Psychophysiological Alterations in Posttraumatic Stress Disorder

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Psychophysiological Alteratios i Posttraumatic Stress Disorder Developmet Over Time ad Respose to Treatmet Michael G. Griffi, Ph.D. This work was supported by NIMH grats MH55688 (Griffi) ad MH55542 (Resick) ad NCCAM grat MH55688 (Galovski)

Why Study Biological Chages i PTSD? Normative Stress Respose vs Abormal Stress Respose Objective Idicator of PTSD: Biological Markers Diagosis Differetial Diagosis Treatmet Outcome & Predictors of Tx Outcome Risk Factors for Developmet of Disorder Idetificatio of PTSD Subtypes (e.g., Dissociative?)

Biological Approaches to! the Study of PTSD Psychophysiological Approach Resposes to Trauma-Specific Stimuli (e.g., scripted imagery, lab moologue) Resposes to Itese Neutral Stimuli (e.g. startle / loud toe) Psychoedocrie Approach Respose to Edocrie Challege (e.g., DST)

Trauma Samples Acute Trauma Survivors studied logitudially (1Mo Post ad 6Mo Post) Trauma Cue Reactivity ad Startle/Loud Toe Reactivity Treatmet Outcome Studies CBT with Cogitive Processig Therapy Trauma Cue Reactivity ad Startle/Loud Toe Reactivity

Ehaced Startle i PTSD Previous studies have geerally show that participats with PTSD have a greater magitude startle respose tha those without PTSD. Combat veteras (Butler, et. al., 1990; Grillo et.al., 1996; Morga et. al., 1995a, 1995b; Orr et.al., 1995, 1997) Mixed trauma victims icludig motor vehicle accidets, sexual assault, ad childhood sexual abuse (Shalev et. al., 1992, 1997, 2000; Morga et. al., 1997; Orr et. al., 1999)!

Startle i Combat Vets 2.5 Heart Rate 2 Eye Blik EMG Heartrate Chage (Sq Root) 2 1.5 1 0.5.005 EMG Chage (Sq Root µv) 1.5 1 0.5.02 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Mea Sig 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Mea Sig SCR Chage (Sq Root µs) 1.2 1 0.8 0.6 0.4 0.2 0 1 2 3 4 Ski Coductace 5 6 7 8 9 10 11 12 13 14 15 Mea Startle Stimuli PTSD No PTSD Sig s Data from Orr, et.al., 1995 J. Aborm. Psych.

Startle Reactivity i PTSD There is little iformatio about the developmet of startle followig trauma There is eve less iformatio about how or if startle respodig is modified by treatmet We have examied these questios by assessig psychophysiological startle reactivity i the laboratory

Methods! Auditory Startle Stimuli Stimuli were te 95 db, 1000Hz pure toes preseted for 500ms with early istataeous rise ad fall times Itertrial itervals were radomly varied from 32-52 secods Startle stimuli were preseted biaurally over headphoes

2sec 0.5-6sec 1sec 40-200msec 5sec 0.5-6sec 1 sec Pre-Toe Levels (Average) Toe Oset Post-Toe (Respose) Levels (Max level)

Results! Heart Rate: Startle Reactivity Heartrate Chage (Sq Root) 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 Oe-Moth Post 4.5 4 3.5 3.s. 2.5 2 1.5 1 0.5 0 1 2 3 4 5 6 7 8 9 10 Mea Sig Startle Stimuli Heartrate Chage (Sq Root) Six-Moths Post.05 1 2 3 4 5 6 7 8 9 10 Mea Sig Startle Stimuli PTSD No PTSD PTSD No PTSD

Results! EyeBlik EMG: Startle Reactivity EMG Chage (Sq Root µv) 5.5 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 Oe-Moth Post 5.5 5 4.5 4 3.5 3.s. 2.5 2 1.5 1 0.5 0 1 2 3 4 5 6 7 8 9 10 Mea Sig Startle Stimuli EMG Chage (Sq Root µv) Six-Moths Post.001 1 2 3 4 5 6 7 8 9 10 Mea Sig Startle Stimuli PTSD No PTSD PTSD No PTSD

PTSD Group Respose! x Time Post Assault EMGR (Sq. Rt.) 4 3.5 3 2.5 2 1.5 1 0.5 0 * <10 Days Post > 20 Days Post N=6 N=10 * p<.05

Treatmet Outcome Research Comparisos Pre Posttreatmet Treatmet Respoders vs Treatmet Norespoders

Utility of Biological Measures! i Treatmet Studies Objective idicators of treatmet outcome. Biological markers may be helpful i determiig treatmet strategy. For example, biological measures that ca be assessed withi therapy may allow a evaluatio of exactly where treatmet begis to produce efficacy or relief from PTSD symptoms. Discussio of biological alteratios ca be therapeutic for the cliet. This icludes helpig the cliet uderstad why they are havig symptoms ad ormalizig their reactios. Added beefit of objectively demostratig alteratios i biological variables followig treatmet.

Methods! Cogitive-Behavioral Treatmet for PTSD Data were collected as part of a ogoig treatmet outcome study for rape ad physical assault survivors with PTSD Treatmet Summary: Assist the cliet to cogitively process accurate, emotio-lade memories ad resolve coflicts betwee memories of the evet which caot be avoided Specific modules to help the cliet modify problematic beliefs i areas frequetly affected by victimizatio: safety, trust, power/cotrol, esteem, ad itimacy Exposure compoet i which cliets are ecouraged to activate their memory of the evet ad to experiece their emotios Treatmet duratio was 6-12 weeks

Methods! Data Aalyses Mai Effect Variables: Group: Based upo Treatmet respoders (N=53) (defied as ot meetig CAPS criteria for PTSD diagosis at posttreatmet) vs Treatmet No-respoders (N=21) (defied as cotiuig to meet CAPS criteria for PTSD at posttreatmet) Time: Based upo Pre- vs Posttreatmet assessmet Iteractio Effect: Group x Time

Results! Cliical Fidigs Pretreatmet Posttreatmet p<.001 p<.001

Results! Cliical Fidigs 35 30 Pretreatmet Posttreatmet ** Mea Score 25 20 15 10 ** ** 5 * 0 Reexp Avoid Arous CAPS Startle Reexp Avoid Arous CAPS Startle Respoders No Respoders ** p<.001, * p=.05

Results! Heart Rate: Startle Reactivity Heartrate Chage (Sq Root) 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 Pretreatmet 4.5 4 3.5 3.s. 2.5 2 1.5 1 0.5 0 1 2 3 4 5 6 7 8 9 10 Mea Sig Startle Stimuli Heartrate Chage (Sq Root) Posttreatmet 1 2 3 4 5 6 7 8 9 10 Mea Sig Startle Stimuli * Trt No Respoders Trt Respoders Trt No Respoders Trt Respoders Group x Time Iteractio (F 1, 57 = 9.0, p<.01) Simple Mai Effects: Group Effects: Pretreatmet =.s. Posttreatmet (F 1, 57 = 15.2, p<.001) NR > R Time Effects: Norespoders Pre-Post =.s. Respoders Pre-Post (F 1, 41 = 23.4, p<.001) Pre > Post

Results! EyeBlik EMG: Startle Reactivity EMG Chage (Sq Root µv) 5.5 5 4.5 4 3.5 3 2.5 2 1.5 1 0.5 0 Pretreatmet 5.5 5 4.5 4.s. 3.5 3 2.5 2 1.5 1 0.5 0 1 2 3 4 5 6 7 8 9 10 Mea Sig Startle Stimuli EMG Chage (Sq Root µv) Posttreatmet 1 2 3 4 5 6 7 8 9 10 Mea Sig Startle Stimuli * Trt No Respoders Trt Respoders Trt No Respoders Trt Respoders Group x Time Iteractio (F 1, 59 = 4.5, p<.05) Simple Mai Effects: Group Effects: Pretreatmet =.s. Posttreatmet (F 1, 59 = 9.8, p<.01) NR > R Time Effects: Norespoders Pre-Post =.s. Respoders Pre-Post (F 1, 43 = 12.2, p<.001) Pre > Post

Discussio Fidigs idicate that treatmet respoders showed a sigificatly smaller startle respose to auditory toes after treatmet compared to treatmet o respoders Treatmet o respoders showed o sigificat chage i startle respodig from pre- to posttreatmet

Discussio Previous studies of trauma survivors suggest that heighteed startle reactivity may become a chroic respose Results suggest that startle respose ca be modified with successful treatmet

Psychophysiological Alteratios Followig! Cogitive Processig Therapy with Hyposis Michael G. Griffi, Ph.D. Uiversity of Missouri - St. Louis Departmet of Psychological Scieces & Ceter for Trauma Recovery Tara E. Galovski, Ph.D. Natioal Ceter for PTSD & Bosto VA Medical Ceter & Kimberly B. Werer, Ph.D. Washigto Uiversity i St. Louis Brow School of Social Work This work was supported by NCCAM grat MH55688 (PI- Galovski)

Curret Study Radomized cotrolled trial of Cogitive Processig Therapy (CPT) preceded for 3 weeks by either a hyposis (hyp) compoet or a sleep ad symptom moitorig (ssm) compoet A primary goal was to evaluate if hyposis would be effective to improve sleep difficulties i trauma survivors Additioal goals icluded icorporatig objective physiological assessmets of treatmet outcome

Treatmet Coditios Sleep & Symptom Moitorig (3 weeks) the Cogitive Processig Therapy (ssmcpt) Three weeks of daily moitorig of symptoms of Sleep, PTSD, & Depressio with weekly phoe checks by their therapist Hyposis Traiig (3 weeks) alog with ssm the Cogitive Processig Therapy (hypcpt) Hyposis protocol icluded 3 weekly 60mi sessios targetig sleep issues icludig sleep oset ad mid-sleep awakeig (relaxatio, hypotic trace iductio, guided imagery)

Cogitive Processig Therapy (CPT) CPT was admiistered idividually ad cosisted of 12 weekly, 60-miute sessios (Resick et.al., 2010). CPT is predomiatly a cogitive therapy i which patiets are taught to idetify, questio, challege ad replace faulty assumptios ad thoughts about the traumatic evet. Patiets egage with the traumatic memory ad allow atural affect to ru its course. CPT first targets specific, iaccurate iterpretatios of the trauma itself ad the targets curret ad future maladaptive ad iaccurate beliefs about world, self, ad others.

Methods Iclusio Criteria Female Sexual or Physical Assault PTSD diagosis (CAPS DSM-IV) Cliically sigificat sleep impairmet (severity score 3 or greater o CAPS D1) At least 3Mo post trauma Stable o ay psychotropic meds All study procedures were approved by the Istitutioal Review Board at the Uiversity of Missouri- St. Louis

Measures Cliicia Admiistered PTSD Scale (CAPS DSM-IV; Blake et.al., 1990) Beck Depressio Ivetory (BDI-II; Beck et.al., 1996) Pittsburgh Sleep Quality Idex (PSQI; Buysse et al, 1989) Isomia Severity Idex (ISI; Mori 1993) Script-Drive Imagery Psychophysiology (Lag et.al., 1983)

Participat Demographics Age: 18-70 (M=36.9, SD=11.8) Race: 50% Africa America; 50% White) Marital Status: 54% sigle; 16% married/cohabitig; 30% divorced/ sep/widowed Educatio: M=14.2 years, SD=2.9 years Icome: 74% < 20K

Trauma Characteristics Lifetime edorsemet of child sexual abuse 71%; child physical abuse 58%; adult sexual assault 63%; other adult victimizatio 32%; domestic violece 56% Idex evet for treatmet ad assessmet: 39% Child Sexual Abuse 11% Child Physical Abuse 26% Adult Sexual Assault 24% Adult Physical Assault

Assessmets Coducted at the followig time poits: Pre-treatmet (prior to ay itervetio) Status Check (followig hyp or ssm) Post-treatmet (after CPT) Follow-up (3 moths post) Physio Assessmet Physio Assessmet

Script-Drive Imagery Procedure Baselie Script Imagie Recovery Rest Playback over headphoes Imagie scee as vividly as possible Rest 30 sec Respose scores were calculated: Script Mea Baselie Mea Imagery Mea Baselie Mea * Adapted from Pitma & Orr

Scripts 2 Persoalized Trauma Scripts 2 Neutral Scees (Livig Room & Sittig i a Law Chair) 1 Positive Scee (Beach) 1 Geeric Stressor (Public Speakig)

CAPS Total Score

BDI Score

CAPS Sleep Item

CAPS Nightmares Item

PSQI Sleep Latecy

Cliically Sigificat Chage i Sleep Scores PSQI Total (Decrease > 1SD) ISI Total (Decrease > 8poits)

Trauma Scripts:! HR Chage from Baselie Script Imagery

Trauma Scripts:! SC Chage from Baselie Script Imagery

Public Speakig Script:! HR Chage from Baselie Script Imagery

Law Chair Script:! HR Chage from Baselie Script Imagery

Beach Script:! HR Chage from Baselie Script Imagery

Trauma Scripts! Trt Respoder vs No Respoder (& Dropouts): HR Chage from Baselie Script Imagery

Coclusios Treatmet cliical outcome: Both coditios successfully treated PTSD ad depressive symptoms (depressio better i hypcpt) Sleep impairmets improved more quickly i the hypcpt coditio The ssmcpt coditio did catch up ad show similar sleep improvemets by the follow-up assessmet

Coclusios Treatmet Psychophysiology Outcome No sigificat differeces betwee the treatmet coditios o psychophysiology Treatmet was accompaied by a sigificat reductio i psychophysiological arousal. This was specific to trauma cues This was also specific to successful treatmet (losig a PTSD Dx) Biology ca be altered by successful treatmet

Ackowledgemets Collaborators: Dr Patricia Resick, Ph.D. Dr. Tara Galovski, Ph.D. Dr. Midy Mechaic, Ph.D. Dr. Kimberly Werer, Ph.D. Curret Graduate Studets i my Lab: Brittay Presto, M.A. Rebecca Delgado, M.A. Sydey Harris, B.A.

Participat Flow Chart 56 Symptom Moitorig + Cogitive Processig (ssmcpt) 25 Completers (21 Physio) 23 Drop-outs 8 Removed 25 Completed post-treatmet 23 Lost to post-treatmet 2 Completers 11 Drop-outs 181 Assessed for Eligibility 108 Radomized 62 Ieligible 11 Did ot complete assessmet 52 Hyposis + Cogitive Processig (hypcpt) 26 Completers (21 Physio) 18 Drop-outs 8 Removed 29 Completed post-treatmet 15 Lost to post-treatmet (all drop-outs)

Affect-Startle Effect Startle Magitude 480 460 440 420 400 380 360 340 320 300 Pleasat Neutral Upleasat Data from Vraa, Spece & Lag 1988

Neural Systems Ivolved i Acoustic Startle Respose Vetral Cochlear Nucleus (VCN) Vetral Nucleus of the Lateral Lemiscus (VLL) Nucleus Reticularis Potis Caudalis (RPC) Medial Logitudial Fasciculus (MLF) Spial Cord Muscle Respose