchangesin theactivityofthebiologicalstresssystemswithchangesinthesubjectiveemotionalexperienceofstress, resultssofarhavebeenmixed,atbest.Toinvestigatethisassociationinastudyemployingexperimental manipulation,wepharmacologicallysuppressedboththeautonomicandtheendocrinestressresponses, andinvestigatedtheeffectsofacutepsychosocialstressontheemotionalstressexperience.
22healthymenandwomenreceiveddexamethasone(2mg)thedaybefore,andpropranolol(80mg) onehourbeforepsychosocialstressinduction.Acontrolgroup(n=24)receivedplacebopillsoneach occasion.Salivarycortisol,alpha-amylaseandheart-rateresponsestostresswereassessedbefore,during andafterstressinduction.Subjectivestress,mood,andstateself-esteemassessmentsweremadebefore andafterstress.
In thepharmacological manipulationgroup, subjectsdemonstrated noincreasein autonomicor endocrinestressresponse,afterexposuretopsychosocialstress.Despitetheseeffects,theemotional stressexperiencewasintactinthisgroupandidenticaltothecontrolgroup.Participantsintheexper- imentalgroupshowedanincreaseinsubjectivestress,greatermooddysregulation,andlowerstate self-esteemfollowingstressexposure,withtheresponsemagnitudecomparabletothecontrolgroup.
Ourfindingssuggestthatatleastacutely,thephysiologicalstressarousalsystemsandtheemotional experienceofstressaredissociated.Thisraisesimportantquestionsabouttheefficacyofourmeasure- mentofsubjectivestress,andtheuniquecontributionsoftheautonomicandendocrineresponsesinthe subjectivestressexperience.
1. Introduction
In1884WilliamJamesfamouslyaskedifonewouldrunaway fromawildbearoutoffearorwhetherthefearwouldcomefrom runningaway (James,1884).The ongoing discussion aboutthe interrelationshipsbetweenthephysiologicalandsubjectivestress responsehassomeresemblancetothisissue−istheexperienceof stressaresultoftheactivationofthephysiologicalstresssystems, orarethesystemsactivatedasaresultoftheexperienceofstress?
Regardlessofwhereonestandsontheissue,oneprerequisiteisthe
∗Correspondingauthorat:DepartmentofPsychology,McGillUniversity,1205 Dr.PenfieldAvenue,Montreal,Montreal,QCH3A1B1,Canada.
E-mailaddress:nida.ali@mail.mcgill.ca(N.Ali).
consistentassociationofthephysiologicalandpsychologicalstate duringstress.
Physiologically, stress related arousalis associated withthe activationoftheautonomicnervoussystem(ANS),resultinginele- vatedheart-rate(HR)andbloodpressure,andincreasedproduction ofdownstreamstressbiomarkerssuchassalivaryalpha-amylase (sAA;(Engertetal.,2011)).Inconjunction,theactivationofthe sloweractinghypothalamic–pituitary–adrenal(HPA)axisresults inthesecretionofcorticotropin-releasing-hormone(CRH),adreno- corticotrophic hormone (ACTH), and the subsequent release of cortisol, the most commonly used stress marker in endocrine research(ChrousosandGold,1992;Ulrich-LaiandHerman,2009).
Whilenumerousstudieshaveshownthatacutestressactivates thephysiologicalstresssystemsandincreasesthesubjectiveemo- tionalexperienceofstress,onlyafew(e.g.,CampbellandEhlert, 2012;Maussetal.,2005)haveexplicitlyexaminedthecorrespon-
Konstanzer Online-Publikations-System (KOPS) URL: http://nbn-resolving.de/urn:nbn:de:bsz:352-2-mi47p444if1c3 Erschienen in: Psychoneuroendocrinology ; 78 (2017). - S. 125-130
https://dx.doi.org/10.1016/j.psyneuen.2017.01.015
dencebetweenthephysiologicalandemotionalstressresponses.
WhileMaussetal.(2005)speakgenerallyofmodestassociations betweenphysiologicalandemotionalexperiences;Campbelland Ehlert(2012)explicitlyreviewtheinterrelationshipsbetweenbio- logicalstressmarkers(suchascortisolandsAA)andpsychological stressmarkers(suchassubjectivestressandnegativemood).Their findingsdemonstratethatsignificantcorrelationsexistbetween the biological and the psychologicalstress experiences in only aboutonequarterofallreviewedstudies(beforeevenconsidering thestrengthoftheassociation).Theauthorsthusnamedvarious possiblefactorsforthis apparentdissociation, amongthem dif- ferencesinassessmentapproachesandmethodologies,aswellas mediatingfactorssuchaspersonalitytraitsandappraisalprocesses.
Onemethodtoinvestigatetheinterrelationshipsbetweenthe physiologicalandpsychologicalsystems,thathassofarbeenabsent fromtheliterature,istoengageinexperimentalmanipulationof theautonomicand/orendocrineaspectsofthestressresponseand observethesubsequenteffectsonthesubjectivestressexperience.
Whilepreviousstudieshaveengagedinpartialsuppressionofthe stressresponsebysuppressingeithertheautonomicsystemorthe endocrinesystem(Andrewsetal.,2012;AndrewsandPruessner, 2013;Maheuetal.,2005),nonehaveexaminedtheeffectsonthe subjectivepsychologicalstressexperienceinthecompleteabsence oftheautonomicandendocrinestressresponses.
Therefore, the goal of the current study was to pharmaco- logicallysuppressboth,theautonomicandtheendocrinestress responsesinordertoinvestigatetheeffectsofacutestressexposure purely onpsychologicalstress perception.In contrast toprevi- ousparadigmsusingpharmacologicalmanipulationstoalterthe functioning of individual stresssystems (Andrews et al., 2012;
AndrewsandPruessner,2013;Maheuetal.,2005),weengaged inadoublesuppressionoftheANSandHPAaxis,priortostress exposure.Keepinginlinewithclassicalandcontemporarytheories ofemotion(James,1884;Lange,1885;SchachterandSinger,1962), wepredictedthat theabsenceoftheautonomic and endocrine activationwouldresult ina markedlyreduced subjectivestress experience.Additionaljustificationforthishypothesisstemsfrom previousstudiesinourlaboratorywherewesuppressedtheANS usingpropranolol,andobservedareductioninthesubjectivestress experience (Andrews and Pruessner, 2013).To the best of our knowledge,nopreviousstudyhasexaminedtheeffectofpsychoso- cialstressonthesubjectiveexperienceofstressintheabsenceof autonomicorendocrineresponse.
2. Methodsandmaterials
46 healthy participants (23 men, mean age=22.43, SD=3.66, range=19-32;23 women,meanage=22.65,SD=4.42, range=18–35),withnocurrentorhistoryofmedicalorpsychiatric illnesseswererecruitedforthestudy.Exclusioncriteriaincluded recreationaldruguse, consuming more thanten alcoholicbev- eragesaweek,smokingmorethan7cigarettesadayandusing medicationsthatmightaffectHPA-axisfunctioning,includingoral contraceptives,forwomen.Womenweretestedduringtheluteal phaseoftheirmenstrualcycle(17–28daysaftertheonsetoftheir lastmenstruation).Toestablishthelutealphase,womenrecorded two menstrual cycles prior to testing. Participants provided writteninformedconsent.ThestudywasapprovedbytheMcGill UniversityFacultyofMedicineInstitutionalReviewBoard.
Participantswererandomlyassignedtotheplacebocondition (PLC; n=24) or the dexamethasone-propranolol condition (DP;
n=22). Toensure that theinvestigators and subjectsremained blindedtothedrugconditions,participantsreceivedtwopills,one totakeatbedtime,thenightbeforetesting(placeboor2mgofdex- amethasone),andone60minbeforetheonsetofstress(placebo
or80mgofpropranolol).Aphysicianwasoncallwhilethedrugs wereactivetocareforparticipantsincaseofpharmacologicalside effects.Noadverseeventsoccurredthroughoutthestudy.
2.1. Testingparadigm
Testingsessions wereheld at thesametime of dayon two consecutivedaysinourlaboratory.Onday1,participantsarrived between9h30and10h00a.m.Onarrivaltheycompletedthecon- sentformandaquestionnairetoconfirmtheabsenceofdepressive symptomatology(Becketal.,1996).Theythenreceivedonepill (placeboordexamethasone)withinstructions totakeitatbed- time.Aresearchassistantsentatextmessagetoeveryparticipant intheevening, remindingthemtotakethepill,andconfirming theappointmentinthemorning.Participantswereencouragedto respondback witha confirmationthat theyhad takenthepill, although notall subjectsdid. On the morning ofthe testing, a researchassistantagainconfirmedthatthepillhadbeentakenas instructed.
Onday2,participantsreceivedonepill(placeboorpropranolol) onehourbeforetheonsetofstress.Aresearchassistantwaspresent toadministerthepill.Participantswerethenseatedinawaiting roomfora60-minrestperiodforthepropranololtotakeeffect.
Participantswerethenexposedtothepsychosocialstressparadigm (describedbelow),followingwhichtheycompletedquestionnaires toassessstressrelatedchangesinstateselfesteemandmood.
2.2. Psychosocialstressparadigm
Toinduceacutepsychosocialstress,subjectswereexposedto theTrierSocialStressTest(TSST;Kirschbaumetal.,1993).TheTSST consistsofa10-minanticipationphaseduringwhichparticipants areaskedtoprepareforajobinterview.Thisisfollowedbya5-min speechanda5-minmentalarithmetictask,performedinfrontof trainedconfederates,onemaleandonefemale.TheTSSTreliably producessignificantincreasesinstressatalllevels:cortisol,sAA, HR,andsubjectivestress(e.g.,AliandPruessner,2012;Engertetal., 2011;Kirschbaumetal.,1993;Nateretal.,2005;Rohlederetal., 2004).
2.3. Stressmarkers
CortisolandsAAwereanalyzedfromsalivasamples(Sarstedt Inc.,Saint-Léonard,QC,Canada).Cortisollevels(nmol/l)weremea- suredusingatime-resolvedfluorescenceimmunoassaydescribed byDressendorferetal.(1992).Salivaryalpha-amylase(U/ml)lev- elsweredeterminedusingtheenzymekineticmethodreferredto inEngertetal.(2011).HRwasmeasuredbyanambulatorysphyg- momanometer(A&DCompany,Tokyo,Japan).Allmeasureswere anchoredto9 time-points, in10-min intervals, throughoutthe experimentfrom−20to+60min.
2.4. Psychologicalassessment 2.4.1. VisualAnalogueScale
Thevisualanaloguescale(VAS)isfrequentlyusedtomeasure thesubjectivestressexperience(Gift,1989).Usinga10-pointVAS, participantsrespondedtothequestion“Howstresseddoyoufeel rightnow?”.Responsesrangedfrom“notatall”to“extremely”.The VASwasadministeredat9time-pointsontestingday2,alongside everysalivasample.
2.4.2. CurrentThoughtsScale
TheCurrentThoughtsScale(CTS;HeathertonandPolivy,1991) isa20-itemscaleusedtomeasuretransientchangesinself-esteem
along3dimensions:performance,social,andappearance.Acom- posite score can also be used to assess state-self esteem as a continuousmeasure.TheCTSwasadministeredtwiceonday2, atbaselinepriortostressinduction,andimmediatelyafterstress.
Allthreesubscalesandthecompositescorewereusedtomeasure stress-inducedchangesinstateself-esteem.
2.4.3. ProfileofMoodStates
TheProfileofMood States(POMS;Lorret al.,1971)isa 65- itemquestionnairethatcapturestemporaryemotionalstatesalong six dimensions: tension-anxiety, depression-dejection, anger- hostility, confusion-bewilderment, vigour-activity and fatigue- inertia.Acompositemeasureoftotalmooddisturbancecanalso beusedtoassessoverallchangesinmood.ThePOMSwasadmin- isteredtwiceonday2,atbaselinepriortostressinduction,and immediatelyafterstress.Allsixsubscalesandthecompositemea- sureoftotalmooddisturbancewereusedtoassessstress-induced changesinmood.
2.5. Statisticalanalyses
Atwo-way(drugXsex)MANOVAwasconductedwithage,BMI, self-esteem,andBDIasdependentvariablestoensurethatgroups didnotdifferonthesevariables.
Tocomparebiomarkersofthedifferentstresssystems,across groups, thevaluesfor each stressbiomarker(cortisol, sAA,and HR) were z-standardized across all participants, over all time points. This allowed us to visualize the crosstalk betweenthe different stress systems using identical units for each system.
Thez-standardizedscoreswereemployedforsubsequentstatis- ticalanalyses,andforvisualization.Giventhatsexdifferencesare observedinphysiologicalstressresponses,sexwasincludedasa between-subjectfactorinallanalyses.
A repeated measuresMANOVA (time×drug×sex)was con- ducted to examine the effects of drug administration on the physiologicalstressvariables,withthe9time-pointsforeachz- transformed biomarker:cortisol, sAA and HRas within-subject factors.
Toexaminetheeffectsofdrugadministrationonthepsycho- logicalstressresponses,repeatedmeasuresANOVAs(timeXdrug) wereconductedfortheVAS(all9time-points)andcompositemea- suresofCTSandPOMS(bothtimepoints)aswithin-subjectfactors.
Toassesschangeinsubjectivestressovertime,areaunderthe curvewithrespecttoincrease(AUCi)wascomputedfortheVAS usingthetrapezoidformuladescribedbyPruessneretal.(2003).
Tomeasure theeffects of stressonchanges inmood andstate self-esteem,wecomputedthedelta-peak−absolutechangefrom baselinetopeakstress-forthepreandpostmeasuresofPOMS(all 7subscales)andtheCTS(all4subscales).
A two-way MANOVA (drug X sex)was conducted withthe AUCi for VAS, and delta peak for each subscale of the POMS and CTS as dependent variables to assess the effects of drug administrationonthesubjectiveemotionalexperiencefollowing stress. Greenhouse-Geisser (GG) corrections were performed if assumptionsofsphericitywereviolated.Significantmaineffects were decomposed using pair-wise comparisons and Bonferroni corrected.StatisticalanalyseswereconductedusingSPSS21for MacintoshOSX10.11.
3. Results
Two participants (women in the PLC condition) had to be excludedfromthedataanalysisbecausetheirscoresontheBDI exceededtheestablished limitfor mild depression (Beck etal., 1996).Finaldataanalysiswasconductedin44participants(PLC n=22;DPn=22).
Fig.1.Z-scoresofthechangeovertimeincortisol,alpha-amylase,andheart-rate responsestotheTSST,inthePlacebo(top)andDex/Prop(bottom)conditions.
Giventhatwehadanearlyequaldistributionofmenandwomen ineachdrugcondition(PLC:12men,10women;DP:11men,11 women),weconductedachi-squareanalysistoexamineifthere weresignificant differencesbetweenthe groups.The resultsof theChi-squaretest(withoutYates’continuitycorrection)revealed thatthedruggroupsdidnotdiffersignificantlybygender(ˆ2(1, N=44)=0.09,p<0.76,=0.05,oddsratio=1.2).Theseresultsheld whenthetestwasconductedwithYates’continuitycorrection:(ˆ2 (1,N=44)=0.00,p=1,=0.05,theoddsratiois1.2).
TheresultsofthefirstsetofMANOVAsrevealednosignificant effectsofsexordrugconditiononage,self-esteem,BMIorBDI(all Fs<2.44,ps>0.1),indicatingthatthegroupswerecomparableon thesefactors.
3.1. Stressbiomarkers
SignificanttimeXdruginteractionswereobtainedforcortisol, F(1.59,63.58)=6.29,p=0.006;sAA,F(3.06,122.56)=4.37,p=0.006;
andHR,F(5.12,204.67)=2.41,p=0.037(Fig.1).
Pairwise comparisons revealed that the pharmacological manipulationsuccessfullysuppressedallstressbiomarkersinthe DPcondition,i.e.cortisol(PLC:M=0.71,SE=0.11;DP:M=−0.69, SE=0.11),sAA(PLC:M=0.10,SE=0.15;DP:M=−0.24,SE=0.15), andHR(PLC:M=0.28,SE=0.17;DP:M=−0.43,SE=0.17).Fig.2 illustratesthestressresponsebetweentheplaceboandDPgroups separately,usinguntransformedvalues,forcortisolsAA,andHR.
There was nosignificant time X sex interaction for any stress biomarkers,thuswereporttheresultsforbothsexescombined.
3.2. Subjectivestressandmood
TheresultsoftherepeatedmeasuresANOVAs(time Xdrug) revealedasignificantmaineffectoftimeforeachmeasurement of subjectivestress, VAS: F(3.21,135.17)=29.75,p<0.001; CTS:
F[1,42]=7.35,p=0.01;POMS:F[1,42]=8.99,p=0.005,indicatinga significantchangeinemotionalstatesafterstress.Theresultsfur-
Fig.2.ChangesinstressresponseovertimeinthePlaceboandDex/Propconditions, usinguntransformedvaluesforcortisol(top),alpha-amylase(middle),andheart- rate(bottom).
therrevealedthattherewasnosignificanttime×druginteraction, indicatingnodifferencesbetweenthePLCandDPconditions.
TheresultsoftheMANOVArevealednosignificanteffects of drugconditionforVAS,CTS(all4subscales),orPOMS(all7sub- scales)(allFs<2.24,ps>0.14),indicatingnosignificantdifferences betweenthePLCandDPgroupsonthesubjectiveemotionalexpe- riencesofstress(Figs.3and4).Further,therewasnosignificant drugXsexinteraction(allps>0.23).
Wheninterpretinganegativeresult,itisimportanttotakeinto considerationthestatisticalpower,toobserveanyeffectinthecur- rentsample,ifthereisindeedadifferenceinthepopulation.Wecan usethestrengthoftheeffectofthepharmacologicalsuppression ofthebiomarkerstoestimatethepower,andtofindeffectsonthe subjectivestressexperience.Themaineffectsize2ofthedrugs oneachstressmarkerwas,2=0.14forsAA,2=0.29forHR,and
2=0.75forcortisol.Thus,assumingameaneffectsizeof2=0.40 wecanestimateapowerT>0.998todetectaneffectonthesub- jectivestressexperienceinthissample,ifindeedexistentinthe population,accordingtotheformulasprovidedbyCohen(1988).
Fig.3. Z-scoresofchangeovertimeinsubjectivestressinresponsetotheTSST,in thePlacebo(top)andDex/Prop(bottom)conditions.
Fig.4. EffectofTSSTonthesubjectiveemotionalexperiencesofstressintheplacebo andDex/Propgroups:A)Mean(+SEM)changefrombaselinefortotalandeachsub- scaleoftheProfileofMoodStates(POMS)(A=anxiety,D=depression,H=hostility, V=vigor,F=fatigue,C=confusion).B)Mean(+SEM)changefrombaselinefortotal andeachsubscaleoftheCurrentThoughtsScale(CTS).
4. Discussion
The goal of this study wasto pharmacologically inhibit the physiologicalstresssystems(ANSandHPAaxis)andinvestigate theeffectsofthissuppressiononthesubjectiveemotionalstress experience,inresponsetoacutestress.Wepredictedthatpharma- cologicalblockadewouldnotonlyimpairthereactivityoftheHPA axisandANSinresponsetoacutestressbutwouldalsoreduce,or dampen,thesubjectiveemotionalexperienceofstress.
Ourresultsindicatethatthedrugmanipulationwaseffective inimpairingtheautonomicandendocrineresponsetopsychoso- cialstress.Specifically, wefoundthatboth menandwomen in theDPconditionhad significantlyblunted cortisol,sAAandHR responsestostress.Therespectivestatisticaltests(MANOVAswith timeastherepeatedmeasureandthevariousstressbiomarkersas thedependentvariables)revealedsignificanteffectsofdrugcon- ditiononthestressresponseovertime(all ps<0.05),indicating thattheusuallystressfulpsychosocialexperiencedidnothavea significanteffectontheautonomicorendocrinestresssystems.To thebestofourknowledge,thisisthefirststudythathassuccess- fullyemployedpharmacologicalsuppressionofbothendocrineand autonomicstressresponsesinhumans.
Incontrast,wefoundthatthesubjectiveemotionalstressexpe- riencewasintact,evenintheabsenceofasignificantautonomicor endocrinestressresponse.Specifically,allparticipantsshowedan increaseinsubjectivestress,greatermooddysregulationandlower stateselfesteemfollowingstressexposure,withnosignificantdif- ferencesbetweenthePLCandDPgroups.Thesefindingssuggest thatthereisaratherstrongdissociationbetweenthephysiological stresssystemsandthesubjectiveemotionalexperienceofstress.
TheindividualsintheDPgroupreportedsimilarpeakamountsof subjectivestressasmeasuredviatheVAS,astheircounterpartsin thePLCgroup.Inaddition,therewasnodifferencebetweengroups inthesubjectivestressdynamicsovertime,withsimilarbaseline, increasefrombaselinetopeak,andreturntobaselinefrompeak, measures.
Toexplainthisunexpectedfinding,severalpossibilitiesemerge:
First,perhapsourmethodofsuppressingthestresssystemswas notstrongenough,andasaresultwecan’tdrawconclusionsabout theinterrelationshipsbetweenthebiologicalandthepsychological stressresponses.Severalargumentsspeakagainstthis,boththeo- reticallyandasevidencedbyourdata.FortheANS,propranololhas alonghistoryasamedicationusedtocontrolhypertension,andhas recentlyreceivedincreasedattentioninthepsychologicalsciences becauseofitsabilitytoblockreconsolidationofemotionalmemo- ries(e.g.,Schwabeetal.,2013,2012).Asabeta-adrenergicreceptor blocker,propranololactswithinthelimbicsystemcentrally,and onbeta-adrenergicreceptorsperipherally,preventingheart-rate increasesduringacutestress,andkeepingbloodpressureinthe normalrange.Thus,wecanberelativelycertainthattheadminis- trationofthisdrughadtheintendedeffect.Thisisevidencedbythe factthatweobservednosignificantheart-rateorsAAincreasesin theexperimentalgroupthroughoutthestressparadigm.
AdministeringdexamethasoneforHPAsuppressionmightnot beimmediatelyintuitive,giventhatitisasyntheticglucocorticoid andleadstoanincreaseinglucocorticoidsin theperiphery (de Kloetetal.,1974).However,atthelevelofthepituitary,adoseof morethan1mgtypicallyresultsinacompleteinhibitionofACTH productionforasustainedperiodoftime.Giventhatdexametha- sonedoesnotcrossthebloodbrainbarrierinsmallerdosages,the negativefeedbackfromthepituitaryresultsinanimmediatereduc- tionofcortisolproduction.Thus,intheperiphery,administrationof dexamethasoneleadstofirstahyper-exposurefollowedbyahypo- exposure,whilecentrallythereisanalmostimmediatereduction ofHPAaxisactivity(Karssenetal.,2005).Sinceinourstudydex- amethasoneadministrationtookplaceatbedtimethenightbefore testing,itcanbeassumedthatparticipantsarrivedfortestingin ahypo-glucocorticoidstate,bothcentrallyandintheperiphery.
Thiswasevidencedbybluntedcortisollevelsobservedinthesub- jectsthroughoutthestudy.Thus,wecanlikelyconcludethatthe suppressionoftheHPAaxiswasalsoeffective.
Anotherpossibilitycouldbethatthepsychologicalmeasures toassessthesubjectiveemotionalexperienceofperceivedstress are inadequate. While this is not a novel idea (cf. Andrews andPruessner,2013;BiondiandPicardi,1999;Hellhammerand Schubert,2012),wesuggestthatthecurrentstudywithitsexper- imentalsuppressionofthebiologicalstressresponserevealsthis inadequacymoredirectly.Thus,itcouldbearguedthatthemea- sures of psychological stress we have at our disposal are too insensitivetoallowanyrealinsightintothepsychologicalstate oftheindividual.Thisargumentcaninpartbesupportedbystud- iesshowingabluntedphysiologicalorendocrinestressresponse, inthepresenceofnormalsubjectiveemotionalresponsestostress (e.g.ChildsanddeWit,2009;Kirschbaumetal.,1999).Thecurrent findingcouldbeinterpretedasasignthatthegeneralthreshold to‘feelstressed’ortoacknowledgethatasituationisstressful,is probablyratherlowandthattheremightbeceilingeffectstothe
subjectiveexperienceofstress,whichthenmaskthepossiblelink withphysiologicalorendocrinesystems.
Ifthecurrentmeasuresofpsychologicalstressareindeedinad- equate,asaconsequence,wewouldeitherhavetoacknowledge this (andstoplookingfor,or stopreadingmeaning into,spuri- ousresults),orweshouldaimtodevelopbettermeasures.While thelatterpointisbeyondthescopeofthecurrentmanuscript,the authorsdowishtodirectthereadertosomeinterestingresearch evolvingaroundimplicitmeasuresandbiologicalstresssystems,as onealternative(see,forexample,theworkofMossinketal.,2015;
Wegneretal.,2014;Wegneretal.,2015).
Anotherpossibilityisthatthemeasuresofsubjectiveemotional experienceofstressasemployedinthisandmanyotherstressstud- iesarenotinadequateafterall,butsimplynotassociatedwiththe biologicalstresssystems.Thistoowouldmeanthattheassessment ofthesubjectiveemotionalstressexperienceinthecontextofthe biologicalstressresponseisnotasusefulaspreviouslythought.
Finally, the question arises about central nervous system processesthatmightbeinvolvedinthisdissociationofthephysi- ologicalandpsychologicalstressresponse.Fromourownimaging studieson neuralactivationduring acutestress perception,we know that frontal and temporal lobe structures (orbitofrontal, anteriorcingulate,insula cortex,amygdala, hippocampus)seem tobeprimarilyinvolvedintheperceptionandprocessingofan acutestressor(Pruessneretal.,2010).Giventhattheseregionsare richinmineralocorticoid(amygdala,hippocampus),glucocorticoid (frontal and temporal lobe, including amygdalaand hippocam- pus), and noradrenergic receptors (amygdala),pharmacological suppressionoftheautonomicandendocrinestressresponsesys- temsarelikelydetectedcentrally,particularlyatthelevelofthe amygdalaandhippocampus.Howeverourresultsindicatethatthis suppressiondidnothaveanyeffectonthesubjectiveexperienceof stress,allowingustohypothesizethatthesestructuresmightnot beimmediatelyandstronglyassociatedwiththemagnitudeofthe subjectivepsychologicalstressexperience.
Takentogether,andrelatingbacktotheinitialquestionraised byJamesin1884,ourfindingssuggestthattheemotionalexperi- enceofstressisnotcontingentuponperceivedcuesofphysiological arousal.Whiletheresultsfromthisstudydidnotrevealanydif- ferencesbetweenmenandwomeninthesubjectiveexperience of stress,oursample size didnotallow ustoexplore sex spe- cificeffects,ifany.Follow-upstudiesshouldconsiderexamining theseeffects,andassesswomeninthefollicularphase,andonoral contraceptives,giventhathormonalandemotionalresponsesare alteredinthesephases.
Overall,ourstudydemonstratestheefficacyofusingpharmaco- logicalmanipulationtosuccessfullysuppressphysiologicalstress arousal,inresponsetopsychosocialstress.Theresultingdissocia- tionbetweenthephysiologicalstressresponseandtheemotional experienceofstressraisesimportant questionsaboutreliability andvalidityofourmeasuresofpsychologicalstress,particularly intheirrelationshipwithmeasuresof biologicalstress,andthe uniquecontributionsoftheautonomicandendocrineresponses inthesubjectivestressexperience.
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