Thursday Abstracts BiOLPSYCHIATRY 1998;43:1S–133S 53s 178. PSYCHOPHYSIOLOGY IN PSYCHIATRIC RESEARCH: METHODOLOGICAL ISSUES K.S. Cadenhead, G.A. Light, M.A. Geyer & D.L. Braff Departmentof Psychiatry,Universityof California,SanDiego,CA 92093-0804 Thehumanstartleresponse(SR),is an importantphysiological response because it can he modifiedunder different experimentalconditions. Prepulseinhibition(PPI) of the eyeblinkSR is the decrementin the startle magnitude in response to presentation of a relatively weak prestimulusprior to the startle eliciting stimulus and an important exampleof the plasticityof the SR. PPI is an operationalmeasureof sensorimotorgatingandis deficientin schizophreniaspectrumsubjects. Cerebral event related potentials(ERP) are usually assessed by using averagedwaveforms.Averagingresponsesfromthesametrialtypeleads to enhancedsignalto noiseratios(SNR)andimprovedidentificationof individualcomponents.Measurementof the SR is often free of the assumptionsinherentin ERPtrial averagingsinceresponsesareusually large, time-locked,have high SNRS,and are easily identifiedin single trials.Smallerstartleresponses,as are elicitedin PPI studies,havelower SNRand can be difficultto discernfrom ongoingEMGactivity. We assessedboth the singletrials and averagedwaveformanalysisap- proachesto scoringstartledatafmm 18normals.The two methodswere highlycm-dated(rho = 0.74-0.98)suggesting thatSR scoringis reliable acrossthese2 differentanalyticalapproaches. It appearsthatthewaveform analyticapproachmay be particuksrlyusetil in assessmentof smaller mS@@ reaponsessuchas thoseseeninprepuke-inhibited SRS. 179. THE “INCREDIBLE SHRINKING” P50 EVENT RELATED POTENTIAL G.A. Light & D.L. Braff Departmentof Psychiatry,Universityof California,Ss23Diego,La Jolla, CA 92093-0804 TheP50mmponentof the auditoryevokedresponsehasbeenutilizedin neuropsychiatric researchfor over 15 years. The P50 wave is typically measrrmd inresponwtorepeatedauditorystimulationofshortdurationclick pairs separatedby 500 milliseconds.P50 suppressionis examinedby averagingmultiple(i.e.30to 120)elechuencephalogmphic responsestothe clicksand measuringthe reductionin amplitude(in micmvolts)of the response. from the 1* to the 2ti click. P50 suppression is viewedas an operationalmeasumof sensorygating and gating deficits have been identiikdinschimphrenicpatientsandtheirrelatives.P50suppressionhas alsobemrthesubjectofrecentimptantgeneticlinkagestudies,increasing the needto understandhow best to measureand utilizethis variable.It appears,basedona reviewofseveralP50studiea,thatthearn@udeofthe P50waveto the 1slof thetwoclicksin theP50suppressionparadigmhas beensteadilydecreasingoverthecouraeoftime.Webaveextractedtheyem of publicationandarnplitndeoftheP50responsetothe Istclickin nd subjectsfrom30P50articlesandfoundthatyearofpublicationaccountsfor close to 60% of the variancein the size of this mmponent(R=O.76, ~1,29)=38.18, p<O.0@31). ‘l%eadvancesinequipmentrecordingmethods, F numberoftrialsaveraged(i.e.120vs.30),andotherprocessingsteps(e.g. offlineartifactand trial rejection)that havebeenusedto claritjIsignalto noiseratiosareamongthepossiblereasonsforthissomewhatparadoxical reductioninP50amplitudeovertime.Weconcludethatresearchersshould notbediscouragedwithresultsyieldingasmallinitialP50.Itisimpmtan tto notethatthew ofpercentage(vs.absolutedit%mmce) scoreswillprobably best enableinvestigatorsto comparetheir futureresultsto the existing litemture. 180. GLUCOCORTICOID FEEDBACK INHIBITION OF THE HPA AXIS IN PTSD E.D. Kanter; E.R. Peskind, D.J. Dottie, C.W. Wilkinson & M.A. Raskind MentalHealti,Service,VA PugetSoundHealthCare System; Departmentof PsychiatryandBehavioralSciences,Universityof WashingtonSchoolof Medicine,Seattle,WA 98108 Alterationsin thehypothalamic-pituitary-adrenal (HPA)axisin posttrau- maticstressdisorder(PTSD)havebeendescribedwhicharedistinctfrom those seen in acute stress or majordepression.Basal cortisollevels are decreasedin PTSD,in contrast to the elevated cortisol levels seen in acutestressor majordepression.Asa mechanismtoexplainthis,Yehuda (Ann NY Acad Sci 1997; 821:57-75)has postulatedenhancednegative feedback sensitivityof the HPA axis in PTSD. A study in combat veteranswith PTSDusingthe 11~-hydroxylase inhibitormetyraponeto blockendogenouscortisolproductionhas shownresultantincreasesin ACTHsignificantlygreaterthanseeninnormalcontrols,consistentwith the hypothesisof enhancednegativefeedback sensitivityof the HPA axis. In orderto cont%nrand extendthis finding,we have employeda metyrapone-cortisolintiwion protocol, recently used to demonstrate decreased sensitivityto negative feedback inhibitionin human aging (Neuroendccrinology1997;65:79-90). Vietnamcombattrauma-exposed subjectsmet DSM-IVcriteriafor PTSDas determinedby the Clinician AdministeredF1’SDScale (CAPS).Subjectshad no active substance abuse and were free of any medicationknownto affect the HPA axis. Endogenouscortisol feedback inhibition was removed by blocking cortisolsynthesiswith oral metyraponetreatment.Feedbackinhibition was then reintroducedby intravenous intirsion of cortisol at 0.03 mt#k@ fm 150min.Physiologicplasmacortisolconcentrationswere achieved.In a placebocondition,placebo tablets were substitutedfor metyraponeand normal saline infusion was substitutedfor cortisol. Blwd samplesweredrawntwicepriorto andat 15tin intervalsfor4 hr followingthe onset of the tisions, and assayedfor lldeoxycortisol, cortisol, and ACTH. Subjects respondedto cortisol infusion with a decrease in circulatingACTH;the rate of decline of ACTH suggests enhancednegativefeedbacksensitivityincombat-relatedPTSD.Studies are underwayusingthe sameprotocolin maleand femalesubjectswith non-combatrauma. 181. SENSORY PROCESSING OF GRADED AUDITORY INPUT IN PTSD PATIENTS K. Getzl, L.M. Konopka2>3,M. Primeaul’2, J. Zadecki2’3& J.W. Crayton2’3 ‘FinchUniversityof HealthScience#I’IreChicagoMedicalSchool, NorthChicago,IL 60064;2HinesVA MedicalCenter,Hines,IL 60141;3LoyolaMedicalCenter,Maywood,IL 60153 Post-traumaticStressDisorder(PTSD)hasbeencharacterizedbyaltered reactivityto sensorystimulation.The auditoryevokedpotential(AEP) intensityparadigmprovidesa methodforexaminingsensoryprmessing in PTSD since individualdifferencesoccur in the correlationbetween AEP amplitudesand input intensities(A/I) whichhave been related to individualdifferencesin cognitivestyles.Thiscorrelationhas alsobeen relatedto centralserotoninactivities.Todate,onestudyhasreportedthat unmedicatedPTSDpatientsexhibita predominateof negativeslopesto their AA curves. We compared 11 healthy controls to 10 patients diagnosedwithPTSDwhoweretakingpsychoactivemedications.These wereantidep~sssnts(SSR3:8 patients,TCI:1),benzodiazepines (2),and antipsychoticmedication (l). PTSD patients ako showed expected differenceson standardize rating scalesof mood(PTSDState Anxiety