Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder (NATO Security Through Science)

NOVEL APPROACHES TO THE DIAGNOSIS AND TREATMENT OF POSTTRAUMATIC STRESS DISORDER

NATO Security through Science Series This Series presents the results of scientific meetings supported under the NATO Programme for Security through Science (STS). Meetings supported by the NATO STS Programme are in security-related priority areas of Defence Against Terrorism or Countering Other Threats to Security. The types of meeting supported are generally “Advanced Study Institutes” and “Advanced Research Workshops”. The NATO STS Series collects together the results of these meetings. The meetings are co-organized by scientists from NATO countries and scientists from NATO’s “Partner” or “Mediterranean Dialogue” countries. The observations and recommendations made at the meetings, as well as the contents of the volumes in the Series, reflect those of participants and contributors only; they should not necessarily be regarded as reflecting NATO views or policy. Advanced Study Institutes (ASI) are high-level tutorial courses to convey the latest developments in a subject to an advanced-level audience Advanced Research Workshops (ARW) are expert meetings where an intense but informal exchange of views at the frontiers of a subject aims at identifying directions for future action Following a transformation of the programme in 2004 the Series has been re-named and reorganised. Recent volumes on topics not related to security, which result from meetings supported under the programme earlier, may be found in the NATO Science Series. The Series is published by IOS Press, Amsterdam, and Springer Science and Business Media, Dordrecht, in conjunction with the NATO Public Diplomacy Division. Sub-Series A. B. C. D. E.

Chemistry and Biology Physics and Biophysics Environmental Security Information and Communication Security Human and Societal Dynamics

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Sub-Series E: Human and Societal Dynamics – Vol. 6

ISSN: 1574-5597

Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder

Edited by

Michael J. Roy Division of Military Internal Medicine, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

Amsterdam • Berlin • Oxford • Tokyo • Washington, DC Published in cooperation with NATO Public Diplomacy Division

Proceedings of the NATO Advanced Research Workshop on Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder Cavtat, Croatia 13–16 June 2005

© 2006 IOS Press. All rights reserved. No part of this book may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, without prior written permission from the publisher. ISBN 1-58603-590-8 Library of Congress Control Number: 2006920943 Publisher IOS Press Nieuwe Hemweg 6B 1013 BG Amsterdam Netherlands fax: +31 20 687 0019 e-mail: [email protected] Distributor in the UK and Ireland Gazelle Books Falcon House Queen Square Lancaster LA1 1RN United Kingdom fax: +44 1524 63232

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LEGAL NOTICE The publisher is not responsible for the use which might be made of the following information. PRINTED IN THE NETHERLANDS

Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Preface We believe that this Advanced Research Workshop has given participants an opportunity to foster essential international collaborative research on the diagnosis and treatment of posttraumatic stress disorder, a common and disabling consequence of war, terrorism, and natural disasters. As a result, it represents an important piece in efforts to help soldiers and civilians of NATO and partner nations in the face of future international conflicts. This publication contains the full papers corresponding to the relevant presentations provided at the workshop. This text is organized so as to provide a coherent picture of the work and thoughts of participants in the ARW, rather than necessarily following the exact order of the presentations as they were provided in Cavtat, although this summary conveys to the reader the manner in which presentations and working groups were conducted. Appropriate financial support was vital for the successful organization and implementation of the workshop. Grateful acknowledgments for generosity go to the primary sponsor, the NATO Security through Science Programme, as well as to a number of Croatian donors, who recognized the importance of this event. As a token of our appreciation, the logos of all sponsors are included here. The workshop was organized and this accompanying publication was assembled by joint dedication and efforts from the members of Uniformed Services University of the Health Sciences (USUHS), Bethesda, MD, and University of Zagreb, Faculty of Electrical Engineering and Computing (FEEC), Croatia. Professor Michael Roy of USUHS, the NATO-country program co-director and organizing co-director, conceived the overall design of the workshop, and with the assistance of his research assistant Patricia Kraus, wrote and submitted an application to NATO. Dr. Roy selected and invited the majority of the speakers and participants, and he and Ms. Kraus edited each of the chapters incorporated in this publication. Professor Kresimir Cosic, the organizing co-director and a member of FEEC, coordinated financial aspects of the ARW, solicited additional funding from Croatian donors, invited representatives of the Government of Croatia, and promoted the workshop within international politico-military circles. He coordinated coverage of the workshop with Croatian Radiotelevision, and organized meals as well as a boat trip to Dubrovnik for participants. Professor Dragica Kozaric Kovacic, the partner-country program co-director and a member of University Hospital Dubrava in Zagreb, Croatia, extended invitations to several international speakers, further improving the quality of the workshop. Assistant Professor Miroslav Slamic, a member of FEEC, handled accreditations, the purchase of consumable supplies, and designed such items as the workshop poster, program cover, and the appearance of compact disks (CDs) of presentations and pictures for participants. He was also the workshop photographer. Sinisa Popovic, a member of FEEC, was the “glue” that held together the planning and smooth running of the workshop, coordinating travel, lodging and meal arrangements, precise estimation of expenses, assembling of workshop materials, and other arrangements with the conference site. Marko Cosic designed

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the gala dinner menu and coupons, and assisted Mr. Popovic with local arrangements and assembling of workshop materials, handled some on-site financial matters, etc. Workshop CDs were made possible through the joint efforts of Miroslav Slamic, Sinisa Popovic, Marko Cosic, and Patricia Kraus. Dr. Roy also gratefully acknowledges the many hours of assistance Ms. Kraus provided in reviewing the manuscripts for this text.

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Program Co-directors Michael Roy, USA

Dragica Kozaric Kovacic, Croatia

Organizing Co-directors Kresimir Cosic, Croatia

Michael Roy, USA

Speakers Amy Adler, USA Randy Boddam, Canada Tim Brennen, Norway Kresimir Cosic, Croatia Paul Emmelkamp, The Netherlands Elke Geraerts, The Netherlands Jamie Hacker Hughes, UK Louis Jehel, France Tanja Jovanovic, Croatia Ivica Kostovic, Croatia David Lam, USA Nela Pivac, Croatia Ronald Poropatich, USA Barbara Rothbaum, USA Charles van der Mast, The Netherlands Brenda Wiederhold, USA

Mariano Alcaniz, Spain Cristina Botella, Spain Gianluca Castelnuovo, Italy JoAnn Difede, USA Azucena Garcia Palacios, Spain John Gruzelier, UK Neven Henigsberg, Croatia Naomi Josman, Israel Ivica Klapan, Croatia Dragica Kozaric Kovacic, Croatia George Naneishvili, Georgia Sinisa Popovic, Croatia Albert “Skip” Rizzo, USA Michael Roy, USA Zoltan Vekerdi, Hungary Joseph Zohar, Israel

Publicity Michael Roy, USA Dragica Kozaric Kovacic, Croatia

Kresimir Cosic, Croatia

Local Arrangements and Social Events Kresimir Cosic, Croatia Marko Cosic, Croatia

Sinisa Popovic, Croatia

Finances Michael Roy, USA Sinisa Popovic, Croatia

Kresimir Cosic, Croatia Marko Cosic, Croatia

Publication Michael Roy, USA Sinisa Popovic, Croatia

Patricia Kraus, USA Miroslav Slamic, Croatia

Workshop Materials and CDs Miroslav Slamic, Croatia Marko Cosic, Croatia

Sinisa Popovic, Croatia Patricia Kraus, USA

Secretary Sinisa Popovic, Croatia Photographer Miroslav Slamic, Croatia

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Croatian Radiotelevision Reportage Guests Kresimir Cosic, Croatia David Lam, USA Barbara Rothbaum, USA JoAnn Difede, USA Michael J. Roy, USA

Organizers

General Sponsor

Sponsors

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Key Speakers CANADA Randy Boddam Psychiatry and Mental Health, Rm 406, Health Care Centre, 1745 Alta Vista Drive, Ottawa, Ontario, Canada, K1A 0K6 CROATIA Kresimir Cosic University of Zagreb, Faculty of Electrical Engineering and Computing, Unska 3, 10000 Zagreb, Croatia Neven Henigsberg Department of Psychopharmacology, Croatian Institute for Brain Research, Medical School, University of Zagreb, Salata 12, HR-10000, Zagreb, Croatia Tanja Jovanovic Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, 1365 Clifton Road, Atlanta, GA 30322, USA Ivo Klapan Zagreb University School of Medicine, and Croatian Telemedicine Society of the Croatian Medical Association, HR-10000 Zagreb, Croatia Ivica Kostovic Croatian Institute for Brain Research, School of Medicine, Zagreb University Hospital Center Gojka Suska 12, HR-10000 Zagreb, Croatia Dragica Kozaric-Kovacic, MD, PhD University Hospital Dubrava, Department of Psychiatry, Referral Centre for the Stress-Related Disorders of the Ministry of Health of the Republic of Croatia Avenija Gojka Suska 6, 10000 Zagreb, Croatia Nela Pivac Division of Molecular Medicine, Rudjer Boskovic Institute, POBox 180, HR-10002 Zagreb, Croatia Sinisa Popovic University of Zagreb, Faculty of Electrical Engineering and Computing, Unska 3, 10000 Zagreb, Croatia FRANCE Louis Jehel Psychotraumatologiy Unit, Tenon, University Hospital, Ap-HP, Paris France, 4, rue de la Chine75020, Paris, France GEORGIA George Naneishvili M.Asatiani Research Institute of Psychiatry, 10 Asatiani St., Tbilisi 0177, Georgia

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HUNGARY Zoltan Vekerdi Operational Division, Medical Command, Hungarian Defence Forces, 1885 Budapest PO Box 25, Hungary ISRAEL Naomi Josman Department of Occupational therapy, University of Haifa, Mount Carmel, Haifa, 31905 Israel Joseph Zohar Chaim Sheba Medical Center Division of Psychiatry Tel-Hashomer, 52621 Israel ITALY Gianluca Castelnuova Applied Technology for Neuro-Psychology Istituto Auxologico Italiano, Casello Postale 1-2892, Intra (Verbania), Italy NORWAY Tim Brennen Department of Psychology, University of Oslo Box 1094 Blindern, Oslo 0317, Norway SPAIN Mariano Alcaniz Medical Image Computing Laboratory. Technical University of Valencia. Camino vera s/n. 46022 Valencia, Spain Cristina Botella Department of Psychology, Universitat Jaume I, Campus de Riu Sec, Avda. Sos Baynat s/n, 12071 Castellon, Spain Azucena Garcia-Palacios Department of Psychology, Universitat Jaume I, Campus de Riu Sec, Avda. Sos Baynat s/n, 12071 Castellon, Spain THE NETHERLANDS Paul Emmelkamp Department of Clinical Psychology, Roetersstraat 15, 1018 WB Amsterdam, The Netherlands Elke Geraerts Department of Experimental Psychology, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands Charles van der Mast Delft University of Technology, Mekelweg 4, 2628 CD Delft, The Netherlands

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THE UNITED KINGDOM John Gruzelier Division of Neuroscience & Mental Health, Faculty of Medicine, Imperial College room 10 L17 Charing Cross Campus St., Dunstan’s Road, London, W6 8RP, England Jamie Hacker Hughes ACDMH, King’s College London, Weston Education Centre, 10 Cutcombe Road, London, England UNITED STATES Amy Adler US Army Medical Research Unit – Europe Nachrichten Kaserne, Karlsruher str. 144 Heidelberg 69126, Germany JoAnn Difede Department of Psychiatry, Weill Cornell Medical College 525 East 68th Street Box 200, New York, New York 10021, USA David Lam University of Maryland Medical School and U.S. Army Telemedicine and Advanced Technology Research Center PSC 79, BOX 145 APO AE 09714, USA Ronald Poropatich US Army Medical Research & Materiel Command 504 Scott Street Fort Detrick Maryland 21702-5012, USA Albert Skip Rizzo University of Southern California Institute for Creative Technologies 13274 Fiji Way, Marina Del Rey, California 90292, USA Barbara Rothbaum Department of Psychiatry, Emory University School of Medicine, 1365 Clifton Road, Atlanta, Georgia 30322, USA Michael Roy Department of Medicine, Uniformed Services University, 4301 Jones Bridge Road, A3062, Bethesda, Maryland 20814, USA Brenda Wiederhold Interactive Media Institute, 6160 Cornerstone Court East, Suite 161, San Diego, CA 92121, USA

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Participants CROATIA Mirjana Grubisic-Ilic University Hospital Dubrava, Department of Psychiatry, Referral Centre for Stress-related Disorders of the Ministry of Health of the Republic of Croatia Avenija Gojka Suska 6 10 000 Zagreb, Croatia Tihana Jendricko University Hospital Dubrava, Department of Psychiatry, Referral Centre for Stress-related Disorders of the Ministry of Health of the Republic of Croatia Avenija Gojka Suska 6 10 000 Zagreb, Croatia Zeljka Mihajlovic University of Zagreb, Faculty of Electrical Engineering and Computing Department of Electronics, Microelectronics, Computer and Intelligent Systems Unska 3 10000 Zagreb, Croatia Dorotea Muck-Seler Division of Molecular Medicine, Ruđer Bošković Institute, PO Box 180, HR-10002 Zagreb, Croatia Miroslav Slamic University of Zagreb, Faculty of Electrical Engineering and Computing, Unska 3, 10000 Zagreb, Croatia CZECH REPUBLIC Pavel Kral Central Military Hospital Prague U Vojenske nemocnice 1200 169 02, Praha 6 Czech Republic Vlastimil Tichy Central Military Hospital Prague U Vojenske nemocnice 1200 169 02, Praha 6 Czech Republic SLOVENIA Robert Donicar NATO COMEDS WG MP ZDRAVSTVENI CENTER MORS, STULA B.S. 1000 Ljubljana, Slovenia Zdravko Strnisa OPK-H. Bracica 2 2000 Maribor, Slovenia

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UNITED STATES Patricia Kraus Department of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, A3056, Bethesda, Maryland 20814, USA

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder Michael J. ROY, MD, MPH, FACP 1 Director, Division of Military Internal Medicine, Professor of Medicine Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA

Background Terrorist events, natural and man-made disasters, and intra- and international conflicts over the past 10–15 years have led to increased attention to the prevalence and adverse health consequences of posttraumatic stress disorder (PTSD). PTSD has an estimated 2–5% point prevalence and 8–12% lifetime prevalence in the general population, with higher rates in primary care settings, and even more so in combat veterans [1–9]. It is especially common after terrorism and natural disasters: for example, 60% of those who sought care after terrorist sarin release still met PTSD criteria 6 months later [10], as did 41% of victims of a terrorist bombing in a Paris subway [11]. Likewise, 43% of earthquake survivors in Turkey were diagnosed with PTSD [12]. With 24-hour television news coverage, such events impact an entire society; after the terrorist attacks in the U.S. on September 11, 2001, one in six adults nationwide had persistent distress 2 months later, and this was associated with poorer function at work, avoiding public places, greater worries, and greater use of alcohol and drugs. [13–14] Persistent PTSD has in turn been implicated in reduced societal resistance, delayed communal recovery, and lesser income earned by the individuals with PTSD [15–18]. Preventing persistence of PTSD may help to alleviate these symptoms of distress that impact every corner of a society after war, terrorism, or disasters, and should materially increase the speed of societal recovery from these insults. PTSD unfortunately often goes undiagnosed, and available diagnostic instruments tend to be either cumbersome and time-consuming, or insensitive. PTSD is associated with a variety of somatic symptoms, markedly higher rates of depression and other psychological conditions, poorer physical health, missing work, impaired function at work and at home, and significantly higher healthcare costs. [15–18] PTSD is not only associated with significant adverse impact on quality of life, but it has also proven to be relatively persistent, and it has been difficult to produce durable, full responses to therapy. Selective serotonin reuptake inhibitors result in improvement for many individuals, but remission is sometimes only partial, and there is a sizeable percentage of patients who do not respond or do not continue with pharmacotherapy due to side effects. Cognitive behavioral therapy that incorporates imaginal exposure elements has been found to be effective in multiple clinical trials, and recent expert consensus treatment guidelines characterize it as the non-pharmacologic treatment of choice. [19–20] Re1

Corresponding Author: LTC Michael Roy. Uniformed Services University of the Health Sciences, Department of Medicine, 4301 Jones Bridge Road, A3062. Bethesda, Maryland, 20814, USA. Telephone: (301) 295 9601; Fax: (301) 295 3557; Email: [email protected].

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cent technologic advances make it possible for virtual reality (VR) scenarios to be realistic enough to effectively confront individuals with stimuli associated with their traumatic experience through progressively more intense exposure, neutralizing behavioral cues. In recent years, virtual reality technology has been utilized to help patients overcome a variety of phobias, anxiety disorders and PTSD. In uncontrolled studies, small numbers of Vietnam War veterans and World Trade Center survivors with PTSD have each been reported to improve through the use of progressively more realistic and intense virtual reality exposures. Investigators in multiple nations have published case reports, as well as trials comparing therapeutic approaches that incorporate VR with usual care or waiting list controls, describing success with the use of VR to treat a variety of psychiatric disorders. There have not yet been studies that clearly define the added benefit that VR might provide when used in addition to pharmacotherapy or other approaches with demonstrable efficacy but still large numbers who have inadequate or incomplete responses. PTSD was first defined in veterans of the Vietnam War, but the symptoms that constitute this disorder have been reported from many nations through centuries of warfare. PTSD and other psychologic sequelae often persist long after physical wounds have healed, preventing the return of sizeable numbers of military service members to the battlefield, and thus impairing readiness. Moreover, persistent PTSD often evolves into, or is accompanied by, depression and other psychiatric conditions, resulting in lower response rates once treatment is initiated, and consequently greater morbidity. Undiagnosed and/or untreated PTSD impairs the resilience of military service members both while they remain on active duty, and when they return to society at large. In 1998, the annual cost of PTSD and related anxiety disorders was estimated at $63 billion dollars (50 billion Euros), in the United States alone, with PTSD representing the most significant healthcare utilization and work limitations of all the anxiety disorders. [21–22]

1. Cavtat, June 13–16, 2005 In June, 2005, in the town of Cavtat on the Adriatic coast of Croatia, we brought together many of the leading researchers in the use of VR therapy in psychological disorders. The purpose of this NATO-sponsored Advanced Research Workshop (ARW) was to give these groundbreaking researchers an opportunity to share their experiences and expertise, to achieve consensus on the best methods for incorporating VR in the treatment of veterans of war and terrorism, and to foster multinational collaborative studies in this regard. To achieve this, invited experts shared the most salient findings of recent research with which they have been involved. We then divided all workshop participants into working groups to focus on four key elements of the challenges faced in utilizing VR and other new technologies in the treatment of PTSD: • • • •

Diagnostic and epidemiologic concerns with PTSD Technological challenges in the use of VR Integration of cognitive behavioral therapy and virtual reality approaches Outcomes measurement and issues in follow up

Each working group drafted a consensus document, which the group leader then presented to all ARW attendees. Feedback was solicited to ensure a general consensus

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and the working group leaders incorporated this into the documents that comprise the final four chapters of this book. The workshop opened with a welcome from several Croatian hosts, including Dr. Dragica Kozaric-Kovacic, Professor Kresimir Cosic, and Deputy Prime Minister Jadranka Kosor. Among other things, they emphasized the magnitude of the problem that PTSD poses for Croatia. The best estimates are that there are 10,000 Croatian Homeland War veterans with PTSD, another 1500 veterans have committed suicide, and since the war was fought on their own soil, countless civilians also have been traumatized by the war. It is estimated that 15–40% of Croatian Homeland War veterans have PTSD, and that 50–90% of them have comorbid psychiatric conditions such as depression. Deputy Prime Minister Kosor emphasized that it is also well-recognized that many veterans have delayed manifestations of disability, which is why the Croatian Parliament agreed to render compensation available to those veterans displaying effects within 10 years after the end of the war. Dr. John Gruzelier of Imperial College, London, reviewed the significance of theta waves on electro-encephalograms (EEGs), emphasizing their association with survival behavior, memory, and anatomical areas of the brain that are thought to be of particular importance in PTSD, such as the hippocampus. He also noted the significance of theta waves in autobiographical positive memories as well as flashbacks. Later in the first day of the conference, Dr. Kostovic, Director of the Croatian Institute for Brain Research, expanded upon this to detail the central role of the amygdala and limbic system in pathways that are central in PTSD. In addition, Dr. Nela Pivac from the Rudjer Boskovic Insitute in Croatia reviewed work on the neurobiologic basis for PTSD, particularly associated changes in various neurotransmitter levels. Dr. Dragica Kozaric-Kovacic, Professor of Psychiatry, Director of the Referral Center for Stress-Related Disorders at the University of Zagreb School of Medicine, Croatia, documented that up to 40% of Croatian Homeland War veterans with PTSD had psychotic symptoms. These symptoms were quite well-circumscribed, representing hallucinations specifically related to their combat exposure, rather than the more bizarre hallucinations characteristic of schizophrenia. She also noted that Croatian veterans completing the Minnesota Multiphasic Personality Inventory, Version 2 (MMPI-2) had their highest average scores on scale 8, unofficially known as the “schizophrenia” scale. She believes that those with psychotic symptoms represent a more severe form of PTSD, and it is her experience that treatment with antipsychotic medication is beneficial to these individuals. Finally, Dr. Kozaric also emphasized the high rate of comorbid psychiatric conditions, upwards of 60%, in those with PTSD; alcohol abuse was the single most common comorbid condition. Dr. Tim Brennen, professor of psychology at the University of Norway, and Elke Geraerts, a doctoral candidate at the University of Maastricht in the Netherlands, reviewed their work on the cognitive processes underlying PTSD, as well as their efforts to model what occurs cognitively after traumatization. They described some fascinating work on the effects of PTSD on memory, utilizing lists of words that included both trauma-related and unrelated terms, then asking PTSD and control patients what they were able to remember. Dr. Brennen documented that those with PTSD have greater difficulty forgetting words associated with their trauma, even when asked to try to do so. He also reported that combat veterans with PTSD are more likely than controls to think they heard trauma-related words that were not on the list, but there was no difference for unrelated words. Ms. Geraerts reported similar findings with women victims of sexual assault.

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Dr. Ronald Poropatich, Senior Advisor to the Telemedicine and Advanced Technology Research Center at the US Army Medical Research and Materiel Command, and Dr. Ivica Klapan, Professor of Otorhinolaryngology at the University of Zagreb, each discussed various applications of new technologies. Dr. Poropatich delineated the potential use of personal digital assistants, “smart dog tags” and other digital formats for storing and transmitting medical records information. He also displayed the wide range of applications for robotics to decrease the exposure of soldiers—including medical personnel—in far-forward areas of the battlefield, from detecting chemical weapons to performing surgery at distant sites. Since his talk was tangential to the subject of PTSD, Dr. Poropatich’s presentation is not covered in this book. Dr. Klapan discussed the application of three-dimensional modelling to increase the level of information available pre-operatively, improving surgical approaches. Dr. Michael Roy, Professor of Medicine at Uniformed Services University, provided vivid examples of the face of PTSD in primary care, drawing upon patients he has seen over the years at Walter Reed Army Medical Center. He outlined the challenges in faced in making the diagnosis in primary care, from competing demands to stigmatization, while emphasizing that similar issues are relevant to combat veterans. Dr. Roy noted the lack of validated diagnostic tools for PTSD in primary care, and the need to conduct studies to establish effective screening measures. In addition, he outlined plans to use the “Virtual Iraq” environment described later in the meeting by Dr. Rizzo, integrated with a cognitive behavioral therapy approach as described by Dr. Difede, to assess the added benefit of CBT/VR to pharmacotherapy in combat veterans. Provided that commensurate funding is obtained, current plans are for this study to begin in both Washington and Zagreb in late 2005, enrolling Operation Iraqi Freedom veterans in Washington, and Homeland War veterans in Zagreb. Mr. Sinisa Popovic of the University of Zagreb provided a presentation on behalf of collaboration with Drs. Kresimir Cosic and Miroslav Slamic. He focused on efforts to integrate physiologic measures of subjects, as well as Subjective Units of Distress (SUDs) scales, into software programs to facilitate guided progression of VR exposures, easing the pressure on the therapist to do so. Dr. Tanja Jovanovic of the University of Zagreb described psychophysiologic measures that could prove useful in supplementing or corroborating responses to questionnaires in diagnosing PTSD. These include cardiovascular (heart rate, heart rate variability, blood pressure) measures, respiratory rate, electromyography, electroencephalography, and skin conductance. Each measure adds something different in terms of the rapidity, duration, or other characteristics of the response, and they can be used to distinguish those with PTSD, in addition to later value in directing the progression of therapy. Dr. Louis Jehel reviewed the diagnostic instruments available for PTSD. He noted that the established gold standard, the Clinician Administered PTSD Scale (CAPS) is too lengthy and time-consuming to be used as a broad screening measure. An optimal cut-off score that has high sensitivity and specificity has not yet been established for the 17-item PTSD Checklist (PCL). Other available instruments still lack validation and/or have limitations. Dr. Brenda Wiederhold, Director of the Virtual Reality Medical Center in San Diego, California reviewed the track record of success that VR has had in treating anxiety disorders. She emphasized that one particular strength of VR is that it does not depend on patients’ ability to imagine scenarios, instead directly confronting the patient with the environment, which is especially valuable in conditions such as PTSD, where

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avoidance is a primary feature of the disorder. Dr. Wiederhold noted that the incorporation of VR into a CBT approach has been shown to result in 33% faster response rates in the treatment of agoraphobia, for example. She also discussed the use of VR to conduct stress inoculation training (SIT), drawing parallels between SIT and treatment, with the former addressing peak performers while the latter focuses on the impaired. Dr. Azucena Garcia-Palacios of Valencia, Spain, expanded upon the data favoring the use of VR in phobias and related disorders. She emphasized the advantage of being able to provide exposures under controlled circumstances without the risks inherent in actual in vivo exposures. In fact, she reported data demonstrating that 81% of patients preferred VR over in vivo exposures. For social phobia and panic with agoraphobia, the medical literature documents superiority for VR over waiting list controls, and comparability with in vivo exposures. Dr. Garcia-Palacios also described more recent applications of VR in eating disorders, addictions, pathological grief, autism, and ADHD. She was followed by her colleague, Dr. Cristina Botella, who reviewed the experience of VR in the treatment of PTSD. Dr. Botella noted that therapists have historically underutilized the exposure component in the conduct of CBT, with one study indicating that only 17% of therapists were using it. She reviewed the historical precedents for VR, based upon PIE—proximity, immediacy, and expectancy, developed during and subsequent to the two world wars; this policy was based upon the belief that soldiers would have better outcomes with prompt return to combat, the exposure that was responsible for their symptoms. Dr. Botella also described the EMMA project, a computer-based interactive therapy modality that enables the patient to incorporate their own elements into the virtual environment, with both visual and auditory elements. Dr. Giancarlo Castelnuovo of Milan reviewed the experience of the VEPSY Updated project in the treatment of anxiety disorders, obesity and other eating disorders, and male sexual disorders. He reported that more than 50,000 individuals have accessed the open, free virtual environment they made available on the internet, and over 500 patients have been enrolled in certified controlled clinical trials. The VEPSY Updated project has made considerable gains in identifying the most effective treatment model for a variety of psychiatric disorders. Dr. Barbara Rothbaum from Emory University in Atlanta, Georgia emphasized that the problem with PTSD is one of extinction—trauma has an effect on everyone initially, but it wears off over the ensuing weeks for most, while it becomes disabling for those with PTSD. VR for the latter individuals provides the opportunity to relive the trauma under therapeutic circumstances until it is no longer traumatic. Dr. Rothbaum also reported some promising initial results with d-cycloserine in the augmentation of VR. Dr. Joann Difede of Weill Medical College at Cornell University in New York City described her use of CBT/VR with firefighters responding to the World Trade Center site on September 11, 2001. Dr. Difede reported that nearly 10% of firefighters met full criteria for PTSD, with almost 25% having subsyndromal PTSD. She then outlined the novel therapeutic approach that was initially used in those firemen who had difficulty complying with imaginal exposure in the course of CBT. A virtual environment was developed that incorporated computer-generated images of planes hitting the World Trade Centers with actual audio from newscasts from 9/11. After four sessions in which therapists used a CBT approach including psychoeducational efforts and the introduction of ujayi breathing techniques, VR was introduced and used over the course of another half-dozen or more 75-minute sessions. The use of VR in this manner had an impressively large effect size in comparison to waitlist controls.

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Dr. Naomi Josman of the University of Haifa, Israel, reviewed the added value of occupational therapy with virtual reality exposure therapy, with an examination of occupational performance before and after therapy. She also discussed the significance of “presence” as a measure of the investment of the patient in VR. Dr. Skip Rizzo of the Institute for Creative Technology at the University of Southern California reinforced Dr. Wiederhold’s comments regarding the ability of VR to ensure that those with PTSD are confronted with their virtual environment, so that they can not avoid it, as those with this disorder are often inclined to do. He emphasized the need for inter-institutional collaboration, and highlighted a series of additional investigators using VR in the treatment of PTSD, including Beck at the University of Buffalo for survivors of motor vehicle accidents, and researchers in Portugal treating combat veterans of wars in former Portuguese colonies in Africa in the 1970’s. In addition, Dr. Rizzo described the importance of sensory input other than vision in VR, noting the well-delineated importance of auditory input, as well as the added value of vibration through the use of a platform, and more recent work incorporating smells. He also introduced the concept of using exposure to a virtual environment as a screening tool after military deployment, identifying those with strong physiologic responses as individuals who might benefit from intervention.

2. Working Groups These presentations set the stage for the four working groups described earlier. All ARW attendees actively participated in the deliberations of the working groups, which were held for an entire afternoon on the second day of the ARW. Group leader presentations ensued the following morning, with active feedback provided from other ARW participants.

3. Special Presentation The following morning, a special presentation was provided by Dr. Joseph Zohar, a researcher with years of experience in the evaluation of PTSD in Israeli combat veterans, who reviewed the results of a large case-control study in which PTSD patients were compared to matched controls with regard to demographic and pre-draft cognitive and behavioral testing. In general, while some of these measures were successful in predicting whether one might develop schizophrenia, they were not useful predictors of the development of PTSD. However, those who appeared to have less resources, as evidenced by such measures as having less education, more siblings, reservist status, and immigrant status, were more likely to seek help for PTSD symptoms on the battlefront rather than waiting until after deployment. While their overall prognosis did not appear different, this information can prove useful in making appropriate resources available.

4. PTSD and NATO Operations The ARW was closed out by a special session examining PTSD and NATO operations. This was opened by a graphic presentation from Dr. Zoltan Vekerdi of the Hungarian

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Defense Force. Dr. Vekerdi detailed his eye-witness account of “Black Sunday” in Kabul in 2003, when four Germans and 2 Afghans were killed, while another 35 required medical treatment of injuries—the result of the suicide bombing of a German motorcade which had been headed to the airport to depart the country after completing a tour of duty. Dr. Amy Adler, a psychologist with the US Army Medical Research Unit— Europe, described the results of psychological screening of soldiers returning from deployment to Afghanistan and Iraq. Their results indicated that the 4-question screen known as the PC-PTSD performed as well in this population as the 17-item PTSD Checklist for Military Populations (PCL-M). The PC-PTSD was more desirable on the basis of its brevity, and it has been incorporated in a U.S. Department of Defense form that is routinely used to screen soldiers after deployment. Dr. Adler also highlighted data that indicate screening should be done at 3–6 months after deployment since many do not develop symptoms until that point, rather than immediately upon return. Dr. Randy Boddam, Chief of Psychiatry for the Canadian Defence Force, reiterated the importance of screening at the 3–6 month period, noting the “honeymoon” phenomenon that is associated with improved mood and other symptoms upon immediate return home. He also noted the value of taking care of family members, identifying a strong correlation between problems with family members at home and those of deployed soldiers. Dr. Boddam detailed the Canadian approach to the management of operational stress, which makes a significant attempt to be proactive, beginning with the recruitment process, and including an algorithm that addresses diagnosis and treatment. Dr. Jamie Hacker Hughes of Kings College in London described the workings of the NATO Research and Technology Group (RTG)-20. Their objective is to develop guidelines for military leaders on stress and psychological support to enhance effectiveness in modern military operations. They developed a report to describe fundamental areas of agreement between NATO members that addresses pre-, during, and postdeployment periods. Among the items agreed upon are that all military service members are responsible for monitoring their own mental health, and that the mental health of the unit will enhance—or detract from—the ability of the unit to carry out their mission. They are also conducting a survey of military line unit leaders to determine what they perceive their needs to be with regard to mental health support. Dr. David Lam ended the meeting on a positive note by describing NATO’s Security through Science Program, and the variety of potential funding categories available to researchers through this program. Since this information is available on the NATO website, it has not been included in this volume.

5. Summary This was an effective, valuable meeting, enabling many of the leading researchers in the application of VR to the treatment of PTSD to come together to share their experiences and ideas. It will undoubtedly spur greater international collaboration to further improve the diagnosis and treatment of this challenging disorder that continues to afflict more soldiers from NATO member nations on a daily basis. VR has tremendous potential that is only beginning to be realized, and it is critical to maintain international collaboration as valuable research is being conducted at many different sites. The historical response rate of PTSD to conventional therapy is poor enough to warrant the

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earliest application of novel therapies as they are proven to provide added value. Future meetings should build upon the spirit of collaboration that was fostered in Cavtat in order to further improve the health of those who defend our nations’ borders.

References [1] JRT Davidson, D Hughes, D Blazer, LK George. Posttraumatic stress disorder in the community epidemiological study. Psychol Med 21 (1991), 1–19. [2] RC Kessler, A Sonnega, E Bromet, M Hughes, CB Nelson. Posttraumatic Stress Disorder in the National Comorbidity Survey. Arch Gen Psychiatry 52 (1995), 1048–60. [3] HS Resnick, DG Kilpatrick, BS Dansky, BE Saunders, CL Best. Prevalence of civilian trauma and posttraumatic stress disorder in a representative national sample of women. J Consult Clin Psychol 61 (1993), 984–91. [4] MB Stein, JR Walker, AL Hazen, DR Forde. Full and partial posttraumatic stress disorder: findings from a community survey. Am J Psychiatry 154 (1997), 1114–9. [5] AY Samson, S Bensen, A Beck, D Price, C Nimmer. Posttraumatic stress disorder in primary care. J Fam Pract 48 (1999), 222–7. [6] MB Stein, JR McQuaid, P Pedrelli, R Lenox, ME McCahill. Posttraumatic stress disorder in the primary care medical setting. Gen Hosp Psychiatry 22 (2000), 261–9. [7] N Breslau, GC Davis, P Andreski, E Peterson. Traumatic events and posttraumatic stress disorder in an urban population of young adults. Arch Gen Psychiatry 48 (1991) 216–22. [8] N Breslau, R Kessler, RC Chilcoat, LR Schultz, GC Davis, P Andreski. Trauma and posttraumatic disorder in the community: the 1996 Detroit area survey of trauma. Arch Gen Psychiatry 55 (1998), 626–32. [9] JRT Davidson, HM Tharwani, KM Connor. Davidson Trauma Scale (DTS): normative scores in the general population and effect sizes in placebo-controlled SSRI trials. Depress Anxiety 15 (2002), 75–8. [10] S Ohbu, A Yamashina, N Takasu, et al. Sarin poisoning on Tokyo subway. Southern Med J 90 (1997), 587–593. [11] L Jehel, C Duchet, S Paterniti, SM Consoli, JD Guelfi. [Prospective study of posttraumatic stress in victims of terrorist attacks] (French). Encephale 27 (2001), 393–400. [12] M Basoglu, E Salcioglu, M Livanou. Traumatic stress responses in earthquake survivors in Turkey. J Trauma Stress 15 (2002), 269–76. [13] S Galea, J Ahern, H Resnick, D Kilpatrick, M Bucuvalas, J Gold, D Vlahov. Psychologic sequelae of the September 11 terrorist attacks in New York City. N Engl J Med 346 (2002), 982–7. [14] MA Schuster, BD Stein, LH Jaycox, et al. A national survey of stress reactions after the September 11, 2001, terrorist attacks. N Engl J Med 345 (2001), 1507–112. [15] SE Ullman, JM Siegel. Traumatic events and physical health in a community sample. J Trauma Stress 9 (1996), 703–20. [16] Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry 61, Suppl 5 (2000), 4–14. [17] AW Wagner, J Wolfe, A Rotnitsky, SP Proctor, DJ Erickson. An investigation of the impact of posttraumatic stress disorder on physical health. J Traum Stress 2000;13:41–55. [18] EA Walker, W Katon, J Russo, P Ciechanowski, E Newman, AW Wagner. Health care costs associated with posttraumatic stress disorder symptoms among women. Arch Gen Psychiatry 60 (2003), 369–74. [19] EB Foa, JRT Davidson, A Frances, R Ross. Expert consensus treatment guidelines for posttraumatic stress disorder: a guide for patients and families. J clin Psychiatry 60, suppl 16 (1999), 1–8. [20] RJ Ursano, C Bell, S Eth, et al. Practice Guideline for the treatment of patients with acute stress disorder and posttraumatic stress disorder. Am J Psychiatry 161, suppl 11 (2004), 1–57. [21] PE Greenberg, T Sisitsky, RC Kessler, et al. The economic burden of anxiety disorders in the 1990s. J Clin Psychiatry 60 (1999) 427–35. [22] RC Kessler. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry 61, Suppl 5 (2000), 4–14.

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Contents Preface Key Speakers Participants Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder Michael J. Roy

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Section I. Epidemiology and Pathophysiology of PTSD Biological Markers in Croatian War Veterans with Combat Related Posttraumatic Stress Disorder Nela Pivac, Dragica Kozarić-Kovačić and Dorotea Mück-Šeler Theta Synchronisation of Hippocampal and Long Distance Circuitry in the Brain: Implications for EEG-Neurofeedback and Hypnosis in the Treatment of PTSD John Gruzelier

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Limbic Circuitry and Posttraumatic Stress Disorder Ivica Kostović and Miloš Judaš

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Investigating Cognitive Abnormalities in Posttraumatic Stress Disorder Elke Geraerts and Tim Brennen

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Psychotic Features of Combat Related Chronic Posttraumatic Stress Disorder and Antipsychotic Treatment Dragica Kozarić-Kovačić and Nela Pivac

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Section II. Diagnosis and Screening Efforts to Improve the Diagnosis and Treatment of Posttraumatic Stress Disorder Michael J. Roy and Patricia L. Kraus

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Assessment of Available Diagnostic Instruments for Posttraumatic Stress Disorder Louis Jehel and Kathleen Dullea

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Psychological Screening Validation with Soldiers Returning from Combat Paul D. Bliese, Kathleen M. Wright, Amy B. Adler and Jeffrey L. Thomas Psychophysiological Responses to Trauma-Related Stimuli in PTSD: Potential for Scenario Adaptation in VR Exposure Therapy Tanja Jovanović, Sinisa Popović and Dragica Kozarić-Kovačić

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87

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Section III. Management of Posttraumatic Stress Disorder Pharmacotherapy Research in Posttraumatic Stress Disorder Neven Henigsberg Canadian Forces Approach to the Identification and Management of Operational Stress Injuries Randy Boddam “Stress and Psychological Support in Modern Military Operations” NATO Human Factors and Medicine HFM081 Research Task Group RTG020 History, Status, Objectives and Achievements to Date Jamie G.H. Hacker Hughes, Amy Adler, Vlastimil Tichy and Yves Cuvelier

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111

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Section IV. Virtual Reality Therapy in the Treatment of Posttraumatic Stress Disorder and Related Psychiatric Conditions Scenario Self-Adaptation in Virtual Reality Exposure Therapy for Posttraumatic Stress Disorder Sinisa Popovic, Miroslav Slamic and Kresimir Cosic Advanced Technologies in Military Medicine Brenda K. Wiederhold, Alex H. Bullinger and Mark D. Wiederhold Indications Provided by the Eating Disorder Module of the VEPSY Updated Project: Towards a New Generation of Virtual Environments for Clinical Applications Gianluca Castelnuovo, Gianluca Cesa, Andrea Gaggioli, Fabrizia Mantovani, Mauro Manzoni, Enrico Molinari and Giuseppe Riva

135 148

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Treatment of Mental Disorders with Virtual Reality Azucena Garcia-Palacios, Cristina Botella, Hunter Hoffman, Rosa M. Baños, Jorge Osma, Verónica Guillén and Conxa Perpina

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Clinical Issues in the Application of Virtual Reality to Treatment of PTSD Cristina Botella, Soledad Quero, Nuria Lasso de la Vega, Rosa Baños, Verónica Guillén, Azucena García-Palacios and Diana Castilla

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Virtual Reality in the Treatment of Survivors of Terrorism in Israel Naomi Josman, Azucena Garcia-Palacios, Ayelet Reisberg, Eli Somer, Patrice L. (Tamar) Weiss and Hunter Hoffman

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Virtual Vietnam: Virtual Reality Exposure Therapy Barbara Olasov Rothbaum

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Developing a Virtual Reality Treatment Protocol for Posttraumatic Stress Disorder Following the World Trade Center Attack JoAnn Difede, Judith Cukor, Nimali Jayasinghe and Hunter Hoffman

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A Virtual Reality Exposure Therapy Application for Iraq War Military Personnel with Post Traumatic Stress Disorder: From Training to Toy to Treatment Albert Rizzo, Jarrell Pair, Ken Graap, Brian Manson, Peter J. McNerney, Brenda Wiederhold, Mark Wiederhold and James Spira

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Section V. Other Aspects of Military Healthcare Advanced 3D Computer-Assisted Technologies in Improving Patient Telecare Ivica Klapan, Ljubimko Šimičić and Sven Lončarić

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War Related Stress George Naneishvili, Nino Okribelashvili and Ketevan Gigolashvili

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PTSD – Hungarian Lessons Learned in Afghanistan and Iraq Zoltan Vekerdi and Laszlo Schandl

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Section VI. Working Groups Posttraumatic Stress Disorder --- Diagnostic and Epidemiological Concerns G. Naneishvili

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Technological Challenges in the Use of Virtual Reality Exposure Therapy Charles van der Mast, Sinisa Popovic, Dave Lam, Gianluca Castelnuovo, Pavel Kral and Zeljka Mihajlovic

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Novel Approaches for the Integration of Behavioural Therapy and Virtual Reality 296 Mariano R. Alcañiz, Carmen L. Juan, Beatriz S. Rey and José Antonio Q. Lozano Posttraumatic Stress Disorder: Assessment and Follow-Up Paul M.G. Emmelkamp

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Author Index

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Section I Epidemiology and Pathophysiology of PTSD

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Biological Markers in Croatian War Veterans with Combat Related Posttraumatic Stress Disorder Nela PIVAC a,1 , Dragica KOZARIû-KOVAýIû b and Dorotea MÜCK-ŠELER a a,1 Division of Molecular Medicine, Ruÿer Boškoviü Institute, Zagreb, Croatia b Referral Centre for the Stress Related Disorders of the Ministry of Health of the Republic of Croatia, Department of Psychiatry, Dubrava University Hospital, Zagreb, Croatia

Abstract. Posttraumatic stress disorder (PTSD) is a severe psychiatric illness associated with disturbances in diverse neurobiological systems. The evaluation of a variety of biomarkers might facilitate a goal of modern medicine, a proper treatment for an individual patient at a given stage of disease. This is especially important in PTSD, a disorder with a complex clinical picture, diverse symptoms, and frequent comorbidities. Biological markers (platelet serotonin, platelet monoamine oxidase, plasma lipid levels, plasma dopamine beta hydroxylase, plasma cortisol and serum levels of thyroid hormones) were determined, and clinical symptoms were evaluated, in 93 male war veterans with chronic combat related PTSD, using the Clinician Administrated PTSD Scale, Positive and Negative Syndrome Scale, and the Hamilton Rating scales for Depression and Anxiety. Platelet serotonin concentration and plasma dopamine beta hydroxylase activity were similar in PTSD subjects and healthy controls. Platelet monoamine oxidase activity, and plasma/serum levels of total and free triiodothyronine and cortisol were increased in war veterans with PTSD compared to controls, indicating that these biomarkers might be used as the trait markers in PTSD. Since a great proportion of our war veterans with chronic combat related PTSD had a severe form of PTSD, complicated with the presence of psychotic or depressive symptoms, further studies are underway to elucidate the association between biological markers and particular symptoms occurring in PTSD.

Keywords. Combat related Posttraumatic Stress Disorder, War veterans, Blood Platelets, Serotonin, Monoamine Oxidase, Plasma Lipid Levels, Dopamine Beta Hydroxylase, Plasma Cortisol Levels, Free and Total Triiodothyronine

Introduction Posttraumatic stress disorder (PTSD) is a severe psychiatric disorder, classified as an anxiety disorder that occurs in some individuals exposed to a life-threatening traumatic event. PTSD is characterized by specific clusters of symptoms: reexperiencing the 1

Corresponding Author: Nela PIVAC, Division of Molecular Medicine, Rudjer Boškoviü Institute, POBox 180, HR-10002 Zagreb, Croatia, E-mail: [email protected]

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trauma, numbing of responsiveness and avoidance, and hyperarousal. War trauma and combat experience result in a high prevalence of PTSD. The disorder is often chronic, frequently complicated with comorbid psychiatric diagnoses such as major depressive disorder, anxiety, mood and substance use disorders. Socio-cultural but also geographically specific comorbidities have been proposed [1,2]. In extensive studies using an ethnically homogenous population of Croatian war veterans with combatrelated PTSD [3], a high prevalence of comorbid diagnoses were found [4]. The most frequent comorbidities were depression, alcohol and drug abuse, panic disorder and phobia, psychosomatic disorder, psychotic disorders, and dementia [5,6]. Recent studies identified a specific, severe, psychotic subtype of PTSD, unresponsive to antidepressant treatment [5-10]. Biomarkers might be used for preclinical screening, diagnosis, disease staging, and monitoring of treatment, and their utility becomes especially important in PTSD, a disorder with a complex clinical picture, diverse symptoms, and variable course, that is complicated by various comorbidities. Disturbances in multiple neurobiological systems (e.g., GABA, glutamate, noradrenalin, dopamine, serotonin, acetylcholine, opioids, and the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitarythyroid (HPT) axes), are responsible for the diverse clinical symptoms (avoidance, anxiety, flashbacks, nightmares, hyperarousal, numbing, anger, impulsivity, aggression) occurring in PTSD [11-14]. In the studies evaluating biological markers in Croatian war veterans with combat related PTSD, we investigated platelet serotonergic markers, i.e. platelet serotonin (5hydroxytryptamine, 5-HT) concentration [15,16], platelet monoamine oxidase (MAO) activity [16,17], plasma lipid levels [18], plasma dopamine beta hydroxylase (DBH) activity [19], plasma cortisol levels [20], and serum thyroid hormones [21].

1. Materials and methods 1. 1. Participants Ninety three subjects with combat related PTSD participated in the study. All participants were Croatian male war veterans, aged 28-48 years, all Caucasians, who were hospitalized at the Referral Centre for the Stress Related Disorders of the Ministry of Health of the Republic of Croatia, Regional Center for Psychotrauma, in the University Hospital Dubrava, Zagreb, Croatia, from 1999 to 2002. The diagnosis of current and chronic PTSD was conducted according to the Structured Clinical Interview based on DSM-IV(SCID). The subjects were asked to describe their traumatic experiences and were given enough time to talk about these and other psychiatric disturbances. Different clinical symptoms (trauma-related, psychotic, and depressive), occurring in this cadre of war veterans were assessed with the CAPS, the Positive and Negative Syndrome Scale (PANSS), and the Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A). All patients were war veterans who had been on active duty in the Croatian armed forces (range of 1-4 years, most with 3 years of continuous combat experience), had similar social and cultural backgrounds, and the great majority were married. All were screened with a comprehensive multidisciplinary evaluation (conducted by 2 psychiatrists and a psychologist) prior to entry into inpatient treatment. Subjects were excluded from the study if they had a positive family

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history of psychosis, or a history of schizophrenia, schizoaffective disorder or bipolar disorder, a serious concomitant medical condition, a history of seizures or misuse of alcohol or drugs (recent use of any psychotropic drugs within one month of baseline), clinically significant abnormalities in electrocardiogram or laboratory findings, or a serious risk of suicide. Combat-related symptoms included intrusive images of screaming soldiers, fire, bombing, rocketing, etc. Individuals taking cholesterollowering drugs were excluded. The procedures were fully explained and written informed consent was obtained from all patients. The local Ethics committee approved this protocol. The control group consisted of 124 healthy male volunteers, with no personal or family history of psychopathology, and receiving no medical treatment. None of the healthy subjects were receiving psychiatric or related treatment before the samples were selected. Groups were matched on age, gender, smoking, and other socio-demographic characteristics. The control subjects agreed, and provided written informed consent, to participate in the study and to provide a blood sample. 1.2. Biochemical determination A forearm vein was cannulated for blood sampling at 08.00 a.m., after an overnight fasting. Blood samples (8 ml) were drawn in a plastic syringe with 2 ml of acid citrate dextrose anticoagulant. Platelet-rich-plasma (PRP) was obtained by centrifugation (935 x g) for 70 s at room temperature. Platelets were sedimented by further centrifugation of PRP at 10,000 x g for 5 min. The platelet pellet was washed with saline and centrifuged again. Platelet 5-HT concentration was determined by the spectrofluorimetric method, as previously described [15,16,22]. Platelet MAO activity was determined spectrofluorimetrically using kynuramine as a substrate, as previously described [16]. Platelet protein levels were measured by the method of Lowry et al. [23]. Serum lipid levels—total cholesterol, high-density lipoprotein (HDL), and triglycerides (TG) levels—were determined by enzymatic color test, while serum lowdensity lipoprotein (LDL) levels were measured using an enzymatic clearance assay. Serum thyroid hormones: total and free triiodothyronine (T3) levels were assayed using an luminoimmunochemical assay kit (Johnson and Johnson Clinical Diagnostic Products, Amersham, UK). Plasma DBH activity was determined by a photometric assay, using tyramine as a substrate, by the method of Nagatsu and Udenfriend [24]. Cortisol levels were determined using a commercially available radioimmunoassay kit from Diagnostic Products Cooperation, CA, USA. 1.3. Data analysis All data (expressed as mean ± S.D.) were evaluated by one-way analysis of variance (ANOVA), followed by Tukey’s multiple comparison test. The level of significance was p<0.05.

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2. Results The mean scores on the CAPS, PANSS, HAM-D and HAM-A scales are shown in Table 1 for war veterans with combat related PTSD. No significant difference (F=0.704, df=1,165 p>0.05, one way ANOVA) was found between the age of war veterans (39.7 ± 8.5 years) and control subjects (38.4 ± 11.9 years).

Table 1. Mean scores in CAPS, PANSS, HAMD and HAMA scales and subscales in 93 war veterans with chronic combat related PTSD

Measures CAPS total PANSS total PANSS positive PANSS negative PANSS general psychopathology PANSS supplementary items HAMD HAMA

Scores (mean r SD) 81.2 84.3 16.9 12.4 45.8 9.2 21.5 24.4

r r r r r r r r

13.1 20.9 6.5 5.1 9.5 2.4 4.8 6.4

Platelet 5-HT concentration did not differ significantly (F=0.069, df=1,152 p=0.079, one way ANOVA) between war veterans with PTSD and control subjects (Figure 1). Plasma cortisol levels differed significantly between groups (Table 2). Plasma cortisol levels were significantly higher (p<0.05, Tukey’s test) in war veterans with PTSD than in control subjects (Table 2).

Table 2. Plasma cortisol levels in 55 male Croatian war veterans with chronic combat related PTSD and in 42 male control subjects Groups PTSD Control group One-way ANOVA

Plasma cortisol (nmol/) 577.0 r 185.3 465.6 r 204.8* F=7.835; df=1,95; p<0.006

N. Pivac et al. / Biological Markers in Croatian War Veterans with Combat Related PTSD

Figure 1. Platelet 5-HT concentration in war veterans with PTSD and control subjects

Figure 2: Platelet MAO activity in war veterans with PTSD and control subjects

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Platelet MAO activity differed significantly (F=18.903; df=1,208; p<0.001, oneway ANOVA) between war veterans with PTSD and control subjects. The enzyme activity in war veterans with PTSD was significantly (p<0.05, Tukey’s test) higher than MAO activity in platelets of control subjects (Figure 2). There were significant differences in serum total T3 levels (F=6.28; df=1,68; p<0.001, one way ANOVA) and serum free T3 levels (F=2.27; df=1,68; p<0.02, one way ANOVA) between war veterans with combat related PTSD and healthy control subjects. Serum total T3 levels were 32% higher in war veterans with combat related PTSD than in healthy control subjects, while serum free T3 levels were slightly but still significantly increased by 8% in war veterans with combat related PTSD when compared to control subjects. Plasma DBH activity was not significantly (F=0.29; df=1,78; p=0.593, one-way ANOVA) different between war veterans with PTSD and control subjects (Figure 3).

Figure 3. Plasma DBH activity in war veterans with PTSD and control subjects

Plasma lipid levels differed significantly (evaluated by one-way ANOVAs) between war veterans with PTSD and control subjects. War veterans with PTSD had significantly (p<0.05, Tukey’s test) higher serum cholesterol and triglycerides levels, and significantly (p<0.05, Tukey’s test) lower HDL levels than the control group (Table 3). War veterans with PTSD and control subjects had similar values of serum LDL levels (Table 3).

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Table 3. Serum cholesterol, triglycerides, HDL and LDL in 37 Croatian war veterans with chronic combat related PTSD and in 33 control subjects. Groups PTSD Control ANOVA df=1,68

Cholesterol (mmol/L) 5.79 r 1.09 4.96 r 1.06* F=3.22; p<0.001

Triglycerides (mmol/L) 2.48 r 1.18 1.29 r 0.94* F=4.69; p<0.001

HDL (mmol/L) 0.89 r 0.30 1.18 r 0.21* F=4.75; p<0.001

LDL (mmol/L) 3.41 r 0.82 3.21 r 0.88 F=0.98; p>0.10

3. Discussion In PTSD, a disorder with a complex clinical picture, diverse symptoms, and different comorbidities, the evaluation of complex biological signals might be used to improve the characterization of the baseline group characteristics, to predict a suicidal risk, to differentiate particular symptoms or syndromes, and to improve the understanding of the underlying neurobiology of PTSD. The rationale for the use of blood platelets as a limited peripheral model for the central 5-HT synaptosomes lies in the similar pharmacodynamics of 5-HT with central 5-HT neurons [25,26]. Recent reports suggest that platelet 5-HT concentration [27,28], and platelet MAO activity [17,29,30] might serve as biological or trait markers for particular mental disturbances. The hypothesis of a deficit of the serotonergic system in PTSD is based on data showing disturbed 5-HT function in PTSD [14]. Serotonergic alterations might contribute to the cognitive disturbances and deficits in the memory systems occurring in PTSD [14], and platelet 5-HT has been reported to be altered in aggression [25] and impulsivity [31]. In line with previous reports [15,16,32], our data indicate that platelet 5-HT concentration is not altered in war veterans with PTSD. Since biological markers have been proposed to be more closely related to basic psychopathological characteristics, i.e. trait markers [26,31], than to nosological entities (such as PTSD), our data confirm this presumption. This finding supports the hypothesis that platelet 5-HT is more related to particular trait markers, such as aggression [25], impulsivity [31], or to particular symptoms [27,28], suicidal behaviour [26-28], than to state characteristics [26,27]. Platelet MAO shares similar biochemical and pharmacological characteristics, and identical amino acid sequences, with brain MAO-B [33], and was proposed to represent a genetic marker for the size or functional capacity of the central monoamine systems and serotonergic system [28]. We have found increased platelet MAO activity in Croatian war veterans with PTSD, in contrast to previous data [16,17,34]. The discrepancies between studies might be explained by the differences in the time course of PTSD (i.e. acute PTSD in the studies [16,17] vs. chronic PTSD in the present study), and the lack of alcohol comorbidity in the present group when compared to the previous study [34]. Our data, showing increased platelet MAO values in the large numbers of war veterans with combat related PTSD, agree with the altered platelet MAO in different personality and temperamental traits, such as sensation seeking and impulsivity [29,30], and impulse and affect dysregulation [35]. Smoking decreases platelet MAO activity [29,30,36], but after controlling for the effect of smoking, the activity of the enzyme remained elevated (data not shown) in our Croatian war veterans with PTSD.

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The noradrenergic system is hyperactive in PTSD, and increased noradrenergic markers, both in cerebrospinal fluid and in plasma and urine, were observed in PTSD patients [11,14]. Noradrenergic neurons arise from the locus ceruleus and project to diverse structures involved in learning and memory (prefrontal cortex, amygdala and hippocampus), and stress response (hypothalamus). These brain regions modulate stress/fear response and emotional memory [11,14]. DBH is an enzyme that catalyzes the conversion of dopamine to noradrenalin. War veterans with chronic combat related PTSD in our study had similar plasma DBH values as healthy subjects. The lack of changes in plasma DBH in our sample might suggest that plasma DBH is not a suitable biological marker of the altered noradrenergic activity in PTSD, or that DBH is altered only in the psychotic subtype of PTSD, as suggested before [37]. To elucidate this relationship, the studies evaluating the relationship of DBH with psychotic PTSD are underway. The altered plasma levels of cortisol, T3, thyroxin (T4) and thyroid-stimulating hormone (TSH) reflect the dysregulated HPA and/or HPT axis activity in stress-related disorders [11]. The concept of a hyperactive HPT axis, with consequent elevation of total and free T3 in PTSD patients, agrees with our data [21], and confirms the link between stress and clinical hyperthyroidism [11]. Hypersecretion of corticosteroids for prolonged periods can harm cognitive processes that are disturbed in PTSD [14]. Our data [20] show increased plasma cortisol levels in war veterans with combat related PTSD, adding to the contradictory findings regarding the status of basal and stimulated cortisol levels in PTSD patients. Since noradrenergic and HPA systems act synergistically in response to acute or prolonged stressful stimuli, disturbances in noradrenergic and HPA axis systems would elicit a cascade of events and disrupt the regulatory mechanisms modulating response to trauma, and add to the development of PTSD symptoms. In line with the data showing altered plasma lipid levels in PTSD [38], we have shown that war veterans with PTSD have increased levels of serum cholesterol, and triglycerides, decreased levels of HDL [18], and unaltered levels of LDL. Since increased serum cholesterol is a risk factor for cardiovascular disease in PTSD patients, these findings call for dietary modification for war veterans with PTSD. The great proportion of our war veterans with chronic combat related PTSD had a severe form of PTSD, complicated with the presence of psychotic or depressive symptoms. Therefore, further studies are underway to elucidate the association between biological markers and particular symptoms occurring in PTSD, and to facilitate the identification of the specific form or subtype of PTSD, disease staging, and monitoring of treatment. The research of biological markers, which reflect the activity of the central neurotransmitter and/or neuroendocrine systems, should focus on efforts to integrate the data, and to explain the multiple interactions among these neurobiological systems in PTSD, in order to achieve a goal of modern medicine, a tailored pharmacological and non-pharmacological treatment for an individual patient with PTSD at an appropriate point in the course of the disorder.

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[9] [10] [11] [12] [13] [14] [15]

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[27] D. Mück-Šeler, M. Jakovljeviü, N. Pivac, Platelet 5-HT concentrations and suicidal behavior in recurrent major depression, J Affect Disord 39 (1996), 73-80. [28] N. Pivac, D. Mück-Šeler, M. Jakovljeviü, Z. Brzoviü, Hypothalamic-pituitary-adrenal axis function and platelet serotonin concentrations in depressed patients, Psychiatry Res 73 (1997), 123-132. [29] L. Oreland, M. Damberg, J. Hallman, H. Garpenstrand, Smoking only explains part of the associations between platelet monoamine oxidase activity and personality, J Neural Transm - Gen Sect 109 (2002), 963-975. [30] L. Oreland, Platelet monoamine oxidase, personality and alcoholism: The rise, fall and resurrection, NeuroToxicology 25 (2004), 79-89. [31] F. Askenazy, H. Caci, M. Myquel, G. Darcourt, Y. Lecrubier, Relationship between impulsivity and platelet serotonin content in adolescents, Psychiatry Res 94 (2000), 19-28. [32] T.A. Mellman, A.M. Kumar, Platelet serotonin measures in posttraumatic stress disorder, Psychiatry Res 53 (1994), 99-101. [33] T. Coccini, G. Randine, A.F. Castoldi, L. Balloni, P. Baiardi, L. Manzo, Lymphocyte muscarinic receptors and platelet monoamine oxidase-B as biomarkers of CNS function: effects of age and gender in healthy humans, Environ Toxicol Pharmacol 19 (2005), 715-720. [34] J. Davidson, S. Lipper, C.D. Kilts, S. Mahorney, E. Hammett, Platelet MAO activity in posttraumatic stress disorder, Am J Psychiatry 142 (1985), 1341-1343. [35] R.J. Verkes, R.C. Van der Mast, A.J.F.M. Kerkhof, D. Fekkes, M.W. Hengeveld, J.P. Tuyl, G.M.J. Van Kempen, Platelet serotonin, monoamine oxidase activity, and [3H] paroxetine binding related to impulsive suicide attempts and borderline personality disorder, Biol Psychiatry 43 (1998), 740-746. [36] N. Pivac, D. Mück-Šeler, D. Kozariü-Kovaþiü, M. Mustapiü, K. Nenadiü-Šviglin, M. Deželjin, Platelet monoamine oxidase in alcoholism, Psychopharmacology ( 2005) accepted for publication. [37] M.B. Hamner, P.B. Gould, Plasma dopamine beta-hydroxylase ativity in psychotic and non-psychotic post-traumatic stress disorder, Psychiatry Res 77 (1998), 175-181. [38] B.L. Kagan, G. Leskin, B. Haas, J. Wilkins, D. Foy, Elevated lipid levels in Vietnam veterans with chronic posttraumatic stress disorder, Biol Psychiatry 45 (1999), 374-377.

Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Theta Synchronisation of Hippocampal and Long Distance Circuitry in the Brain: Implications for EEG-Neurofeedback and Hypnosis in the Treatment of PTSD John GRUZELIER Ph.D1 Division of Neuroscience & Mental Health, Faculty of Medicine, Imperial College London, UK

Abstract. The significance of the brain’s theta rhythm is considered for its role in synchronising electrical activity in the hippocampus and over widely distributed brain regions, circuitry which is of cardinal importance for post traumatic stress disorder (PTSD). This circuitry is involved in memory retrieval, survival behaviour, navigation including virtual reality tracking, wellbeing, and the integration of emotion and cognition. These processes are all implicated in the cognitive neuroscience of PTSD. Two modalities of treatment are outlined that have been found effective in contributing to the treatment of PTSD - hypnosis and EEG-neurofeedback. Both elevate the brain’s theta rhythm, and both warrant further study in contributing to the treatment of PTSD, and the nascent potential of virtual reality (VR) exposure. E-mail contact: [email protected] Keywords. Theta rhythm, hippocampus, brain circuitry, PTSD, hypnosis, EEGneurofeedback.

1. The Theta Rhythm 1.1. Survival Behaviour and the Hippocampus Theta activity is a brain rhythm that oscillates between 4 and 8 cycles per second and is positioned in the EEG spectrum between the slower delta rhythm and the faster alpha rhythm. In animals it spans a wider band (4 – 12 Hz) and is termed “rhythmic slow activity” (RSA). It has been historically linked with the hippocampus [1] and behaviourally with locomotion and exploratory activity, or a spatial map [2], all categorised as “species-specific survival” behaviour, and thought to be adaptively reprocessed in memory during REM sleep [3,4]. Place cells were first discovered 1

Corresponding author: John GRUZELIER. Division of Neuroscience & Mental Health, Faculty of Medicine, Imperial College Room 10L17, Charing Cross Campus St Dunstan's Road London W6 8RP, England Tel: + 44 20 8846 7246 Fax: + 44 20 8846 1670

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in the hippocampus by Petsche [5], and recently “theta-modulated place-by-direction” cells have been discovered in rodents [6]. Now through intracerebral EEG recording, place cells in epileptic patients have been shown to resonate at theta frequencies in virtual reality studies [7], with theta augmented by active navigation when compared with passive navigation [8]. 1.2. Entrainment of Circuitry for Integrating Cognition and Emotion The hippocampus is involved in circuitry synchronised by the theta rhythm. Non-rhythmic neuronal impulses of brain stem origin, once they have been relayed to the septum, are converted into rhythmic theta bursts and are transmitted to the hippocampus and then to the cortex (and so are detectable by scalp electrodes). These are maintained via feedback loops [3]. Recent research extends the domain to other limbic structures. This includes a recurrent network involving the hippocampus, medial mammilliary bodies, anterior thalamus, post cingulated entorhinal cortex and subiculum, and then back to the hippocampus. There is in addition an ascending modulatory circuit from the supramammillary nucleus of the hypothalamus which contains cells determining the frequency of the theta rhythm. This circuit can act independently of the hippocampus, and via reciprocal connections can modulate the hippocampus, infralimbic cortex and prefrontal cortex [9]. Therefore circuitry is available for the integration of cognition and emotion. This occurs through topographically specific connections from neocortex and ascending connections from the brainstem. 1.3. Long Range, Top-Down Connectivity Theta synchronisation extends beyond this circuitry. It has a fundamental role in all long distance regional connectivity in the brain. Long range connectivity is essential to navigation, the historical signature of theta in animals. Furthermore Bland and Oddie [10] have proposed that theta oscillations coordinate activity in brain regions involved in updating motor plans on the basis of sensory input. In other words theta is the conduit for sensory-motor integration, where afferent sensory input is organised and directed to regions orchestrating a motor plan and allowing for a motivated navigational response. Similarly, during a virtual movement, taxi driver navigational task, theta oscillations were recorded from intra cranial electrodes in epileptic patients [11]; with searching distinguished from goal seeking behaviour by the frequency and distribution of theta. A similar coordinating role for theta is inherent in Miller’s [3] theory of resonant self organising loops that orchestrate representations of the salient memory “context” against which sensory input is compared. Here theta entrainment is seen to strengthen the connection weights of hippocampal-cortical loops phase-locked to the theta rhythm. These loops are widely dispersed to distal parts of the brain. In a landmark study Von Stein et al [12] on the basis of empirical studies proposed an inverse relation between the frequency of the EEG oscillation and the scale and range of functional synchrony. Synchronisation of the fast gamma frequencies involved in perception and encoding, or “bottom up” processing, was local in extent, whereas long range synchronisation, connecting distal parts of the brain was mediated by the slow theta and alpha frequencies involved in internal mental processes such as visual imagery and working-memory. This “top down” processing role of theta has been exemplified by a mental calculation study combining EEG with fMRI [13]. Theta oscillations were associated with the fMRI blood oxygenation signals representing both activation and deactivation. The process of mental calculation disclosed theta synchronisation of a network distributed through frontal, temporal and parietal cortices.

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Therefore, of the waking EEG frequencies, theta has a special role in synchronising the circuitry that is widely distributed in the brain, circuitry especially brought into play by top-down internalised processing. 1.4. Consciousness Theta activity has long been associated with altered states of consciousness, including dreaming, meditation, hypnosis, and hypnogogia - the border between waking and sleeping. Relations between theta and normal consciousness have now been affirmed through studies of working memory, becoming popularised through considerations of theta as the electrical signature of the hippocampus in animals and the role of the hippocampus in encoding and retrieval of episodic memory in man. To mention three studies, Burgess and Gruzelier [14] found that theta power increased with the conscious recognition of words, while Klimesch et al [15] showed that aside from theta accompanying the recognition process itself, during encoding only the words that were later to be recognised were accompanied by increases in theta power. When contrasting reports of remembering when there was a clear conscious recollection, versus reports of knowing without recollection, both were found to be accompanied by increases in theta when compared with “ no awareness” reports, however, these qualitatively different conscious judgements were distinguished by the time course of the increase in theta, occurring later and longer for remembered judgements [16]. A recent meditation study comparing long versus short term meditators practising Sahaja Yoga underscores the fundamental roles of theta not only in meditation, but also in wellbeing, and in top down and long range connectivity [17]. When instructed through internalised attention to meditate to achieve a state of bliss, long term meditators were best distinguished from novices by theta activity in anterior and midline regions. Subjective ratings of bliss also correlated positively with theta activity. The synchronisation of theta disclosed a locus in the left prefrontal region, and from this locus synchronisation was widely distributed, extending to posterior association cortices bilaterally. It is noteworthy that the left prefrontal locus has before been associated with both the expression of positive affect and with internalised attention. 1.5. Summary of the Functional Implications of Theta •

• • • • •

Theta has long been regarded as a signature of hippocampal function, modulating place cells and having associations with comparator memory functions such as orienting and survival behaviour and involving integration of both cognitive and affective contexts. Theta is augmented in conscious memory judgements. Theta is involved in top-down internalised processing exemplified by visual imagery, working memory and meditation. Theta is associated with positive emotion. Theta synchronises hippocampal circuits which organise sensory input and orchestrate a motor plan, and which coordinate cognition and emotion. Theta is involved in long range circuitry in the brain and facilitates connectivity.

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2. Neurophysiology of PTSD There are a number of resonances between the functional significance of theta and contemporary understandings of the neurophysiology of PTSD. 2.1. The Hippocampus Considering first the hippocampus, this has been implicated in PTSD through its role in episodic memory retrieval, as well its susceptibility to stress [18]. A reduction in hippocampal volume has been reported in a majority of studies of PTSD [19]. This may be reversible, for following antidepressant treatment evidence was found of hippocampal neurogenesis and an increase in volume in PTSD, along with alleviation of stress [20]. 2.2. Brain Circuitry Regarding circuitry and connectivity, recall of traumatic events involves neural circuitry involving limbic structures such as the hippocampus, paralimbic structures such as the anterior cingulated and orbitofrontal cortex, as well as prefrontal structures such as the left inferior prefrontal cortex and Broca’s area. Putatively abnormal functional connectivity has been reported in a standard working memory task in a mixed group of PTSD patients [21]. Whereas bilateral parietal areas and the left precentral gyrus were more activated in PTSD than in controls, other areas were less activated and these included the inferior medial frontal lobe, bilateral middle frontal gyri and right inferior temporal gyrus. This was interpreted as reflecting disconnectivity of working memory functional networks in keeping with the patients’ dependence on nonverbal memory. Lannis et al [22] took this hypothesis further by examining the memory circuits involved in the recall of traumatic events which were provoked by scripts and compared with the recall of neutral events. Comparisons were made between trauma patients with PTSD who experienced the recall as flashbacks (flashbacks which were accompanied by raised heart rate), PTSD patients without flashbacks and non-PTSD control patients. In support of dependency on nonverbal episodic memory with PTSD there was a striking laterality effect. Whereas in patient controls a left hemispheric circuit underpinned autobiographical memory retrieval, in both PTSD groups the right hemisphere was activated in line with image-based retrieval. Furthermore in patients with PTSD without flashbacks, interpreted as exhibiting a dissociative response to trauma, circuitry was consistent with the evocation of heightened awareness of bodily sensations [23]. 2.3 Electrophysiology EEG recordings in PTSD are sparse. Considering first the EEG spectrum, Begic and colleagues [24, 25] have conducted two studies with Croatian war veterans, replicating an elevation in fast wave beta activity which was found to be widely distributed. Elevated beta activity is consistent with raised levels of anxiety. Similarly in a study which examined EEG asymmetry in PTSD, right parietal activation was found associated with an anxious arousal syndrome. The right lateralised effect supported the right hemispheric involvement reported in functional imaging studies [22]. Regarding EEG connectivity, Chae et al [26] examined an EEG measure called nonlinear dynamical complexity which has been interpreted as indexing connectivity of neuronal cell assemblies and the integration of sensory input with ongoing neuronal activity [27]. The higher the complexity, the higher the connectivity. Patients had suffered PTSD for an average of 6 years

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due to motor accidents, assault or witnessing trauma, and were medication-free for two weeks. Lower complexity, an index of reduced connectivity, was disclosed in patients in over half of the 16 derivations recorded, and while these included the 4 temporal lobe electrodes the effects were more widely distributed. Similarly, in a conference abstract Leiberg et al [28] report EEG coherence patterns of motor accident survivors recorded while viewing trauma relevant pictures. Reduced coherence (connectivity) was disclosed between temporal, centroparietal and frontal areas. 2.4. Summary of the Neurophysiology of PTSD and Implications for Theta and Hippocampal Circuits. • • • •

Hippocampal processes involved in PTSD include survival behaviour such as conscious retrieval of traumatic episodic memories, the comparator process which underpins orienting/startle and susceptibility to stress, and all involving theta synchronisation. There are abnormalities of circuitry in PTSD widely distributed in the brain and with a limbic locus, in keeping with both abnormal integration and with evidence of reduced complexity (connectivity). In PTSD there is atypical right hemispheric circuitry, in keeping with image-based retrieval which is dissociated from left hemispheric narrative processes, and associated with anxious arousal. In PTSD there is EEG evidence of elevated fast frequency activity and right parietal activity in keeping with an anxious arousal syndrome.

3. Hypnosis and EEG-Neurofeedback Theta Training 3.1. Neurophysiology of Hypnosis EEG studies have consistently associated theta activity with hypnosis [29], perhaps assisted by the mentally relaxing effects of hypnosis [30]. Functional imaging studies show that hypnotizable subjects following hypnosis may alter their perceptual abilities in line with instructions, as would follow from increased cognitive and physiological flexibility and mental efficiency [29, 31]. Neural circuitry is altered and there is evidence of an uncoupling of lateral left frontal functions [31], hypothesized to facilitate the orchestration of behaviour by the therapist [32]. Theoretically hypnosis has obvious affinities with the symptoms of PTSD. In fact trauma may be viewed as an hypnotizing agent, for trauma can trigger responses with hypnotic features such as amnesia, identity distortion, dissociation, numbing, verbal stupor and stupor [33]. Spiegel [34] has articulated three clusters of symptoms of PTSD in parallel with hypnosis as follows: intrusive flashbacks and nightmares with hypnotic absorption; dissociation with hypnotic dissociation; exaggerated response to disturbing stimuli with hypnotic automaticity. Hypnosis can enable the access of these symptoms and facilitate their reprocessing. High hypnotisability has often been found to be a characteristic of patients who suffer from PTSD [35]. 3.1.1. Hypnotherapy and PTSD Hypnosis has been widely used as a treatment for PTSD for over a century [36], but there are few controlled studies or systematic case studies [37]. In a meta analysis of Flammer and Bongartz [38] only one controlled study [39] was cited and this involved a successful brief intervention

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with 52 patients. Since then Bryant et al [40] reported a controlled study with civilian trauma survivors randomly assigned to six sessions of either cognitive-behavioural therapy (CBT) consisting of exposure, cognitive restructuring and anxiety management, to the same CBT package coupled with hypnosis, or to counseling. At 6 month follow-up counseling was less successful than the other approaches, with CBT when combined with hypnosis the more successful in reducing the reexperiencing of symptoms. In a single case study Degun-Mather [41] effectively treated a Korean war veteran who 40 years later presented with depression and was unable to further contain PTSD with dissociative fugues. This will be presented in some detail to provide a flavour of the hypnotic approach. Hers was a multimodal treatment approach designed in three phases. The first stage involved stabilization through education and CBT with hypnosis. The second was grounded in hypnotic reprocessing of traumatic memories through a safe-remembering method and hypnotic dreams, along with cognitive reevaluation of traumatic events to resolve negative affect. The third involved further memory integration aided by dream elaboration with and without hypnosis, and rehabilitation. The hypnotherapy process she conceptualized, after Brende [42], as follows: 1) Stabilizing and grounding the patient through anxiety reduction using ‘special place’ and ‘anchor’ techniques, post hypnotic suggestion, and self-hypnosis training for relaxation and identification of triggers. 2) An uncovering technique facilitating recall of fragmented memories through re evoking the state in which the events occurred, and talking through and integrating fragmented memories into a narrative. 3) Re-associating with dissociated feelings. 4) Client led re-evaluation of traumatic events by utilizing ideomotor responses and at a pace that could rapidly shift to a calmer state facilitating reappraisal. 5) Post-hypnotic dream suggestions and hypnotic dream elaboration with written narratives that the patient experienced with an automatic hypnotic quality. 6) Reintegrating the dissociated psyche using ego-state therapy, and introducing an older self to a younger self both in hypnosis and through posthypnotic suggestion. 3.2. Elevating the Theta/Alpha Ratio Elevating the theta/alpha ratio is a widely used clinical and optimal performance EEGneurofeedback protocol which we have recently validated [43]. It was originally developed to produce an hypnogogic state for the purposes of enhancing creativity when benefits were found in enhanced wellbeing and psychic integration [44]. Subsequently it was effective as one part of a multimodality approach along with temperature biofeedback, visualization, systematic desensitization, rhythmic breathing and autogenic training in the treatment of veterans with alcoholism and alcoholism with depression [45-47], and importantly war veterans with PTSD [48]. The protocol aims to facilitate a rise in levels of theta (4-8 Hz) over alpha (8-12 Hz) in a state of eyes-closed relaxation. Normally on closure of the eyes and onset of relaxation the EEG displays high amplitude rhythmic alpha activity. With further deactivation alpha activity slowly subsides and slower theta activity gradually becomes predominant. The point in time when theta activity supersedes alpha activity, the so-called theta/alpha “crossover”, is commonly associated with loss of consciousness and the onset of early sleep stages. By teaching participants to raise theta over alpha activity while not falling asleep, the alpha/theta protocol aims to produce consciously a state of deep relaxation and deactivation, apparently resembling a meditative state that would normally be unconscious. Until our studies, though widely practiced by EEG-neurofeedback practitioners, this apparently promising approach lacked validation, though an accumulation of results with other EEG protocols in the field of ADHD through small scale controlled studies [49] suggested that therapeutic claims may well be of promise. We first provided evidence of operant control of the

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theta/alpha ratio [50] and demonstrated that this was highly effective in enhancing artistic aspects of music performance in replicable results with conservatory students [51]. This was in comparison with training elevations in the faster oscillations including the 12-14 HZ “SMR” band and the beta 1 band, and in comparison with other approaches including aerobic fitness, mental skills training, the Alexander technique which is universally applied in music conservatories to relieve somatic stress and improve posture, as well as in comparison with standby controls. We went on to demonstrate mood enhancement in socially anxious medical students when compared with a mock feedback control [52], and to extend the music results to ballroom dance performance [53]. The advantages of theta training for the performing arts went beyond anxiety reduction and relaxation training [43, 50, 51]. The order of magnitude of the benefits for theta training were of professional significance, were replicable, and by their nature - the enhancing of artistic aspects of music performance - were consistent with associations between the hypnogogic state and creativity [52]. These effects can best be understood through both the cognitive and affective effects of theta. Cognitive effects are the result of memory enhancement synchronizing properties, and sensory-motor integration via theta’s long range network,, whereas affective influences operate by enhancing well being. 3.3 Summary of the Relevance of Hypnosis and Theta Training for PTSD • • • • • • •

Hypnosis is associated with elevated theta, in keeping with internalized top-down processing including visual imagery and memory retrieval, and deep relaxation. Trauma may trigger responses with hypnotic features and shared processes such as absorption, dissociation and automaticity. Hypnotherapy has been used successfully to treat PTSD alone or as an adjunct to CBT. PTSD patients are characterized by hypnotic susceptibility. Hypnotherapy assists in memory revivification and the integration of fragmented episodic memories, against a background of anxiety reduction, empowerment and psychic integration. Theta training has been found effective in treating PTSD as part of a multimodal programme. Theta training has elevated mood and empowerment.

4. Future Directions This NATO workshop has disclosed that VR holds promise of substituting for, or replacing, in vivo exposure procedures in the CBT treatment of PTSD. As hypnosis has been shown in controlled studies to benefit PTSD, integration with VR would be of interest, as would integration of VR with EEG-neurofeedback training to enhance the theta/alpha ratio, training which has also been found efficacious with PTSD. Other EEG-neurofeedback protocols such as elevation of the 12-14 Hz “sensory motor rhythm” band may also assist with the anxious arousal PTSD syndrome, for this protocol provides mental relaxation [53], a relaxed attentional focus [54, 55], has been efficacious in treating ADHD [49], and has been found to improve verbal working memory [55]. From the evolving neuroscience of PTSD, abnormalities of circuitry have been inferred. Therefore, techniques such as theta training and hypnosis, which through the elevation of theta facilitate the synchrony of long distance connectivity in the brain, are likely to provide a valuable adjunct to CBT approaches. Finally, the advent of wireless bluetooth EEG recording has potential

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in providing important ongoing feedback to help guide the therapist in the choice of VR scenarios and CBT strategies.

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[26] J-H Chae, J Jeong, B.S. Peterson, D-J Kim, W-M Bahk, T-Y Jun, S-Y Kim, K-S Kim, Dimensional complexity of the EEG in patients with posttraumatic stress disorder, Psychiatry Research Neuroimaging 131 (2004), 79-89. [27] G. Tononi, G.M. Edelman, Schizophrenia and the mechanisms of conscious integration, Res. Brain res. Rev 31 (2000), 391-400. [28] S. Leiberg, U. Buhss, S. Rabe, A. Maercker, A. Karl, Altered theta EEG Coherence in subjects with post-traumatic stress disorder (PTSD) indicates diminished stimulus discrimination. Abstracts of the Annual Meeting of the German Society of Psychophysiology, Journal of Psychophysiology 18 (2004), 212-213. [29] H. Crawford, J.H. Gruzelier, A midstream view of the neuropsychophysiology of hypnosis: Recent research and future directions. E. Fromm and M.R. Nash Editors, Guilford Press, New York, 1992. [30] J.D. Williams, J.H. Gruzelier, Differentiation of hypnosis and relaxation by analysis of narrow band theta and alpha frequencies, International Journal of Clinical and Experimental Hypnosis 49(3) (2001), 185-206. [31] T. Egner, G. Jamieson, J.H. Gruzelier, Hypnosis decouples cognitive control from conflict monitoring processes of the frontal lobe.,Neuroreport (2005) in press. [32] J.H. Gruzelier, A working model of the neurophysiology of hypnosis: A review of the evidence, Contemporary Hypnosis 15 (1998), 3-21. [33] E. Vermetten, J.D. Bremner, Functional brain imaging and the induction of traumatic recall: A cross-correlational review between neuroimaging and hypnosis, International Journal of Clinical and Experimental Hypnosis 52(3) (2004), 280-312. [34] D. Spiegel. Hypnosis in the treatment of post-traumatic stress disorder. Casebook of Clinical Hypnosis. American psychological Association, Washington (1996), 99-112. [35] H.E. Hollander, S.S. Bender ECEM (Eye Closure Eye Movements): Integrating aspects of EMDR with hypnosis for treatment of trauma, American Journal of Clinical Hypnosis.44 (2001), 187-201. [36] J.G. Watkins, The psychodynamic treatment of combat neuroses (PTSD) with hypnosis during World War II, International Journal of Clinical and Experimental Hypnosis 48(3) (2000), 324-335. [37] E. Cardena, Hypnosis in the treatment of trauma: a promising, but not fully supported, efficacious intervention, International Journal of Clinical and Experimental Hypnosis 48(2) (2000), 225-238. [38] E. Flammer and W. Bongartz, On the efficacy of hypnosis: a meta-analytic study, Contemporary Hypnosis 20 (2003),179-197. [39] D. Brom, R.J. Kleber, P. B. Defares, Brief psychotherapy for post-traumatic stress disorders, Journal of Consulting and Clinical Psychology 57(5) (1989), 607-612. [40] R.A. Bryant, M.L. Moulds, R.M. Guthrie, R.D.V. Nixon, The additive benefit of hypnosis and cognitive-behavioral therapy in treating acute stress disorder, Journal of Consulting and Clinical Psychology 73(2) (2005), 334-340. [41] M. Degun-Mather, The value of hypnosis in the treatment of chronic PTSD with dissociative fugues in a war veteran, Contemporary Hypnosis 18 (2001), 4-13. [42] J.O. Brende, The use of Hypnosis in Post-traumatic conditions. Post-traumatic Stress Disorder and the War Veteran, W.E. Kelly Editor, Brunner/Mazel, 1985. [43] J.H. Gruzelier, T. Egner, Critical validation studies of neurofeedback., Child and Adolescent Psychiatr Clinics of North America 14 (2005), 83-104. [44] T.H. Budzynski, J.M. Stoyva. Biofeedback techniques in behavior therapy. In D. Shapiro, T. X. Barber, L. V. DiCara, J. Kamiya, N. B. Miller, & J. M. Stoyva Editors, Biofeedback and Self-Control (437-459), Aldine, Chicago (1972). [45] E.G. Peniston, P.J. Kulkosky, Alpha-theta brainwave training and beta endorphin levels in alcoholics, Alcoholism: Clinical and Experimental Results 13 (1989), 271-279. [46] E.G. Peniston, P.J. Kulkosky, Alcoholic personality and alpha-theta brainwave training, Medical Psychotherapy 3 (1990), 37-55. [47] E. Saxby, E.G. Peniston, Alpha-theta brainwave neurofeedback training: An effective treatment for male and female alcoholics with depressive symptoms, Journal of Clinical Psychology 51 (1995), 685-693. [48] E.G. Peniston, P.J. Kulkosky, Alpha-theta brainwave neurofeedback for Vietnam veterans with combat-related posttraumatic stress disorder, Medical Psychotherapy 4 (1991), 47-60.[49] D. Vernon, T. Egner, N. Cooper, T Compton, C. Neilands, A. Sheri, J.H. Gruzelier, The effect of training distinct neurofeedback protocols on aspects of cognitive performance, International Journal of Psychophysiology 47 (2003), 75-85. [50] T. Egner, E. Strawson, J.H. Gruzelier, EEG signature and phenomenology of alpha/theta neurofeedback training versus mock feedback, Applied Psychophysiology and Biofeedback 27 (2002), 261-270. [51] T. Egner, J.H. Gruzelier, Ecological validity of neurofeedback: Modulation of slow wave EEG enhances musical performance, NeuroReport 14(2003), 1221-1224. [52] J. Raymond, C. Varney, J.H. Gruzelier, The effects of alpha/theta neurofeedback on personality and mood, Cognitive Brain Research 23 (2005), 287-292. [53] J. Raymond, I. Sajid, L.A. Parkinson, J.H. Gruzelier, Biofeedback and dance performance: A preliminary investigation, Applied Psychophysiology and Biofeedback 30 (2005), 65-73. [54] A. Koestler, The Act of Creation, Penguin, London, 1989.

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[55] J.Edge, L.Lancaster, Phenomenological analysis of superior musical performance facilitated by neurofeedback: Enhancing musical performance through neurofeedback: playing the tune of life, Transpersonal Psychology Review 82) (2004) in press. [56] T. Egner, J.H. Gruzelier, Learned self-regulation of EEG frequency components affects attention and event-related brain potentials in humans, NeuroReport 12 (2001), 4155-4159.[57] T.Egner, J.H. Gruzelier, EEG Biofeedback of low beta band components: Frequency-specific effects on variables of attention and event-related brain potentials, Clinical Neurophysiolog, 115 (2004a), 131-139. [58] D. Vernon, T. Egner, N. Cooper, T. Compton, C. Neilands, A. Sheri, J.H. Gruzelier, The effect of training distinct neurofeedback protocols on aspects of cognitive performance, International Journal of Psychophysiology 47 (2003), 75-85.

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Limbic Circuitry and Posttraumatic Stress Disorder Ivica KOSTOVIû 1 and Miloš JUDAŠ, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, Croatia

Abstract: The objective of this review is to outline problems which should be considered in trying to define PTSD as neurobiological disorder with abnormal neuronal circuitry. The amygdala is the central neuronal structure for expression of fear memory and fear conditioning (emotional function). Due to the prominent connections with the cingulate and prefrontal cortex and hypothalamus, the amygdala can be considered as a part of the limbic circuitry. For regulation of contextual stimulus (cognitive function), the amygdala interacts with the memory circuit of the hippocampal cortex. Limbic circuitry, which incorporates structures of the great limbic lobe, prefrontal cortex and cingulate cortex, conveys impulses to the hypothalamus, which is the main executive structure for the interaction with endocrine pituitary and brainstem tegmental autonomic and transmitter (neuromodulatory) functions. Human stressrelated changes of emotional functions show specificities related to phylogenetic specialization of the human cortex and developmental differences related to the prolonged developmental vulnerability throughout childhood and adolescence. Keywords: amygdala, limbic system, stress, emotional brain

1. The Limbic Lobe and Limbic «System»

Recent scientific studies provide evidence that PTSD is a brain disorder with biological underpinnings [1,2]. For contemporary neuroscience it is a challenging task to disclose the psychobiological mechanisms of PTSD. The crucial question is to determine abnormalities of neuronal circuitry which underlie the cascade of biological and psychological responses following the activation of fear-related neuronal systems. Functional and structural changes in the so-called «limbic» circuitry and limbic structures are frequently associated with PTSD. Although many researchers suggest the rather poorly defined term and concept of limbic circuitry should be abandoned from use [3], the concept of the limbic system is still 1 Corresponding Author: Ivica Kostovic. School of Medicine, Zagreb University Hospital Center Gojka Šuška 12, HR-10000 Zagreb, Croatia

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frequently used in the current literature, and the term «limbic» is often associated with the «emotional» brain. We believe that the topographical and structural characteristics of the so-called limbic structures, as well as their predominant connections, justify the use of the term «limbic» in certain well-defined contexts. The following arguments can be used in support of this approach: The limbic structures form the great limbic lobe of Broca, in a topographically specific manner (limbus means margin) closely associated with two subcortical structures – the amygdala and the septum. The limbic cortices such as the hippocampus and anterior cingulate cortex, together with subcortical structures such as the amygdala, are frequently altered in individuals with PTSD. The amygdala, which is responsible for fear reactions [4,5,2,3], is closely associated with two regions, namely the frontal cortex and hypothalamus, which were included in the limbic system according to the concept presented by Nauta [6]. The hypothalamus, extensively connected to the limbic cortical and subcortical structures, can be considered as the executive part of the limbic circuitry, receiving input from the hippocampus, amygdala and frontal lobe, and conveying impulses to the periaqueductal gray (part of the limbic midbrain area) and the pituitary gland. Through the hypothalamus, limbic structures can regulate autonomic and endocrine responses following stress. For a long time, limbic emotional functions were considered to be separate from cognitive-memory functions. Today we know that contextual stimulus (cognitive function) and fear conditioning (emotional function) form the so-called contextual fear conditioning, and require both the amygdala and hippocampus [3]. Thus, through fear conditioning, emotional and cognitive function of limbic structures in the primate brain work together and their function seems to be disturbed in PTSD.

2. Abnormalities Of Neuronal Circuitry in Ptsd At the moment, the exact abnormalities of the neuronal circuitry underlying PTSD are not known. The significant changes observed in PTSD patients in the anterior cingulate cortex and hippocampus with neuroimaging techniques does not necessarily mean causal relationship. Thus, it is not known whether these are just consequences of abnormal brain function at the level of different chemical-transmitter pathways throughout the prolonged period. The chemically identified transmitter pathways which innervate the limbic cortex (Figure 1) and subcortical structures (frontal cortex, anterior cingulate cortex, amygdala) are affected in different mental disorders and are not specific for PTSD. Dopaminergic, serotonergic, noradrenergic and cholinergic pathways which modulate emotional behavior and cognitive functions were reported to be affected in PTSD [2] but also in other mental disorders.

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An additional problem in the analysis of transmitter systems is that certain transmitters may display different levels and regulation acutely after exposure to stress than they do later when PTSD develops. Therefore, it is better to analyze transmitter dysregulation.

Figure 1. The midbrain limbic area is the source of noradrenergic (shown) and dopaminergic-serotonergiccholinergic (not shown) pathways which innervate the limbic cortex and the amygdala.

Another problem in the interpretation of transmitter changes in the neuronal circuitry are interindividual (probably at least partly genome-based) differences in response to stress. Sex and gender differences in organization of emotional circuitry are probably an additional confounding factor influencing abnormalities of transmitters in PTSD. For example, it was recently reported [7] that the activity of the amygdala on the left side of the brain relates to memory for emotional material in women. In men, however, memory for the same emotional material relates to the activity of the amygdala on the right side of the brain. Furthermore, women activate a smaller network involving the left amygdala, but demonstrate greater overlap between brain areas involved in ongoing emotional processing and memory, which might explain why women tend to have stronger emotional memories than men.

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Figure 2. Papez's circuit connects the limbic cortex of the hippocampus and the cingulate gyrus with the hypothalamus and thalamus.

3. Limbic Circuitry One of the most famous limbic circuits is Papez's circuit, initially described in 1937 as a hypothetical circuit for emotional functions. At the time, it was unclear where emotional reactions were integrated, but Papez selected the great limbic lobe of Broca as the most likely candidate structure for those functions. Subsequent intensive studies of visceral and emotional brain regions [8] in fact confirmed that some components of Papez' circuit are involved in different aspects of emotional behavior, namely autonomic, motor and hormonal responses. Papez' circuit (Figure 2) connects the hippocampus, its prominent projections to the hypothalamus (mammillary body), the «limbic» anterior thalamic nucleus, and the cingular frontal cortex which projects along the cingulum bundle to the entorhinal area, which sends short perforant and alveolar pathways back to the hippocampus. One portion of that circuit, which connects the hippocampus, is today known as the memory circuit.

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Figure 3. Topographical position and connections of amygdala. Note the afferent connections from the auditory cortex and efferent connections to the hypothalamus (stria terminalis) and cortex.

Subsequent findings on the connectivity of the limbic cortex and associated subcortical nuclei (amygdala, septum) have enlarged the extent of limbic circuitry. Thanks to modern tracing techniques, it was shown that most of the pathways streaming to the limbic cortex and out of the limbic cortex pass through the lateral hypothalamus (i.e. medial forebrain bundle), and connect the midbrain tegmentum which is rich in dopaminergic, cholinergic, noradrenergic, and serotonergic nuclei projecting to the limbic cortex through the lateral hypothalamus. In addition, it has been shown that the prefrontal cortex also projects to the hypothalamus and receives various limbic projections. The projections of the orbitofrontal cortex to the amygdala and hypothalamus represent an additional reason why the orbitofrontal cortex was considered to be important for different aspects of emotional behavior. Altogether, limbic circuitry involves classical limbic structures, the hypothalamus, and prefrontal and cingulate cortices. Through the hypothalamus, all endocrine functions of the hypophysis can be controlled; the projection to periaqueductal gray matter provides control of autonomic functions, while the presence of steroid receptors provides feedback mechanisms for the effects of adrenal and steroid hormones.

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Figure 4. Schematic representation of connections between the cortex, amygdala and hypothalamus. Note the central position of the amygdala and key executive position of the hypothalamus.

4. The Amygdala The amygdala is definitively a central structure in the regulation of expression of fear memory (Figure 3). In order to provide this function, especially fear conditioning, the amygdala receives massive projections from sensory cortices (Figure 4). The afferent projections required for auditory provoked conditioning originate from primary and

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associative auditory cortex, but there is also input from the medial geniculate nucleus [3,9]. For the processing of visually conditioned stimuli and the well-known function of the amygdala in negative emotions related to the recognition of faces [4,5], more complex cortical processing is needed between primary and associative visual areas of the occipitotemporal lobe. These sensory driven inputs terminate in the lateral nucleus of the amygdala. From the lateral nucleus, there are extremely elaborate intra-amygdaloid connections [9,3,10,11] to the central nucleus of the amygdala (Figure 4). In order to convey amygdala output, several crucial pathways exist which can explain different functions of amygdala. Brainstem projections to the periaqueductal gray matter are involved in autonomic expression of fear responses, with participation from the lateral hypothalamus. For neuroendocrine control, there are well defined projections through the bundle known as stria terminalis, which terminates in the hypothalamic nucleus, the socalled bed nucleus of the stria terminalis. The stria terminalis is also known as the neuroendocrine pathway of the amygdala. These projections are also crucial for control of pituitary functions. However, the most massive projection is the amygdalofugal pathway to orbitofrontal and medial frontal cortex, essential for interactions of fear memory and working memory.

5. Phylogenetic Specializations of The Limbic Circuitry in The Human Brain In considering experimental data on stress-related changes of brain function, one must consider that human limbic circuitry is composed of a number of phylogenetically specialized areas. First of all, the prefrontal cortex which is the granular cortex, is the most developed part of the cortex in the human brain, which has a greater number of processing modules and greater diversity of inputs than in other anthropoid apes. The anterior cingulate area, which represents the anterior attention system of the brain, believed to have a central role in PTSD, contains special corkscrew giant neurons [11] which are not found in monkeys. It has been demonstrated that the anterior cingulate cortex contains spindleshaped corkscrew cells which can be activated during emotional tasks and the entire area containing these cells can be called an affective division of the cingulate cortex [11].

6. Developmental Differences in Response of Limbic Circuitry Many PTSD investigators note that there are many differences in frequency, presentation and response to stressors between children, adolescents and adults. In addition, it is clear that persons who were abused in childhood more frequently develop PTSD after traumatic events [2]. From a neurobiological point of view, this is expected. First of all, all transmitters involved in the innervation of limbic areas—and known to change in PTSD— show significant developmental shifts. The most notable is the development of dopaminergic innervation in the frontal cortex [12]. Second, it is known that pyramidal

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neurons of the frontal cortex mature relatively late [13] and that synaptogenesis in the limbic cortex shows significant changes throughout childhood and adolescence [14]. During the early postnatal months, there is a significant reorganization of cortical pathways [15], which implies significant plasticity of the developing brain. This is evidence that limbic circuitry is different in children in comparison to adults, in terms of the number of synapses, the position of growing axons, the presence of trophic factors, and maturation of pyramidal and nonpyramidal neurons.

References [1] [2] [3] [4] [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15]

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Yehuda R (2000) Biology of posttraumatic stress disorder. J Clin Psychiatry 61(suppl 7):14-21. Vermetten E, Bremner JD (2002) Circuits and systems in stress. II. Applications to neurobiology and treatment in posttraumatic stress disorder. Depression & Anxiety 16:14-38. LeDoux JE (2000) Emotion circuits in the brain. Annu Rev Neurosci 23:155-184. Adolphs R, Tranel D, Damasio H, Damasio AR (1995) Fear and the human amygdala. J Neurosci 15(9):5879-5891. Damasio AR (1998) Emotion in the perspective of an integrated nervous system. Brain Res Rev 26:83-86. Nauta WJH (1979) Expanding borders of the limbic system concept. In: Functional Neurosurgery, ed. T Rasmussen, R Marino, pp. 7-23. New York: Raven. MacDonald A (2003) Mars and Venus? BrainWork – The Neuroscience Newsletter (September-October 2003), pp. 2-3. MacLean PD (1949) Psychosomatic disease and the «visceral brain»: recent developments bearing on the Papez theory of emotion. Psychosom Med 11:338-353. McDonald AJ (1998) Cortical pathways to the mammalian amygdala. Prog Neurobiol 55:257-332. Pitkänen A, Savander V, LeDoux JL (1997) Organization of intra-amygdaloid circuitries: an emerging framework for understanding functions of the amygdala. Trends Neurosci 20:517-523. Zald DH (2003) The human amygdala and the emotional evaluation of sensory stimuli. Brain Res Rev 41:88-123. Cassell MD, Freedman LL, Shi C (1999) The intrinsic organization of the central extended amygdala. Ann NY Acad Sci 877:217-241. Allman J, Hakeem A, Watson K (2002) Two phylogenetic specializations in the human brain. The Neuroscientist 8(4):335-346. Goldman-Rakic PS, Lidow MS, Smiley JF, Williams MS (1992) The anatomy of dopamine in monkey and human prefrontal cortex. J Neural Transm (Suppl) 36:163-177. Kostoviü I, Škaviü J, Strinoviü D (1988) Acetylcholinesterase in the human frontal associative cortex during the period of cognitive development: early laminar shifts and late innervation of pyramidal neurons. Neurosci Lett 90:107-112. Granger B, Tekaia F, Le Sourd AM, Rakic P, Bourgeois JP (1995) Tempo of neurogenesis and synaptogenesis in the primate cingulate mesocortex: comparison with the neocortex. J Comp Neurol 360(2):363-376. Kostoviü I (1990) Structural and histochemical reorganization of the human prefrontal cortex during perinatal and postnatal life. Prog Brain Res 85:131-147.

Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Investigating Cognitive Abnormalities in Posttraumatic Stress Disorder a

Elke GERAERTS a, 1 and Tim BRENNEN b Department of Experimental Psychology, Maastricht University, The Netherlands b Department of Psychology, University of Oslo, Norway

Abstract. Over the past decade, researchers have increasingly drawn upon concepts and methods developed in cognitive psychology to reveal cognitive processes underlying symptoms of Posttraumatic Stress Disorder (PTSD). These studies have shown that individuals with PTSD display difficulties retrieving specific autobiographical memories in response to cue words, instead recalling overgeneral memories. Moreover, they exhibit difficulty forgetting trauma-related words during directed forgetting, and exhibit enhanced false memory effects for trauma-related material. Such findings suggest that experimental methods can supplement conventional self-report inventories to elucidate cognitive abnormalities underlying PTSD symptomatology. However, to reach a better understanding of the phenomenon, one should also take symptom overreporting into account.

Keywords. Posttraumatic Stress Disorder, cognitive processes, false memories, malingering

Introduction Some people who are exposed to terrible events persist in reexperiencing these events in flashbacks, nightmares, and intrusive recollections, often qualifying for a diagnosis of Posttraumatic Stress Disorder (PTSD). Other people exposed to equally shocking events 1 Corresponding Author: Elke Geraerts, Department of Experimental Psychology, Maastricht University, PO Box 616, 6200 MD, Maastricht, The Netherlands. Tel.: +31-433882468; fax: +31433884196. E-mail: [email protected].

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only show this distress for a short period of time, after which they recall these experiences in a relatively normal manner. This diversity in response to trauma entails that people differ in the way they process these incidents. The continuing involuntary and intrusive cognitive phenomena imply dysfunctions in the mechanisms of memory. Indeed, among the anxiety syndromes, PTSD is the one that can most correctly be characterised as a disorder of memory [1]. That is why, during the last decade, researchers have begun to employ paradigms of cognitive psychology to characterise mental abnormalities in PTSD patients. Besides this line of research, increasingly sophisticated theories have been developed that endeavored to keep pace with new findings while at the same time remaining anchored in basic psychological research [2]. The aim of this chapter is to describe how cognitive processes underlying PTSD symptoms can be revealed, by providing a review of prior research and focusing on recently conducted studies with survivors of war and childhood sexual abuse. Finally, we will discuss topics related to the overreporting of PTSD symptoms.

1. Prior Research 1.1. PTSD and Autobiographical Memory Since it has recently been argued that PTSD can be seen as a disorder of memory, several studies have explored the connection between PTSD symptoms and memory processes. For instance, a series of studies has shown a connection between overgeneral memory and PTSD [3-4]. In one study, Vietnam combat veterans with PTSD, relative to healthy combat veterans, had difficulty recalling specific personal memories in response to cue words with either a positive (e.g., kindness), negative (e.g., panic) or neutral (e.g., appearance) meaning [3]. Despite having been trained to retrieve specific autobiographical memories, PTSD participants tended to slide back into an overgeneral retrieval style during the experiment. Patients with PTSD who had been emotionally primed by viewing a combat-related videotape, had more difficulties accessing specific memories than those who had viewed a videotape related to a neutral theme (i.e., furniture). In a further study [4], Vietnam combat veterans with and without PTSD were asked to retrieve specific personal memories illustrating traits indicated by positive (e.g., loyal) and negative (e.g., guilty) cue words. Veterans with PTSD, relative to healthy veterans, exhibited difficulties retrieving specific autobiographical memories, especially in response to positive cue words. That is, while PTSD patients showed equivalent rates of specific memory retrieval for positive and negative cues, healthy veterans found it easier to think of episodes when they had exhibited positive traits than when they had exhibited negative traits. 1.2. PTSD and Directed Forgetting

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Besides research concerning autobiographical memory, cognitive psychologists have tested controversial hypotheses by using traumatised populations. Some authors state that certain experiences may be so traumatic that victims deal with them in an avoidant-dissociative way [5]. For instance, this style would enable survivors of childhood sexual abuse (CSA) to disengage attention from threatening stimuli and would result in impoverished, i.e. repressed or dissociated, autobiographical memories of traumatic events [6]. Although possibly adaptive under the circumstances of chronic abuse, this encoding style presumably puts people at risk for developing subsequent psychiatric problems. McNally and colleagues [7] reasoned that a particular variant of directed forgetting paradigm would be well-suited to testing whether psychiatrically impaired adults with histories of childhood sexual abuse are indeed characterised by an avoidant encoding style. In an item-specific directed forgetting paradigm, participants are presented with words one at a time. Immediately after each word appeared, participants are instructed either to remember or to forget that particular word. After this encoding phase, memory for both the to-be-remembered (TBR) and the to-be-forgotten (TBF) words is tested, and the standard result in this paradigm is that when participants are given a surprise recall of the entire set of stimuli, they recall fewer TBF words than TBR words [8]. The key mechanism behind this directed forgetting effect is presumed to be encoding activities, because better recall of TBR words can be explained by the fact that participants terminate encoding and rehearsal processes as soon as the forget instruction follows a TBF word [9]. Accordingly, if psychiatrically impaired survivors of childhood sexual abuse develop an ability to avoid encoding trauma-related material, they should show memory deficits for trauma-related TBR words relative to neutral and positive TBR words. Put another way, for such a group, directed forgetting ought to be observed only for neutral (e.g., mailbox) and positive (e.g., celebrate) material but not for trauma-related material (e.g., incest). McNally et al. tested this with three groups of participants: The first group comprised women reporting histories of childhood sexual abuse and who were diagnosed with PTSD; the second group comprised women with similar abuse histories but no PTSD. Finally, the third group included women without abuse histories and without PTSD. Contrary to the avoidant encoding hypothesis, participants with PTSD only displayed overall memory deficits compared to the other groups for neutral and positive words, which they were supposed to remember equally well. Additionally, they remembered trauma-related words very well, including those they were instructed to forget. In contrast, healthy survivors and participants with no history of childhood abuse recalled TBR words better than TBF words, irrespective of word valence. Taken together, these data imply that individuals with PTSD easily encode and recall trauma-related material, and that persistent trauma-related thoughts may undermine the encoding of material that is not related to the trauma. It can be seen that cognitive research on PTSD has depicted cognitive processes that may figure in the source of certain symptoms of the disorder. Results of the studies described above can be clearly linked to classic symptoms of PTSD like intrusions and avoidance. Studies imply, for example, that enhanced accessibility and failure of inhibition are candidates for the mechanism underlying the phenomenon of intrusive recollection. This evident link between PTSD symptoms and underlying cognitive deficits displayed in

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these studies, underlines the importance of research investigating the cognitive patterns in PTSD patients and trauma-exposed controls.

2. Cognitive Models of PTSD Besides research exploring these cognitive abnormalities underlying PTSD, several models of cognitive functioning in PTSD have been proposed [10-12]. The model of Ehlers and Clark [12], for example, describes a network of cognitive processes, including strategies that the person chooses to use that lead from the traumatic situation itself to the maintenance of persistent PTSD. The model reflects the notion that strategies with which the person attempts to keep unpleasant mental intrusions to a minimum may paradoxically make their elimination more difficult. Implicit in this and other models is that trauma exposure per se is not enough to produce and maintain PTSD: amongst other variables, particular cognitive strategies that only arise in a subset of trauma-exposed people are necessary to produce that. Furthermore, in the models, the cognitive differences between people with PTSD and trauma-exposed people are predicted to be most marked for traumarelated material. That is, PTSD is assumed to have effects on cognitions thematicallyrelated to the traumatising event, and therefore a general prediction of the framework is that, compared to trauma-exposed controls, PTSD patients should have worse performance on tests of trauma-related cognition but not on tests with neutral stimuli.

3. PTSD and False Memories The Deese-Roediger-McDermott (DRM) task is a laboratory paradigm that is very effective in eliciting false memories [13-14]. In it, participants study a list of words that are strong semantic associates of a word not presented on the list - the critical lure. For example, participants may study words like bed, rest, awake, tired, and so forth, all of which are strongly related to the nonpresented critical item, sleep. On a subsequent test, participants often falsely recall and recognise the critical lure (in this case, sleep). A number of researchers have argued that susceptibility to false memories may be due to a deficit in source monitoring, i.e., incorrect judgments about the origin or source of information [15]. On this view, the presentation of semantically associated words activates a concept that is common to all words on the list, namely the critical nonpresented lure. Thus, the DRM paradigm requires participants to differentiate between internally generated thoughts and genuine memories of the studied words [16]. There is reason to believe that PTSD patients may have particular problems with source-monitoring, and thus a tendency towards higher production of false memories, due to the connection between the disorder and dissociation. For instance, Bremner and colleagues [17] demonstrated a link between war-induced PTSD and dissociation, and Winograd and co-workers [18] showed that scores on dissociative scales were positively correlated with susceptibility to false memories on the DRM task. This hypothesis has been tested in two studies employing the DRM paradigm with people reporting traumatic

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experiences, with or without PTSD. On the one hand, Bremner et al. [19] studied women with memories of childhood sexual abuse who were suffering from PTSD. The authors found that these women displayed a higher frequency of false recognition than abused women without PTSD. However, there were no differences in correct recognition between the groups. Zoellner and colleagues [20], on the other hand, reported that victims of criminal assaults with or without PTSD did not differ on either falsely recognising critical lures or on correctly recognising presented words. When comparing the two traumaexposed groups on recall of words from DRM lists, Zoellner et al. [20] reported no differences in the number of correctly recalled words, whereas Bremner et al. [19] found that PTSD patients recalled fewer words than participants without PTSD. On numbers of critical lures mistakenly recalled, neither study reported significant differences between the two groups, and in both cases the trend was actually for non-PTSD participants to recall more lures. The study of Brennen and colleagues [21] aimed at investigating the discrepancy between these results on correct recall of words from DRM lists and to shed more light on the unexpected finding in both previous studies that trauma-exposed groups have equivalent susceptibility to recall critical lures, apparently at odds with the models of cognition in PTSD. In addition, a novelty of this study was that, in addition to neutral word lists, trauma-related DRM lists were used. If PTSD patients and trauma-exposed non-PTSD patients are found to show similar patterns on trauma-related cognitive tasks, this would undermine models of cognition in PTSD, where PTSD patients are predicted to have impaired trauma-related cognition. For instance, in Ehlers and Clark’s [12] model, several sets of factors intervene between trauma exposure and the development of persistent PTSD: besides the characteristics of the trauma and its sequelae, a person’s beliefs and coping style will play a role, as well as peritraumatic processing, and of most relevance here, an individual’s cognitive strategies aimed at inhibiting the reminders of the unpleasant event. In this model PTSD patients have self-reinforcing thought patterns, where their attempts at pushing thoughts of the trauma out of their mind actually have the opposite effect of making the unpleasant thoughts rebound into consciousness more often. Trauma-related cognition would thus be expected to be impaired for PTSD patients compared to traumaexposed controls. To test this question, Brennen et al. [21] tested 50 participants with war-related PTSD and 50 traumatised controls without PTSD. The inducing events for the PTSD patients had occurred at least 7 years previously, during the war in Bosnia. Based on cognitive models, it was expected that war-related source-monitoring should be worse in PTSD, leading to more false recall of the war-related critical lures. The study revealed that PTSD patients did not show a higher susceptibility to falsely recalling neutral critical lures. This finding is consistent with previous results [19-20]. However, PTSD patients exhibited higher rates of false recall of war-related critical lures, while simultaneously showing a lower rate of correct recall. In agreement with models such as Ehlers and Clark’s [12], trauma-related sourcemonitoring appears to be impaired in PTSD patients, even compared to a group of traumaexposed controls. Taken together, this study provides evidence suggesting that PTSD

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patients have a particular susceptibility to trauma-related false memories, but backs up previous findings of no difference for recall of neutral false memories.

4. Recovered Memories and False Memory Effects By far the most controversial topic in the field of trauma concerns the accuracy of recovered memories of childhood sexual abuse. The concept of repressed and recovered memories has been deeply divisive in psychology and psychiatry and has led to the socalled ‘memory wars’ [22-23]. Some scholars claim that amnesia for trauma and/or subsequent recovery of traumatic memories can be demonstrated in clinical populations [5, 24], whereas others have questioned the existence of repressed and recovered memories because of the lack of solid evidence for such memories [25-26]. Moreover, skeptics have warned that memories may be susceptible to distortions [27] and hence that therapies intended to recover memories of childhood sexual abuse may unintentionally foster false memories of childhood sexual abuse [28]. Despite the furore surrounding recovered memories, almost no research has been conducted on the cognitive functioning of people at the heart of this debate, namely people with reported repressed and recovered memories of a trauma. This situation may have arisen because few clinicians possess expertise in laboratory research and few cognitive psychologists have access to trauma populations. In fact, Richard McNally, Susan Clancy, and their colleagues at Harvard University were the first to apply experimental methods to investigate memory functioning in people reporting repressed and recovered memories of childhood sexual abuse. More specifically, McNally and his group have been conducting studies on four groups of participants: adults who report remembering the abuse after years of not thinking about it (recovered memory group), adults who believe they were sexually abused as children but who have no explicit autobiographical memories of childhood abuse (repressed memory group), adults who have always remembered being abused (continuous memory group), and adults without a history of abuse (control group) [26]. By using several cognitive tasks, McNally and colleagues showed that the repressed and recovered memory group did not exhibit a superior ability to forget trauma-related words on directed forgetting tasks [29-30; see also 31]. Furthermore, they showed that people with recovered memories of childhood sexual abuse are more prone to exhibit false memory effects on neutral DRM word lists [32]. However, no study has considered these false memory effects for trauma-related material in survivors of childhood sexual abuse. Would people with recovered memories of abuse show the same trauma-related source monitoring deficit that is seen in PTSD survivors in the study of Brennen and colleagues [21]? Recently, Geraerts and colleagues [33] addressed these questions by employing neutral and trauma-related DRM lists to traumatised individuals. They investigated whether participants who reported having recovered memories of childhood sexual abuse would display higher rates of false recall and recognition for neutral and trauma-related words relative to other participants. Following the procedure of Clancy et al. [32], they recruited participants through advertisements in local newspapers. In these advertisements, they invited women to come

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to the lab when they a) had recovered memories of childhood sexual abuse, b) believed they had been sexually abused as a child, c) had a history of sexual abuse which had never been forgotten or d) had no history of sexual abuse. The results replicated the robust false recall and recognition effects typically found with the DRM paradigm [14]. That is, overall, participants falsely remembered many of the critical lures. Replicating earlier findings of Clancy et al. [32], the results also lend support to the idea that women reporting recovered CSA memories are more susceptible than other participants to this memory illusion. More specifically, women with recovered memories of CSA exhibited higher rates of false recall and false recognition of critical lures than the other participants. This study was the first to show that this was true for both neutral and trauma-related word lists. As already mentioned, a number of researchers have argued that susceptibility to false memories may be due to a deficit in source monitoring [15]. The results of Geraerts et al. [33] suggest that women reporting recovered CSA memories may have a source monitoring deficit for all types of material, whether the content is neutral or trauma-related. It can be speculated that especially these women have difficulties with the identification of the origin of a memory and that they may have a tendency to adopt an internally generated thought as being a genuine memory. This could have serious real-life implications, both for the reliability of their autobiographical memory and for the development of their knowledge and beliefs. Additionally, it might well be the case that source monitoring confusion can produce pseudomemories. Therefore, it is very important to recognise that the influence of source monitoring on the origin of recovered memories warrants further study.

5. Malingering and Trauma The debate about repressed and recovered memories of sexual abuse is however not the only controversy in the field of trauma. Whereas all the aforementioned studies relate to benign memory distortion, one should be aware that false claims of PTSD are a reality. For instance, Frueh and colleagues [34] demonstrated the problem of deliberate exaggeration of symptoms in veterans seeking to obtain a diagnosis of PTSD. Because in many countries there are civil and criminal laws that regulate financial compensation for victims of war trauma, it is obvious that, in some cases, people present themselves as victims in an attempt to profit from financial or judicial regulation. Sparr and Pankratz [35] were the first to identify such false claims of PTSD in individuals reporting disability from combat in Vietnam when in fact it can be shown that the claimants had never been to that country. Until recently, such false claims remained largely ignored. Burkett and Whitley [36] pointed out how widespread the problem was by describing many cases where entire combat histories had been falsified. In a recent study, Kozariü-Kovaþiü and co-workers [37] explored the change in the diagnosis of PTSD which was related to the introduction of a new national regulation on compensation-seeking by Croatian war veterans. The legal regulation of compensation-seeking of these veterans was first established in 1992 within a law, including all immediate combat and civilian victims of war trauma. This regulation was extended in 2001, allowing war veterans that had not

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been covered by the previous law to apply for compensation due to prolonged or delayed PTSD [38]. It was found that there were significant differences in the diagnosis of PTSD made before and after the introduction of the new law in 2001. The diagnoses made by psychiatrists changed towards the diagnoses with higher compensation rates. On a related note, it has also been shown that the details of the rules governing compensation appear to influence the way some veterans report their symptoms when they are being evaluated for PTSD [39]. Clinical researchers need to increase the attention given to these issues and to realise that it is essential to differentiate between malingered and genuine PTSD symptoms. Therefore, psychometric instruments for the evaluation of malingered PTSD are needed. One promising test is the Morel Emotional Numbing Test (MENT) [40]. This is a forcedchoice task to detect response bias in PTSD assessments. Updated in 2004 [41], it consists of 60 two-alternative items. Briefly, the test uses 20 coloured slides of 10 facial expressions posed by a man and a woman. Their expressions reflect happiness, frustration, sadness, anger, fear, calmness, surprise, shyness, confusion, and sleepiness. The slides are presented on a computer screen along with verbal labels describing emotions. The participant is instructed to identify the emotion word that best matches the expression portrayed on the slide. In a first series of 20 trials, participants see one slide on the computer screen and are asked to circle one of two words (e.g., “happy”; “surprised”) describing the slide. In a second run of 20 trials, participants view two slides, but only one word and are asked to identify the slide that best matches the word. In a final run of 20 trials, participants are shown two slides and two words which have to be matched to each other. Before the task is given to participants, they are primed with the instruction that many PTSD patients suffer from emotional numbness and that this may cause them to have difficulties with the recognition of facial expressions. The idea is that individuals who tend to overreport PTSD symptoms will intentionally produce more errors on this deceptively simple test. Findings from Morel [40] pointed out that war veterans who were suspected for false PTSD claims made more errors on the MENT than credible claimant groups and patient groups with alcohol dependency or schizophrenia. At the moment, the MENT is being employed in a large sample of compensation-seeking Croatian war veterans. The aim of this ongoing study is to examine the possibility of distinguishing between simulated and genuine symptom presentation, based on scores on the MENT and several other diagnostic tools [42].

6. Summary and Clinical Implications Cognitive research on PTSD has produced substantial evidence that PTSD patients show deficits in memory for trauma-related material. Studies on autobiographical memory reveal impairments in the ability of PTSD patients to access specific episodes from their past. Additionally, the hypothesis that trauma survivors, especially those with a history of childhood sexual abuse, have developed skills for expelling disturbing material from awareness has been undermined by directed forgetting methods. These methods even point in the opposite direction: trauma survivors exhibit an impaired ability to forget disturbing

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material. Likewise, studies using a false memory paradigm point out that PTSD patients show enhanced false memory effects for trauma-related material. This cognitive research on PTSD is required to elucidate the information-processing characteristics associated with PTSD and to test the main tenets of psychological theories of PTSD. Furthermore, several clinical implications are suggested by this line of research. For example, problems accessing specific episodes from the past should alert clinicians to difficulties patients may come across in cognitive therapy or in other interventions that require one to access specific episodes from one’s past. Furthermore, clinicians should take into account that PTSD patients are more prone to falsely recalling trauma-related material, at least in the laboratory. Additionally, one should be attentive for the relationship between source monitoring deficits and recovered memories of childhood sexual abuse. Finally, it is important to realise that a diagnosis of PTSD should not only rely on self-report inventories or other assessment procedures which may be vulnerable to symptom overreporting.

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McNally, R.J. (1998). Experimental approaches to cognitive abnormality in posttraumatic stress disorder. Clinical Psychology Review, 18, 971-982. Brewin, C.R., & Holmes, E.A. (2003). Psychological theories of posttraumatic stress disorder. Clinical Psychology Review, 23, 339-376. McNally, R.J., Litz, B.T., Prassas, A., Shin, L.M., & Weathers, F.W. (1994). Emotional priming of autobiographical memory in post-traumatic stress disorder. Cognition and Emotion, 8, 351-367. McNally, R.J., Lasko, N.B., Macklin, M.L., & Pitman, R.K. (1995). Autobiographical memory disturbance in combat-related posttraumatic stress disorder. Behaviour Research and Therapy, 33, 619-630. Terr, L.C. (1994). Unchained memories: True stories of traumatic memories, lost and found. New York: Basic Books. Harvey, M.R., & Herman, J.L. (1994). Amnesia, partial amnesia, and delayed recall among adult survivors of childhood trauma. Consciousness and Cognition, 3, 295-306. McNally, R.J., Metzger, L.J., Lasko, N.B., Clancy, S.A., & Pitman, R.K. (1998). Directed forgetting of trauma cues in adult survivors of childhood sexual abuse with and without posttraumatic stress disorder. Journal of Abnormal Psychology, 107, 596-601. Bjork, E.L., Bjork, R.A., & Anderson, M.C. (1998). Varieties of goal-directed forgetting. In J.M. Golding, & C.M. MacLeod (Eds.), Intentional forgetting: Interdisciplinary approaches (pp. 103-137). Mahwah, N.J.: Lawrence Erlbaum Associates. Basden, B.H., Basden, D.R., & Gargano, J.G. (1993). Directed forgetting in implicit and explicit memory tests: A comparison of methods. Journal of Experimental Psychology: Learning, Memory & Cognition, 19, 603-616. Brewin, C.R., Dalgleish, T., & Joseph, S. (1996). A dual presentation theory of posttraumatic stress disorder. Psychological Review, 103, 670-686. Foa, E.B., & Rothbaum, B.O. (1998). Treating the trauma of rape: Cognitive behavioral therapy for PTSD. New York: Guilford Press. Ehlers, A., & Clark, D.M. (2000). A cognitive model of posttraumatic stress disorder. Behaviour Research and Therapy, 38, 319-345. Deese, J. (1959). On the prediction of occurrence of particular verbal intrusions in immediate recall. Journal of Experimental Psychology, 58, 17-22. Roediger, H.L. III, & McDermott, K.B. (1995). Creating false memories: Remembering words not presented in lists. Journal of Experimental Psychology: Learning, Memory, and Cognition, 21, 803-814. Johnson, M.K., Hashtroudi, S., & Lindsay, D.S. (1993). Source monitoring. Psychological Bulletin, 114, 328.

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[16] Roediger, H.L. III, Watson, J.M., McDermott, K.B., & Gallo, D.A. (2001). Factors that determine false recall: A multiple regression analysis. Psychonomic Bulletin & Review, 8, 385-407. [17] Bremner, J.D., Southwick, S., Brett, E., Fontana, A., Rosenchek, R., & Charney, D.S. (1992). Dissociation and posttraumatic stress disorder in Vietnam combat veterans. American Journal of Psychiatry, 149, 328332. [18] Winograd, E., Peluso, J.P., & Glover, T.A. (1998). Individual differences in susceptibility to memory illusions. Applied Cognitive Psychology, 12, S5-S27. [19] Bremner, J.D., Shobe, K.K., & Kihlstrom, J.F. (2000). False memories in women with self-reported childhood sexual abuse: An empirical study. Psychological Science, 11, 333-337. [20] Zoellner, L.A., Foa, E.B., Brigidi, B.D., & Przeworski, A. (2000). Are trauma victims susceptible to false memories? Journal of Abnormal Psychology, 109, 517-524. [21] Brennen, T., Dybdahl, R., & Kapidžiü, A. (submitted). Trauma-related and neutral false memories in warinduced Posttraumatic Stress Disorder. [22] Schacter, D.L. (1995). Memory wars. Scientific American, 272, 135-139. [23] Loftus, E.F. (1997). Dispatch from the (un)civil Memory Wars. In J.D. Read & D.S. Lindsay (Eds.), Recollections of trauma: Scientific evidence and clinical practice (pp. 171-198). New York: Plenum. [24] Brown, D., Scheflin, A.W., & Whitfield, C.L. (1999). Recovered memories: The current weight of the evidence in science and in the courts. Journal of Psychiatry & Law, 27, 5-156. [25] Kihlstrom, J.F. (2004). An unbalanced balancing act: Blocked, recovered, and false memories in the laboratory and clinic. Clinical Psychology: Science and Practice, 11, 34-41. [26] McNally, R.J. (2003). Remembering trauma. Cambridge, MA: Belknap Press/Harvard University Press. [27] Schacter, D.L. (1999). The seven sins of memory: Insights from psychology and cognitive neuroscience. American Psychologist, 54, 182-203. [28] Loftus, E.F., & Ketcham, K. (1994). The myth of repressed memory. New York: St. Martin’s Press. [29] McNally, R.J., Clancy, S.A., Barrett, H.M., & Parker, H.A. (2004). Inhibiting retrieval of trauma cues in adults reporting histories of childhood sexual abuse. Cognition and Emotion, 18, 479-493. [30] McNally, R.J., Clancy, S.A. & Schacter, D.L. (2001). Directed forgetting of trauma cues in adults reporting repressed or recovered memories of childhood sexual abuse. Journal of Abnormal Psychology, 110, 151-156. [31] Geraerts, E., Smeets, E., Jelicic, M., van Heerden, J., & Merckelbach, H. (submitted for publication). Retrieval inhibition of trauma-related words in women reporting repressed or recovered memories of childhood sexual abuse. [32] Clancy, S.A., Schacter, D.L., McNally, R.J., & Pitman, R.K. (2000). False recognition in women reporting recovered memories of sexual abuse. Psychological Science, 11, 26-31. [33] Geraerts, E., Smeets, E., Jelicic, M., van Heerden, J., & Merckelbach, H. (in press). Fantasy proneness, but not self-reported trauma is related to DRM performance of women reporting recovered memories of childhood sexual abuse. Consciousness and Cognition. [34] Frueh, B.C., Hamner, M.B., Cahill, S.P., Gold, P.B., & Hamlin, K.L. (2000). Apparent symptom overreporting in combat veterans evaluated for PTSD. Clinical Psychology Review, 20, 853-885. [35] Sparr, L., & Pankratz, L.D. (1983). Factitious posttraumatic stress disorder. American Journal of Psychiatry, 140, 1016-1019. [36] Burkett, B.G., & Whitley, G. (1998). Stolen Valor: How the Vietnam generation was robbed of its heroes and its history. Dallas, TX: Verity. [37] Kozariü-Kovaþiü, D., Bajs, M., Vidošiü, S., Matiü, A., Karin, A.A., & Peraica, T. (2004). Change of diagnosis of post-traumatic stress disorder related to compensation-seeking. Croatian Medical Journal, 45, 427-433. [38] Kozariü-Kovaþiü, D., & Boreveþki, A. (2004). Malingering PTSD. In T.A. Corales (Ed.), Focus on Posttraumatic Stress Disorder (pp. 185-208). Hauppauge, NY: Nova Science Publishers. [39] Frueh, B.C., Elhai, J.D., Gold, P.B., Monnier, J., Magruder, K.M., Keane, T.M., & Arana, G.W. (2003). Disability compensation seeking among veterans evaluated for posttraumatic stress disorder. Psychiatric Services, 54, 84-91. [40] Morel, K.R. (1998). Development and preliminary validation of a forced-choice test of response bias for posttraumatic stress disorder. Journal of Personality Assessment, 70, 299-314. [41] Geraerts, E., Merckelbach, H., & Jelicic, M. (submitted for publication). Symptom overreporting in women with recovered memories of childhood sexual abuse.

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[42] Geraerts, E., Kozariü-Kovaþiü, D., Merckelbach, H., Candel, I., & Jelicic, M. (in preparation). Assessing malingered posttraumatic stress disorder in Croatian war veterans.

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

Psychotic features of combat related chronic posttraumatic stress disorder and antipsychotic treatment Dragica KOZARIû-KOVAýIûa 1 , Nela PIVACb Referral Centre for the Stress Related Disorders of the Ministry of Health of the Republic of Croatia, Department of Psychiatry, Dubrava University Hospital, Avenija Gojka Šuška 12, HR-10000 Zagreb, Croatia, b Division of Molecular Medicine, Rudjer Boskovic Institute, POBox 180, HR-10002 Zagreb, Croatia, a,

Abstract. Combat-related posttraumatic stress disorder (PTSD) is a severe debilitating psychiatric illness associated with different comorbidities. When complicated with comorbid psychotic features, PTSD is usually refractory to treatment and requires the use of other pharmacotherapeutic strategies, i.e. typical or atypical antipsychotics. In 81 male war veterans with chronic combat related PTSD with psychotic features, treatment response, clinical symptoms and adverse events were assessed using Watson‘s PTSD questionnaire, Positive and Negative Syndrome Scale (PANSS), Hamilton Rating Scale for Depression (HAMD), Clinical Global Impression Severity Scale (CGI-S), CGI-Improvement (CGI-I), Patient Global Impression Improvement Scale (PGI-I) and Drug Induced ExtraPyramidal Symptoms Scale (DIEPSS). War veterans were treated for 6 weeks with fluphenazine (27 patients), olanzapine (28 patients) in a dose range of 5-10 mg/day, or risperidone (26 patients) at a dose of 2-4 mg/day, as monotherapy. Treatment with the atypical antipsychotic olanzapine or risperidone for 6 weeks improved significantly most of the PTSD and psychotic symptoms in war veterans with combat-related chronic psychotic PTSD. Olanzapine and risperidone showed similar efficacy and tolerability and induced fewer side effects than fluphenazine, suggesting that atypical antipsychotics might have beneficial effects in war veterans with treatment-resistant psychotic PTSD. In an open study the effect of clozapine was evaluated in war veterans with combat-related PTSD complicated with severe insomnia and nightmares: 34 patients were treated for 7 days with clozapine, and 37 patients with sedatives. Clozapine was shown to be effective in veterans with PTSD as well as in severe sleep disorders and nightmares, due to its strong sedative and anxiolytic effect. Keywords. Combat related Posttraumatic Stress Disorder, War veterans, Psychotic features, Treatment, Atypical Antipsychotics, Olanzapine, Risperidone, Clozapine

1. PTSD and Co-morbidity

1

Corresponding author: Dragica KOZARIû-KOVAýIû, Referral Centre for the Stress Related Disorders of the Ministry of Health of the Republic of Croatia, Department of Psychiatry; Dubrava University Hospital, Avenija Gojka Šuška 6, HR-10000 Zagreb, Croatia, E-mail: [email protected]

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Epidemiologic and clinical studies have shown that posttraumatic stress disorder (PTSD) commonly occurs with other psychiatric disorders [1-5]. The rate of comorbidity is especially high in combat-related PTSD. A recent epidemiological survey indicated that approximately 80% of combat veterans with PTSD meet criteria for at least one psychiatric diagnosis. The most frequent diagnoses are major depressive disorder, other anxiety disorders, substance abuse, somatization, personality disorders, and dissociative disorders [6]. Comorbidity patterns in combat-related PTSD have been suggested to be socioculturally and geographically specific [7]. There are also atypical clinical pictures of PTSD, as well as the difference in clinical presentation of symptoms. Recently, it has been shown that 30-40% of combat related PTSD patients have psychotic symptoms [3,8,9]. Psychotic features add to the severity of symptoms in combat related PTSD patients [8]. Some studies show different subtypes of PTSD with depressive, psychotic, and panic features. Levels of cognitive, emotional, and behavioral disturbances in patients with comorbid PTSD and psychotic disorders exceed those seen in patients with PTSD without psychosis, or in patients with only another psychotic disorder. The question is whether a patient had any psychotic episode before his current diagnosis, i.e. current and chronic PTSD, or the psychotic episode occurred after the development of PTSD. There is active debate regarding whether the psychotic symptoms should be recognized as an unique entity, a malignant form of a disorder, or psychosis comorbid with PTSD or major depressive disorder. Before the incorporation of PTSD into American Diagnostic Nomenclature (DSM-III), patients suffering from PTSD were diagnosed with schizophrenia or other psychotic disorders. Many of these patients presented hallucinations, paranoid ideation, or disorganized behavior. Up to 40% of combat veterans with PTSD may have comorbid psychotic symptoms or meet criteria for a comorbid psychotic disorder diagnosis. PTSD with psychotic features may be a distinct subtype of the disorder [8, 10-15], and it has been found that psychotic features may occur in 30-40% of patients with combat PTSD [8]. Positive symptoms of psychosis, e.g. hallucinations that are moderate to severe in intensity, are now included as an aspect of “flashbacks” in the re-experiencing phenomena of the diagnostic criterion in PTSD. The avoidance symptoms of PTSD— avoidance of activities, places, or people reminiscent of the trauma, feeling detached or estranged from others, restricted range of affect, and diminished interest or participation in significant activities—resemble the negative symptoms associated with schizophrenia.

2. Clinical picture of psychotic symptoms in PTSD and psychometric assessment Combat veterans with PTSD on the Minnesota Multiphasic Personality Inventory (MMPI / MMPI-2) have their highest mean elevation on clinical scale 8 (the “schizophrenia” scale), suggesting prominent symptoms of thought disturbances and psychosis [16]. Patients with psychotic features scored at least 4 (moderate severity) on the Positive and Negative Syndrome Scale (PANSS) positive items (delusions, conceptual disorganization, hallucinatory behavior, suspiciousness/persecution) [8]. Hamner et al. [15] described psychotic features in PTSD which include auditory and visual hallucinations and delusional thinking. The content of hallucinations may refer

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to the traumatic experience (“soldiers screaming” or “incoming rockets”), but also may include not readily identifiable content (the sounds of “garbled voices” or “shadows seen out of the corner of patient‘s eye”). Delusions are generally paranoid or persecutory in nature. PTSD patients are generally distressed by the psychotic symptoms and retain some reality testing and insight. They do not have the characteristic disturbances(e.g., constricted or inappropriate) of affect or thought disorder (e.g., loose associations or disorganized responses). Complex, bizarre, or absurd delusions, which are common in schizophrenia, are rare in PTSD.

3. Croatian combat war veterans and comorbidity In studies of Croatian war veterans with combat-related PTSD, Kozariü-Kovaþiü and Borovecki [17] found that 57-62 % of patients met criteria for comorbid diagnoses. The most prevalent diagnoses were: alcohol abuse, major depressive disorder, anxiety disorders, panic disorder and phobia, psychosomatic disorder, psychotic disorders, substance abuse, and dementia. The study included 680 men who experienced combat stress and had diagnoses of PTSD. The psychotic symptoms in PTSD consisted of two types: depressive or schizophrenia-like. Psychotic disorders were confirmed in 17% and major depressive disorder with psychotic features in 15% of patients with PTSD. Psychotic symptoms were accompanied by auditory or visual hallucinations in 68% of patients. Delusional paranoid symptoms occurred in 32% of patients.

4. Are there implications of comorbid psychotic features for understanding the biology of PTSD? The concentration of plasma dopamine beta-hydroxylase (DBH) is elevated in psychotic vs. nonpsychotic PTSD and normal control subjects [18], a finding directly opposed to the findings observed in psychotic depression, i.e. a reduced DBH concentration. Altered DBH may be a biological marker reflecting the increased risk to develop psychotic symptoms in the context of trauma. Since DBH catalyzes the conversion of norepinephrine to dopamine, higher DBH would yield more norepinephrine relative to dopamine biosynthesis. Higher norepinephrine biosynthesis may be characterized by more severe PTSD symptoms and consequent psychotic symptoms. In extensive studies evaluating the activity of the hypothalamic-pituitary-adrenal (HPA) axis in PTSD, Yehuda and her group [19,20] demonstrated that some aspects of the biology of PTSD differ from that of major depression. PTSD is associated with alterations in the HPA axis, including increased concentrations of cerebrospinal fluid (CSF) corticotrophin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH), low baseline urinary cortisol, and alterations in the secretion and metabolism of norepinephrine and dopamine [20,21]. CRF is released throughout the brain during stress, and mediates endocrine and behavioral responses to stress. CRF released from the hypothalamus increases the release of ACTH from the anterior pituitary, which subsequently stimulates the release of cortisol from the adrenal gland [22]. In PTSD, CRF is elevated, as demonstrated by high basal CSF concentrations of CRF obtained via a single lumbar puncture [23], and from serial lumbar puncture sampling [24]. The

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finding that PTSD with psychotic symptoms is associated with elevated CRF shows that PTSD with psychotic features is characterized by extreme perturbations of the neuroendocrine system, supporting the hypothesis that PTSD with psychotic symptoms is a distinct subtype of PTSD [25]. Noradrenergic dysregulation has long been implicated in PTSD [26], with exaggerated norepinephrine responses to pharmacological [27], psychological [28], and physical [29] stressors. Yehuda et al. [30] reported a positive correlation between urinary norepinephrine excretion and PTSD symptoms. Severe PTSD symptoms in patients with psychotic PTSD, reflected by the strong correlation between CAPS and PANSS ratings, may be mediated by norepinephrine dysregulation, and elevated DBH concentrations support this hypothesis. PTSD with secondary psychotic symptoms (PTSD-SP) is associated with increased somatotropin-release-inhibiting hormone (SRIF), an inhibitory peptide that has wide cortical and limbic distribution. SRIF is released from the anterior pituitary and serves to inhibit the secretion of growth hormone-releasing factor, ACTH, and other pituitary hormones. High levels of SRIF, that covary with CRF [31], have been reported in PTSD [23].

5. The relationship between PTSD-SP and schizophrenia It is important to determine whether the psychotic symptoms that occur in PTSD with psychotic features are similar to schizophrenia, or are unique to PTSD. PTSD-SP is not associated with a family history of schizophrenia, hence it has been proposed that PTSD with psychotic features may be a severe subtype of the disorder that is distinct from the primary psychosis [32]. These findings are supported by other studies, showing a high prevalence of psychotic symptoms in combat PTSD patients, assessed with a strict exclusion criteria for schizophrenia [3,8,15,17].

6. Possible etiologies of psychotic symptoms in psychotic PTSD The increased activation of CRF circuitry could produce psychotic symptoms by several different mechanisms [25]. One hypothesis is that the increased activation of the neuroendocrine axis in PTSD-SP causes psychosis by increasing activity of the mesocortical dopaminergic system. Increased secretion of hypothalamic CRF would produce increased cortisol secretion from the adrenal gland, which would increase CNS dopamine activity. This hypothesis is supported by findings from animal studies showing that the peripheral administration of corticosterone leads to the release of dopamine in the prefrontal cortex [33], and increases in homovanillic acid (HVA) concentration from the caudate nucleus [34]. The intraperitoneal administration of dexamethasone increases dopamine metabolites in the nucleus accumbens and hypothalamus [35]. Clinical studies supporting this hypothesis have demonstrated that the administration of ACTH and cortisol leads to delayed increases in plasma HVA in normal control subjects [36]. Other studies have shown that psychotic depression is associated with more prominent activity of the HPA axis [37], and higher plasma HVA levels [38], than non-psychotic depression.

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A second hypothesis is that the higher levels of CRF found in PTSD-SP patients produce psychotic symptoms through the mechanism of CRF achieved at the cyclic adenosine monophosphate (cAMP) level in the frontal cortex [39]. This hypothesis presumes that high levels of CRF in PTSD-SP augment dopaminergic stimulation of cyclic AMP in frontal cortex, because both CRF receptor subtypes use G-protein stimulatory receptors that increase cyclic AMP levels when activated by CRF. Stimulation of the D1 dopamine receptor, but not the D2 receptor, increases levels of cAMP. The D1 receptor is most often associated with antipsychotic effects after pharmacologic blockade, which decreases the intraneuronal levels of cAMP when activated by dopamine. The third hypothesis: since CRF brain circuits are located outside the HPA axis, which mediate emotional responses and arousal, it is possible that increase in frontal dopamine circuit activity during psychotic symptomatology activates some of these systems, resulting in increased secretion of CRF in the CSF of patients with PTSD-SP. Regions outside of the hypothalamus that contain CRF include the locus ceruleus (LC), cortical areas, bed nucleus of the stria terminalis, amygdala and hippocampus. Psychological stressors can activate some of these circuits without involving the hypothalamic CRF neuroendocrine system [40].

7. Pharmacotherapy of psychotic PTSD Since PTSD is classified as an anxiety disorder, the treatment of PTSD includes the use of specific psychotherapeutic and pharmacotherapeutic interventions, primarily antidepressants such as tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors (SSRIs), adrenergic and antianxiety agents, benzodiazepines, and mood stabilizers [41,42]. Due to the occurrence of psychotic symptoms in PTSD, and/or persistence and refractoriness of the symptoms, thymoleptics or atypical neuroleptics might be used. The presence of psychotic symptoms in PTSD is often associated with treatment resistance, and requires additional pharmacological strategies, such as the use of neuroleptics or atypical antipsychotics. There are few studies assessing the efficacy of different neuroleptics [43-45], or antipsychotics such as risperidone [46-50], olanzapine [44,51-55] or quetiapine [56,57] in PTSD. Hamner [58] reported a good response to clozapine in a veteran with comorbid PTSD and psychosis. Preliminary open-trial experience suggested that low doses of atypical antipsychotics may alleviate positive symptoms of psychosis in some PTSD patients. Initial reports suggest that atypical antipsychotics may be helpful either alone or as adjunct therapy to antidepressants or other agents, at least when targeting the comorbid psychosis. In a preliminary open trial of add-on therapy [57], 20 combat veterans meeting DSM-IV criteria for PTSD were treated for 6 weeks with quetiapine. The starting dose was 25 mg at bedtime with subsequent titration based on tolerability and clinical response. Quetiapine demonstrated significant improvement in the core PTSD symptoms, positive and negative psychotic symptoms, general psychopathology, and depressive symptoms in war veterans. The tolerability of quetiapine was high with few reported side effects. Patients experiencing sedative effects noted increased duration of

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sleep and reduction in frequency and intensity of nightmares, other nocturnal anxiety symptoms, and night time awakenings.

8. Studies with Croatian war veterans

Figure 1: Baseline scores in Positive and Negative Syndrome Scale (PANSS) subscales (mean ± SD) in Croatian war veterans with psychotic PTSD before 6 weeks treatment with fluphenazine (Flu), olanzapine (Olan), or risperidone (Risp)

In the studies evaluating the effects of antipsychotics in the trials in Croatian war veterans with psychotic combat-related PTSD [44,50], 81 male war veterans with combat-related PTSD participated in the 6 weeks open studies (Figures 1-6, Table 1). War veterans (27 patients) were treated with fluphenazine, 28 patients received olanzapine (5-10 mg/day), and 26 patients were treated with risperidone (2-4 mg/day), as a monotherapy. Fluphenazine exhibits a high affinity of D2 and D1, and moderate affinity for H1 histaminergic receptors [59]. Olanzapine has a high affinity for the 5HT2A, 5-HT2C, 5-HT3, D1adrenergic, dopamine D1, D2 and D4, and muscarinic M1 to M5 receptors [60]. Risperidone has the affinity for 5-HT2A, 5-HT7, dopamine D2, D1, D2 adrenergic receptors and its high 5-HT2A/D2 ratio is characteristic of the atypical antipsychotic profile [60]. The presence of psychotic symptoms in PTSD was associated with treatment resistance. Patients included in this study were those with current and chronic PTS who had comorbid psychotic symptoms. The diagnosis of current and chronic combatrelated PTSD was confirmed by administration of the structured clinical interview for DSM-IV disorders. The existence of current PTSD was also assessed with Watson’s PTSD questionnaire based on DSM-III-R. Patients were excluded from this study if they had any psychiatric disorder before the war, major depressive disorder, a primary

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diagnosis of another psychiatric disorder (currently or in the previous three months), a serious concomitant medical condition, clinically significant ECG or laboratory findings, serious risk of suicide, history of seizure, or misuse of alcohol or drugs.

Figure 2: Scores in Positive and Negative Syndrome Scale (PANSS) subscales (mean ± SD) in Croatian war veterans with psychotic PTSD treated for 6 weeks with fluphenazine (Flu), olanzapine (Olan), or risperidone (Risp)

Psychotic symptoms were evaluated by the PANSS in 4 categories: positive items (delusions, conceptual disorganization, hallucinatory behavior, suspiciousness/ persecution); negative items (emotional withdrawal, and passive/apathetic social withdrawal); the general psychopathology subscale (guilt feelings, depression, motor retardation, unusual thought content, disorientation, disturbance of volition, poor impulse control, and active social avoidance); and the supplementary subscale (anger and affective lability).

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The clinical picture of psychotic symptoms could be categorized into a) the schizophrenia-like characterized mostly by conceptual disorganization, delusions and suspiciousness/persecution; b) the psychotic depression-like, manifest by hallucinatory behavior, depressive psychotic accusations, anddepressive delusions; and c) a mixed clinical picture, with conceptual disturbances and disorganization, persecutive and depressive delusions, visual and auditory hallucinations. All patients were evaluated before and after 6 weeks of treatment. Instruments used to measure outcomes were: Watson‘s PTSD Scale to assess PTSD symptoms; Positive and Negative Syndrome Scale (PANSS) to assess change in positive psychotic symptoms, negative symptoms, global psychopathology, and supplementary items; Clinical Global Impression Severity Scale (CGI-S), Clinical Global Impression Improvement Scale (CGI-I), and Patient Global Impression Improvement Scale (PGII). For safety and tolerability assessments, vital signs and adverse events were recorded using the Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS). Before treatment, the age of patients, duration of combat experience and scores in all measurement instruments were similar among veterans with combat-related PTSD receiving fluphenazine, olanzapine or risperidone treatment.

Figure 3: Baseline scores in Watson’s trauma re-experiencing, avoidance and hyperarousal scores (mean ± SD) in Croatian war veterans with psychotic PTSD before 6 weeks treatment with fluphenazine (Flu), olanzapine (Olan),or risperidone (Risp)

After 6 weeks of treatment, all three antipsychotics (fluphenazine, olanzapine and risperidone) were associated with comparable significant reductions in the symptoms listed in PANSS positive (Figures 1 and 2), and Watson’s trauma re-experiencing (Figures 3 and 4) subscales. However, treatment with olanzapine or risperidone induced greater reductions in PANSS negative, general psychopathology and supplementary items subscales (Figures 1 and 2) than fluphenazine treatment. In addition, olanzapine or risperidone reduced more the scores in Watson’s avoidance and increased arousal

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(Figures 3 and 4) subscales, and in scores in CGI-S (Figure 5), CGI-I, and PGI-I (Figure 6), than fluphenazine treatment When compared to fluphenazine, olanzapine and risperidone reduced cognitive and depressive symptoms, alleviated aggression, suicidality, and impulsivity, and had beneficial effects on nightmares and flashbacks, while improving participation in social activities in psychotic PTSD patients. In addition, olanzapine and risperidone improved the symptoms of insomnia, nightmares, hypobulia, and anhedonia, and increased the interest and pleasure in daily activities in PTSD patients. Olanzapine and risperidone decreased the frequency and intensity of intrusive thoughts and visual images.

Figure 4: Scores in Watson’s trauma re-experiencing, avoidance and hyperarousal scores (mean ± SD) in Croatian war veterans with psychotic PTSD after 6 weeks treatment with fluphenazine (Flu), olanzapine (Olan), or risperidone (Risp)

Fluphenazine induced more extrapyramidal symptoms (Figure 6) than olanzapine or risperidone treatment. Olanzapine and risperidone demonstrated overall greater improvement than fluphenazine.

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Figure 5: Clinical Global Impression Severity Scale (CGI-severity) scores (mean ± SD) in Croatian war veterans with psychotic PTSD after 6 weeks treatment with fluphenazine, olanzapine, or risperidone

Figure 6: Scores (mean ± SD) in Clinical Global Impression-Improvement (CGI-I), Patient Global Impression Improvement Scale (PGI-I), and Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS) in Croatian war veterans with psychotic PTSD after 6 weeks fluphenazine (Flu), olanzapine (Olan), or risperidone (Risp) treatment

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Treatment with the atypical antipsychotic olanzapine or risperidone for 6 weeks significantly improved most of the PTSD and psychotic symptoms in war veterans with combat-related PTSD. Olanzapine and risperidone showed similar efficacy and tolerability and induced fewer side effects than fluphenazine. Our data suggest that atypical antipsychotics might have beneficial effects in war veterans with treatmentresistant psychotic combat-related PTSD.

9. Sleep disturbances in PTSD The most prominent symptoms of PTSD are sleep disturbances. Treatment of severe insomnia and nightmares in war veterans with PTSD with clozapine is effective in the malignant form of PTSD, or PTSD with psychotic features. Clozapine affects large number of neurotransmitters, and interacts with serotonergic 5-HT2A, 5-HT6, 5-HT7 receptors, D2, D1, D4 receptors, muscarinic and histaminergic receptors [60]. An open-label study was done with 71 war veterans with combat-related PTSD having severe insomnia and nightmares with a duration of at least 4 weeks prior the beginning of the study [61]. The diagnoses were determined by ICD-10 criteria, investigation variant. The patients had a stable leucocyte count and were without psychotic symptoms. They CGI-S and PGI-S scale scores or at least 4. Patients with comorbid diagnoses, head trauma, central nervous system disturbances, epilepsy, liver and kidney diseases or other heavy physical diseases were excluded. The patients were divided into two groups. Thirty-four patients received 50mg dose of clozapine each evening for 7 days, and 37 patients (control group) were given a sedative (flurazepam 30mg or zolpidem 10mg). The Hamilton depression scale (HAM-D) items for insomnia, D1 item from Watson‘s scale, CGI-S, and PGI-S were used as outcome measures. In Croatian war veterans with combat related PTSD and severe insomnia and nightmares, 7 days of treatment with clozapine significantly decreased all measured items for the particular sleep disturbances. Clozapine showed better efficacy than the sedatives.

Table 1. Analysis of variance (ANOVA) for the group of PTSD patients treated with clozapine N=34) and PTSD patients treated with classical sedatives (Sedatives, N=37) significance two-tailed 1st day 7th day Scales Clozapine Sedatives Clozapine Sedatives Clozapine HAMD items 5.08 ± 0.71 5.11 ± 0.77 1.17 ± 0.79 2.22 ± 0.63 0.001 for insomnia W-PTSD D1 5.41 ± 0.93 6.05 ± 0.66 1.62 ± 0.49 2.54 ± 0.51 0.001 item CGI-S 5.85 ± 0.56 5.97 ± 0.60 1.79 ± 0.88 3.03 ± 0.69 0.001 PGI-S 5.91 ± 0.75 6.27 ± 0.61 1.97 ± 0.79 3.57 ± 0.55 0.001

10. Conclusions

(Clozapine,

Sedatives

0.911 0.001

0387

0.032

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We believe that psychotic features in combat related PTSD represent a specific subtype of chronic PTSD and should be included as a distinct nosological entity in the future classifications of mental disorders. Treatment with the atypical antipsychotic olanzapine or risperidone for 6 weeks significantly improved most of the PTSD and psychotic symptoms in war veterans with chronic combat-related PTSD. Olanzapine and risperidone showed similar efficacy and tolerability; each was more effective and induced fewer side effects than fluphenazine. Atypical antipsychotics might have beneficial effects in war veterans with treatment-resistant psychotic combat-related PTSD. Clozapine was shown to be efficient in veterans having PTSD as well as in severe sleep disorders and nightmares due to its strong sedative and anxiolytic effect.

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[44] N. Pivac, D. Kozariü-Kovaþiü, D. Mück-Šeler, Olanzapine versus fluphenazine in an open trial in patients with psychotic combat-related posttraumatic stress disorder, Psychopharmacology 175 (2004), 451-456. [45] M.J. Sternyak, T.R. Kosten, A. Fontana, R. Rosenheck, Neuroleptic use in the treatment of posttraumatic stress disorder, Psychiatr Quarterly 72 (2001), 197-193. [46] D. Krashin, E.W. Oates, Risperidone as an adjunct therapy for posttraumatic stress disorder, Military Med 164 (1999), 605-606. [47] G. Bartzokis, T. Freeman, V. Roca, Risperidone treatment for PTSD, Eur Neuropsychopharmacol 11 (2001), Suppl 3, S 262. [48] I. Eidelman, S. Seedat, D.J. Stein, Risperidone in the treatment of acute stress disorder in physically traumatized in-patients, Depress Anxiety 11 (2000), 187-188. [49] M.B. Hamner, R.A. Faldowski, H.G. Ulmer, B.C. Frueh, M.G. Huber, G.W. Arana, Adjunctive risperidone in posttraumatic stress disorder: a preliminary controlled trial of effects on comorbid psychotic symptoms, Int Clin Psychopharmacology 18 (2003), 1-8. [50] D. Kozariü-Kovaþiü, N. Pivac, D. Mück-Šeler, B.O. Rothbaum, Risperidone in combat related posttraumatic stress disorder with psychotic features, J Clin Psychiatry 66 (2005), 922-927. . [51] M.J. Butterfield, M.E. Becker, K.M. Connor, S. Sutherland, L.E. Churchill, J.R.T. Davidson, Olanzapine in the treatment of posttraumatic stress disorder: a pilot study, Int Clin Psychopharmacol 16 (2001), 197-203. [52] L.A. Labate, S. Douglas, Olanzapine for nightmares and sleep disturbance in post-traumatic stress disorder (PTSD), Can J Psychiatry 45 (2000), 667-668. [53] T.I. Prior, Treatment of post-traumatic stress disorder with olanzapine, Can J Psychiatry 46 (2001), 182. [54] F. Petty, P.F. Brannan, J. Casada, et al., Olanzapine treatment for post-traumatic stress disorder: an open-label study, Int Clin Psychopharmacol 16 (2001), 331-337. [55] M.B. Stein, N.A. Kline, J.L. Matloff, Adjunctive olanzapine for SSRI-resistant combat related PTSD: a double blind placebo controlled study, Am J Psychiatry 159 (2002), 1777-1779. [56] S.P. Satar, B. Ucci, K. Grant, S.C. Bhatia, F. Petty, Quetiapine therapy for posttraumatic stress disorder, Ann Pharmacotherapy 36 (2002), 1875-1878. [57] M.B. Hamner, S.E. Deitsch, P.S. Brodrick, H.G. Ulmer, J.P. Lorberbaum, Quetiapine treatment in patients with posttraumatic stress disorder: an open trial of adjunctive therapy, J Clin Psychopharmacol 23 (2003), 15-20. [58] M.B. Hamner, Clozapine treatment for a veteran with comorbid psychosis and PTSD, Am J Psychiatry 153 (1996), 841. [59] J. Hyttel, J.J. Larsen, A.V. Christensen, J. Arnt, Receptor binding profile of neuroleptics, Psychopharmacology Suppl 2 (1985) 9-18. [60] F.P. Baymaster, D.O. Calligaro, J.F. Falcone, et al., Radioreceptor binding profile of the atypical antipsychotic olanzapine, Neuropsychopharmacology 14 (1996) 87-96. [61] D. Kozariü-Kovaþiü, N. Pivac, D. Mück-Šeler, Pharmacotherapy of psychotic posttraumatic stress disorder with antipsychotic drugs, Period Biol 106 (2004), Suppl 1, 58.

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Section II Diagnosis and Screening

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Efforts to Improve the Diagnosis and Treatment of Posttraumatic Stress Disorder Michael J. ROY, MD, MPH 1 , and Patricia L. KRAUS. Division of Military Internal Medicine, Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD, USA.

Abstract. Posttraumatic stress disorder (PTSD) is a frequent and debilitating consequence of exposure to war and other life-threatening events. PTSD often goes undiagnosed and even when it is diagnosed; treatment is all too often inadequate or ineffective. It is imperative to identify more effective diagnostic and therapeutic approaches. We discuss currently available screening and treatment measures, and present approaches we are planning to try to improve each of these modalities. Keywords: Posttraumatic stress disorder, combat stress, depression, pharmacotherapy, virtual reality, behavioral therapy

Introduction Posttraumatic stress disorder (PTSD) became part of our lexicon in the aftermath of the Vietnam War, but the symptoms and associated functional impairment it represents have been known for centuries. Perhaps Cain was the first to suffer the torment of this disorder, and Homer certainly depicts its symptoms in his account of Achilles in The Iliad. More recently, the medical literature has featured hundreds of accounts from the American Civil War, both World Wars, and other national and international conflicts. Authors identify myriad physical and psychological symptoms that escape efforts to ascribe them to specific environmental factors, but are linked to the stress of war. PTSD is also well documented in many victims of terrorism, genocide and personal assaults such as rape. An estimated 10,000 Croatian Homeland War veterans (15% prevalence) have PTSD, with an alarmingly high suicide rate. The current conflict in Iraq, involving snipers and suicide bombings, as 1 Corresponding Author: LTC Michael Roy. Department of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, A3062, Bethesda, MD, 20814 USA. Telephone: (301) 295-9601; Fax: (301) 295-3557; Email: [email protected].

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well as concerns about prisoner mistreatment, is a recipe for PTSD. This provides an opportunity to improve the care of combat veterans while defining optimal diagnostic and therapeutic approaches.

1. Psychological Effects of Traumatic Experiences The first large study of American troops returning from duty in Iraq, conducted by Hoge et al., documented a rate of 12.9% meeting a strict case definition and 18% meeting a more broad definition of PTSD [1]. Subsequent evaluations of injured soldiers receiving care at Walter Reed Army Medical Center have indicated that initial screens may miss as many as 70% of those who meet criteria within 6 months, indicating both high rates and the need for repeated screening. Early experience with veterans of the Iraq conflict also underscores the high prevalence of other psychiatric disorders after all are common after such experiences, with nearly 30% of those surveyed by Hoge et al. meeting criteria for some mood or anxiety disorder. In addition, rates of alcohol and substance abuse have been found to be higher in individuals diagnosed with PTSD. In patients with PTSD, one national study identified a lifetime history of at least one other psychiatric disorder in 88% of men and 79% of women with PTSD [2], underscoring the importance of screening for more than just PTSD. The PRIME-MD is a particularly useful validated instrument that screens for depression, panic and other anxiety disorders, eating disorders, somatoform disorders, and alcoholism [3]. PTSD is not solely associated with war, but has also been identified as a common reaction to traumatic events ranging from personal assaults such as rape or mugging to lifethreatening acute medical conditions. Briefly, PTSD is characterized by symptoms that can be divided into three categories, which persist for at least one month, following a threatening event that initially elicited fear, helplessness, or horror. The first category covers symptoms of re-experiencing the event, including intrusive thoughts, recurrent dreams, flashbacks, and physiologic changes induced by stimuli reminiscent of the event. The second category includes manifestations of avoidance of stimuli associated with the trauma, such as avoiding activities, places, thoughts or feelings related in any way to the trauma, inability to recall an important aspect of the trauma, anhedonia, detachment from others, restricted range of affect, and a sense of a foreshortened future. The final category incorporates symptoms of increased arousal, such as insomnia, irritability, impaired concentration, hyper-vigilance, and an exaggerated startle response. In the general population, while a history of some traumatic exposure is more likely than not, PTSD has an estimated point prevalence of 2-5%, a lifetime prevalence of 8-12% and higher yet in combat veterans [2, 4-12]. The current environment in Iraq is likely to result in particularly high rates of PTSD. It often goes undiagnosed for months or years; consequently effective treatment is not provided. PTSD is associated with high rates of depression and other psychological conditions, poorer physical health, missing work, impaired function at work and at home, and significantly higher healthcare costs. Rapid diagnosis could enhance individual function and military readiness. PTSD is associated with increased somatic complaints, making it even more likely that someone with PTSD

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will seek the help of their primary care physician, so that the prevalence of PTSD in primary care is undoubtedly significantly higher than in the general population. Recent studies in primary care found that 9-12% of patients met criteria for PTSD [7-8]. Samson et al. identified PTSD in 38.6% of patients who were referred by their primary care providers for mental health services based on suspicion of depression or anxiety [7]. However, like most mental disorders, PTSD often goes undiagnosed in primary care, and such patients are frequently not referred to mental health. Several studies have examined the likelihood of developing PTSD after a traumatic event, and estimates that combine all stressors range from 9.2% to 25% [2, 8-10, 12]. Terrorist events have been shown to result in markedly elevated rates of PTSD. After terrorists released the nerve agent sarin in a Tokyo subway, 60% of those who presented for medical care after the incident had symptoms of PTSD that persisted at least 6 months, even though most did not have evidence of physical exposure to sarin [13]. In fact, PTSD not uncommonly results in those not directly exposed to the event, as evidenced by the 7.5% of Manhattan residents (including 20% of those living near the World Trade Center) meeting criteria for PTSD 5-8 weeks after September 11, 2001[14]. Moreover, 44% of adults outside of New York City reported substantial symptoms of distress 3-5 days after 9/11/01 [15]. Wartime deployment is also associated with high rates of PTSD—we identified PTSD in 83 of 651 (12.7%) veterans of Operation Desert Shield/Desert Storm, upon completion of evaluation at Walter Reed Army Medical Center 4-6 years after their deployment, consistent with other reports [16-17]. PTSD is in turn associated with noticeably higher rates of depression and other psychological conditions, poorer physical health, missing work, impaired function at work and at home, and significantly higher healthcare costs [18-21]. Subthreshold PTSD, represented by the multiple symptoms but failure to meet strict criteria for the full disorder, has been reported to have at least an equal, if not greater, prevalence compared to full PTSD, and has also been shown to be associated with significant disability [6,11].

2. Screening Instruments 2.1 A model: The PHQ-9 for Depression The under-diagnosis, comorbidities, somatic complaints, functional impairment, and health care utilization described for PTSD are also characteristic of depression. The PHQ-9 (Patient Health Questionnaire) is a 9-item screen for depression that has been validated in 3000 primary care and 3000 obstetrics and gynecology patients [22]. The PHQ-9, included in Appendix B, consists of nine questions taken directly from the DSM-IV criteria for major depression. A score is given for each of the 9 responses, based upon whether the symptom bothered the individual not at all (0), for several days (1), more than half the days (2), or nearly every day (3), in recent weeks. A composite score can then be generated, with a range from 0 to 27; the scores have been shown to correlate with the severity of depression, as well as the frequency of physician visits, and measures of functional status. The PHQ-9 has been shown to identify about twice as many cases as primary care physicians were able to diagnose on their own. Using a cut-off score of 10 to diagnose

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depression, the PHQ-9 has a sensitivity and specificity of 88% each [22]. The scores can be used not only to make an initial diagnosis of depression, but also, upon re-administration of the questionnaire, to monitor the response to therapy, to determine whether an individual patient is satisfactorily responding to treatment or not. In this way, the PHQ-9 provides an invaluable tool for the primary care physician, who has long had effective monitoring measures for other chronic diseases that are frequently encountered: hypertension (blood pressure cuff), diabetes mellitus (hemoglobin A1C), and hyperlipidemia (LDL). Prior to the PHQ-9, there was not such an instrument for depression, rendering diagnosis more difficult, with numerous studies indicating that depression was missed about half the time in a primary care setting. The PHQ-9 fulfills ideal criteria for a screening instrument. It is quick, inexpensive, easy to administer, is well validated, with relatively high accuracy, can educate patients in providers with regard to criteria for the diagnosis, can be used to follow progress over time, and there is also some evidence that its use is associated with improved prognosis. 2.2 Existing screens for PTSD Numerous screens for PTSD have been previously developed. However, most are complex and time-consuming. A previous review of available instruments found that nearly all did not have well-established validity and reliability. Of those with some evidence of validity, it has generally not been demonstrated across both combat veteran and civilian populations. Since the time of that review, two instruments have become popular. The first is the Clinician-Administered PTSD Scale (CAPS), which is 17 pages long, must be administered by a professional, and features detailed instructions and complex scoring [23]. The CAPS has become the gold standard instrument for the diagnosis of PTSD in the research setting, with a recent review confirming strong validity and documenting its use in more than 200 studies [24]. However, it is not a practical instrument for use in a high-volume, rapid turnover setting, whether the primary care physician’s office, or with combat veterans returning from deployment and eager to be reunited with their families. Efforts to use the CAPS to follow response to treatment have also proven more problematic [25]. The other widely used instrument is the PTSD Checklist (PCL), a 17-item screen, which can be selfadministered, having the advantages of rapid completion, little expenditure of professional time in administration, and relatively simple scoring. Although it compared favorably with the CAPS for initial diagnosis of PTSD in combat veterans, it was less effective in assessing response to treatment [26]. Unfortunately, it also fared poorly in the only study to assess its utility in primary care, with a sensitivity of 32% [7], and while using a lower threshold score would improve the sensitivity, the PCL still may not be very useful to primary care physicians trying to diagnose this enigmatic condition. Since our experience with the PHQ-9 at Walter Reed has been overwhelmingly positive, as a site for its initial validation as well as a site where it is used on a regular basis to screen primary care patients, we chose to develop a PTSD screen patterned after the PHQ-9. Like the PHQ-9, it is comprised of questions taken directly from DSM-IV criteria for the disorder being screened for, and each is then scored on a scale from 0-3 based on the self-reported frequency of the feature. We seek to compare the efficacy of this instrument, as well as

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other available brief screens, in comparison to the more cumbersome, but gold-standard, CAPS. Since it has twelve questions, we have given our new instrument the appellation of PTSD-12.

3. Treatment of PTSD Over the past decade, selective serotonin reuptake inhibitors (SSRIs) such as sertraline, fluoxetine and paroxetine have been shown to be superior to placebo in the treatment of PTSD [27-28], as well as in preventing relapse if they are continued after achieving a clinical response [29]. SSRIs improve the quality of life of those with PTSD in multiple domains, improve functional status, decrease symptom severity, and reduce vulnerability to stress. In addition, non-pharmacologic therapies such as cognitive behavioral therapy (CBT) and exposure therapy have also shown efficacy, and probably have a greater duration of response in the absence of ongoing treatment [30-32]. CBT corrects irrational beliefs and thoughts and promotes rational behavioral changes, while exposure therapy helps individuals to confront stimuli associated with their traumatic experience through progressively more intense exposure, to identify and neutralize behavioral cues. Exposure therapy appears to be most useful when employed within the context of CBT. A recent Cochrane review demonstrated that CBT/exposure therapy had clear superiority over usual care and other psychological therapies such as supportive therapy and psychodynamic therapy [33]. While the identification of effective therapies for PTSD is good news, the downside is that sizeable numbers of those with PTSD have an inadequate response. Overall, it appears that pharmacotherapy results have a response rate of 40-60%, and nonpharmacologic approaches are not appreciably better. We postulate that a combination of pharmacologic and non-pharmacologic therapies should prove superior to either alone. This hypothesis has not yet been adequately tested, and it is important to do so, as the possibility that one form of therapy might interfere with the other can not be rejected out of hand. Functional magnetic resonance imaging (fMRI) or some other objective measure of the effect on neural pathways might be a particularly valuable measure to incorporate in such studies, to assess the interaction, if any, between the two different approaches. Virtual reality (VR) is a form of exposure therapy with particularly high potential. In recent years, virtual reality technology has been utilized to help patients overcome phobias (e.g., claustrophobia [34], fear of flying [35], fear of heights [36], fear of spiders [37-38], and fear of driving after an automobile accident [39] ), as well as for anxiety disorders [40] and PTSD. In the latter case, small numbers of Vietnam War veterans [41] and World Trade Center survivors [42-43] have each been reported to improve through the use of progressively more realistic and intense virtual reality exposures. Imaginal exposure therapy has been found to be effective in multiple clinical trials, and expert consensus treatment guidelines published in 2000 characterized it as the non-pharmacologic treatment of choice [44], but it is only recently that technology has reached the point where virtual reality has reached sufficient quality to make it a realistic manner of administering this form of therapy.

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While both exposure therapy and pharmacotherapy are effective treatment for PTSD, there are still significant numbers of patients who will not respond to one or the other. No study has previously examined both types of therapy combined, but given the diversity of the alternatives, it is reasonable to consider that combination therapy may result in a higher response rate than either therapy alone. On the other hand, the fact that each form of therapy has demonstrated superiority to placebo makes it unethical to include a pure placebo arm. Prior studies with both pharmacotherapy and desensitization therapy suggest that patients with PTSD are more sensitive than those with other psychiatric disorders, so that medication should be started at a low dose and gradually increased. Starting with too high a dose, even though such a starting dose might be appropriate for a condition such as depression, may exacerbate anxiety and lead to discontinuation of the therapy. Similarly, desensitization is most likely to be successful if started slowly, with most of the successful studies taking this approach; however, there is less experience with desensitization, and some believe efficacy may be greater with relatively intense exposure early in the course of treatment. We have assembled an experienced team of experts on both sides of the Atlantic to conduct a randomized controlled trial assessing the efficacy of combined pharmacotherapy and CBT/VR exposure therapy vs. mono-therapy. The study will be carried out at both Uniformed Services University in the Washington, DC area, and the University of Zagreb in Croatia, in order to facilitate treatment of both recent American veterans from the Iraq and Afghanistan theaters, as well as veterans of the Croatian Homeland war with PTSD of longer duration. Inclusion of the diverse study populations will facilitate generalizability of results.

4. Summary In a relatively short period of time, PTSD has been clearly identified and delineated, and effective treatment has been established. Simple approaches may improve diagnostic rates, and new technologies have the potential to significantly enhance the efficacy of treatment further. In an increasingly complex world, the likelihood of exposure to life-threatening disasters is greater than ever, and medical science must keep pace.

References [1] [2] [3] [4]

Diagnostic and Statistical Manual of Mental Disorders: Fourth Edition. Washington DC: American Psychiatric Association; 1994. Kessler RC, Sonnega A, Bromet E, Hughes M, Nelson CB. Posttraumatic Stress Disorder in the National Comorbidity Survey. Arch Gen Psychiatry 1995;52:1048-60. Spitzer RL, Kroenke K, Williams JBW, and the Patient Health Questionnaire Primary Care Study Group. Validation and Utility of a Self-report Version of PRIME-MD. JAMA 1999;282:1737-44. Davidson JRT, Hughes D, Blazer D, George LK. Posttraumatic stress disorder in the community: an epidemiological study. Psychol Med 1991;21:1-19.

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[5] Resnick HS, Kilpatrick DG, Dansky BS, Saunders BE, Best CL. Prevalence of civilian trauma and posttraumatic stress disorder in a representative national sample of women. J Consult Clin Psychol 1993;61:984-91. [6] Stein MB, Walker JR, Hazen AL, Forde DR. Full and partial posttraumatic stress disorder: findings from a community survey. [7] Samson AY, Bensen S, Beck A, Price D, Nimmer C. Posttraumatic stress disorder in primary care. J Fam Pract 1999;48:222-7. [8] Stein MB, McQuaid JR, Pedrelli P, Lenox R, McCahill ME. Posttraumatic stress disorder in the primary care medical setting. Gen Hosp Psychiatry 2000;22:261-9. [9] Breslau N, Davis GC, Andreski P, Peterson E. Traumatic events and posttraumatic stress disorder in an urban population of young adults. Arch Gen Psychiatry 1991;48:216-22. [10] Breslau N, Kessler R, Chilcoat RC, Schultz LR Davis GC, Andreski P. Trauma and posttraumatic disorder in the community: the 1996 Detroit area survey of trauma. Arch Gen Psychiatry 1998;55:626-32. [11] Davidson JRT, Tharwani HM, Connor KM. Davidson Trauma Scale (DTS): normative scores in the general population and effect sizes in placebo-controlled SSRI trials. Depress Anxiety 2002;15:75-8. [12] Hidalgo RB, Davidson JRT. Posttraumatic stress disorder: epidemiology and health-related considerations. J Clin Psychiatry 2000;61:5-13. [13] Ohbu S, Yamashina A, Takasu N, et al. Sarin poisoning on Tokyo subway. Southern Med J 1997;90:587593. [14] Galea S, Ahern J, Resnick H, Kilpatrick D, Bucuvalas M, Gold J, Vlahov D. Psychologic sequelae of the September 11 terrorist attacks in New York City. N Engl J Med 2002;346:982-7. [15] Schuster MA, Stein BD, Jaycox LH, et al. A national survey of stress reactions after the September 11, 2001, terrorist attacks. N Engl J Med 2001;3435:1507-112. [16] Wolfe J. Women veterans: updates and trends. National Center for PTSD Clinical Quarterly. 1(2):9-10. [17] Frueh BC, Elhai JD, Gold PB, Monnier J, Magruder KM, Keane TM, Arana GW. Disability compensation seeking among veterans evaluated for posttraumatic stress disorder. Psychiatric Services 2003;54:84-91. [18] Ullman SE, Siegel JM. Traumatic events and physical health in a community sample. J Trauma Stress 1996;9:703-20. [19] Kessler RC. Posttraumatic stress disorder: the burden to the individual and to society. J Clin Psychiatry 2000;61(Suppl 5):4-14. [20] Wagner AW, Wolfe J, Rotnitsky A, Proctor SP, Erickson DJ. An investigation of the impact of posttraumatic stress disorder on physical health. J Traum Stress 2000;13:41-55. [21] Walker EA, Katon W, Russo J, Ciechanowski P, Newman E, Wagner AW. Health care costs associated with posttraumatic stress disorder symptoms among women. Arch Gen Psychiatry 2003;60:369-74. [22] Kroenke K, Spitzer RL, Williams JBW. The PHQ-9: validity of a brief depression severity measure. JGIM 2001;16:601-13. [23] Blake DD, Weathers FW, Nagy LM, Kaloupek DG, Gusman FD, Charney DS, Keane TM. The development of a clinician-administered PTSD scale. J Trauma Stress 1995;8:75-90. [24] Weathers FW, Keane TM, Davidson JR. Clinician-administered PTSD scale: a review of the first ten years. Depress Anxiety 2001;13:132-56. [25] Betemps EJ, Smith RM, Baker DG, Rounds-Kugler BA. Measurement precision of the clinicianadministered PTSD scale (CAPS): a RASCH model analysis. J Appl Meas 2003;4:59-69. [26] Forbes D, Creamer M, Biddle D. The validity of the PTSD checklist as a measure of symptomatic change in combat-related PTSD. Behavior Res Ther 2001;39:977-86. [27] Davidson JRT, Rothbaum BO, van der Kolk BA, Sikes CR, Farfel GM. Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Arch Gen Psychiatry 2001;58:485-92. [28] Marshall RD, Beebe K, Oldham M, Zaninelli R. Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study. Am J Psychiatry 2001;158:1982-8. [29] Davidson JRT, Pearlstein T, Londborg P, Brady KT, Rothbaum B, Bell J, Maddock R, Hegel MT, Farfel G. Efficacy of sertraline in preventing relapse of posttraumatic stress disorder: results of a 28-week doubleblind, placebo-controlled study. Am J Psychiatry 2001;158:1974-81. [30] Foa EB. Psychosocial treatment of posttraumatic stress disorder. J Clin Psychiatry 2000;61(Suppl 5):43-8. [31] Resnick PA, Nishith P, Weaver TL, Astin MC, Feuer CA. A comparison of cognitive-processing therapy with prolonged exposure and a waiting condition for the treatment of chronic posttraumatic stress disorder in female rape victims. J Consult Clin Psychol 2002;70:867-79.

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[32] Rothbaum BO, Schwartz AC. Exposure therapy for posttraumatic stress disorder. Am J Psychother 2002;56:59-75. [33] Bisson J, Andrew M. Psychological treatment of post-traumatic stress disorder (PTSD). Cochrane Database Syst Rev. 2005 Apr 18;(2):CD003388. [34] Botella C, Banos RM, Perpina C, Villa H, Alcaniz M, Rey A. Virtual reality treatment of claustrophobia: a case report. Behav Res Ther 2002;36:239-46. [35] Rothbaum BO, Hodges L, Smith S, Lee JH, Price L. A controlled study of virtual reality exposure therapy for the fear of flying. J Consult Clin Psychol 2000;68:1020-6. [36] Emmelkamp PM, Bruynzeel M, Drost L, van der Mast CA. Virtual reality treatment in acrophobia: a comparison with exposure in vivo. Cyberpsychol Behav 2001;4:335-9. [37] Carlin AS, Hoffman HG, Weghorst S. Virtual reality and tactile augmentation in the treatment of spider phobia: a case report. Behav Res Ther 1997;35:153-8. [38] Garcia-Palacios A, Hoffman H, Carlin A, Furness TA, Botella C. Virtual reality in the treatment of spider phobia: a controlled study. Behav Res Ther 2002;40:983-93. [39] Walshe DG, Lewis EJ, Kim SI, O’Sullivan K, Wiederhold BK. Exploring the use of computer games and virtual reality in exposure therapy for fear of driving following a motor vehicle accident. Cyberpsychol Behav 2003;6:329-34. [40] Rothbaum BO, Hodges LF. The use of virtual reality exposure in the treatment of anxiety disorders. Behav Modif 1999;23:507-25. [41] Rothbaum BO, Hodges LF, Ready D, Graap K, Alarcon RD. Virtual reality exposure therapy for Vietnam veterans with posttraumatic stress disorder. J Clin Psychiatry 2001;62:617-22. [42] Difede J, Hoffman H, Jaysinghe N. Innovative use of virtual reality technology in the treatment of PTSD in the aftermath of September 11. Psychiatr Serv 2002;53:1083-5. [43] Difede J, Hoffman HG. Virtual reality exposure therapy for World Trade Center posttraumatic stress disorder: a case report. Cyberpsychol Behav 2002;5:529-35. [44] Ballenger JC, Davidson JR, Lecrubier Y, Nutt DJ, Foa EB, Kessler RC, McFarlane AC, Shalev AY. Consensus statement on posttraumatic stress disorder from the International Consensus Group on Depression and Anxiety. J clin Psychiatry 2000;61:60-6.

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Assessment of Available Diagnostic Instruments for Posttraumatic Stress Disorder Louis JEHEL, MD, PH.D1 Kathleen DULLEA Psychotraumatologiy Unit, Tenon, University Hospital,Ap-HP, Paris France

Abstract. The under recognition of the psychological effects of trauma in medicine requires a modification of clinical evaluation strategies, given the gravity of the consequences of such conditions if left untreated. The most significant problems are Acute Stress Disorder (ASD) and Post Traumatic Stress Disorder (PTSD), along with comorbid disorders. The most significant comorbidities are abusive alcohol consumption, depressive episodes, symptoms of generalized anxiety, phobia symptoms, of panic disorders, as well as somatic complaints. We distinguish between the measures requiring the intervention of an evaluator and self-report measures. To follow a patient and adapt a treatment it is necessary to know the severity of the peritraumatic reaction. Two major characteristics of the trauma response have been clearly identified; dissociation (measured with the Peri-traumatic Dissociative Experience Scale and distress (measured with the Peri-traumatic Distress Inventory). Some Instruments have been validated that measure the psychopathological consequences related to a traumatic event. The recognized gold standard (Clinician Administered PTSD Scale, or CAPS) is time-consuming and requires an experienced professional to administrate. The most frequently used self-report measures are the Impact of Event Scale-Revised and the Posttraumatic Check List. To measure non-specific psychological consequences of a traumatic event we propose the General Health Questionnaire-28 and The Beck Depression Inventory. Other potentially useful measures are described to aid with the evaluation of traumatized patients. Keywords. Posttraumatic psychometry, validity

Stress

Disorder;

depression,

selfreport,

evaluation,

Introduction In general, PTSD (Post-Traumatic Stress Disorder) is not necessarily difficult to diagnose, if the clinician investigates the trouble with the appropriate questions. The under recognition of PTSD in medicine requires a modification of clinical evaluation strategies given the gravity of the consequences of such a disorder if left untreated. Whether the event is recent or not, before deciding on a treatment strategy, the clinician must evaluate the range of symptoms and their severity. Some have expressed concern that thorough, systematic questioning could have a suggestive effect on reported symptomatology, but 1 Corresponding author : Louis JEHEL Psychotraumatologiy Unit, Tenon, University Hospital,Ap-HP, Paris France, 4, rue de la Chine75020 Paris France. [email protected]

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there is not in fact evidence to support such concern; quantitative evaluation must be supplemented by congruent global assessment performed by the clinician. Screening tools should be used when clinically indicated, and the clinician should tailor the evaluation and the choice of instruments according to the circumstances of the meeting and the clinical state of the patient. Evaluations should assist both the clinician and the patient.

1. Challenges in Evaluation The diagnosis of PTSD rests on specific anxiety features following a traumatic event, but associated comorbid disorders and assorted symptoms may also ensue following the trauma, and may contribute significantly impairment of function. Acute Stress Disorder (ASD) and Post Traumatic Stress Disorder (PTSD) represent the most salient consequences of trauma. In this work we have chosen DSM-IV criteria, which we will detail; we also cite the principle criteria of the International Classification of Diseases, 10 th Edition (CIM-10), which provides additional tools. The DSM criteria have been criticized for their reductionist character, differentiating frequently observed symptoms in pathological states, such as psychosomatic symptoms. The DSM IV is also criticized for its inability to identify the severity of the disorder by a dimensional approach, but its greatest value is to permit standardized assessment, facilitating comparisons with other studies utilizing these criteria and enabling a scientific approach to clinical psychopathology. Post-traumatic psychological problems evolve spontaneously over time, most often resulting in a reduction in the number and severity of symptoms [1]. Many authors, including Kessler [1], Breslau et al. [2], and McFarlane & Papay [3], also note that the evolution also witnesses the development of a series of comorbid symptoms and disorders, especially abusive alcohol consumption, depressive episodes, symptoms of generalized anxiety, phobias, panic disorders, and somatic complaints.

2. Objectives of Quantitative Evaluation Quantitative evaluation enables both identification of the disorder, as well as assessment of the severity. DSM-IV and CIM-10 (International Classification of Diseases) are categoryspecific instruments because they assign a diagnostic category to an individual. An alternative, or perhaps additive, measure is to evaluate where the patient is situated along an explored dimension to give an indication of intensity or severity. One speaks in this case about instruments of dimensional measure. The dimensional approach examines psychological phenomena that may not be directly measurable, but are linked to the accumulation of indicators that are directly measurable. The instruments discussed in the ensuing section are intended to evaluate the severity, or intensity, of symptoms associated with PTSD.

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3. The Main Instruments We distinguish here between measures that require administration by an expert, versus selfreported or self-administered questionnaires. 3.1. Instruments specifically related to traumatic reaction Two major Characteristics of the trauma response have been clearly identified. 3.1.1. Peri-traumatic Dissociative Experience Questionnaire This questionnaire consists of 10 items, scaled from 1 to 5. It measures the intensity of the dissociative state following a traumatic event. According to the authors, dissociation is one of the best indicators of acute stress and is an excellent predictor of PTSD [4] The symptoms of disassociation are characterized by reduced consciousness, and/or a focalization or blunting of affect with a feeling of being detached from the environment. A score is obtained by an average of the responses to 10 items. The "clinical threshold” of this measure is an average of 1.5. The translation and validation in French of this instrument was coordinated by Alain Brunet [5] with the collaboration of the authors: Marmar, C.R., et al [6]. 3.1.2. Peri-traumatic Distress Inventory (PDI) This instrument was constructed by Alain Brunet [7] to measure criterion A2 of PTSD in the DSM-IV classification, and was translated and validated in France by Louis Jehel and collaborators [8]. It is currently being developed in other languages as well. It consists of 13 items coded 0 to 4. The scores range from 0 to 52. The instructions for each item are to mark the response according to “what you felt during and immediately after the critical event”. The average score is obtained by totaling the items and dividing by the number of items. The quality of the psychometrics and its capacity to predict post-traumatic disorders [9], warrant recommending the use of this instrument.

3.2. Instruments that Measure the Psychopathological Consequences Related to a Traumatic Event First we cite valid measures for an evaluator performed -evaluation done by a trained clinician, then the measures allowing self-evaluation by patients, providing information on the severity of symptoms and not on the diagnosis. *Instruments available for a clinician performed evaluation The Clinician Administered PTSD Scale (CAPS): The CAPS [10] measures the frequency and intensity of each symptom using standard questions. The CAPS permits the evaluation of current PTSD as well as post traumatic disorders occurring in the individual’s past. The CAPS rigorously follows the diagnostic criteria of PTSD as defined by the DSMIV. The CAPS-1, the most frequently used, investigates symptoms that have duration of at

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least a month. Another version, the CAPS-2, focuses on symptom prevalence in the previous week, facilitating more regular response to treatment, such as in the case of pharmacological studies. In the research setting, the CAPS is the instrument of choice to establish the PTSD diagnosis according the DSM-IV criteria. This instrument has been used in more than 200 published studies on psychological trauma; the psychometric qualities of the original version are excellent [11]. Other instruments relating to global standardized evaluation of psychiatric disorders with a specific module related to PTSD are the MINI and the SCID which are presented below. 3.2.1. Available Instruments for self-evaluation 3.2.2. The Impact of Event Scale-Revised (IES-R). This is a revised version of the original Horowitz scale (IES). The IES-R was validated using a specific traumatic event evaluated during the specific time frame of the past 7 days. It consists of 22 items scored from one to five, yielding a severity score of posttraumatic symptoms with 3 sub-scores which must be averaged: intrusion, avoidance and hyperarousal. The IES-R does not provide a diagnosis as there are no “cutoff” points. However, this instrument is not only the most widely used and the oldest (IES) but also provides an evaluation of the severity of the acute stress of PTSD. It has been recognized for use in clinical trials, among the validated scales of severity, by a committee of experts assembled by the ECNP-ECST [12]. This measure is validated in many languages, including Chinese [13], French [9], German [14] Japanese [15], and Spanish [16], and its psychometric quality has been proven in each to be comparable to the English language version. This measure is recommended for use in future research to continue to trace the waxing and the waning course of symptoms of PTSD [17]. 3.2.3. Posttraumatic Check List (PCL) This scale evaluates the severity of post-traumatic stress, incorporating 17 items that represent the criteria of DSM-IV. Three versions are developed: “C” for civilian, “M” for Military and “S” to describe a reaction to a Specific event. The validity of the English language version has been verified [18], as has the French translation done by Cottraux [1920]. For each item the intensity is evaluated for the past month, according to the traumatic event described, based on a scale of 1 (not at all) to 5 (very often). The total score represents the sum of each of the 17 items. Three sub-scales can be researched which correspond to the criteria B, C, and D from DSM-IV, with measures of repetition for intrusion in items 1-5, avoidance in 6-12, and hyperarousal in 13-17. A notable quality of this measure is the identification of a threshold at 44 recommended by Blanchard et al [21], to consider the presence of PTSD by PCL-S. Less information is available concerning the civilian version. With the military version the preferred cutoff is at 50.

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3.2.4. The PTSD-Interview Though developed for veterans by Watson and colleagues [22], it can also be used for civilian populations. Seventeen items reflect PTSD symptoms as outlined in the DSM-IIIR. Any symptoms receiving a score of 4 or higher count towards a PTSD diagnosis. It was designed to be suitable for use by lay interviewers. The two final questions determine whether symptoms were present for at least one month, and if they occurred the previous month or not. The scale appears to have sufficient validity and reliability in veteran populations, including in French and Spanish translations. In table 1 we present the main characteristics of specific questionnaires of PTSD. Table 1. Summary Descriptions of 17 Standardized Self-Report Measures of Posttraumatic Stress (Norris & Hamblen 2004) Scale

Number of items

Evidence of Stability

Evidence of consistency

Evidence of validity

Reporting period

NWS Module PTDS

20+ 17

Kappa = .45 r = .83

na .92

Strong Strong

PCL

17

r = .96

.97

Strong

Davidson TS Purdue PTSD-R

34 17

r = .86 r = .71

.97 .91

Strong Moderate

PTSD-Interview SPTSS

20 17

r = .95 na

.92 .91

Strong Moderate

SRIP

22

.60 – .97

.90 – .94

Strong

10–12 26

na r = .96

.85 – .90 .94

TSC.-40 TSI

40 100

na na

.90 – .92 .74 – .90

MMPI-PTSD

46

r = .94

.95

CR-PTSD

28

na

.93

Moderate Moderatestrong Moderate Moderatestrong Moderatestrong Moderate

Lifetime Past month Past month Past week Past month Lifetime Past 2 weeks Past 4 weeks Past week Past Week

SCL-Supplemented PTSD Revised Civilian Mississippi HTQ

43

na

na

Moderate

30

r = .84

.86 – .92

16 + 14

r = .92

.96

Moderatestrong Moderatestrong

PTSS Perm inventory

Note. NA: data not available.

Anchored to identified event No Yes Varies Yes Yes Yes No No No No

2 months 6 months

No No

Not explicit Past 2 weeks Past 2 weeks Varies

No

Partially

NA

Partially

No No

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3.3. Instruments That Measure Non-Specific Psychological Consequences of a Traumatic Event. The strongest comorbidity is found for mood disorders, followed by anxiety disorders such as phobias and panic attacks [1, 23-25]. 3.3.1. Available Instruments for a clinician administered evaluation: •

The SCID : Structured Clinical Interview for DSM

The SCID [26] is the structured tool most commonly used in the diagnosis of general psychopathology. It systematically uses all the criteria and symptoms in the clinical tables as they were defined by DSM-IV, featuring a question that the clinician or researcher must ask the patient with regard to each disorder. It is not limited to Axis I of the DSM, since a specific version (the SCID II) evaluates Axis II disorders (personality disorders). A module is devoted to acute stress disorder and another to the post traumatic stress disorder. The general evaluation thus allows one to investigate psychiatric comorbidity and personality disorders. The dichotomous nature of this instrument does not provide an evaluation in terms of severity. It has been used in many studies on populations of victims of post traumatic events [27, 24]. The French version has not been validated. •

The MINI

Le M.I.N.I (M.I.N.I. Mini International Neuropsychiatric Interview French Version 5.0.0) was constructed thanks to a coordinated collaboration by Yves Lecrubier for the French version and David Sheehan [28] for the English language version. It is currently used internationally. Its objective is to put at the disposal of health professionals a tool that facilitates the diagnosis of primary psychiatric disorders according to DSM-IV criteria. It consists of a structured interview featuring several modules. It includes module A for Major Depression, module E for Panic Disorder, module F for Agoraphobia and module L for Post-Traumatic Stress Disorder. This information provides a standardized categorical evaluation. 3.3.2. Available Instruments for a clinician administered evaluation : General Health Questionnaire 28 [29]. This instrument has particular relevance for the prospective evaluation of psychological repercussions of victims [30,31]1998). Darves-Bornoz has demonstrated the validity of this measure in a population of victims of sexual aggression. It features four components that constitute a measure of the validity of depression, social dysfunction, the intensity of somatic disorders and somatisation, and a measure of anxiety symptoms. The GHQ consists of 28 items—7 for each component: somatic symptoms, anxiety and insomnia, social dysfunction and major depression. Here again these scores only reflect the dimensional aspects of symptomatology and do not necessarily correspond to a psychiatric diagnosis. The sensitivity of the GHQ varies from 44% to 100% in various studies, with a specificity

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of 74 to 93% (average 82%). If one wants to detect a specific case, different thresholds have been proposed. For the GHQ-28, a threshold of 4 or more is commonly recognized [32]. •

The Beck Depression Inventory (BDI)

This questionnaire is the most widely used in adult populations to measure the intensity of depression. The revised version, the BDI-II [33], corresponds better to DSM-IV criteria. The validity of the French version has been verified and threshold marks have been identified. This questionnaire consists of 20 items. Each item is coded from 0 to 3 and a global score is obtained by adding the items. This version is available from Editions du Centre de Psychologie Appliquée. The original BDI has been used by Mezey and Taylor [34] in the study of trauma victims. •

The Scale “Hospital Anxiety and Depression” (HAD)

The HAD scale is a self-report questionnaire consisting of 14 structured items, developed by Zigmond and Snaithin [35] to screen for the most common psychopathological symptoms. Its goal is to identify the existence of pathologic anxiety and then to evaluate its severity. It has the distinction of not taking into account somatic symptoms in order to avoid confusion with somatic pathologies, and for this reason it is commonly used with outpatients and hospitalized patients, including both surgical and psychiatric patient populations. Each symptom is marked from 1 to 3 according to the intensity of symptoms during the previous week. The anxiety subscale contains 7 items, the same as for depression. The range of possible scores is from 0 to 21 for each subscale. Some authors [36] recommend a score of 8 as the optimal threshold for each subscale, though others [37] favor a global threshold score of 19 to diagnose an episode of major depression. This scale is therefore dimensional in nature with less attention to symptom features. •

The Social Support Questionnaire (SSQ)

The SSQ (Sarason et al [38]) provides two different measures of social support, one addressing the number of available people and the second the perceived quality of support, consisting of 6 items each. A French version has been adapted by Bruchon-Sweitzer et Paulhan[39, 19]. This measure is easily used and is considered as a reference [40].

4. The Sensitivity of the instruments to change Sensitivity, as defined by Pichot [40], describes the discrimination provided by an instrument. It is directly related to the number of items in the scale and the number of scores for each item. A compromise is necessary because a scale containing a large number of items is more sensitive but its use will be more difficult. Categorical instruments focusing on a response of yes / no for a diagnosis are less sensitive to change, excluding the CAPS, which offers an evaluation of intensity and a diagnosis but its usability remains difficult outside the research setting. As noted by Weathers et al [11], the CAPS has been

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used in more than 200 published studies, has excellent psychometric properties, and is notable for its sensitivity to change. Among the dimensional instruments which offer the best compromise to measure the change of intensity of post-traumatic stress disorder with the best sensitivity, one can recommend the use of the IES-R and the PCL. For depressive symptomatology, the HAD is a good compromise given its ease of use.

5. Research Perspectives A diagnosis whose validity is contested but which corresponds to a number of clinical situations is « complex PTSD » [42] (Friedman 2003) or DESNOS (Disorder of Extreme Stress Not Otherwise Specified [43]). This covers symptoms which are not incorporated in the diagnosis of PTSD, such as behavioral troubles (impulsivity, aggressivity, hypersexuality, eating disorders, substance or alcohol abuse, and self-destructive behavior), emotional disorders, (affective instability, anger, depressive mood, panic symptoms), cognitive difficulties, (fractured thinking, dissociative symptoms, partial amnesias) and somatic disorders. This diagnosis of DESNOS can be made in association with PTSD or independently. DESNOS is more common in individuals with a history of repeated traumas [44] but there is no currently consensual instrument to identify this disorder. It is an area where further research is required.

6. Conclusions The choice of measurement instruments in psychopathology depends on the objective of the evaluation and the method of implementing the evaluation. In general, self-evaluation is favored for a first evaluation in particular with a large population [45]. It is important to assess whether the proposed measures correspond to the questions posed and are adapted to the size and availability of the population. It is then necessary to assure the validity of the instrument using rigorous criteria, including for translated versions. Regarding this subject, one can demand precision from authors or translators. The translation of an instrument into a foreign language requires a precise process. The use of questionnaires appears often to be the simplest and most efficacious procedure, but it must always be done within a strict ethical context because it constitutes for the patient an important step. The patient must be clearly informed about what is expected from this measure.

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[22a] Watson C.G. Juba M.P. Manifold V. Kucala T. Anderson P.E.D. et al. The PTSD Interview : Rationale, description, reliability, and concurrent validity of a DSM III based Technique- Journal of Clinical Psychology 1991(3), 47, 179-188 [22b] D. Watson, L.S. Clark, A.R. Harkness, Structures of personality and their relevance to psychopathology Abnorm Psychol 103:18-31, 1994 [23] G. Lopez, D. Colle, & J.M. Catin, Conséquences psychologiques des agressions avec pénétrations sexuelles. Enquête épidémiologique des UMJ Paris. Psychologie Médicale, 1992, 24, 5, 447-451 [24] J.M. Darves-Bornoz, Rape-related psycho-traumatic syndromes. European Journal of Obstetrics & Gynecology and Reproductive Biology 71,59-65, 1997. [25] A.Y. Shalev S. Freedman, T. Peri D. Brandes T. Sahar S.P. Orr SP. R.K. Pitman, Prospective study of Posttraumatic Stress Disorder and Depression Following Trauma.American Journal of Psychiatry, 1998, 155, 5 : 630-637 [26] R. Spitzer, J.B. Williams, M. Gibbon, M.B. First, (1990). Structural Clinical Interview for DSM-IV. Washington DC : american psychiatric press inc. [27] T.M. Keane, L.C. Kolb, D.G. Kaloupek, Utility of psychosocial measurement in the diagnosis of posttraumatic stress disorder : results from the Department of Veterans Affair cooperative Study. J consult Clin Psychol, 1998, 66: 914-923 [28] D. Sheehan, Y. Lecrubier. Harnet Sheehan K. Amorim P. Janvis J. Weiller E. Herguetta T. Baker R. Dunbar G. The MINI International Neuropsychiatric Interview. The development and validation of a structured diagnostic psychiatric interview. Journal of Clinical Psychiatry, 1998: [suppl 20] 22-33. [29] M. Bolognini, W. Bettschart, M. Zehndergubler, L. Rossier, The validity of the French Version of the GHQ28 and PSYDIS in a Community Sample of 20 years olds in Switzerland. Eur. Arch. Psychiatr. Neurol. Sci.,1989, 238, 161-168 [30] P.E. Mullen, S. Romans-Clarkson, V.A. Walton, Herbison GP. Impact of physical and sexual abuse on women’s mental health. Lancet 1988, 16, 841-41 [31] J.M. Darves-Bornoz, F. Pierre, J.P. Lepine, A. Degiovanni , Gaillard, Screening for psychologically traumatized rape victims. P. Eur J Obstet Gynecol Reprod Biol 1998;77 : 71-75 [32] P. Pariente, J.P. Lepine JP. HA C. Lellouch J. Self-reported psychotropic drug use and associated factors in a French community sample. Psychol.med. 1992,22, 181-190 [33] Beck The Beck Depression Inventory (BDI) The revised -version is the BDI-II (1996) [34] G.C. Mezey, PJ. Taylor, Psychological reactions of women who have been raped. A descriptive and comparative study. Br J Psychiatry. 1988 Mar;152:330-9 [35] A.S. Zigmond, R.P. Snaith, The Hospital Anxiety and Depression Scale. Acta Psychiatr. Scand, 1983, 67, 361-370. [36] P. Barczack, N. Kane, S. Andrews, A.M. Congdon, J.C. Clay, T. Betts, Patterns of psychiatric morbidity in a genito-urinary clinic : a validation of the Hospital Anxiety Depression scale (HAD). Brit. J. Psychiatry, 1988, 152, 698-700. [37] D. Razavi, N. Delvaux, C. Farvacques, E. Robaye,Validation de la version française du HADS dans une population de patients cancéreux hospitalisés. Rev. Psychol. App., 1989, 39, 295-308. [38] I.G. Sarason, H.M. Levine, R.B. Bahsam,. Assessing Social Support: the Social Support Questionnaire. J Pers Soc Psychology 1983, 44: 127-139 [40] P. Kowal, J. Guelfi, V. Gaillac, « Instruments de mesure de l’adaptation sociale in Psychopathologie Quantitative, edtrs Guelfi J.D. Gaillac V. Dardennes R, 240-247 Masson 1995 278 Pages [41] P. Pichot,Historique du développement d’une échelle in Psychopathologie Quantitative Guelfi JD, Gaillac V, Dardennes R, 1995, Masson Paris , 9-22, 278 pages [42] M.J. Friedman, Post traumatic Stress Disorder. The latest Assessment and Treatment Strategies, ed Compact Clinical, Kansas city 2003, 108 pages [43] B. Van der Kolk, Assesment and treatment of complex PTSD, in Treating Trauma Survivor with PTSD, 127156, Ed Yehuda R, American Psychiatric Publishing Inc, Washington DC 2002

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[44] S. Roth, E. Newman, D. Pelcovitz, B. Van der Kolk F.S. Mandel F.S., Complex PTSD in Victims exposed to Sexual and Physical Abuse : Results from the DSM-IV field Trial for Posttraumatic Stress Disorder. Journal of Traumatic Stress, 1997, 4, 539-556 [45] A.Y. Shalev,. S. Freedman, T. Peri, D. Brandes, T. Sahar, Predicting PTSD in trauma survivors : prospective evaluation of self-report and clinician-administered instrument. British Journal of Psychiatry, 1997, 170 : 558-564

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

Psychological Screening Validation with Soldiers Returning from Combat Paul D. BLIESE, Kathleen M. WRIGHT, Amy B. ADLER 1 , and Jeffrey L. THOMAS Walter Reed Army Institute of Research Note: The views expressed in this abstract are those of the authors and do not reflect the official policy or position of the US Department of the Army or Department of Defense.

Abstract. Soldiers returning from combat military operations are at risk for developing a range of psychological problems. One way to facilitate the identification of these atrisk soldiers is to have them complete a psychological screening survey. Such a survey can be used to link soldiers reporting psychological problems with appropriate mental health services. The challenge of developing such a screen is to ensure that it is valid, short, and easy to administer. The US Army Medical Research Unit-Europe has been at the forefront of developing a valid psychological screen for use with soldiers at postdeployment. Research conducted prior to 2004 showed that screening needed to include five domains: post-traumatic stress disorder, depression, alcohol problems, anger, and relationship problems. Blind validation studies conducted in 2004 led to the selection of scale items and cut-offs for each domain resulting in an effective short screen with good sensitivity and specificity values. Finally, the question of when to conduct psychological screening at post-deployment has also been addressed through a comparison of prevalence estimates at immediate reintegration and three months postdeployment. Future research will examine scale refinement and the use of sleep problem questions in subsequent screening efforts. Keywords: Combat stress, posttraumatic stress disorder, mental health screening, deployment health

1. Psychological Screening Validation with Soldiers Returning from Combat Psychological screening in the US military provides service members with the opportunity to identify themselves as needing mental health support. While various mechanisms for screening exist, the U.S. Army Medical Research Unit-Europe (USARMU-E), an overseas activity of the Walter Reed Army Institute of Research, is engaged in developing a short, easily-administered and validated screening procedure for use with military personnel pre1

Corresponding Author: LTC Paul Bliese. Commander US Army Medical Research Unit-Europe. Nachrichten Kaserne, Karlsruher Str. 144, 69126 Heidelberg, Germany. Telephone: ++49-6221-17-2626, email: [email protected].

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and post-deployment. The goal of such screening is not selection, nor is it an effort to identify which individuals are fit to join the military and which should be excluded. Rather, psychological screening is a pro-active attempt to bring military mental health support to service members. The procedure is also transparent. The screen is designed to be straightforward, and service members know the purpose of the screen and the consequence of endorsing symptoms (e.g., that they will potentially be referred for further mental health evaluation).

2. Background Originally, psychological screening was mandated by the Office of the Secretary of Defense for Health Affairs in 1996 for U.S. service members deployed for more than 30 days to the Bosnia Area of Operations. The scales selected for inclusion in the original screening program were primarily scales published in the open literature and validated on civilian populations. The degree to which these scales and their associated cut-offs were valid for the military population, however, was not known. After the screening program in Bosnia was concluded in 1999, psychological screening continued to be requested by commanders for other operations (for a review of the program, see Wright et al. [1]. Thus, screening remained an important component of the health support provided to military personnel across the deployment cycle. In 2003, a mandated screening program was implemented with service members returning from combat operations in Iraq and Afghanistan (Department of Defense Form 2796). This newly mandated program underscores the continued importance that psychological screening has as part of the US military’s health program for deploying military personnel. Throughout the implementation and development of the psychological screening program, USAMRU-E has analyzed screening data and published several reports [2-3, 1-4, 5]. In total, USAMRU-E has processed screening data on over 100,000 Soldiers. Across a range of screening contexts, 15-28% of Soldiers have scored positive on the primary screening survey and 2 to 12% were recommended for a follow-up evaluation based on a brief clinical interview. Less than 1% of those screened were found to need immediate services because of threat to self or others.

3. Screening Validation Research In 2002, USAMRU-E research on psychological screening shifted to focus on assessing the validity of the scales and cut-offs used on the primary screening survey. At that time, a series of USAMRU-E studies developed the groundwork for systematically validating the psychological screening program [4]. The first in this series of studies involved the screening of US Soldiers preparing to deploy on a peacekeeping operation. This study was designed to assess the content validity of the screen. In all, 885 Soldiers were interviewed and 864 consented to have their data

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analyzed for research purposes. From this study [4], five content areas were identified as targets for screening: (1) traumatic stress, (2) depression, (3) relationship problems, (4) alcohol problems, and (5) anger problems. In addition, the screening survey also included selected background questions such as demographic information and clinical and personal history items. These additional questions were included because previous research had found them to be useful variables in predicting those who required follow-up services [1, 6]. Although the optimal content areas were identified, the scales that were used to screen for these clinical dimensions were lengthy. In addition, the scoring on some of the scales tended to be complicated. The scales were also a combination of those selected from the literature and had not been specifically validated with military personnel. Thus, there was a need to develop shorter, validated scales that could be used in a quick screening procedure. The subsequent USAMRU-E validation studies have focused on reducing the number of scale items and improving the sensitivity and specificity of the clinical scales. In each of the three studies conducted so far, a specific validation procedure was used. The procedure began with the administration of the psychological screening survey. All of those Soldiers exceeding previously established criteria on the clinical scales were interviewed as were a random selection of 20-30% those not exceeding established criteria. Those clinicians conducting the interview were blind to the individual’s status on the screening survey. A determination was then made based on the structured clinical interview as to whether follow-up clinical evaluation and/or services were needed. A flowchart describing the process is presented in Figure 1.

No Follow-up Needed

Primary Screen completed and scored

Exceed cut off?

100% of Yes

20% of No

Structured interview

Moderate Symptoms (subclinical) Standard Evaluation by Mental Health

Immediate Evaluation by Mental Health Figure 1. Flowchart for psychological screening research procedures.

This screening procedure was used twice in 2004. First, 732 US Soldiers stationed in Germany preparing to deploy to Iraq for a year were screened. In all, 356 were interviewed. Results from the pre-deployment screening study found that 75 (10.2%) Soldiers were referred for follow-up evaluation based on a brief clinical interview. Second, 1,568 US Soldiers recently returned from a year in Iraq were screened, and 592 were interviewed. Results from the post-deployment screening study found that 106 (6.8%) were referred for follow-up based on a brief clinical interview.

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Note that although these two studies included a pre-deployment and post-deployment sample, these were two very different units located in two different countries. A third study, conducted in 2005, involved post-deployment screening of those Soldiers who had participated in the 2004 pre-deployment data collection. Data presented here are taken from the 2004 studies only. Complete reports on these data are available [7-8].

4. Screening Results Sensitivity and specificity analysis compared the scores on the primary screening surveys with results from the structured clinical interviews (in part adapted from the MiniInternational Neuropsychiatric Interview [M.I.N.I., 9]. Bliese, Wright, Adler, Thomas [7] provided a detailed review of the sensitivity and specificity associated with each of the five clinical domains compared to the structured clinical interview results. For the purposes of the present brief report, we primarily review the results from the analysis assessing posttraumatic stress disorder. Post-traumatic stress disorder and trauma-related symptoms were the most common reason for referral to follow-up mental health services in the postdeployment sample. Thus, this clinical domain seems particularly relevant to Soldiers’ post-deployment psychological health. In predicting traumatic stress referrals we evaluated two measures: (1) the 17-item Post-Traumatic Stress Checklist [10], and (2) the 4-item Primary Care – Post-Traumatic Stress Disorder screen (PC-PTSD) which is also used in the DD Form 2796, the mandated Department of Defense screening form. The stem question on the PC-PTSD was “Have you ever had any experience that was so frightening, horrible, or upsetting that, in the past month, you…” (1) Have had any nightmares about it or thought about it when you did not want to? (2) Tried hard not to think about it or went out of your way to avoid situations that remind you of it? (3) Were constantly on guard, watchful, or easily startled? (4) Felt numb or detached from others, activities, or your surroundings? Response options were no and yes. Table 1 shows how various cut-off values on the PC-PTSD correspond to clinical providers' ratings as a result of the brief clinical interview based on the PTSD Module from the M.I.N.I. When the cut-off value was set at one, the primary screen identified 32 of the 37 Soldiers who were identified as positive by the clinical providers. This resulted in a sensitivity value of 0.86. At the same time, however, the criterion of requiring only one of the four items to be endorsed produced 148 false positives for a specificity value of 0.73. Table 1: PC-PTSD survey scores compared with provider referrals for post-traumatic stress symptoms Primary Screen with 1 or More

Clinical Provider

Negative

Positive

Negative

405

148

Positive

5

32

Clinical Provider

Negative

Primary Screen with 2 or More Positive

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Negative Positive

488

65

10

27

Primary Screen with 3 or More Clinical Provider

Negative

Positive

Negative

538

15

20

17

Positive

Primary Screen with 3 or More Clinical Provider

Negative

Positive

Negative

552

1

Positive

29

8

A large reduction in false positives was garnered by requiring Soldiers to endorse at least 2 items. In this case, the sensitivity and specificity were 0.73 and 0.88, respectively. When the cut-off value required Soldiers to endorse 3 or more items, the test sensitivity dropped fairly dramatically (0.46) and more referred Soldiers were missed by the primary screen than were identified. At the same time, though, the specificity increased to 0.97 and very few false positives were identified. A summary of the sensitivity and specificity values is provided in Table 2 (see also [8] for complete details). The table also includes phi-coefficients. These are measures of association bounded by 1 and -1. Values above 0.30 suggest moderately strong to strong relationships. Table 2: Sensitivity and Specificity for post-traumatic stress disorder screening cut-offs Index used for Evaluating Cut-off Cut-Off on PC-PTSD

Phi-Coefficient

Sensitivity

1 or more

0.31

0.86

Specificity 0.73

2 or more

0.41

0.73

0.88

3 or more

0.46

0.46

0.97

4 or more

0.42

0.22

1.00

When we compared the PC-PTSD to the PCL, we found that the three cut-offs recommended in the literature for the 17-item PCL (i.e. 30, 44 and 50) performed no better than did the four-item PC-PTSD. As can be seen in Table 3 below, sensitivity and specificity from the PCL was .94 and .79, respectively for the cut-off of 30; .60 and .96, respectively for the cut-off of 44, and .29 and .98, respectively for the cut-off of 50. Table 3: PCL survey scores compared with provider referrals for post-traumatic stress symptoms Primary Screen with PCL Score of 30 or More Clinical Provider

Negative

Positive

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Negative

435

115

Positive

2

33

83

Primary Screen with PCL Score of 44 or More Clinical Provider

Negative

Negative

530

Positive 20

Positive

14

21

Clinical Provider

Negative

Primary Screen with PCL Score of 50 or More Positive

Negative

539

11

Positive

25

10

Based on the need to create a short and highly specific test in screening survey, we recommend the PC-PTSD, using a cut-off value of 3 or more positive responses as the short screen criteria for identifying Soldiers with symptoms of traumatic stress. Soldiers’ responses to the PC-PTSD questions corresponded well to clinical providers’ evaluations. However, providers may want to consider a lower cut-off value depending upon interview resources. These results are comparable to results from a validation of the PC-PTSD conducted with civilians [11]. Initial validation work was also completed on depression. Two measures of depression were compared: The PHQ-Depression measure [12] and the Self-Rating Scale for Depression [13]. In general, PHQ-Depression items were generally more predictive of referrals than Zung items. The four best items from the PHQ were identified and a cut-off of one item resulted in good sensitivity and specificity both with the post-deployment sample (.77 and .88, respectively) and with the pre-deployment sample (.80 and .81, respectively). The four items selected were: (1) Little interest or pleasure in doing things, (2) Feeling down, depressed, or hopeless, (3) Poor appetite or overeating, and (4) Trouble concentrating on things such as reading the newspaper or watching television. Based on the validation study results from both pre- and post-deployment, we recommend using the four item PHQ-Depression measure and selecting individuals for follow-up clinical interviews if they report having one of these symptoms “More than Half the Days” in the last 2 weeks. The remaining dimensions, relationship problems, anger problems, and alcohol problems, also had acceptable sensitivity and specificity values and are presented in a separate technical report [7]. Further development is currently underway to increase their accuracy and ease of scoring. The two validation studies thus resulted in the selection of items for inclusion in a short screen, and a focus on those items that need to be improved in terms of their sensitivity and specificity. Furthermore, results from the screening studies identified an interesting problem in terms of the optimal timing for conducting psychological screening at post-deployment.

5. Timing

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In terms of timing, post-deployment screening has been conducted anywhere from the immediate post-deployment reintegration period to several months later. The postdeployment psychological screening study conducted by USAMRU-E in 2004, however, showed an increase in psychological symptom levels at 90 to 120 days post-reintegration in Soldiers returning from combat in Iraq [7]. In a matched sample of 509 Soldiers providing data both immediately post-reintegration and at 120 days post-reintegration, USAMRU-E found reports of depression, PTSD, anger, and relationship problems increased (see Table 4 for results from this matched data set). Interestingly, co-morbidity also increased over time. That is, at reintegration, over 80% of the soldiers who scored positive endorsed only one dimension; whereas 120 Days later, less than 60% endorsed only one dimension. Table 4. Comparison of symptom rates at Reintegration and 120 Day Post-Reintegration

Immediate Reintegration

120 Days PostReintegration

Traumatic Stress

Values 15 / 488

Percent 2.98%

Values 42 / 457

Percent 8.42%

Depression (PHQ)

5 / 502

0.99%

26 / 478

5.16%

General Distress (K6)

4 / 503

0.79%

24 / 479

4.77%

Anger Scale

44 / 456

8.64%

97 / 402

19.44%

Any of the above

53 / 448

10.58%

110 / 379

22.49%

While the 120-day rates in the matched sample of 509 are lower than rates reported in other comparative samples at the same time point [14], the results nonetheless show that psychological symptoms increase during the time from immediate reintegration to 120 days post-reintegration. This, in turn, suggests psychological screening may be particularly useful at 90 to 120 days post-reintegration relative to being conducted immediately at reintegration. Based on these results, the Commanding General of the US Army, Europe (USAREUR) tasked the Europe Regional Medical Command (ERMC) to develop a plan to screen all USAREUR Soldiers at 90 to 120 days after returning from a combat deployment.

6. Program Implementation The first Army unit to be affected by this plan, the 1st Armored Division (1AD), adopted the USAMRU-E’s newly developed short screen for their 120 day post-deployment screening program. The 1AD was able to implement the plan using primarily Division medical resources. Execution was delegated to Brigade Surgeons and in a little over two weeks nearly 6,000 Soldiers were screened. Estimates from this screening experience can

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be made to predict the impact of screening combat Soldiers at post-deployment on mental health resources. Specifically, from this experience, it is estimated that 27.5% of every 1000 combat Soldiers screened at post-deployment will score above cut-off criteria. Furthermore, we can estimate that for every 1,000 Soldiers, 28 Soldiers will require immediate referral to assess for harm to self or others; 8 Soldiers will be referred for alcohol problems; 17 Soldiers will be referred for family/relationship problems; 69 will require a standard mental health care appointment; and 153 will not require any referral, will refuse care, or will be lost to follow-up. Subsequent to the 1AD implementation of the screening program, the US Army, Europe screening program was noted by the Office of the Secretary of Defense for Health Affairs and a 26 January 2005 press release announced the wide-scale implementation of the screening program. On 10 March 2005, an official policy letter was signed, mandating 120-day post-deployment screening across the entire military [15]. The actual screening tool to conduct this screening is currently under consideration. USAMRU-E meanwhile is still engaged in further refining measures and optimal cut-off scores.

7. Future Directions USAMRU-E is engaged in re-validating the short screen and improving the measurement of alcohol problems and relationship problems. In addition, USAMRU-E is assessing a short, valid screen for sleep problems because research with the 1AD showed there were high prevalence rates of sleep problems particularly among those Soldiers with high combat exposure. Finally, USAMRU-E has just conducted the first program evaluation of the screening program. This program evaluation is one part of an additional goal to determine the impact screening has on the stigma associated with mental health problems and on perceptions of barriers to care. Through the development of an efficient one-page screening tool, recommendations for a brief structured clinical interview, and procedures that may help reduce stigma and other barriers to care, the USAMRU-E psychological screening program of research is geared to meet the needs of service members across the deployment cycle.

References [1] [2] [3] [4]

Wright, K.M., Huffman, A. H., Adler, A. B., & Castro, C. A. (2002, October). Psychological screening program overview. Military Medicine, 167, 853-861. Adler, A.B., Huffman, A.H., Bliese, P.D., Castro, C.A. (2005). The impact of deployment length and experience on the well-being of male and female soldiers. Journal of Occupational Health Psychology, 10(2), 121-137. Adler, A.B., Wright, K.M., Huffman, A.H., Thomas, J.L. & Castro, C.A. (2002). Deployment cycle effects on the psychological screening of soldiers. U.S. Army Medical Department Journal, 4/5/6, pp. 31-37. Wright, K.M., Thomas, J.L., Adler, A.B., Ness, J.W., Hoge, C.W., & Castro, C.A. (2005). Psychological screening procedures for deploying U.S. Forces. Military Medicine 170.

86 [5] [6] [7] [8] [9] [10] [11] [12] [13] [14] [15]

P.D. Bliese et al. / Psychological Screening Validation with Soldiers Returning from Combat Martinez, J.A., Huffman, A.H., Adler, A.B., & Castro, C.A. (2000). Assessing psychological readiness in U.S. soldiers following NATO operations. International Review of the Armed Forces Medical Services, 73, 139-142. American Psychiatric Association. (1994). Diagnostic and Statistical Manual of Mental Disorders (4th ed.). Washington, DC: Author. Bliese, P.D., Wright, K.M., Adler, A.B., Thomas, J.L. (2004). Validation of the 90 to 120 day postdeployment psychological short screen (U.S. Army Medical Research Unit-Europe Research Report 2004002). Heidelberg, Germany: USAMRU-E. Bliese, P.D., Wright, K.M., Adler, A.B., Thomas, J.L., & Hoge, C.W. (2004). Screening for traumatic stress among re-deploying soldiers (U.S. Army Medical Research Unit-Europe Research Report 2004-001). Heidelberg, Germany: USAMRU-E. Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E., et al. (1998). The MiniInternational Neuropsychiatric Interview (M.I.N.I.): The development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical Psychiatry, 59, 22-33. Weathers, F.W., Litz, B.T., Herman, D.S., Huska, J.A, Keane, T.M. (1993). The PTSD Checklist (PCL): Reliability, validity, and diagnostic utility. Paper presented at the annual meeting of the International Society for Traumatic Stress Studies, San Antonio. Prins, A., Ouimette, P. Kimerling, R., Cameron, R.P., Hugleshofer, D.S., Shaw-Hegwer, et al. (2004). The primary care PTSD screen (PC-PTSD): Development and operating characteristics. Primary Care Psychiatry, 9 (1), 9-14. Spitzer, R.L., Kroenke, K., & Williams, J.BW., and the Patient Health Questionnaire Primary Care Study Group. (1999, November). Validation and utility of a self-report version of PRIME-MD: The PHQ primary care study. Journal of American Medical Association, 282(18), 1737-1744. Zung, W. W. K. (1965). A Self-Rating Depression Scale. Archives of General Psychiatry, 12, 63-70. Hoge, C.W., Castro, C.A., Messer, S.C., McGurk, D., Cotting, D.I., & Koffman, R.L. (2004). Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. New England Journal of Medicine, 351(1), 13-22. Assistant Secretary of Defense for Health Affairs Memorandum, Policy for Department of Defense Postdeployment Health Assessment, March 10, 2005.

Acknowledgments We thank Ms. Rachel Prayner, Ms. Angela Salvi, Ms. Andrea Bellis, Ms. Kelley Rice, SGT Deena Carr, and SPC Nicol Sinclair for their technical support and gratefully acknowledge the support of the Europe Regional Medical Command (ERMC); the Southern European Task Force (SETAF); COL Richard Trotta, Commander, Vicenza Health Clinic and CPT Robert Johnson, Division Psychologist, 1st Infantry Division.

Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Psychophysiological Responses to TraumaRelated Stimuli in PTSD: Potential for Scenario Adaptation in VR Exposure Therapy Tanja JOVANOVIûa,1 , Sinisa POPOVIûb, and Dragica KOZARIû-KOVAýIû c Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA b University of Zagreb, Faculty of Electrical Engineering and Computing, Zagreb, Croatia c Referral Centre for the Stress Related Disorders of the Ministry of Health of the Republic of Croatia, Department of Psychiatry, Dubrava University Hospital, Zagreb, Croatia

a,1

Abstract. The following article reviews the use of psychophysiological tools in diagnosis and treatment assessment of posttraumatic stress disorder (PTSD). Several different psychophysiological systems are described and evaluated in terms of their diagnostic utility. The article further makes recommendations regarding strategies for the use of psychophysiology in future assessment of the disorder and for implementation within virtual reality exposure therapy. Keywords. Combat related Posttraumatic Stress Disorder, War veterans, Psychophysiological responses, Startle, Heart rate, Skin Conductance, Blood Pressure

Introduction One of the central symptoms of posttraumatic stress disorder (PTSD) is hyper-arousal in response to trauma reminders. Such arousal induces physical symptoms, such as racing heart, sweating, and shortness of breath. These symptoms are controlled by the autonomic nervous system and can be measured using psychophysiological equipment. Psychophysiological measurements include recordings of several autonomic nervous system outputs, such as heart-rate, blood pressure, skin conductance, respiratory rate, and body temperature. Thus, these measurements provide an objective way to measure the 1 Corresponding Author: Tanja JOVANOVIC, Department of Psychiatry & Behavioral Sciences, Emory University School of Medicine, 1365 Clifton Road, Atlanta, Georgia 30322, E-mail: [email protected]

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hyper-arousal symptoms related to trauma reactivity. Technological advances in the last decade have made such measurements possible with only a few pieces of equipment and without extensive training in psychophysiology. In other words, hyper-arousal can be measured in most clinical settings, and can be used in the diagnosis and treatment of PTSD.

1. Overview of psychophysiological measures Based on the DSM-IV criterion of hyper-arousal in PTSD [1], several investigators have examined the utility of psychophysiological recording in diagnosing the disorder (see [2] for recent review). Most of these studies have recorded from multiple psychophysiological systems, namely, the cardiovascular, electrodermal, electromyographic, and electrocortical systems. The first two systems are under the control of the autonomic nervous system (ANS), whereas the second two are under the control of the central nervous system (CNS) [3]. The cardiovascular measurements include electrocardiograms (ECG), blood pressure (systolic BP and diastolic BP), and respiratory rate (see Figure 1). Electrodermal responses measure changes in sweat gland activity and are measured from the skin on the fingers (see Figure 2). Electromyographic (EMG) measurements include measuring the muscles that control facial expression and eyeblink [3]. Electrocortical recordings are made from the scalp and record evoked response potentials from cortical areas—as opposed to the first few measurements, these require much more sophisticated equipment and are not as readily interpreted; therefore, we will focus on the first three systems. 1.1. Cardiovascular system Electrocardiograms can be used to analyze heart-rate in beats per minute (BPM), heart-rate variability (inter-beat interval, IBI), and respiratory sinus arrhythmia (RSA). Heart-rate is a direct index of sympathetic nervous system activation and is a very good indicator of hyper-arousal. Heart-rate variability and RSA are measures of parasympathetic nervous

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X

X

Figure 1. Placement of electrodes for facial electromyograph (EMG), and electrocardiogram (ECG). The X’s mark the placement of ECG electrodes (on the skin surface). The chest band measures respiration rate.

system activity which inhibits arousal; therefore, these measures are good indicators of individual differences in resilience to trauma. These measures can be easily recorded from electrodes placed on the wrist or on the chest. The chest placement is less sensitive to motion artefact and is therefore preferred over the wrist placement. Blood pressure and respiration rate can also be automatically measured using a wrist sensor and chest band, respectively (see Figure 1). These measures are useful concomitants to ECG, and respiration rate is necessary in order to assess RSA. 1.2. Electrodermal system Electrodermal measurements assess changes in sweat gland activity in the skin (Figure 2) that affect the electrical conductivity of the skin [3]. The electrodermal response measures skin conductance level (or skin resistance) and is also a direct index of sympathetic nervous system activation and thus a good measure of arousal. Historically it has been termed the Galvanic skin response (GSR) and is the most commonly used indicator of physical arousal. It has been used to measure habituation and learning effects as well as hyper-arousal. Electrodes can be placed either on the index and middle finger (Figure 2) or on the palm.

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Figure 2. Placement of electrodes for measuring skin conductance response

1.3. Electromyographic system Electromyographic measurements target the muscles in the face that control facial expression (Figure 3) [3], most commonly the zygomaticus muscles (cheek muscles that stretch the face during smiling, Figure 3A), the corrugator muscles (eyebrow muscles that control frowning, Figure 3B), and the frontalis muscles (forehead muscles that arch the eyebrows, Figure 3C). Electromyographic recordings are also made of the orbicularis muscles (Figure 3D) that contract during the eyeblink component of the startle reflex. Since these are under the control of the central nervous system, they are also under some degree of voluntary control. Thus, facial expressions, such as smiling or frowning can be purposefully generated or suppressed by the individual. For this reason, these measures are not as objective as the cardiovascular or electrodermal responses, which are not under voluntary control. However, electromyographic measurements of facial muscles are preferred when the stimuli can have either negative or positive interpretations [4]. Studies that examine positive as well as negative emotions can measure facial expressions using this system. While these muscle groups would not necessarily be of interest in analyzing hyper-arousal to trauma reminders, it may be useful in investigations of emotional numbing symptoms of PTSD.

C B D A Figure 3. Placement of facial EMG electrodes. A=zygomaticus muscle, B=corrugator muscle, C=frontalis muscle, and D=orbicularis muscle.

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Another muscle group that is measured using electromyographic equipment is the orbicularis muscle which contracts during the startle reflex (Figure 3D). This measure has been used frequently to assess exaggerated startle response, which is one of the most commonly reported symptoms of PTSD. While blinking is to some degree under voluntary control, the startle reflex has a short latency (30-120 ms) and thus occurs too quickly to be intentionally generated. However, the startle reflex itself can be modulated by different emotional states, such as fear. A large body of literature has examined the increase in the startle response during fearful situations, called fear-potentiated startle [5]. This is also a good laboratory measure of fear and has the potential to be used in assessment of PTSD.

2. Psychophysiology as a diagnostic tool for PTSD 2.1. Hyper-arousal to audiovisual combat stimuli As mentioned above, one of the cardinal symptoms of PTSD, according to the DSM-IV, is physiological hyper-arousal, or exaggerated reactivity, to trauma reminders [1]. Early studies capitalized on this symptom and used combat-related stimuli to evoke arousal in Vietnam veterans with PTSD. The first studies to examine hyper-arousal using physiological measurements used standardized combat stimuli, such as combat sounds like mortar explosions or gunfire, and standardized pictures of combat. In these studies all participants would be exposed to the same sets of stimuli while their responses were measured. In a series of studies, Blanchard and collaborators have successfully discriminated veterans with or without PTSD on the basis of heart-rate responses to combat sounds (95% correct for veterans with PTSD and non-veteran controls [6]; 81% correct [7]; 86.4% correct for combat veterans with PTSD vs. without PTSD [8]). They measured heart-rate, systolic and diastolic blood pressure, skin conductance, and frontalis EMG in response to three conditions: (a) resting, (b) mental arithmetic, and (c) a combination of music, silence, and combat sounds and found that PTSD veterans had higher heart-rate responses to all sounds relative to non-PTSD veterans (Figure 4). Furthermore, Blanchard, Kolb, and Prins [9] found that a discriminant function based on measures of heart-rate alone correctly identified an initial sample of 84% of combat veterans with PTSD and 75% of all veterans. Studies using standard audiovisual combat imagery found that heart-rate was the most sensitive psychophysiological measure in distinguishing traumatized individuals with and without PTSD. While heart-rate alone showed a high degree of discrimination, there was still a relatively high rate of both false positive (i.e. non-PTSD patients classified as PTSD), and false negatives (PTSD patients classified as non-PTSD) according to interview diagnoses.

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PTSD VETERANS

HEART RATE (bpm)

COMBAT VETERANS 84 79 74 69 64 MUSIC

SILENCE

COMBAT SOUNDS

Figure 4. Heart-rate in response to different sounds in veterans with and without PTSD. Adapted from Pallmeyer et al. [8]

While the advantage of using standardized combat stimuli is that all participants have the same exposure and therefore the differences in response could be attributed to the disorder, it is possible that the standard stimuli did not encompass all possible combat experiences, i.e., that some veterans experienced different types of trauma and the “standard” stimuli might not serve as trauma reminders for a particular individual’s unique experiences. Therefore, a veteran with PTSD may not show hyper-arousal to stimuli that are not part of his traumatic experience [2]. 2.2. Hyper-arousal to script-driven imagery In order to address the problems with standardization of trauma imagery, Orr and Pitman [10] modified a procedure developed by Lang and colleagues to study phobias [11]. In this method, the participant describes an actual traumatic event from their combat experience (see Box 1). This event is then edited into a 30-second script which is read and recorded by the experimenter [10]. The script is then played back to the participant who is then instructed to imagine the scene while psychophysiological data are recorded and compared to physiological recordings made during a resting period. This method has been used with many different PTSD populations: World War II veterans [12], Korean War veterans [12], Vietnam War veterans [13], Israeli War veterans [14], Vietnam War combat nurses [15], as well as sexual assault victims [16]. In all these populations, PTSD patients exhibit a stronger HR and SC response to scripts than non-PTSD trauma survivors (Figure 5) [11, 12, 13, 15, 16]. In studies using script-driven imagery, skin conductance was found to be the most sensitive measure of hyper-arousal in PTSD. Pitman and colleagues [11] have suggested that the skin response may be more sensitive to specific autobiographical combat trauma rather than standard combat images, and thus may have more discriminative power than heart-rate. While script-driven imagery is more flexible in evaluating different types of

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trauma, it is relatively time consuming, introduces variability, and may decrease hyperarousal by pre-exposing the individual during script construction.

You’re at a field hospital in Vietnam. It’s been another long day in the oppressive heat and you’re very tired. Suddenly you hear the sound of incoming helicopters. You take a deep breath and your heart starts to pound. You pause for a minute to listen more closely. The sounds are stronger and louder than usual. This can only mean another mass casualty situation. Your muscles tensing, you spring into action to get ready for the wounded. As you look down at the first young victim, you feel a trickle of sweat roll down your neck. You try not to recoil at the sight of his devastating wounds. Despite the nausea you feel inside, you force yourself to smile reassuringly. [17] Box 1. Example of a trauma script from a Vietnam War nurse.

SC CHANGE

8 6 4 2 0 PTSD

CONTROL

SC RESPONSE (microohm)

HEART RATE (bpm)

HR CHANGE 0.6 0.5 0.4 0.3 0.2 0.1 0

PTSD

CONTROL

Figure 5. Heart-rate and skin conductance change in response to trauma imagery compared to resting baseline. Adapted from Pitman et al. [13]

In 1998 Keane and colleagues [18] published the results of the largest study to date to look at the utility of psychophysiological measures in diagnosing PTSD. The study was a multi-site Department of Veterans Affairs Cooperative Study investigating 1,461 Vietnam veterans using script-driven imagery and standardized combat images with psychophysiological recordings. While the study did not find a perfect correlation between interview-based PTSD diagnosis and psychophysiological reactivity, the authors concluded that psychophysiological data did provide useful and objective assessment of the disorder. However, there was still concern regarding false positives and false negatives in terms of classification, indicating the need for further study to explore whether the interview processes needs re-evaluation or the psychophysiology alone does not provide enough information for assessment.

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2.3. Exaggerated startle response Although exaggerated startle response was one of the earliest symptoms related to combat stress, the psychophysiological evaluation of startle in PTSD patients has not yielded consistent results; in fact, this finding is the most equivocal of all (reviewed in [2]). Studies of Gulf War veterans with PTSD found both self-reported [19] and physiologically [20] exaggerated startle compared to non-PTSD veterans. On the other hand, Vietnam veterans with PTSD did not show increased startle [21], unless they were subjected to a threatening context [22]. Grillon [23] concluded that increased baseline startle may be related to recency of combat exposure and may decline after a few years. On the other hand, all veterans may be more sensitive to anxiety or fear-potentiated startle [23]. 2.4. Dissimulation of response Given the argument that psychophysiological measurements provide an objective assessment tool free of the risk of malingering and subjectivity of self-report measures, it is important to address whether psychophysiological reactivity can be “faked”. Several studies have examined this issue. In the first study Gerardi and colleagues [7] instructed veterans with PTSD to consciously lower their physiological responses in order to appear to be without PTSD; while veterans without PTSD were instructed to consciously elevate their physiological responses to combat stimuli so as to appear to have PTSD. While the PTSD veterans could not decrease their physiological response, non-PTSD veterans could elevate their heart-rate and frontalis EMG response. However, when blood pressure and resting heart-rate were included in the analysis, both the “real” and “fake” PTSD patients were correctly classified to their respective categories with high accuracy. In another study Orr and Pitman [24] replicated the findings with non-PTSD veterans. When instructed to respond to the combat stimuli “as if they had PTSD” and to get “emotionally worked-up”, the non-PTSD veterans could elevate their heart-rate; however, there were still significant differences in skin conductance and corrugator EMG between the “real” and the “fake” PTSD veterans to allow a discriminant function to accurately classify the patients to their categories. In terms of the exaggerated startle response, the reflexive contraction of the eyeblink muscle occurs approximately 30 to 120 ms after the auditory stimulus—this time frame is too short to allow for conscious elevations of startle; thus it may be the most difficult to influence voluntarily. Taken together, these studies indicate that some psychophysiological measures may be easier to dissimulate than others; therefore, several different measures should be collected in order to achieve reliable psychophysiological assessments.

3. Psychophysiology as assessment of PTSD treatment As markers of arousal, psychophysiological measurements can provide useful information during treatment, especially during exposure-based therapy. First, psychophysiological data can indicate the level to which the patient is engaged in the exposure, or activated by the

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memories of the traumatic events. One of the key components of exposure therapy is to activate the patient during exposure so that he or she is reliving the traumatic experience. Second, psychophysiological monitoring can indicate within-session habituation to the exposure treatment; this information can guide the therapist in increasing or decreasing the level of exposure. Finally, psychophysiological reactivity to traumatic stimulation can be used as an outcome measure for treatment efficacy. Most therapists use subjective units of distress (SUDs) or other similar subjective measures to gauge the patient’s level of engagement and habituation throughout the exposure therapy session. However, psychophysiological data offer the benefit of objective measurement of these phenomena. Several early case reports of Vietnam veterans [25, 26] measured psychophysiological responding during imaginal flooding, a technique similar to exposure therapy, and found that the patients were highly activated during exposure and decreased responding with treatment. A study by Boudewyns and Hyer [27] examined psychophysiological responding during script-driven imagery and found that 3 month follow-up reductions in symptoms were associated with decreases in heart-rate and especially skin conductance responses to traumatic imagery immediately after therapy. Finally, Pitman and colleagues [28] examined heart-rate, skin conductance, and facial EMG during imaginal flooding treatment and found that the heart-rate habituation to exposure within a session and between sessions was associated with fewer daily memory intrusions of the traumatic event that was treated. A recent study used heart-rate and acoustic startle response as a treatment outcome measure for cognitive-behavior therapy in PTSD [29]. These research studies suggest that measures of physiological responses to traumatic imagery can be a valuable objective evaluation of therapeutic interventions. The accessibility of these techniques should increase their use as evaluation tools in treatment, especially with the increase in new approaches to exposure therapy, such as virtual reality exposure therapy (VRET).

4. Virtual reality exposure therapy and PTSD Virtual reality provides a new way to use exposure therapy in treatment of PTSD. It has been successfully used in treatment of phobias, such as fear of flying [30] and fear of heights [31]. There have been two studies that have used virtual reality in PTSD treatment. The first study was with Vietnam veterans (Virtual Vietnam [32, 33]) and the second was with survivors of the 9/11/2001 terrorist attacks on the World Trade Center in New York (Virtual WTC [34, 35]). In both of these studies, the exposure treatment resulted in decreases in SUDs; however, psychophysiological responses were not measured. The studies with treatment of phobias in virtual reality that have monitored physiological response found that changes in heart-rate and skin conductance were associated with immersiveness or presence in the virtual environment. Thus the psychophysiological data, as an objective index of arousal, can provide useful markers of the patient’s activation in the virtual reality exposure therapy session. Furthermore, Ressler and colleagues [31] found that a reduction in the number of fluctuations in skin conductance during exposure to the virtual elevator in the fear of heights study was associated with across-session habituation and symptom improvement.

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5. Future use of psychophysiology in virtual reality exposure therapy Future studies as well as clinical treatment trials using VRET should make use of psychophysiological monitoring in diagnosis and assessment of treatment. New computer technology allows for cross-integration of psychophysiological output and computergenerated exposure therapy so that the computer can adjust the virtual exposure and adapt the scenario for each individual patient. In such a closed loop feedback system the computer could increase or decrease the level of stimulation according to the arousal level of the patient. However, it is important to note that the psychophysiological information should not be used to the exclusion of therapists. As mentioned above, the psychophysiological data and interview-based diagnoses do not correspond perfectly. Thus it is very important to use several different measures of psychophysiological systems and to use these measures in conjunction with standard self-report symptom scales and clinicianbased interviews. Such a multi-modal assessment plan would have a high degree of sensitivity and specificity for the disorder. Furthermore, the exposure therapy should still be guided by a clinician who can interpret the psychophysiological data as well as use clinical judgment with regard to the patient’s activation and habituation during VRET.

6. Design of VRET study in Croatia 6.1. Participants The participants will be Croatian combat veterans with and without PTSD. The sample will be recruited from an estimated 1,000,000 people exposed to combat trauma from 1991 to 1995 [36]. PTSD will be diagnosed using a multi-modal assessment plan, including structured diagnostic interview, psychiatric evaluation, psychometric examination, tests of malingering, and psychophysiological assessment. The psychophysiological assessment will evaluate hyper-arousal in response to trauma stimuli and startle to loud sounds. 6.2. Apparatus Patients will be tested for hyper-arousal before and after treatment using the Biopac system MP150 (Biopac Systems, San Diego, CA) for psychophysiological data recording. We will record heart-rate, systolic and diastolic blood pressure, respiration rate, skin conductance, body temperature and facial EMG. The combat stimuli will be presented in the Virtual environment. In the Virtual environment the patients will first be habituated to the VE for 10 minutes after which we will collect resting baseline data on all the psychophysiological measures. We will measure psychophysiological responsiveness to the combat imagery as both a component of diagnostic assessment and to track activation and progress in the VE.

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References [1] American Psychiatric Association. Diagnostic and statistical manual of mental disorders (4th ed.) (1994). Washington, DC. [2] S.P. Orr, L.J. Metzger, M.W. Miller, D.G. Kaloupek. Psychophysiological assessment of PTSD. J.P. Wilson, T.M. Keane, Ed. Assessing Psychological Trauma and PTSD (2nd ed.). (2004). Guilford Press: New York, NY. [3] J. T. Cacciopo, L.G. Tassinary, G. G. Bernston. Handbook of Psychophysiology (2nd ed.). (2004). Cambridge University Press [4] P.J. Lang, M.M. Bradley, B.N. Cutberth. Emotion, attention, and the startle reflex. Psychological Review, 97 (1990), 377-395. [5] M. Davis, D.L. Walker, Y. Lee. Roles of the amygdala and bed nucleus of the stria terminalis in fear and anxiety measured with the acoustic startle reflex: Possible relevance to PTSD. Annals of the New York Academy of Sciences, 821 (1997), 305-331. [6] E.B. Blanchard, L.C. Kolb, T.P. Pallmeyer, R.J. Gerardi. A psychophysiological study of post traumatic stress disorder in Vietnam veterans. Psychiatric Quarterly, 54 (1982), 220-229. [7] R.J. Gerardi, E.B. Blanchard, L.C. Kolb. Ability of Vietnam veterans to dissimulate a psychophysiological assessment for post-traumatic stress disorder. Behaviour Therapy, 20 (1989), 229-243. [8] T.P. Pallmeyer, E.B. Blanchard, L.C. Kolb. The psychophysiology of combat-induced post-traumatic stress disorder in Vietnam veterans. Behaviour Research and Therapy, 24 (1986), 645-652. [9] E.B. Blanchard, L.C. Kolb, A. Prins. Psychophysiological responses in the diagnosis of posttraumatic stress disorder in Vietnam veterans. Journal of Nervous and Mental Disease, 179 (1991), 97-101. [10] R.K. Pitman, S.P. Orr, D.F. Forgue, J.B. de Jong, J.M. Claiborn. Psychophysiologic assessment of posttraumatic stress disorder imagery in Vietnam combat veterans. Archives of General Psychiatry, 44 (1987), 970-975. [11] P.J. Lang, D.N., Levin, G.A. Miller, M.J. Kozak. Fear behaviour, fear imagery, and the psychophysiology of emotion: The problem of affective response integration. J Abnormal Psychology, 92 (1983), 276-306. [12] S.P. Orr, R.K. Pitman, N.B. Lasko, L.R. Hertz. Psychophysiological assessment of posttraumatic stress disorder imagery in World War II and Korean combat veterans. J Abnormal Psychology, 102 (1993), 152159. [13] R.K. Pitman, S.P. Orr, D.F. Forgue, B. Altman, J.B. de Jong, L.R. Hertz. Psychophysiologic assessment to combat imagery of Vietnam veterans with posttraumatic stress disorder. J Abnormal Psychology, 99 (1990), 49-54. [14] A.Y. Shalev, S.P. Orr, R.K. Pitman. Psychophysiological assessment to traumatic imagery in Israeli civilian patients with posttraumatic stress disorder. American J Psychiatry, 49 (1992), 870-875. [15] M.A. Carson, L.A. Paulus, N.B. Lasko, L.J. Metzger., J. Wolfe, S.P. Orr, R.K. Pitman. Psychophysiologic assessment of posttraumatic stress disorder of Vietnam nurse veterans who witnessed injury or death. J Consulting and Clin Psychology, 68 (2000), 890-897. [16] S.P. Orr, J.L. Meyerhoff, J.V. Edwards, R.K. Pitman. Heart rate and blood pressure resting levels and responses to generic stressors in Vietnam veterans with posttraumatic stress disorder. J Traumatic Stress, 11 (1998), 155-164. [17] S.P. Orr, L.J. Metzger, D. Sussman, N. Pole. Psychophysiology 101: Introduction to measures and methods. Presented at the 20th Annual Meeting of the International Society of Traumatic Stress Studies (2004). [18] T.M. Keane, L.C. Kolb, D.G. Kaloupek, S.P. Orr, E.B. Blanchard, R.G. Thomas, F.Y. Hsieh, P.W. Lavori. Utility of psychophysiological measurement in the diagnosis of posttraumatic stress disorder: Results from a Department of Veterans Affairs cooperative study. J Consulting and Clin Psychology, 66 (1998), 914-923. [19] S.M. Southwick, C.A. 3rd Morgan, A. Darnell, J.D. Bremner, A.L. Nicolaou, L.M. Nagy, D.S. Charney. Trauma-related symptoms in veterans of Operation Desert Storm: a 2-year follow-up. American J Psychiatry, 152(1995),1150-1155. [20] C.A. 3rd Morgan, C. Grillon, S.M. Southwick, M. Davis, D.S. Charney. Exaggerated acoustic startle reflex in Gulf War veterans with posttraumatic stress disorder. American J Psychiatry, 153(1996), 64-68. [21] C. Grillon, C.A. 3rd Morgan, S.M. Southwick, M. Davis, D.S. Charney. Baseline startle amplitude and prepulse inhibition in Vietnam veterans with posttraumatic stress disorder. Psychiatry Research, 64 (1996), 169-178.

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[22] C. Grillon, C.A. 3rd Morgan, M. Davis, S.M. Southwick. Effects of experimental context and explicit threat cues on acoustic startle in Vietnam veterans with posttraumatic stress disorder. Biological Psychiatry, 44 (1998), 1027-1036. [23] C. Grillon, J. Baas. A review of the modulation of the startle reflex by affective states and its application in psychiatry. Clin Neurophysiol, 114 (2003), 1557-1579. [24] S.P. Orr, R.K. Pitman. Psychophysiologic assessment of attempts to simulate posttraumatic stress disorder. Biological Psychiatry, 33 (1993), 127-129. [25] J.A. Fairbank, T.M. Keane. Flooding for combat-related stress disorders: Assessment of anxiety reduction across traumatic memories. Behavior Therapy, 13 (1982), 499-510. [26] T.M. Keane, D.G. Kaloupek. Imaginal flooding in the treatment of a posttraumatic stress disorder. Journal of Consulting & Clinical Psychology, 50 (1982),138-140. [27] P. Boudewyns, L. Hyer. Physiological response to combat memories and preliminary treatment outcome in Vietnam veteran PTSD patients treated with direct therapeutic exposure. Behavior Therapy, 21 (1990), 63-87. [28] R.K. Pitman, S.P. Orr, B. Altman, R.E. Longpre, R.E. Poire, M.L. Macklin, M.J. Michaels, G.S. Sketekee. Emotional processing and outcome of imaginal flooding therapy in Vietnam veterans with chronic posttraumatic stress disorder. Comprehensive Psychiatry, 37 (1996), 409-418. [29] M.G. Griffin, P.A. Resick, Psychophysiological responses as treatment outcome indicators in PTSD. Presented at the 19th Annual Meeting of the International Society for Traumatic Stress Studies, (2003). [30] B.K. Wiederhold, D.P. Jang, S.I. Kim, M.D. Wiederhold. Physiological monitoring as an objective tool in virtual reality therapy. Cyber Psychology & Behavior, 5 (2002), 77-82. [31] K.J. Ressler, B.O. Rothbaum, L. Tannenbaum, P. Anderson, K. Graap, E. Zimand, L. Hodges, M. Davis. Cognitive enhancers as adjuncts to psychotherapy: use of D-cycloserine in phobic individuals to facilitate extinction of fear. Archives of General Psychiatry. 61 (2004), 1136-1144. [32] B.O. Rothbaum, L. Hodges, R. Alarcon, D. Ready, F. Shahar, K. Graap, J. Pair, P. Hebert, D. Gotz, B. Wills, D. Baltzell. Virtual reality exposure therapy for PTSD Vietnam Veterans: a case study. Journal of Traumatic Stress. 12(1999), 263-271. [33] B.O. Rothbaum, L. Hodges, D. Ready, K. Graap, R. Alarcon. Virtual reality exposure therapy for Vietnam veterans with posttraumatic stress disorder. Journal of Clinical Psychiatry. 62 (2001), 617-622. [34] J. Difede, H.G. Hoffman. Virtual reality exposure therapy for World Trade Center post-traumatic stress disorder: A case report. Cyber Psychology & Behavior, 5 (2002), 529-535. [35] J. Difede, H.G. Hoffman, N. Jaysinghe. Innovative use of virtual reality technology in the treatment of PTSD in the aftermath of September 11. Psychiatric Services 53 (2002), 1083-1085. [36] D. Kozaric-Kovacic, A. Borovecki. Malingering PTSD. T.A. Corales, Ed. Focus on Posttraumatic Stress Disorder Research. (2005). Nova Science Publishers

Section III Management of Posttraumatic Stress Disorder

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Pharmacotherapy Research in Posttraumatic Stress Disorder Neven HENIGSBERG 1 Croatian Institute for Brain Research, Medical School, University of Zagreb, Croatia

Abstract. Given the high prevalence and considerable individual and societal costs of PTSD, there are relatively few randomized, placebo-controlled trials in PTSD. Four placebo controlled trials have been performed with MAOIs, three with TCAs. Only one randomized placebo controlled trial was performed with benzodiazepines class, showing no effect of alprazolam on core PTSD symptoms. The majority of trials were done with SSRIs and novel antidepressants, the most of them showing moderate effect sizes over placebo. In past clinical trials antidepressants appeared with the best overall efficacy for the treatment of PTSD, although their effect may not be present in all symptom clusters. Although duration of majority of trials in psychiatry is conventionally set to 12 weeks, clinical trials in PTSD may require the acute phase of treatment to go beyond initial 12 weeks of treatment, especially if the trial includes more severely ill patients. Further clinical research is warranted, using new compounds, as well as those already marketed for other indications. It remains essential to investigate if certain treatments are more effective for particular symptom sets or for some subgroup of PTSD patients. Due to high placebo response and moderate effects of drugs researched in PTSD it is difficult to avoid the use of placebo in PTSD trials. Keywords. Pharmacotherapy, pharmacological treatment, PTSD, medications, SSRIs, antidepressants, benzodiazepines, placebo, effect size

1. Use of Placebo in PTSD Trials Khan et al.[1] evaluated the Food and Drug Administration (FDA) Summary Basis of Approval (SBA) reports to compare the magnitude of placebo response, magnitude of psychotopic drug response, and drug placebo differences among various diagnostic groups such as depression, anxiety, and psychotic disorders. In all psychiatric indications placebo response was considerable. The average percent improvement on placebo in PTSD trials was around 32% on primary outcome measure. This finding suggests that placebo use should be continued for newer agents being tested for all of the psychiatric disorders, including PTSD. This is further corroborated by 38% of placebo responders in PTSD trials, the percentage which was found in several trials involving both investigational drugs and placebo. Due to so high placebo response in PTSD clinical trials, the most clear ground to establish the superiority of test drug remains the trial involving placebo. The other 1 Corresponding Author: Neven Henigsberg, Head, Department of Psychopharmacology, Croatian Institute for Brain Research, Medical School, University of Zagreb, Salata 12, HR-10000, Zagreb, Croatia; E-mail: [email protected].

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approach, based on showing non-inferiority of the test drug over the drug with already known efficacy was not used so far in published trials, probably because the large sample sizes would be needed to reach appropriate statistical power.

2. Effect Size Estimation Clinical trials are usually performed within a framework of hypothesis testing. Assuming that a new treatment is more effective than a comparative one, researcher would create the null hypothesis that the new treatment is not effective, and then will try to reject it. An alternate hypothesis is then accepted, stating that the new treatment is significantly better than the comparative one. Such an approach fits the purpose of a particular trial, but observed level of statistical significance could not be usefully compared between the different trials. If a researcher would like to compare results from two different trials, both involving comparable study design, an alternative approach of constructing confidence intervals around a point estimate for a difference between active drug and placebo could be used. That approach is appropriate only if the same primary parameters were used in both studies. However, a number of outcome measures have been employed in clinical trials in PTSD, making impossible direct comparison of primary endpoints. The standardized mean difference is the effect size generally recommended in clinical trials assessing treatment effects on outcomes measured on a different continuous scales. Unlike significance tests, these indices are independent of sample size. In general, effect size is measured as the standardized different between two means, where pooled standard deviation is denominator. By standardizing the effect, the effect size becomes dimensionless. Cohen[2] defined effect sizes as "small, d = .2," "medium, d = .5," and "large, d = .8". Generally, the larger the effect size, the greater is the impact of an intervention. In order to enable comparisons between different outcome measures used in PTSD trials, effect size estimation is used in this paper to compare efficacy of different medications wherever possible.

3. Medications Studied in PTSD Review of scientific literature shown only 26 randomized placebo-controlled clinical trials in PTSD. Active medication studied in these trials, duration of trials and number of subjects included in them is displayed in Table 1. As could be noted, four drug classes were investigated more extensively in PTSD: monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs) and serotonin-potentiating non-SSRIs. Only two MAOIs were studied in randomized, controlled trials (RCTs): phenelzine and brofaromine, the later being studied in considerably larger number of subjects. Of the four placebo-controlled trials with MAOIs, there is one positive and one negative phenelzine trial, and one partly positive and one largely negative brofaromine report. Similarly with TCA trials, most MAOIs studies were performed with combat veterans known to be treatment-refractory. The SSRIs are the most studied drug class in PTSD, with the largest number of placebo-controlled, double blind clinical trials, and with largest number of study

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subjects enrolled in those trials. Sertraline and paroxetine have the largest databases regarding placebo-controlled, double-blind clinical studies in PTSD, and these two SSRIs are the only FDA-approved drugs for PTSD.

Table 1. Summary of randomized clinical trials in PTSD

Trial

Active Treatment

Monoamine Oxidase Inhibitors Shestatzky et al. (1988)[3] phenelzine Kosten et al. (1991)[4] phenelzine Katz et al. (1994)[5] brofaromine Baker et al. (1995)[6] brofaromine Tricyclic Antidepressants Reist et al. (1989)[7] desipramine Davidson et al. (1990)[8] amitriptyline Kosten et al. (1991)[4] imipramine Selective Serotonin Reuptake Inhibitors van der Kolk et al. (1994)[9] fluoxetine Connor et al. (1999)[10] fluoxetine Hertzberg et al. (2000)[11] fluoxetine Martenyi et al. (2002)[12] fluoxetine Brady et al. (2000)[13] sertraline Amital et al. (1999)[14] sertraline Davidson et al. (2001)[15] sertraline Zohar et al. (2002)[16] sertraline sertraline, Tucker et al. (2003)[17] citalopram Tucker et al. (2001)[18] paroxetine Marshall et al. (2001)[19] paroxetine Serotonin-Potentiating Non-SSRIs Davis et al. (2004)[20] nefazodone Davidson et al. (2003)[21] mirtazapine Mood Stabilizers Hertzberg et al. (1999)[22] lamotrigine Antipsychotics Butterfield et al. (2001)[23] olanzapine Benzodiazepines Braun et al. (1990)[24] alprazolam Other Kaplan et al. (1996)[25] inositol Raskind et al. (2003)[26] prazosine Heresco-Levy et al. (2002)[27] D-cycloserine low-dose Aerni et al. (2004)[28] cortisol

Number of Subjects

Duration of Trial

13 37 68 113

5 weeks 8 weeks 14 weeks 12 weeks

18 46 41

4 weeks 8 weeks 8 weeks

64 53 12 301 187 51 208 42

5 weeks 12 weeks 12 weeks 12 weeks 12 weeks 10 weeks 12 weeks 10 weeks

58

10 weeks

307 551

12 weeks 12 weeks

41 29

12 weeks 8 weeks

15

12 weeks

15

10 weeks

16

5 weeks

13 10 11

4 weeks 20 weeks

3

3 months

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Serotonin-potentiating non-SSRIs is the group of medications that predominantly potentiates serotonin though a number of different mechanisms[29]. They may block the reuptake of serotonin, but they are non-selective. Some block various post-synaptic serotonergic and noradrenergic receptors, while others may block the reuptake of norepinephrine to a lesser extent. Of that class, only nefazodone and mirtazapine were studied, but both studies included low number of patients. Nefazodone primarily blocks serotonin 5-HT2 post-synaptic receptors but also it moderately inhibits the pre-synaptic reuptake of serotonin and norepinephrine, causing the diffuse stimulation of 5-HT receptors, expect 5-HT2. Nefazodone posses potent anxiolytic properties. Mirtazapine is an antagonist to 5-HT2 and 5-HT3 receptors, and is a potent antagonist of D2 – autoreceptors, that results in potentiation of both norepinephrine and serotonin. The use of anticonvulsants in treating PTSD arouse from the fact that some of the symptoms belonging to the hyperarousal cluster, especially anger outbursts and irritability, occur also in epilepsy and are effectively treated by anticonvulsants. It’s potential use in PTSD is also along with a kindling model suggested to elucidate some PTSD symptoms. Until now, only one RCT was performed with anticonvulsant medication in a study by Hertzberg et al. The most promising finding of that study was that 50% of subjects of the lamotrigine group versus 25% of the placebo group were assessed responders. A number of retrospective trials indicated a possible role of benzodiazepine treatments in PTSD, but only one RCT was performed, failing to prove these assumptions. Braun et al. performed a 5-week crossover design study, but no betweengroup differences between alprazolam and placebo were observed in core PTSD symptoms. As this study enrolled only seven subjects, it may miss the appropriate power to show the effect. Still, although benzodiazepines may seem a logical choice for the treatment, use of benzodiazepines in PTSD was not proven by RCTs. Since some preventive studies performed with benzodiazepines shown aggravating effect of drugs, instead of improvement, further research of benzodiazepines in RCT is certainly indicated. The observed lack of benzodiazepines efficacy in PTSD is consistent with neuroimaging findings of reduced benzodiazepine receptor binding in prefrontal cortex in PTSD. This is along with the results of animal experiments evidencing that stress downregulates benzodiazepine receptor binding in the frontal cortex and hippocampus. Recently, neurobiological studies analyzed the role of dopamine in amygdala and other limbic structures implicated in PTSD, proposing that dopaminergic transmission could have a modulatory role in function of limbic system. Only olanzapine was tested in PTSD in a placebo-controlled clinical trial. Olanzapine was also studied as an adjunctive therapy in a double-blind controlled study. Stein et al. (2002) found that olanzapine was associated with significantly reduced PTSD symptoms when used as an adjunctive therapy for PTSD with comorbid depressive symptoms and sleep disturbances that had not responded to an SSRI. The large effect size (1.07) was observed in this study. Adrenergic agents were also investigated in PTSD and reports are suggesting their efficacy particularly in treating nightmares and hyperarousal symptoms. Thus, although some medication classes are commonly used in clinical practice to treat PTSD symptoms, their efficacy was still not confirmed by controlled clinical trials. This particularly refers to benzodiazepines, anticonvulsants and antipsychotics. No placebo-controlled trials were performed in pediatric or geriatric subjects.

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4. Response Rates Response rates in larger clinical trials, usually defined as 30% improvement on the primary parameter, are displayed in Table 2. The most of drugs studied in larger PTSD trials displayed proportion of responders ranging from 53% to 60%. Still, placebo responders were also numerous, in range from 32% to 44%. Interestingly to note, response rate in meta-analysis of psychotherapy trials was comparable to the rate observed in medication trials: in trials using psychotherapy it was 62% for psychotherapy and 38% for placebo.

5. Comparative Efficacy It should be repeated that in majority of trials sample sizes were very small, which could in some cases lead to uncertain estimation of the effect size. Still, the observed effect size may be used as a rough indication of overall efficacy of the treatments. As assessed by Stein et al. (2005) the overall effect size of psychopharmacological treatment is 0.46. This estimation includes those studies that have used rating scales based on DSM diagnostic criteria sufficiently different that a standardized mean difference was determined. The effect size of such magnitude confirms the efficacy of medication over placebo, but displays only near a moderate effect for the whole group.

Table 2. Response rates in major clinical trials in PTSD

sertraline sertraline fluoxetine paroxetine paroxetine

Davidson, 2001 Brady, 2000 Martenyi, 2002 Tucker, 2001 Marshall, 2001

mirtazapine nefazodone

Davidson, 2003 Hidalgo et al, 1999 (meta-analysis of 6 trials) Hertzberg, 1999 Sherman, 1998

lamotrigine psychotherapy

Active Treatment 60% 53% 59.9% 60% 62% (20 mg/day) 58% (40 mg/day) 65% 46%

Placebo 38% 32% 43.8% 38% 38%

50% 62%

25% 38%

22%

Table 3. Effect sizes in placebo-controlled clinical trials in PTSD

Reference

Active treatment

Frank et al. (1988) Katz et al. (1994) Kosten et al. (1991) Shestatzky et al. (1988)

imipramine[30] brofaromine[31] phenelzine[32] phenelzine[32]

Effect Size (active treatment over placebo) 0.25 0.4 0.95 -0.17

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Reference

Active treatment

Davidson et al. (1990) Reist et al. (1989) Van der Kolk et al. (1994) Conner et al. (1999) Brady et al. (2000) Davidson et al. (2001) Marshall et al. (2001) Davidson et al. (2003) Braun et al. (1990)

amitryptiline[30] desipramine[30] fuoxetine[32] fluoxetine[31] sertraline[30] sertraline[30] paroxetine[30] mirtazapine[30] alprazolam[32]

Effect Size (active treatment over placebo) 0.64 0.05 0.77 0.91 0.3 0.4 0.5 0.49 0.25

Despite earlier reports suggested that serotonin more specific agents are more effective than other classes, the current evidence base of controlled trials is unable to demonstrate superior efficacy or acceptability for any particular medication class[31], and even the analysis of drop-out rates does not confirm superior tolerability of SSRIs over other classes.

6. Duration of the Trial The majority of performed clinical trials lasted from 8 to 12 weeks. The appropriate duration of the trial in PTSD is still doubtful. Despite duration of trial of 2-3 months is a kind of a standard in clinical trials in psychiatry, there is some evidence that longer duration may be more appropriate in clinical trials in PTSD. In a 24-weeks study by Londborg et al.[33] which was continuation of initial 12-weeks of sertraline treatment , it was found that the huge majority of patients (92%) who had responded during an initial 12 weeks of treatment continued to respond in additional 6 months. On the other side, over the half (54%) of the patients who had not responded in initial 12 weeks of sertraline treatment were responders in the prolonged phase. It is of particular interest that delayed treatment response was associated with a higher severity of baseline PTSD symptoms. Although duration of majority of trials in psychiatry is conventionally set to 12 weeks, clinical trials in PTSD may require the acute phase of treatment to go beyond initial 12 weeks of treatment, especially if the trial includes more severely ill patients.

7. Efficacy in Relation to Baseline or Symptom Characteristics It difficult to find any clinical trial in PTSD showing balanced effect on all cluster of symptoms. The imipramine study by Kosten et al. displayed decrease of intrusive symptoms relative to placebo, but no imipramine benefit was observed for avoidance symptoms. The same was found in a study with phenelzine. The largest trial with fluoxetine shown a significantly greater response to fluoxetine versus placebo, significantly greater response on the intrusive cluster, and

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the hyperarousal cluster, but only a trend for the avoidance cluster. Finding of interest is also that having combat-related trauma and being young were associated with significantly greater improvements. As with SSRIs, in treatment with novel antidepressants the response was better in patients who experienced civilian trauma. Sertraline was evaluated by large trial of Brady et al. in 187 patients. Avoidance, numbing and hyperarousal clusters shown significant improvement in a 12 weekperiod, but re-experiencing cluster did not. Post hoc analyses in sertraline trial displayed a significant difference in women. However, subsequent analyses did not confirm a gender effect. Better effect of medication on intrusion than on avoidance symptoms was also displayed in meta-analysis by Stein et al. (2005): summary statistics of trials show that weighted mean difference for intrusion on the Impact of Events Scale was -3.81, while for avoidance cluster it was -3.31. Therefore, all major clinical trials in PTSD displayed some differences in relation to baseline characteristics of study population or differences in efficacy by symptom clusters. Antidepressants have the largest database in relation to randomized clinical trials in PTSD. Despite medications belonging to that class are primarily aimed to treat depressive symptoms, meta analysis of RCTs shown that the effect size in treating anxiety symptoms present in PTSD patients was considerably higher than the effect size on treating depressive symptoms. This may suggest that depressive symptoms within PTSD are more difficult to treat or are driven by different mechanism[34]. Southwick et al. (1994) in their meta-analysis of trials where patients were treated with antidepressants for comorbid PTSD and major depressive disorder had the same assumption and have indicated that PTSD symptoms responded independently of the antidepressant effect. With respect to a substantial proportion of patients who do not respond to pharmacological treatment, and considering assumptions that phenomenology of PTSD is heterogeneous, it remains essential to investigate if certain treatments are more effective for particular symptom sets or for some subgroup of PTSD patients.

Comorbid symptoms Studies: sertraline, amitriptyline, imipramine, phenelzine

Figure 1. Effect size on global PTSD symptoms, depression and anxiety (data from Stein, 2005)

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8. Prevention Studies Studies aimed to prevent the PTSD have been performed with different drug classes, including antidepressants and benzodiazepines. Trial using imipramine and chloral hydrate resulted in greater reduction in acute stress disorder symptoms in a group receiving imipramine. Promising results were also observed in trial using morphine in burns and hydrocortisone in septic shock. Mellman et al. found that benzodiazepines were not effective in preventing PTSD. Furthermore, use of benzodiazepines could be even detrimental, as they found PTSD present in 69% of those treated with benzodiazepines, and only 15% in a control group. In addition, depression later developed in 54% of benzodiazepine treated, whereas in a control group was not present.

9. Summary Relatively few placebo-controlled, randomized clinical trials were performed in PTSD. The majority of them involved very small number of subjects. Recent decade acknowledged the heterogeneity and complexity of clinical features observed in PTSD. There is growing evidence that certain medications are effective in acute treatment of PTSD. Clinical research, using new compounds, as well as those already marketed is clearly warranted. In past clinical trials antidepressants appeared with the best overall efficacy for the treatment of PTSD, although their effect may not be present in all symptom clusters. Benzodiazepines were not proven as effective to treat core PTSD symptoms, so far. Mood stabilizers show some promise, especially for the treatment of impulsivity and mood fluctuation. There is still limited data demonstrating efficacy of the atypical antipsychotics in PTSD. Further clinical research is warranted, using new compounds, as well as those already marketed for other indications.

Table 4. Main results of prevention studies

Trial Reference Robert et al (1999)[35]

Active treatment imipramine vs chloral hydrate in ASD

Duration 2 weeks

Pitman et al (2002)[36]

propranolol vs placebo

10 days

Saxe et al (2001)[37]

morphine (in burns) vs other medication

Mellman et al (2002)[38] Gelpin et al (1996)[39] Schelling et al (2001)[40]

benzodiazepines

short term

benzodiazepines

prolonged

hydrocortisone in septic shock

short term

Main result greater reduction in ASD symptoms in imipramine treatment no significant difference in PTSD symptoms 1 and 3 months posttrauma significant effect on reduction on PTSD symptoms at 6 months follow-up no protection from developing full PTSD criteria higher rates of PTSD lower incidence of PTSD after 2.5 years

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Khan A, Kolts RL, Rapaport MH, Krishnan KR, Brodhead AE, Browns WA. Magnitude of placebo response and drug-placebo differences across psychiatric disorders. Psychol Med. 2005;35(5):743-9. Cohen, J. Statistical power analysis for the behavioral sciences (2nd ed.). Hillsdale, NJ: Lawrence Earlbaum Associates. 1988. Shestatzky M, Greenberg D, Lerer B. A controlled trial of phenelzine in posttraumatic stress disorder. Psychiatry Research 1988;24:149-55. Kosten TR, Frank JB, Dan E, McDougle CJ, Giller Jr. EL. Pharmacotherapy for posttraumatic stress disorder using phenelzine or imipramine. Journal of Nervous & Mental Disease 1991;179:366-70. Katz RJ, Lott MH, Arbus P, Crocq L, Herlobsen P, Lingjaerde O, Lopez G, Loughrey GC, MacFarlane DJ, McIvor R, et al. Pharmacotherapy of post-traumatic stress disorder with a novel psychotropic. Anxiety 1994;1:169-74. Baker DG, Diamond BI, Gillette G, Hamner M, Katzelnick D, Keller T, Mellman TA, Pontius E, Rosenthal M, Tucker P, et al. A doubleblind, randomized, placebo-controlled, multi-center study of brofaromine in the treatment of post-traumatic stress disorder. Psychopharmacology 1995;122:386-9. Reist C, Kau.mann CD, Haier RJ, Sangdahl C, DeMet EM, Chicz-DeMet A, Nelson JN. A controlled trial of desipramine in 18 men with posttraumatic stress disorder . American Journal of Psychiatry 1989;146:513-6. Davidson J, Kudler H, Smith R, Mahorney SL, Lipper S, Hammett E, Saunders WB, Cavenar Jr. JO. Treatment of posttraumatic stress disorder with amitriptyline and placebo. Archives of General Psychiatry 1990;47:259-66. van der Kolk BA, Dreyfuss D, Michaels M, Shera D, Berkowitz R, Fisler R, Saxe G. Fluoxetine in posttraumatic stress disorder. Journal of Clinical Psychiatry 1994;55:517-22. Connor KM, Sutherland SM, Tupler LA, Malik ML, Davidson JR. Fluoxetine in post-traumatic stress disorder. Randomised, doubleblind study. British Journal of Psychiatry 1999;175:17-22. Hertzberg MA, Feldman ME, Beckham JC, Kudler HS, Davidson JR. Lack of efficacy for fluoxetine in PTSD: a placebo controlled trial in combat veterans. Ann Clin Psychiatry 2000;12:101-5. Martenyi F, Brown EB, Zhang H, Prakash A, Koke SC. Fluoxetine versus placebo in posttraumatic stress disorder. J Clin Psychiatry 2002;63:199-206. Brady K, Pearlstein T, Asnis GM, Baker D, Rothbaum B, Sikes CR, Farfel GM. Efficacy and safety of sertraline treatment of posttraumatic stress disorder: a randomized controlled trial. Jama 2000;283:1837-44. Amital D, Zohar J, Kotler M, et al. A placebo-controlled pilot study of sertraline in PTSD [abstract no. NR331 + poster]. American Psychiatric Association Annual Meeting: New Research Program and Abstracts; 1999 May 15-20; Washington, DC, 156-7 Davidson JR, Rothbaum BO, van der Kolk BA, Sikes CR, Farfel GM. Multicenter, double-blind comparison of sertraline and placebo in the treatment of posttraumatic stress disorder. Arch Gen Psychiatry 2001;58:485-92. Zohar J, Amital D, Miodownik C, Kotler M, Bleich A, Lane RM, Austin C. Double-blind placebocontrolled pilot study of sertraline in military veterans with posttraumatic stress disorder. J Clin Psychopharmacol 2002;22:190-5. Tucker P, Potter-Kimball R, Wyatt DB, Parker DE, Burgin C, Jones DE, Masters BK. Can physiologic assessment and side effects tease out differences in PTSD trials? A double-blind comparison of citalopram, sertraline, and placebo. Psychopharmacol Bull. 2003 Summer;37(3):135-49. Tucker P, Zaninelli R, Yehuda R, Ruggiero L, Dillingham K, Pitts CD. Paroxetine in the treatment of chronic posttraumatic stress disorder: results of a placebo-controlled, flexible-dosage trial. J Clin Psychiatry 2001;62:860-8. Marshall RD, Beebe KL, Oldham M, Zaninelli R. Efficacy and safety of paroxetine treatment for chronic PTSD: a fixed-dose, placebo-controlled study. Am J Psychiatry. 2001 Dec;158(12):1982-8. Davis LL, Jewell ME, Ambrose S, Farley J, English B, Bartolucci A, Petty F. A placebo-controlled study of nefazodone for the treatment of chronic posttraumatic stress disorder: a preliminary study. J Clin Psychopharmacol. 2004;24(3):291-7. Davidson JR, Weisler RH, Butterfield MI, Casat CD, Connor KM, Barnett S, van Meter S. Mirtazapine vs. placebo in posttraumatic stress disorder: a pilot trial. Biol Psychiatry. 2003 Jan 15;53(2):188-91. Hertzberg MA, Butter.eld MI, Feldman ME, Beckham JC, Sutherland SM, Connor KM, Davidson JR. A preliminary study of lamotrigine for the treatment of posttraumatic stress disorder. Biological Psychiatry 1999;45:1226-9. Butterfield MI, Becker ME, Connor KM, Sutherland S, Churchill LE, Davidson JR. Olanzapine in the treatment of post-traumatic stress disorder: a pilot study. Int Clin Psychopharmacol 2001;16:197-203.

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[24] Braun P, Greenberg D, Dasberg H, Lerer B. Core symptoms of posttraumatic stress disorder unimproved by alprazolam treatment. Journal of Clinical Psychiatry 1990;51:236-8. [25] Kaplan Z, Amir M, Swartz M, Levine J. Inositol treatment of posttraumatic stress disorder. Anxiety 1996;2:51-2. [26] Raskind MA, Peskind ER, Kanter ED, Petrie EC, Radant A, Thompson CE, Dobie DJ, Hoff D, Rein RJ, Straits-Troster K, Thomas RG, McFall MM. Reduction of nightmares and other PTSD symptoms in combat veterans by prazosin: a placebo-controlled study. Am J Psychiatry. 2003;160(2):371-3. [27] Heresco-Levy U, Kremer I, Javitt DC, Goichman R, Reshef A, Blanaru M, Cohen T. Pilot-controlled trial of D-cycloserine for the treatment of post-traumatic stress disorder. Int J Neuropsychopharmacol. 2002;5(4):301-7. [28] Aerni A, Traber R, Hock C, Roozendaal B, Schelling G, Papassotiropoulos A, Nitsch RM, Schnyder U, de Quervain DJ. Low-dose cortisol for symptoms of posttraumatic stress disorder. Am J Psychiatry. 2004;161(8):1488-90. [29] Asnis GM, Kohn, SR, Henderson M, Brown NL. SSRIs versus non-SSRIs in post-trautmatic stress disorder. An update with recommendations. Drugs 2004;64(4):383-404 [30] Schoenfeld FB, Marmar CR, Neylan TC. Current concepts in Pharmacotherapy for posttraumatic stress disorder. Psychiatric Services 2004;55(5):519-31. [31] Stein DJ, Zungu-Dirwayi N, van der Linden GJH, Seedat S. Pharmacotherapy for post traumatic stress disorder (PTSD). Wiley & sons. The Cochrane Collaboration. 2005 [32] Penava SJ, Otto MQ, Pollack MH, Rosenbaum JF. Current status of pharmacotherapy for PTSD: an effect size analysis of controlled studies. Depression and Anxiety 1997;4:240-2 [33] Londborg PD, Hegel MT, Goldstein S, Goldstein D, Himmelhoch JM, Maddock R, Patterson WM, Rausch J, Farfel GM. Sertraline treatment of posttraumatic stress disorder: results of 24 weeks of open-label continuation treatment. J Clin Psychiatry. 2001 May;62(5):325-31. [34] Albucher RC, Liberzon I. Psychopharmacological treatment in PTSD: a critival review. Journal of Psychiatric Research 2002;36:355-367 [35] Robert R, Blakeney PE, Villarreal C, Rosenberg L, Meyer WJ 3rd. Imipramine treatment in pediatric burn patients with symptoms of acute stress disorder: a pilot study. J Am Acad Child Adolesc Psychiatry. 1999;38(7):873-82. [36] Pitman RK, Sanders KM, Zusman RM, Healy AR, Cheema F, Lasko NB, Cahill L, Orr SP. Pilot study of secondary prevention of posttraumatic stress disorder with propranolol. Biol Psychiatry. 2002;51(2):189-92. [37] Saxe G, Stoddard F, Courtney D, Cunningham K, Chawla N, Sheridan R, King D, King L. Relationship between acute morphine and the course of PTSD in children with burns. J Am Acad Child Adolesc Psychiatry. 2001;40(8):915-21. [38] Mellman TA, Bustamante V, David D, Fins AI. Hypnotic medication in the aftermath of trauma. J Clin Psychiatry. 2002;63(12):1183-4. [39] Gelpin E, Bonne O, Peri T, Brandes D, Shalev AY. Treatment of recent trauma survivors with benzodiazepines: a prospective study. J Clin Psychiatry;57(9):390-4. [40] Schelling G, Briegel J, Roozendaal B, Stoll C, Rothenhausler HB, Kapfhammer HP. The effect of stress doses of hydrocortisone during septic shock on posttraumatic stress disorder in survivors. Biol Psychiatry. 2001;50(12):978-85.

Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Canadian Forces Approach to the Identification and Management of Operational Stress Injuries Col Randy Boddam CD, BSc, MD, FRCPC1

Abstract. Military Operations expose personnel to stresses not normally experienced in garrison or in civilian life. The consequence of such exposure is the development of Operational Stress Injuries. The Canadian Forces has developed and continues to improve upon a phased response to assist its members in better being able to respond to these stresses beginning at recruitment and extending throughout the military career. This process is summarized. As a final point, early intervention, a subject of considerable discussion in the literature is addressed through a proposed model aimed at promoting resiliency and early treatment where needed. Keywords. posttraumatic stress disorder, stress, early intervention, screening, military psychiatry

Introduction Military operations expose Canadian Forces (CF) personnel to stressors and experiences which may lead to mental illnesses or other forms of suffering. While Posttraumatic Stress Disorder (PTSD) is the first illness that usually comes to mind when thinking about psychological suffering related to operations, the range of potential suffering is much broader. In fact, the Operational Stress Injury Social Support (OSISS) programme has coined the term “Operational Stress Injury” (OSI) to cover this range of suffering. It has been defined by OSISS as, “An operational stress injury (OSI) is any persistent psychological difficulty resulting from operational duties performed by a Canadian Forces member.”[1] The CF has taken a staged and sequential approach to the management of OSI’s. Management of OSI’s begins with recruitment and, with the help of our colleagues at Veterans Affairs Canada (VAC) extends beyond active duty. This paper will outline the steps undertaken by the CF at differing stages of the service career to address OSI’s. It will then focus upon the work of the Operational Trauma and Stress Support Centres (OTSSC’s) as they work towards the assessment and treatment of OSI’s. Finally, the paper will

1 Corresponding Author: Col R Boddam, Rm 406, Health Care Centre, 1745 Alta Vista Drive, Ottawa, Ontario, Canada, K1A 0K6. Email to:[email protected]

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conclude with on overview of a proposed model for early intervention for CF members exposed to potentially traumatic events (PTE’s).

1. Recruitment Not all people are created equal in terms of their potential vulnerability to operational stress. Stating that, however, there are very few absolute contraindications, from a psychiatric perspective, to enrolment in the military. Selection of candidates for service in the CF is a difficult task. On the one hand there is the need of the CF for personnel. On the other hand the Canadian Charter of Rights and Freedoms protects Canadian citizens from undue discrimination. This challenge is further compounded by a relative lack of empiric evidence concerning longer term psychological fitness. Clearly, psychotic disorders and recurrent mood disorders represent one class of illness for which operations pose a risk. That risk is, of course, bidirectional; operational stress and exigencies may predispose the individual for a recurrence of their illness and their illness may recur during deployment placing themselves and other members of their unit at risk. A person presenting with such a medical history can be easily screened from enrolment. What about a person with a past history of, say, sexual abuse? Literature and experience has demonstrated that such a person is at increased risk of suffering PTSD if exposed to a PTE. [2-4] The reality, however, is that not all people with such a history will develop PTSD if operationally exposed. Protective or resiliency factors, as yet hard to measure, may also mitigate the effects of traumatic stress. Further, the disorder can occur in the absence of such a history. Accordingly, and in the absence of a sensitive and specific screening tool with significant positive predictive power some people will be recruited who may carry a relatively increased risk of developing an OSI. The recruitment process can be seen as only a very course filter from which further work to mitigate PTE’s and minimize the risk of OSI’s. Basic training is the next step following recruitment and, similarly, it is the site of the next focus of intervention. Although basic training is configured, by its very nature, as a vehicle by which recruits are exposed to stress and learn some basic mechanisms by which to handle it, other activities can be undertaken. Recently and as part of career long educational programme developed by OSISS recruits have been exposed to a half day of training concerning the history, nature and presentation of OSI’s including education about what to do in the face of suffering or observing a colleague suffering with an OSI. Similar training is currently being developed under the supervision of the Canadian Defence Academy and with the oversight of the CF’s OSI Steering Committee (OSI SC) for inclusion at other developmental phases of a service member’s career. Such training targets officers and non-commissioned members alike.

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2. Baseline Care Recently, the CF undertook an epidemiologic survey, conducted by Statistics Canada (the national statistical organization) and in concert with Statistics Canada’s Canadian Community Health Survey (CCHS Ver 1.2). This survey, using structured interviews and the Composite International Diagnostic Interview developed by Kessler et al allowed the CF to look, for the first time in its history, at the level of psychopathology in its members. [5,6] Although one of the reasons for doing so was to better understand what the health care service requirements of its members are, another advantage of this survey was that it permitted the putting of a “real face” on the nature and extent of mental illness in the CF. 1 year and lifetime prevalence figures for members of the Regular Force are summarized in Table 1.[7] Table 1. CIDI-derived 1 yr and Lifetime prevalence figures for six disorders studied by the CCHS Ver 1.2 epidemiologic survey. Prevalence figures are presented as percentages of the population. MDD is Major Depressive Disorder, GAD is Generalized Anxiety Disorder. Diagnostic Criteria are derived from the Diagnositce and Statistical Manual for Mental Disorders, Fourth Edition

Disorder MDD Alcoholism Social Phobia PTSD Panic Disorder GAD

1 yr 7.6 4.0 3.6 2.7 2.2 1.8

lifetime 16.2 8.3 8.7 7.2 5.0 4.7

It is important to note that when compared to age and sex-matched Canadian civilians that the prevalence values of MDD and panic disorder are significantly increased relative to the civilian population. Two of the listed disorders were not measured in the Canadian civilian population. When compared to other published, epidemiologic surveys both PTSD and GAD appear to be as prevalent as found in civilian populations. Another relevant finding of this study was the correlation between number of deployments and lifetime burden of suffering with PTSD as shown in Table 2.[7] These data suggest that deployment, not surprisingly, is a risk factor for the development of PTSD and the more often that a CF member deploys, the higher the likelihood of having developed this disorder.

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Table 2. Prevalence of PTSD as a percentage of the population expressed as a function of the number of deployments (Depl) that CF members had engaged in. RegF refers to members of the Regular Force whereas ResF refers to reservist members. The Reserve results, due to relatively small numbers having deployed more than twice and to maintain statistical power, have been collapsed into either a having deployed or not having deployed category. The Survey was conducted in 2002.

lifetime

last year # Depl none 1-2 3+

RegF 1.7 2.7 4.7

ResF 0.9 2.4

RegF 5.9 6.7 10.3

ResF 4.2 7.2

To address the clinical needs of CF personnel, revitalization and restructuring of health care have been undertaken. This restructuring, under the supervision of Project Rx 2000, aims to provide health care to at least that available to the average Canadian, regardless of where the CF member is employed.[8] Mental health care delivery is similarly being restructured to improve access to and delivery of mental health clinical services. At the same time, a new directorate, Force Health Protection, has been established. The healthy lifestyle cell of this directorate is engaged in disseminating activities and programmes that promote resiliency. One such programme is “Take Charge!”, a skill building programme aimed at helping CF members improve their ability to manage stress. Although yet to be seen, it is anticipated that these combined activities will both lower the point prevalence of mental illness (thereby reducing vulnerability) while enhancing the resiliency of CF members when confronted with PTE’s.

3. Deployment As deployment poses a risk for the development of an OSI, it seems reasonable that this time should be used to make a more focussed effort to prevent the disorder. There are, however, distinct phases that a serving member transits during the deployment cycle. These phases derive from the time frame the CF member is in relative to their deployment and are called, predeployment phase, deployment phase, and postdeployment phase. When a unit or units are tasked to undertake a mission one of the first activities is an administrative review of the personnel selected to go. This review (part of the Departure Assistance Group or DAG) assesses whether a CF member is “fit” to deploy. A relatively recent addition to this process is a psychological screen consisting of the Short Form 36, the PRIME-MD and the PCL followed by an interview with a mental health care provider and subsequent referral as needed. This activity has demonstrated a relatively low yield, unfortunately, raising the question of its value as a predeployment activity. Other activities during the predeployment phase are aimed at enhancing resiliency. Consistent with the principles of Stress Inoculation Training, realistic mission training forms one means by

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which resiliency is developed.[9] Perceived support, or the ability of the service member to feel that their peers and work environment is there to support them, is another. Undergoing predeployment training as formed groups is an area that leadership attempts to assure so as to bring about that important group cohesion. Educational briefs are also provided about stress, OSI’s and means by which PTE’s can be managed. A further predeployment activity involves the training of peer debriefers. It is believed that these individuals are given extra skills which enhance the sense of support that the unit provides to a member who experiences a PTE. When a service member is deployed they are, depending upon the size of the deployment, accompanied by a uniformed mental health care provider. That person is there, in addition to the routine medical staff, to facilitate early interventions for those who may develop emotional distress. They also function to facilitate repatriation of individuals for whom that is the only response to their level of suffering. MH care providers are encouraged, as much as possible, to integrate and get to know the units that they are supporting. In this way the threshold of presentation is hoped to be lowered so that care can be delivered as quickly as possible. In this way the “I” of the PIE acronym (Proximity, Immediacy and Expectancy) developed for the management of Combat Stress Reaction is respected. Although the PIE approach was developed for the management of CSR it is thought to have general relevance to other mental illnesses and OSI’s. More prominent in the past, Critical Incident Stress Management techniques may still be employed. Psychological Debriefings may still be provided but are no longer considered to be mandatory and need to be requested by the unit in which exposure to a PTE/critical incident has occurred. Another activity that happens during the deployment is the provision of reintegration briefings. These briefings are aimed at providing for the service member education about the stresses and strains they will face as they return to Canada after having been away from home. Families go on and life goes on but when a family member has not been a part of it he or she may not be in tune with role changes and history that the family has experienced. Reinsertion into the family can lead to challenges and difficulties. If the mission commander suspects that the degree of change is substantial, such as moving from a warfighting environment to downtown Canada, then “third location decompression” can be undertaken. This activity was employed when members of the 3rd Battalion, The Princess Patricia’s Canadian Light Infantry came home from Kandahar in 2002 and was generally felt to be a helpful activity. That mission was perceived as a war fighting operation and the Commanding Officer felt it important that a suitable period of time be given to his unit to make the cognitive shift from War to Peace. Objective data assessing the preventive value of these activities does not, regrettable exist although consumer satisfaction is reported as high. Given that deployments are associated with a greater risk for the development of PTSD the next challenge is to try to find cases so that they can be addressed early, and hopefully at a time in the clinical trajectory that will reduce longer term disability and suffering. In addition to a basic medical screen when CF members return home from their mission there is a post-deployment questionnaire and interview (exactly like the predeployment interview) aimed at case finding. This activity has met with high acceptance and has led to

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the referral to appropriate mental health care services of members who hadn’t otherwise presented for care. Accordingly it is believed to be a clinically valuable tool. In addition to this active case finding, the usual system of mental health care delivery continues to support CF members should they feel the need for care.

4. Operational Trauma and Stress Support Centres In 1995 and in response to Senate committee recommendations the Psychiatry Department of National Defence Medical Centre created the PTSD programme. Patterned on a Day Hospital model it offered four weeks of care to members who had been diagnosed as suffering with PTSD. This programme underwent significant revision in 1997 and by 1998 senior CF leadership wanted PTSD clinics “across the country” to deal with the perceived need of peacekeepers who were returning from increasingly dangerous peacekeeping missions. Recognizing that PTSD is one of several OSI’s these clinics were established but their mandate was broadened to deal with the range of OSI’s. They were to be “Centre’s of Excellence” maintaining a cutting edge knowledge of various OSI’s, providing three basic services, in order of priority: Clinical Assessment and Consultation, Clinical Educative Outreach to health care providers caring for CF members who may have an OSI, and limited treatment. The doors were opened in 1999 and since that time they have seen many patients.[10] An early problem was a relative shortcoming in the civilian clinical community upon which the OTSSC’s were depending for access to individual therapy— clinicians specializing in trauma work were in short supply. The OTSSC’s responded individually to attempt to address this need resulting in drifting away from the central mission. Accordingly, the mental health restructuring team also took on the task of standardizing clinical care in the OTSSC’s. The goal of this standardization work was to build upon what made clinical sense, that is, comprehensive assessment and care with interdisciplinary input and case review. As an example of this interdisciplinary input a working group was held in June 2001 to standardize the assessment protocol to be used by all of the OTSSC’s. This working group included membership from each of the OTSSC’s as well as the VAC Ste Anne’s Hospital (Ste Anne de Bellevue, near Montreal, Quebec). This latter Hospital was this working group is demonstrated in figure 1.

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Figure 1. The flowchart here represents the assessment model that was developed in June 2001. The model has changed slightly since development (walk-ins, for example are no longer accepted directly) but the principle elements (initial diagnostic assessment followed by an interdisciplinary case conference followed be other assessments followed by a final case conference to develop a treatment plan) remain in place.

Since that time other work has been undertaken with an aim of ensuring that patients can depend upon the same manner of assessment and care, no matter where their duty takes them. There is a treatment standardization committee that exists to review the literature and ensure that best practices are employed in the care of OTSSC patients. 5. Ongoing Improvement

Practices are informed by experience and research. What was considered fashionable and sound a few decades ago can become inefficient, inappropriate or potentially harmful. The CF is committed to ongoing review of its healthcare practices. An example of this is found in the approach to early intervention in the face of a PTE. In the late 1980’s and early 1990’s there was considerable interest in what was then called critical incident stress debriefing. In fact, in Canada a specific policy was developed to ensure that CF members who had sustained a critical incident would undergo this process. The hope was that it would prevent the development of PTSD. For many clinicians the model made sense. Experience, scientific review and discussion with peers and colleagues started to show,

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however, that Critical Incident Stress Management (CISM) did not have the preventive effects that we hoped it might have. [11] Alternatively, the CISM process did provide the opportunity to intervene fulfilling a need commanders have to support their personnel in difficult times. Participants also reported that they found the process to be satisfying. The challenge is then to determine if there is a technique or intervention (or series of interventions) that will provide what CISM was hoped to. Military personnel engage in inherently stressful tasks. Providing mechanisms to enhance their resiliency in such circumstances becomes a “force multiplier”. Literature suggests that perceived support is an important predictor of posttraumatic distress. History indicates that unit cohesion and leadership are also important mitigators of stressful operational environments. Using these facts a new model has been proposed and is currently being reviewed for potential implementation in the CF. The model is shown in Figure 2. As shown in Figure 2, stress management is seen as a process that starts before exposure to any PTE. The Directorate of Force Health Protection (FHP) of the CF Health Services is responsible for the development and deployment of programmes that prevent adverse health outcomes. One such programme, Healthy Lifestyles, has as one of its components, stress management. Techniques to manage stressful events are taught and skills developed by participants. It is anticipated that CF members will use these skills as they experience PTE’s. It is hoped that through realistic training, a form of stress inoculation, CF members will have ample opportunity to put these skills into practice. Mental health care and mental illness both carry a stigma in both civilian and military cultures in Canada. Regrettable (and the focus of concerted efforts through a number of avenues) but this reality also has to be taken into consideration in the development of a response to a PTE. Exposure to a PTE carries with it the risk of the development of a stress injury such as PTSD. Earlier treatment creates a better prognosis. Accordingly, a successful early intervention programme needs to tackle the stigmata that present a barrier to presentation for necessary treatment. One way to accomplish this is to build a constructive and positive relationship between health care providers and the population that they serve. Uniformed mental health care providers will build this relationship by participating in training and other experiences with units with which they will form an habitual association. They will also be involved in periodic teaching and other such activities. It is hoped that these activities will make it easier for people who need care to present.

R. Boddam / Canadian Forces Approach to the Identification and Management of OSI

Unit Context/Culture

Educ ation ab out care availab ility and warni ng signs

Unit Associated MH Care Provider

E motional support Red uc e 2ar y trauma B as ic H um an N eeds Ongoi ng follo w-u p / monitori ng

Disaster Critical Incident

Force Health Protection Stress Mgmt / Health y Lifestyle

119

F ac ilitate refer ral

CF Member

Peer / Leadership / Chain of Command Fac ilitate Refer ral

Early Development of Symptoms

F ac ilitate Referral

Late Development of Symptoms

Facilitate Refer ral

Problematic lifestyle / personality changes Life Goes On

Figure 2. Proposed model and flow for early intervention for members of the Canadian Forces. The model relies upon the development of a supportive unit, preparation through learning stress management techniques and supportive leadership. At any stage after exposure to a PTE leadership or peers can facilitate a referral to mental health care providers. This referral process has been facilitated by the development of a positive and constructive relationship with uniformed mental health care providers established prior to PTE exposure.

It is expected that two factors will be important stress mitigators at the time of exposure to a PTE. Unit cohesion and stress management techniques should reduce the experience of posttraumatic distress. At the same time leadership can intervene possibly by attending to basic needs, reducing secondary trauma, reinforcing support and stress management and remaining vigilant for persons experiencing excessive distress or dysfunction. At any time thereafter this latter observation can promote earlier presentation for professional assessment or definitive treatment as is appropriate.

6. Summary Military operations carry the risk of psychological injury for those members who deploy. A number of points in a CF member’s career, from enrolment to retirement, have been targeted to enhance the resiliency or remove potential barriers for those who may need mental health care. This process is not static; as data and experience demonstrate the need for improvement interventions can evolve to best ensure that the fewest CF members possible will be left with the scar of an Operational Stress Injury.

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References [1] [2]

www.osiss.ca Peleikis, D.E. et al. The relative influence of childhood sexual abuse and other family background risk factors on adult adversities for female outpatients treated for anxiety disorders and depression. Child Abuse Negl. 2004. 28(1): 61-76. [3] Thompson, K.M. et al. Psychopathology and sexual trauma in childhood and adulthood. J Trauma Stress. 2003. 16(1): 35-8. [4] Johnson, DM et al. Factors predicting PTSD, depression and dissociative severity in female treatmentseeking childhood sexual abuse survivors. Child Abuse Negl. 2001. 25(1):179-98. [5] Kessler, RC et al. Clinical calibration of DSM-IV diagnoses in the world mental health version of the World Health Organization (WHO) Composite International Diagnostic Interview (WMHCIDI). Int J Methods Psychiatr Res2004. 13(2): 122-139. [6] Kessler, RC and TB Ustun. The World Mental Health Survey Initiative version of the World Health Organization (WHO) Composite International Diagnostic Interview. Int J Methods Psychiatr Res2004. 13(2): 93-121. [7] www.forces.gc.ca/health/information/op_health/stats_can/engraph/StatsCan_home_e.asp [8] www.forces.gc.ca/health/news_pubs/engraph/hcreform_home_e.asp?Lev1=4&Lev2=6 [9] Saunders, T et al. The effect of stress inoculation on anxiety and performance. J Occup Health Psychol 1996. 1(2):170-186. [10] www.forces.gc.ca/health/services/engraph/otssc_home_e.asp?Lev1=1&Lev2=2 [11] Rose S et al. Psychological debriefing from preventing post traumatic stress disorder (PTSD) The Cochrane Database of Systematic Reviews 2002, Issue 2. Art. No.: CD000560. DOI: 10.1002/14651858.CD000560.

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“Stress and Psychological Support in Modern Military Operations” NATO Human Factors and Medicine HFM081 Research Task Group RTG020 History, Status, Objectives and Achievements to date Jamie G H HACKER HUGHES, PsychDa1, Amy ADLER, PhDb, Vlastimil TICHY, MD, Lt Colc, & Yves CUVELIER, Lt Kold a ACDMH, King’s College London, UK b US Army Medical Research Unit – Europe cCentral Military Hospital, Prague d Chair, RTG-020

Abstract. The NATO Human Factors and Medicine Panel (HFM081) Research Task Group (RTG) 020 provides military mental health professionals from 19 nations with an opportunity to work together to develop and exchange information related to guidelines for military leaders on stress and psychological support in order to enhance effectiveness in modern military operations. The RTG, initially organized in 2002, was approved for full status in 2003. Bi-annual meetings facilitate the work of the RTG members and have resulted in the completion of reports on best practices, unit climate assessments, clinical tools, education and training requirements for military mental health professionals and education and training for military members on mental health issues. The RTG has also produced a draft series of guidelines for mental health support before, during and after military operations, which is currently under review by operational commanders and military mental health professionals in each participating nation. By 2006, the RTG’s goal is to complete a Military Leaders’ Survey on perceived mental health training and support needs across the deployment cycle and to conduct a NATO HFM (Human Factors and Medicine) symposium. Information from feedback on the draft report, the survey and symposium will be integrated into a final series of guidelines, also to be promoted as a lecture series, which can be adapted for use as a NATO standard for mental health support on modern military operations. Keywords. Stress, psychological support, military operations

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Corresponding Author: Jamie Hacker Huges. ACDMH, King’s College London, Weston Education Centre, 10 Cutcombe Road, London, Telephone: ++44 (0) 207 848 5144 Fax: ++44 (0) 207 848 5408 ; Email: [email protected]

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Introduction NATO RTG 020 is an international group of military mental health professionals from NATO or PfP (Partnership for Peace) nations whose objective is to develop information and practical guidelines for military leaders on stress and psychological support in order to enhance effectiveness in modern military operations. This RTG is a timelimited working group with specific objectives. The development of the RTG, the work that has been produced to-date, and the timeline for completing the group’s objectives are reviewed here.

1. Formation of RTG 020 In 2002, an Exploratory Team, ET016, was established by NATO’s Research and Technology Organization (RTO) and the Human Factors and Medicine Panel (HFM) to consider the topics of stress and psychological support in modern military operations within the context of NATO and PfP. (Information on RTO and HFM can be found at: RTO: http://www.nato.int/docu/handbook/2001/hb141201.htm and RTA:http://www. rta.nato.int). ET016 first met in Brussels, Belgium, from 24-26 April 2002. Fourteen delegates attended from nine nations (Austria, Belgium, Canada, France, Germany, Luxemburg, Sweden, the Netherlands and United Kingdom). At the second ET meeting in Gosport, UK, from 11-13 October 2002, fourteen delegates from ten countries attended, with the nine original countries having now been joined by Croatia. Following this second meeting, the RTB (Research and Technology Board) approved HFM-081 RTG-020 - Stress and Psychological Support in Modern Military Operations (S&PSiMMO) as an official RTO activity with any participant to this Task Group (TG), from NATO, PfP or any other nation sponsored by a member-nation, requiring to be officially nominated by their National Coordinator with a security clearance being sent to RTO. An HFM-081/RTG-020 initialized forum was instituted for all communication via www.rta.nato.int allowing the group to have all files in one central place and allowing the Group to upload and review documents and inform all members by e-mail.

2. RTG 020 Meetings After RTG 020 was approved by HFM, bi-annual meetings were conducted in order to facilitate the exchange of information, clarification of group objectives, and the delivery of a series of products. These meetings provide an explicit framework for communication that occurs throughout the year among representatives in the RTG. Sub-groups addressing the group’s goals communicate between meetings via a listserver, established especially for the purpose, and results are then presented for the review of the entire membership. These meetings are rotated across member nations. Thus far, there have been five meetings held with three more meetings planned before the end of the RTG’s period of activity:

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The first meeting of HFM 081 RTG 020 “Stress and Psychological Support in Modern Military Operations” took place in Paris (France) from 28 to 30 April 2003. A considerable enlargement of the group was achieved with 25 delegates attending from 17 nations including, for the first time, Czech Republic, Denmark, Lithuania, Slovakia, Romania, Spain and Sweden. The second meeting of RTG-020 was held in the German Air Force Institute of Aviation Medicine (Division VI – Aviation Psychology) in Furstenfeldbruck (Germany) from 17-19 September 2003. 22 members from 14 nations attended this meeting. The third meeting of the RTG was held in Split (Croatia) between 21-23 April 2004. 28 team members from 17 different countries participated in the meeting. The fourth meeting of the Group was held in Bratislava (Slovakia) between 05 and 08 October 2004. 25 team members from 16 different countries participated. The fifth meeting of the working group was held in Quebec City (Canada) from 12 to 15 April 2005. 25 members from 15 countries were present. Future meetings are planned for the fall of 2005 (in Kaunas, Lithuania), the spring of 2006 (in Brussels, Belgium), and the fall of 2006 (in Bucharest, Romania).

3. Participating Nations and Membership At the time of writing the Group consists of over 30 members from 20 nations: 17 NATO countries - Belgium*, Bulgaria, Canada, Czech Republic, Denmark, France, Germany, Hungary, Lithuania, Luxemburg, The Netherlands, Romania, Slovakia, Spain, UK and USA and 3 PfP countries – Austria, Croatia and Sweden. The goal is to establish a point of contact for all remaining NATO nations. The Chair is Lt Col Yves Cuvelier (Belgium). The members are all military or civilian clinical and industrial / organizational or occupational psychologists, psychiatrists, sociologists and social workers.

4. Achievements So far the Group has produced reports based on an exchange of information among member countries. These include reports on best practices, unit climate assessments, clinical tools (for assessment and intervention with individuals or groups before, during and after operations) and education and training for service personnel on mental health issues. 4.1 Draft Guidelines The Group has also produced a report which describes fundamental areas of agreement for psychological support on modern military operations (the “Interim Report”). The report is organized by deployment phase: before deployment, during deployment, and

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after deployment. The appendices to this report include the results of the information exchange. The fundamental areas of agreement which are addressed in the report include: • Assessing the risks for psychological stress across operations • Psychological preparation before deployment • Psychological assessment before deployment • Psychological support during deployment • Psychological support after deployment • Psychological support for families • Practical organization of psychological support The fundamental premise underlying the interim report is that the success and effectiveness of psychological support requires two things. Firstly, it is the individual responsibility of service members to monitor their own mental health and to seek assistance when needed. Just as military personnel are accountable for their physical fitness; military personnel are accountable for their individual psychological fitness. Military personnel should prioritize their psychological health, as it is a critical component of the overall mission fitness of their organization. Secondly, it is the military’s responsibility to provide psychological support and create and facilitate access to mental health services. Individual mental health is critical for the readiness and performance of military units and has the potential to enhance (or detract from) the mission fitness of the organization as a whole. Thus, the recommendations provided in the Interim Report involve guidelines for supporting the mental health of service members across the deployment cycle. By their very nature, these recommendations are global statements based on areas of agreement - despite national differences in approaches and assumptions. A review of research conducted by the Group showed a paucity of relevant research in many areas and therefore some of the recommendations are based on consensus agreement by Team Members on what constitutes best practice. The Interim Report describes what some countries are already doing to support mental health of service members and provides a framework for countries just beginning to address these issues. Several different issues are addressed in the guidelines provided by the Interim Report. For example, in terms of pre-deployment issues, the Group agreed that the purpose of psychological support, and details of how it may be accessed, should be addressed during pre-deployment training and informational briefings. Such training should address such questions as: (1) What can an individual or unit expect on a deployment? (2) What healthy coping tools are at the unit or individual’s disposal? And (3) How can individuals or units access outside help? Guidelines for mental health support during deployment are also addressed in the Interim Report. For example, the Group agreed that the military should conduct continuous monitoring of personnel to detect adverse reactions early, by formal or informal assessment by peers, leadership, and/or recognized psychological support professionals. It was also recommended that the military should consider unit-level monitoring to detect adverse reactions to deployment-related stress and that Military Leaders should have access to the necessary tools in order to perform psychological monitoring of their troops. The final section of the Interim Report addresses guidelines for mental health support after deployment. For example, it was agreed upon by the Group’s member

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nations that a structured homecoming and reintegration program should be provided for service personnel and their families. The program should be designed to ease the process of transition to family, work, and social life following a deployment. Military Leaders should consider providing long term support in terms of telephone support services and medical services. The Group’s Interim Report also contains an acknowledgement that there continues to be a need to research long term effects of deployment. 4.2 Feedback on Interim Report The Interim Report and the areas of agreement identified in the draft document are now being reviewed by member nations. Feedback from operational leaders, policy makers, and mental health professionals is now being sought in each country. This feedback will be used to revise the guidelines for mental health support on modern military operations provided in the report. 4.3 Military Leaders’ Survey In addition, a Military Leaders’ Survey has been designed and is currently being administered by members of the RTG. The goal of the survey is to conduct a needs assessment from the perspective of military operational leaders on psychological support before, during and after military operations. Sample areas addressed in the survey include (1) Is the training they receive on mental health support of subordinates adequate to their needs? (2) What kind of training do operational leaders want in handling subordinates’ psychological stress? These questions are to be administered either as a survey or a semi-structured interview. Although not intended to provide a scientific sampling of operational leaders across RTG nations, the Military Leaders’ Survey is designed to provide feedback from military leaders across a range of ranks, operational experience, and national backgrounds. The common themes identified by the survey will serve as a basis which can inform that final draft of the Group’s guidelines for mental health support on military operations. 4.4 HFM Symposium Another source of information that will be used to develop the final report and series of guidelines is a NATO symposium entitled, “Human dimensions in military operations: Military leaders’ strategies for addressing stress and psychological support”. This symposium, sponsored by RTG 020 as a joint initiative with the NATO Committee on Medical Services Military Psychiatry Working Group (the COMEDS MP WG , will be held in Brussels (Belgium) from 24 to 26 April 2006. The goal behind the symposium is to provide a venue for exchange between military mental health professionals and military leaders. Various tracks will be offered, including one for Junior Leaders. The six primary areas or tracks basically parallel the objectives of the Interim Report topics: • Assessing, building and maintaining unit morale • Assessing individual mission fitness • Psychological preparation for military operations

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Families and military operations Incident handling, psychological first aid and early interventions. The psychological contract (and significance in terms of retention issues)

4.5 Final Report Feedback on the Interim Report, results obtained from the Military Leaders’ Survey, and information from the workshops held as part of the HFM Symposium will be integrated into the development of the final report from RTG 020. This final report will be adapted so that it may be suitable for use as a NATO standard for mental health support on modern military operations. The report will be made available on the internet and also as a CD-ROM, thus making all the material in the report and appendices available for both military mental health professionals and operational leaders across the range of interested nations. 4.6 Lecture Series Finally, it is the intention of the Group to organize an RTO Lecture Series to promote the messages contained in the Intermediate and Final Reports and Appendices informed by the results of the Military Leaders’ survey and the Symposium.

5. Conclusion Participation in military operations is potentially harmful to the mental health of service members. Historically, the negative effects of exposure to potentially traumatic events on military operations has been recognised and documented using different terminology (shell shock, combat fatigue, combat stress, PTSD, etc.). Regardless of the terminology, it is also recognized that effective military leadership can moderate the effect of deployment stressors on service members and can sustain operational readiness and morale. The role of the military leader in managing the effects of stress on service members is critically important to unit effectiveness and well-being. The RTG is focused on supporting these military leaders on modern military operations. Modern military operations encompass the range of military missions from peace enforcement, peace support and humanitarian operations as well as combat operations. Each of these different kinds of operations has the potential to expose service members to significant stressors, including forced neutrality and non-intervention, witnessing atrocities, culture shock and separation from one’s family as well as existential questions induced by the situation. Every one of these stressors can disrupt the normal psychological functioning of the individual soldier, sailor or aviator who might deploy on such operations. Psychological stress is not just limited to high intensity conflicts in which killing and life threatening situations occur frequently. That this is so not only affects the operational effectiveness and mental well being of the individual during the operation, it also affects family, social and work reintegration together with attitudes towards the organisation following the operation. Adverse stress reactions may have long term

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detrimental effects on an individual’s functioning and well being and on the well being of the service man or woman’s family unit. By providing guidelines to military leaders on assessment for psychological risk, psychological preparation of individuals and units, psychological education and training, psychological support before, during and after operations, psychosocial support of partners and families and on the organization of psychological support services. It is the goal of the RTG that these may be adopted as standardized NATO and PfP practice as part of a range of measures to support our Armed Forces on military operations which they may be asked to carry out on behalf of all of us whatever or whenever that may be.

6. Persons to contact If you wish to comment, find out more about the task group’s work or to assist in our objectives, please contact your RTG-020 national representative or the Chairman*. National representatives AUSTRIA LtCol Mag. Christian LANGER Psychology Service of the Austrian Armed Forces Am Fasangarten 2 A 1130 VIENNA (WIEN) AUSTRIA Tel.: + 43 1 5200 55400 Mobile: +43 676 7036752 email: [email protected] or [email protected] BELGIUM LtCol Psy Yves CUVELIER* DOO-SAO Kwartier Koningin Astrid Bruynstraat 200 1120 NEDER-OVER-HEEMBEEK (BRUSSELS) BELGIUM Tf: +32 – (0)2 – 264 5300 Fax: +32 – (0)2 – 264 5461 email: [email protected] CANADA Mr Jason DUNN DQOL 9-2 Research Directorate of Quality of Life NDHQ – National Defence Headquarters 101 Col By Drive OTTAWA, ON CANADA KIA OK2

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Tf: +1 – (613) – 995 – 0706 Fax: +1 – (613) – 995 – 9175 email: [email protected] CROATIA Major Mladen TRLEK Ministry of Defense of the Republic of Croatia Zvonimirova 12 10000 ZAGREB CROATIA Tf: +385 1 3786489 Fax: +385 1 3786763 email: [email protected] CZECH REPUBLIC LtCol Jiri KLOSE Clinical Psychology Dept. Central Military Hospital PRAGUE CZECH REPUBLIC Tf: +42 (0) 973 203470 Fax: +42 (0) 973 203465 email: [email protected] DENMARK Ms Birgitte HOMMELGAARD Psychologist, MA Institute for Military Psychology Royal Danish Defense College Ryvangs Alle 1 DK – 2100 Copenhagen OE Tf: +45 39 15 19 44 Fax +45 30 15 19 01 email: [email protected] FRANCE Médecin en Chef Patrick CLERVOY Professeur agrégé du Val-de-Grâce Service de psychiatrie Hôpital d’instruction des armées Sainte-Anne BP 600 83 998 TOULON NAVAL – France Tel : +33 (0)4 94 09 91 85 Fax : +33 (0)4 94 09 98 35 email : [email protected] GERMANY Mr Bernd WILLKOMM FlMedInstLw/Div VI

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P.O. Box 1264 KFL D-82242 FUERSTENFELDBRUCK Tf : +49 – (0)8141 – 5360 – 2212 Fax : + 49 – (0)8141 – 5360 – 2909 email : [email protected] LITHUANIA Lt Danute LAPENAITE Military Clinical Psychologist KAUNAS Military Medical Center LITHUANIA Tf: +370 37 320702 Fax: +370 37 204602 email: [email protected] LUXEMBURG LtCol Psy Alain WAGNER Psychologue de l’Armée Caserne Grand-Duc Jean BP 166 L-9202 DIEKIRCH LUXEMBURG Tf : + 352 – 26809 302 or 352 – 021 – 184441 Fax : + 352 – 809474 email : [email protected] + [email protected] ROMANIA Col. (Ret’d) Dr. Gheorghe PERTEA Head of Laboratory for Military Psychology Military Intelligence General Directorate GENERAL VASILE MILEA street, number 3-5 District 5 7000 BUCHAREST ROMANIA Phone:+40214102590 Fax: +40214113502 E-mail: [email protected] or [email protected] SLOVAKIA Major Dr. Pavol SMYKALA Armed Forces Head Psychologist J1 General Staff Slovak Ministry of Defence Kutuzovova 8 832 28 BRATISLAVA SLOVAKIA Tf: + 421- 960 313127 or + 421-960 312359 Mobile : + 42-1907 735 777 email: [email protected] or [email protected]

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SPAIN Captain Psy José María PUENTE Inspección General de Sanidad/Unidad de Psicología (Inspection) General of Medical Service/Unit of Psychology) C/Reina Mercedes, 21 28020 MADRID SPAIN Tf: +34 91 456 1969 Fax: +34 91 456 1976 email: [email protected] and [email protected] SWEDEN Dr. Kristina POLLACK Director Military Psychology HQ GRO/UTB S-107 85 STOCKHOLM SWEDEN Tf: +46 – (8) 788 75 45 Fax: +46 email: [email protected] THE NETHERLANDS LtKol Coen van den BERG MSc Royal Netherlands Military Academy Faculty of Military Management Sciences Social and Behavioral Sciences and Philosophy P.O Box 90.002 4800 PA BREDA The NETHERLANDS Tf: + 31 (0)76-5273279 Fax: + 31 (0)76-5273255 email: [email protected] LtKol drs Peter H.M. van KUIJCK Military Psychologist – Certified Mental Health Psychologist Personnel and Organization Service Behavioural Sciences Division Frederikstraat 467-469 2514 LN DEN HAAG The NETHERLANDS Tf: +31 – (0)70 – 316 5458 or 5450 Fax: +31 – (0)70 – 316 5452 email: [email protected] UNITED KINGDOM Mr Paul CAWKILL Human Sciences Room G003, Building A3 Dstl

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Ively Road Farnborough Hants GU14 0LX UNITED KINGDOM Tf: +44 - (0)1252-455779 Fax: +44 - (0)1252-455062 email: [email protected] UNITED STATES LTC Paul BLIESE US Army Medical Research Unit – Europe/Walter Reed Army Institute of Research Nachrichten Kaserne Karlsruher Strasse 144 69126 HEIDELBERG GERMANY Tf: + 49-6221-17-2626 Fax: email: [email protected] HFM EXECUTIVE Cdr Marten Meijer, PhD HFM Executive Tel: +33 15561 2260 Fax: +33 15561 9645 E-mail: [email protected]

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Section IV Virtual Reality Therapy in the Treatment of Posttraumatic Stress Disorder and Related Psychiatric Conditions

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Scenario Self-Adaptation in Virtual Reality Exposure Therapy for Posttraumatic Stress Disorder Sinisa POPOVIC 1 , Miroslav SLAMIC, Kresimir COSIC University of Zagreb, Faculty of Electrical Engineering and Computing, Croatia

Abstract. Several studies using VR exposure therapy for PTSD have been conducted to date, with promising results. The need for better accuracy of the patient’s arousal assessment requires aggregation of various measures of arousal, including physiological ones, which may increase the mental burden on the therapist. Assessment of the patient’s arousal, automated by the computer, may therefore be useful. As the therapist also needs to manipulate user interface to introduce appropriate trigger stimuli in the virtual environment, automated adaptation of VR scenarios in response to the patient’s level of arousal may alleviate this task. This paper describes the architecture of the software that performs appropriate automation according to the rules of graded exposure therapy, and discusses issues for successful implementation of such software. Keywords. VR exposure therapy, PTSD, automated adaptation, adaptive control, physiology, SUDs, arousal, anxiety, self-adaptation.

Introduction Several studies using VR exposure therapy (VRET) for PTSD have been conducted to date, with promising results. PTSD patients involved in these studies include Vietnam War veterans [1-2] and survivors of the September 11 attack on World Trade Center (WTC) [3]. In an uncontrolled study of 10 Vietnam War veterans with PTSD, average reduction in PTSD symptoms between 15 and 67 percent was noted [2,4]. A case report of a PTSD-suffering survivor of WTC attack documented a decrease in depression and PTSD symptoms of 83 and 90 percent, respectively. Also, the prototype virtual environment (VE) and clinical interface have been built, and further development efforts are currently ongoing, for the VRET of military personnel coming home from Iraq; initial clinical trials are expected in 2005 [5,6]. To improve the benefits of using VR in exposure therapy, it is also necessary to evaluate and minimize downsides and inconveniences of the technology for the users. Consequently, human factors are an important research topic [7-8]. A dissertation addressing usability issues in VRET provides a variety of suggestions regarding usability improvements in the therapist’s user interface [9]. Therapist-oriented usability improvements are also addressed in this paper.

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Corresponding Author: Sinisa Popovic, University of Zagreb, Faculty of Electrical Engineering and Computing, Unska 3, 10000 Zagreb, Croatia; E-mail: [email protected].

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We present the architecture of the software for performing automated adaptation of scenarios in VRET for PTSD according to various measures of the patient’s arousal, and discuss issues for successful implementation of such software. The concept of automated adaptation of VR scenarios has been previously discussed in another context [10], and VR systems driven by the patient’s physiology have been described elsewhere [11]. Automated adaptation could improve the usability of PTSD VRET systems, with regard to the speed of acquaintance and ease of use by the therapist, because it would decrease the therapist’s efforts related to the assessment of the patient’s arousal and changes in the patient’s exposure. The quality of the therapy could also be improved as a result, since the therapist could concentrate better on the communication with the patient during exposure sessions. In particular, high-accuracy assessment of the patient's arousal might become a mentally-intensive process for the therapist, when various arousal-related measures are used and need to be aggregated, including subjective units of discomfort (SUDs), physiological measures (e.g. skin conductance, heart rate, etc.), changes in the patient’s behavior (e.g. anxious movements), and so on.

1. Therapist’s General Reasoning in Graded Exposure Therapy The topmost goal of the therapist during exposure therapy is to cure the patient [9]. Regardless of the medium used in the exposure therapy, this goal may be broken down into three sub-goals [9], two of which have direct impact on the therapy: to determine patient’s fear (alternatively, arousal), and to change patient’s exposure. Changing the patient’s exposure is based on the therapist's assessment of the patient's arousal, where the therapist tries to produce an optimal therapeutic effect on the patient. In particular, with PTSD, during the patient's imaginal recollection and description of the trauma, the therapist communicates with the patient and tries to avoid two extreme conditions—that patient becomes totally overwhelmed by the trauma, or that the patient is unable to engage emotionally [12]. For non-extreme situations, the therapist conducting graded exposure therapy for PTSD exposes the patient to a hierarchy of increasingly evocative scenarios which address the patient's traumatic memories [1,3], and the patient should progress through these scenarios at his/her own pace [12]. Such reasoning of the therapist may be described by these few general rules: x If the patient is emotionally detached, then try to engage the patient in the memory via conversation, by asking specific questions [12] x If the patient has habituated (arousal is low), then increase the intensity of exposure (e.g. move the patient to the next scenario in the hierarchy) x If the patient has not habituated (arousal is significant), then maintain the intensity of exposure (e.g. repeat the same scenario until the patient has habituated) x If the patient is overwhelmed by the trauma (arousal is too high), then decrease the intensity of exposure. The therapist may accomplish this by reinforcing the patient’s feeling of safety [12]. In VRET, the therapist may also need to close the VE, show a relaxing scenario, or re-introduce a prior scenario, for the most therapeutic effect in particular circumstances. In order to apply these rules successfully by the computer during graded VRET for PTSD, the means to assess the patient’s arousal and to change the intensity of the

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patient’s exposure are necessary. The software support for the use of these rules in graded VRET for PTSD is described in more detail later, and the next section addresses the literature relevant for automation of the assessment of the patient’s arousal.

2. Patient’s Arousal Assessment There are several different measures of arousal; one source describes the following four, in an increasing order of objectivity: SUDs, self-report scales, overt behavioral observation, and physiology [13]. All measures except self-report scales may be used to determine the patients' arousal during the actual exposure sessions. 2.1. PTSD Studies with VR The studies of VRET for Vietnam veterans and WTC attack survivor contextually present the closest literature to the issue of software assessment of the patient's arousal—both deal with PTSD, and both include VR as a source of trauma-related stimuli. With respect to the arousal evaluation measures applied during exposure sessions, these studies have used SUDs and, likely, overt behavioral observation. In the case of VRET administered to WTC attack survivors, the authors have used a welldefined SUDs-based rule to determine the appropriate moment to suggest the next sequence of events to the patient. That is, this rule together with behavioral observation of the patient has been used to determine when the patient has reached adequate habituation. The use of SUDs in these studies belies the importance and convenience of SUDs for assessment of the patient’s arousal in VRET for PTSD, which is not surprising, since SUDs have been used frequently in a variety of research studies. As these two VR-PTSD studies do not address physiological measures of arousal, additional possible sources of relevant literature seem to be PTSD studies employing physiological measures with methods of stimuli presentations different from VR. 2.2. PTSD Studies without VR In two recent reviews of the psychophysiology of PTSD, a vast amount of related literature has been addressed [14-15]. Some mentioned differences between the individuals with and without PTSD are that PTSD individuals exhibit heightened physiological responsiveness to trauma reminders, exaggerated startle, and elevated tonic or baseline physiological activity [14]. Of these, heightened physiological responsiveness to trauma-related stimuli is found to be highly replicable across the examined studies, and able to discriminate PTSD from non-PTSD individuals with a sensitivity between 60 and 90 percent and specificity of 80 to 100 percent. In the other review article [15], the authors advocate a greater role for direct psychophysiological evidence in the diagnosis of PTSD, referring to substantial consistent findings in the literature regarding physiological reactivity to trauma cues. The authors mention that psychophysiological information needs to be viewed in the context of other assessment methods like self-report or interviews. Different measures viewed together may provide ambiguous evidence, in which case aggregation from

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multiple sources of evidence is necessary. Despite this, the divergence of evidence can be highly informative regarding the patient's state. Further emphasis is given to the fact that the majority of psychophysiological research, focused on differences between PTSD and non-PTSD groups, has limited value for the clinician and an individual patient [15]. For example, even though there are many studies demonstrating heightened physiological responsiveness in a group of individuals with PTSD, they help little in determining whether a physiological response of a given individual is "heightened." The authors point out the need for research leading to future diagnostic criteria that will offer standards for determining whether a particular response represents a clinically meaningful elevation or diminution. Such research would be of direct relevance for the automation of the patient’s arousal assessment. 2.3. Studies of Other Psychological Disorders with VR Studies merging VR and other anxiety disorders, which incorporate physiological measures of the patients' arousal, can also provide some useful insight. Physiology has been applied in VR exposure therapy for fear of flying VEs, acrophobia VEs, fear of public speaking VEs, and perhaps others, addressing the topics like: evocation of presence in VEs [16-19], discrimination of phobics from nonphobics in VR exposures [17-18,20], monitoring of treatment progress in VRET [20-21], and the impact of physiological feedback to patients on sustainability of effects [21]. The physiological channels that have shown some significant discriminating powers in various contexts addressed by these studies include skin resistance/conductance [16,18,20-21], heart rate [16-17], and skin temperature [16]. There is also evidence that brain wave activity offers the potential to discriminate in several frequency bands between the subjects who self-report high subjective arousal and those who self-report low subjective arousal [13]. Interestingly, one fear of flying study had a group of subjects who progressed through the scenarios solely by their skin resistance level, and not by typically used SUDs [21]. This change appeared to have no adverse impact on the effectiveness of the treatment (100% of these patients later flew a plane without medications or alcohol). Therefore, various physiological measures may be desirable complements to SUDs and overt behavioral observation in determining the patient's arousal, in order to guide the patient’s exposure in VRET sessions. The literature related to VRET also recognizes that subjective and physiological arousal do not have to occur simultaneously [13]. When both of these arousals occur, they are overall positively correlated [22], but the subjective and physiological arousals do not necessarily fluctuate in the same manner during an entire therapy session. Related to this is Hodgson and Rachman's concept of synchrony, which describes the effect when physiological and subjective measures move together over treatment [13]. The breaks in synchrony present ambiguous evidence regarding the patient’s arousal, which is problematic for software decision making, unless the ambiguity has been studied, explained, and the resolving strategy has been incorporated into software.

3. Architecture of PTSD VRET System with Automated Scenario Adaptation Scenario self-adaptation includes the identification of the patient’s arousal level, as well as control over the patient’s exposure, to achieve the best therapeutic results. In

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the process of experimental identification, based on input and output measurements, a mathematical model of a system can be derived, including identification of its parameters [23]. However, from a control system theory aspect, the patient’s PTSD structural dynamics are unknown, complex, nonlinear, time variant, multi-input multioutput, with state vector of unknown dimension, i.e. definitely black-box. In control of such systems, some form of intelligent control must be applied, such as fuzzy logic rules and/or artificial neural networks [24].

Figure 1. Architecture of PTSD VRET system with automated scenario adaptation

Figure 1 illustrates the constituent components of the VRET system that includes automated adaptation of VR scenarios, together with the users of the system. By means of visual, audio, and perhaps other types of input stimulations, the patient’s subjective, physiological, and kinematical reactions are elicited. These reactions are captured by the Data Acquisition Subsystem and sent to the Adaptive Control Software (ACS), which computes appropriate control signals for therapeutic changes in the VE. The therapist engages in observation and conversation with the patient, and interacts with the ACS and the VE by means of user interface. Automated adaptation of VR scenarios may be viewed as minimization of the therapist’s input to these two parts of the system; dashed pointing lines on Figure 1indicate this. The therapist’s general reasoning during graded exposure therapy, outlined in section 1, may be captured by decomposition of the ACS into three computational components on Figure 1: x Arousal Level Computation (represents the antecedents of general rules from section 1). This component determines the patient’s arousal by using various inputs: subjective (SUDs), physiological (skin conductance (SC), heart rate (HR), EEG, blood pressure (BP), skin temperature (ST), respiration rate (RR), EMG…), kinematical (pitch, yaw and roll angles from the head tracker, which

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may be potential arousal indicators as they describe the patient’s head movements) x Adaptation Goal Selection (represents the actual general rules from section 1). Decision making in this component determines the general goal for the scenario adaptation on the basis of the patient's level of arousal from Arousal Level Computation x VE Modification Selection (represents the consequences of general rules from section 1). This component selects the specific changes in the VE, based on the goal of adaptation received from Adaptation Goal Selection component Further design and development of lower-level decision making within the ACS may also benefit significantly from the therapists’ insight. ACS may become an expert system if it ends up relying heavily on the therapist’s line of thinking on both high and low levels. However, ACS is not currently anticipated to use all the channels that the therapists naturally have at disposal for gathering information about the patient’s emotional state. For example, conversation and overt behavioral observation still may be too complex for handling by the software, given current state of the art in the fields of real-time natural language processing [25], video analysis and interpretation [26], and affective computing [27]. Although the remainder of the paper focuses on ACS computational components, ACS also contains supporting storage facilities—Log, Baseline Knowledge Database and PTSD Patient Knowledge Database (Figure 1). Log is used to store in sufficient detail the data flowing within ACS, so as to allow subsequent scenario replay and provide the developers with a low-level insight into ACS execution. Baseline Knowledge Database keeps the baseline physiological data of healthy subjects and patients, against which the baseline measurements of a given patient may be compared in a variety of ways. PTSD Patient Knowledge Database contains aggregated patient’s data, which ACS computational components can use in decision making and the therapist can find useful for session review. Each ACS computational component has a somewhat different mechanism used in its decision-making logic. We expect Arousal Level Computation to use if-then rules with fuzzy antecedents and fuzzy consequents, as it is likely that the relationship between the patient’s manifestations of arousal and the actual level of arousal is a fuzzy one. Adaptation Goal Selection may then use the patient’s fuzzy arousal level to determine the crisp general goal of adaptation—"next scenario", "habituation", "previous scenario", "relaxation scenario", or "shutdown"—according to the if-then rules from section 1. Based on this goal, VE Modification Selection can determine the appropriate changes to the VE, according to state machines that define its decisionmaking logic. 3.1. Arousal Level Computation Input variables for Arousal Level Computation, namely SUDs, SC, HR, EEG, BP, ST, RR, EMG, pitch, yaw, roll and the output variable arousal may be represented as linguistic variables typically consisting of from three to seven fuzzy sets with characteristic names, like {"small", "medium", "big"}, {"zero", "small", "medium", "big"},…, {"negative big", "negative medium", "negative small", "zero", "positive small", "positive medium", "positive big"}. It should be noted that the names of input variables here do not only relate to the raw measures, but actually refer to a set of relevant derived measures that are used to assess patient's arousal. For example, SUDs

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may include raw SUDs and change in SUDs [9], SC may include raw SC and relative change in SC with regard to baseline [19] etc. Likewise, the output variable arousal represents several forms of arousal needed for successful automated scenario adaptation, like current arousal at a given moment and average arousal during the execution of a given scenario. The former is important for assessing whether the patient becomes overwhelmed with the exposure, plus for calculating the latter, and the

Figure 2. Possible membership functions defining input and output linguistic variables

latter may be needed for determining whether the patient shows habituation on repeated exposures to the same scenario. Besides deciding on the number of fuzzy sets for each linguistic variable, further degrees of freedom relate to the type and actual shape of membership functions defining the fuzzy sets. Figure 2 illustrates a few types of membership functions (triangular, trapezoid, Gaussian …), with partitions into fuzzy sets, for the output variable arousal and two measures belonging to the SC input variable. The universe of discourse for arousal is a [0, 1] segment, which is arbitrary; the actual membership functions are the part that is important in decision making. Input linguistic variables each have their own physical units, so sets comfortably containing the typical ranges for human beings may be taken as universes of discourse. For example, raw SC is in the range of 2–20 ȝS (microsiemens) for humans [28], yielding a segment [0 ȝS, 30 ȝS] as a sufficiently wide universe of discourse. The universe of discourse for relativeSC on Figure 2 is provisionally [–1, 1] and may be adjusted if needed. Decision making in Arousal Level Computation is accomplished by if-then rules of the form: if (SUDs = and SC = and HR = and EEG = …) then (arousal = ), where is a placeholder for the name of any fuzzy set included in a particular linguistic variable. Only input variables that have been shown in the literature to be sensitive enough, and those that prove sensitive in the actual experiments, will be used in these rules. For example, an actual rule may be:

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if (rawSUDs =“small” and relativeSC = “zero” and relativeHR = “zero”) then (arousal = “small”), where relativeSC is defined as in Figure 2, and relativeHR is defined analogously. Aside from a challenge to define suitable membership functions and rules experimentally, a particular issue in determining the patient’s arousal properly is related to the ambiguity resulting from various measures during exposure. Addressing several topics may be helpful here: x The identification of frequently occurring types of ambiguity during VR exposure therapy (e.g. SUDs vs. SC, SUDs vs. HR, SC vs. HR …). This is helpful for identifying which antecedents in fuzzy rules indicate ambiguity x The rationale for why particular types of ambiguity occur. Determining the patient’s arousal when faced with explainable ambiguity is easier than if ambiguity cannot be explained x A detailed understanding of the methods used by therapists to assess the patient’s arousal in the presence of significant and unexplained ambiguity. It may be helpful to assess the importance of the methods of overt behavioral observation and conversation with the patient in such situations, since these methods are very difficult to implement in the software as mentioned before. A "prerequisite experiment" for determining the precise decision-making logic of Arousal Level Computation could use VRET with currently available manual scenario modifications conducted by the therapist via user interface. The software would be enhanced with meticulous logging in time of the patient's SUDs, various physiology channels, and the moments of therapist's modifications to the VE. As the systems for physiological measurements, visualization and analysis are already available, one would need to add custom software tools for recording of SUDs (which have been shown useful for the therapists [9]), and software support for manual or automatic registration of the changes in the VE introduced by the therapist. Similar software may already exist, like the Phloem tool set developed at University of Southern California Institute for Creative Technologies [29]. The analysis within the experiment needs to address the issues we have previously noted, such as confirming the most appropriate channels for arousal assessment, finding the best-derived measures, and observing ambiguity and synchrony between channels. Instances of ambiguity should be documented with regard to factors such as their intensity, the channels and situations in VE where they typically show up, and the therapist’s assessment of the patient’s arousal when faced with ambiguity. If the cases of unexplained ambiguity occur during the therapy session anyway, the software may also be programmed to behave cautiously and to address those measures that imply greater arousal in order to avoid stressing the patient outside the therapeutic limits. 3.2. Adaptation Goal Selection As goals within Adaptation Goal Selection are selected on the basis of the patient’s arousal, the rule base of this component has fuzzy antecedents corresponding to the arousal linguistic variable. Crisp rule consequents corresponding to adaptation goals are used instead of fuzzy ones, since a particular goal can either be selected or not selected. A simple weighting scheme may be used for resolving the selection of the goal if multiple rules are activated. For example, if the numerical value of the arousal

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variable that comes out of Arousal Level Computation has membership in fuzzy sets “small” and “medium”, both following rules will become eligible for activation: if (arousal = “small”) then (goal if (arousal = “medium”) then (goal = “habituation”),

=

“next

scenario”),

but the higher value of membership will determine the actual goal to be selected. Some current approaches to changing the patient’s exposure in VRET can be mapped to similar rules. Approaches we encountered in the literature include: x The therapist suggests to the patient that more evocative content be introduced in the VE when the patient’s SUDs during the scenario decrease by at least 50% of their initial value [3] x Changes in the VE are introduced based exclusively on physiological measures, like skin resistance (SR) [21] x The therapist introduces changes in the VE during verbal communication with the patient while attempting to match the patient’s trauma description [1] Since the computers are unable, with the current state of technology, to conduct conversation with people like humans can, the implementation of the last approach is not considered here. The first approach may be represented by the following rule: if (SUDs < 0.5*initialSUDs) then (goal = “next scenario”). Regarding the second approach, we have been unable to find the exact logic of using SR to progress through VR scenarios. If this logic uses a comparison with some threshold, it may be represented by a rule similar to the previous one: if (SR > threshold) then (goal = “next scenario”), where SR may stand for some measure derived from the raw SR, like the relative change from the average baseline value, perhaps also averaged across the duration of a given scenario. Since both SUDs and physiology are used within Arousal Level Computation to compute arousal, the outlined current approaches to changing the patient’s exposure are taken into account in the design of the software architecture. 3.3. VE Modification Selection After Adaptation Goal Selection decides on the general adaptation goal, VE Modification Selection turns this goal into exact control signals that produce the desired changes in the VE. These changes need to be well structured to aid automated handling by the software, while still providing enough flexibility to accommodate the modifications that can currently be accomplished by therapists. We assemble the structure according to a description of exposure changes in Virtual Vietnam [1, 30], as these have been described in some detail and appear as sufficiently diverse representatives of exposure changes in VRET-PTSD literature. The application has two major scenarios, a Huey helicopter and an open field environment. The Virtual Huey scenario includes the patient taking off on a Huey, riding and landing, during which the therapist can add a variety of visual and audio effects according to his/her own judgment (e.g. explosions, B52 rumble etc.). This

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indicates that exposure changes may be conducted on several hierarchical levels: scenario selection, main scenario logic, and additional scenario logic. The top level of the control logic in VE Modification Selection deals with changing entire scenarios in response to the goals output by Adaptation Goal Selection. This logic is a simple state machine, with scenarios as states and adaptation goals as conditions that trigger transitions between states (Figure 3).

Figure 3. Scenario selection logic

Figure 4. Structure of a generic scenario, with mapping of example scenario

The scenarios have all the information about both static (e.g. 3D models of objects) and dynamic (e.g. behavior) characteristics of the VE. Thus, when a scenario is selected, it defines the static content of the VE, but also activates its two-level control logic, where both levels may be defined via state machines. The main scenario logic may be viewed as describing the plot of the scenario, while the additional logic may expose the patient within this plot to some typical combat-related events that may improve realism, increase the exposure, or perhaps prevent scenario staleness if the scenario is executed several times in a row. Figure 4 illustrates the structure of the generic scenario according to the reasoning just presented, and shows how the logic of the Virtual Huey scenario maps on the generic scenario. The main logic of the Virtual Huey scenario is sequential, but in any state of the main logic, there may potentially be more simultaneously active states in the additional logic. Appropriate software already exists that provides flexibility to incorporate into the scenario logic such as more complex behavior, like autonomous goal-driven entities and their coordination; one example is a hierarchical concurrent

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state machine (HCSM) framework [31]. The figure also does not show the conditions associated with transitions in either state machine of the Virtual Huey scenario. It appears these transitions are under the control of the therapist in the Virtual Vietnam application [30], but we are unaware which specific conditions instruct the therapist to introduce corresponding changes. If the therapist performs some changes in the VE arbitrarily, these may be modeled in the software via random selection of available events. In all other situations the therapist relies on some preconditions, and these preconditions need to be implemented before the state machine can use them to execute its transitions.

4. Conclusions and Future Work This article has presented our approach for assisting the therapist during VRET in the aggregation of multiple measures when assessing the patient’s arousal, and for relieving him/her of user interface manipulation when changing the content of the VE to keep patient’s exposure optimal. Delegating these tasks to the software may improve the quality of the therapy, since the therapist will be able to focus more on the therapeutic conversation with the patient. Therefore, architecture of the software intended to perform these tasks automatically has been presented, together with issues that need to be addressed in future research so that automation can be done properly. Important issues are related to proper inferring of the patient’s arousal from multiple arousal-related subjective, physiological and kinematical measures. In order to avoid the possibility that the software makes any inappropriate decisions in actual therapy, there is a paramount need for its thorough validation, starting in early development. One safe approach is that the software only makes recommendations to the therapist with regard to the patient’s arousal and the need to change the exposure, but the therapist has the freedom to accept or entirely disregard these recommendations based on their appropriateness. Thus, VRET may be conducted as it currently, with the therapist assessing the patient’s arousal, deciding when to introduce the changes in exposure and, sometimes, which changes to introduce, and finally performing these changes via user interface. The only enhancements are the recommendations from the software that the therapist may freely accept or reject. By keeping track of the therapist’s evaluations, and communicating with the therapists, the development team can get insight into strengths and weaknesses of the software for subsequent improvements. Even after the software starts making proper recommendations frequently, for safety’s sake the therapist may need to retain ultimate control over changes in the patient’s exposure.

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S. Popovic et al. / Scenario Self-Adaptation in Virtual Reality Exposure Therapy for PTSD Rizzo A, Pair J, McNerney PJ, Eastlund E, Manson B, Gratch J, Hill R, Swartout B, Roy M. An immersive virtual reality therapy application for Iraq war veterans with PTSD: from training to toy to treatment. 24th Annual Army Science Conference; 2004 Nov 29-Dec 2; Orlando, FL, USA. Rizzo A, Pair J, McNerney PJ, Eastlund E, Manson B, Gratch J, Hill R, Roy M, Swartout W. From training to toy to treatment: design and development of a post traumatic stress disorder virtual reality therapy application for Iraq War veterans. Proceedings of the 3rd Annual International Workshop on Virtual Rehabilitation; 2004; Lausanne, Switzerland. p. 35-42. Stanney KM, Mourant RR, Kennedy RS. Human factors issues in virtual environments: a review of the literature. Presence 1998 Aug;7(4):327-51. Lewis CH, Griffin MJ. Human factors consideration in clinical applications of virtual reality. In: Riva G, editor. Virtual Reality in Neuro-Psycho-Physiology. Amsterdam: IOS Press; 1997 Schuemie MJ. Human-computer interaction and presence in virtual reality exposure therapy [dissertation]. Delft University of Technology; 2003. Cosic K, Slamic M, Popovic S, Rac Z. VR based adaptive stimulation in estimation of whiplash injuries. Proceedings Vision, Modeling and Visualization; 2002 Nov 20-22; Erlangen, Germany. Wiederhold BK, Wiederhold MD. The future of Cybertherapy: improved options with advanced technologies. In: Riva G, Botella C, Légeron P, Optale G, editors. Cybertherapy: Internet and Virtual Reality as Assessment and Rehabilitation Tools for Clinical Psychology and Neuroscience. Amsterdam: IOS Press; 2004. p. 263-70. Astin MC, Rothbaum BO. Exposure therapy for the treatment of posttraumatic stress disorder. Clinical Quaterly 2000;9(4):49,51-54. Wiederhold BK, Wiederhold MD. Lessons learned from 600 virtual reality sessions. Cyberpsychology & Behavior 2000;3(3):393-400. Orr SP, Metzger LJ, Pitman RK. Psychophysiology of post-traumatic stress disorder. Psychiatric Clinics North America. 2002 Jun;25(2):271-93. Orr SP, Metzger LJ, Miller MW, Kaloupek DG.. Psychophysiological assessment of PTSD. In: Wilson JP, Keane TM, editors. Assessing Psychological Trauma and PTSD. 2nd ed. New York: Guilford Publications; 2004. p. 289-343. Meehan M, Insko B, Whitton M, Brooks Jr. FP. Physiological measures of presence in stressful virtual environments. ACM Transactions on Graphics 2002;21(3):645-52. Slater M, Pertaub D-P, Barker C, Clark D. An experimental study on fear of public speaking using a virtual environment. 3rd International Workshop on Virtual Rehabilitation; 2004 Sep; Lausanne, Switzerland. Wiederhold BK, Davis R, Wiederhold MD. The effects of immersiveness on physiology. In: Riva G, Wiederhold BK, Molinari E, editors. Virtual environments in clinical psychology and neuroscience. Amsterdam, Netherlands: IOS Press; 1998. Wiederhold BK, Jang DP, Kaneda M, Cabral I, Lurie Y, May T. An investigation into physiological responses in virtual environments: an objective measurement of presence. In: Riva G, Galimberti C, editors. Towards cyberpsychology: mind, cognitions and society in the internet age. Amsterdam: IOS Press; 2001. p. 175-83 Wiederhold BK, Jang DP, Kim SI, Wiederhold MD. Physiological monitoring as an objective tool in virtual reality therapy. Cyberpsychology & Behavior 2002;5(1):77-82. Wiederhold BK, Gevirtz RN, Spira JL. Virtual reality exposure therapy vs. imagery desensitization therapy in the treatment of flying phobia. In: Riva G, Galimberti C, editors. Towards cyberpsychology: mind, cognitions and society in the internet age. Amsterdam: IOS Press; 2001. p. 253-72. Wiederhold BK. A review of the success of VR in phobias & other anxiety disorders. NATO ARW Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder; 2005 Jun 13-15; Cavtat-Dubrovnik, Croatia. Fasol KH, Jörgl HP. Principles of model building and identification. 5th IFAC Symposium on Identification and System Pa-rameter Estimation. 1979 Sep; Darmstadt, Germany. El-Nasr MS, Yen J. Agents, emotional intelligence and fuzzy logic. Proceedings of IEEE NAFIPS '98; 1998 Aug; Pensacola, FL, USA. Chowdhury G. Natural language processing. Annual Review of Information Science and Technology 2003;37:51-89. Ekinci M, Gedikli E. Silhouette based human motion detection and analysis for real-time automated video surveillance. Turk J Elec Engin 2005;13(2):199-229. Picard RW, Affective medicine: technology with emotional intelligence. In:Bushko RG, editor. Future of Health Technology. Amsterdam: IOS Press; 2001. Cacioppo JT, Tassinary LG, Bernston GG, editors. Handbook of psychophysiology. 2nd ed. Cambridge University Press; 2000.

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Advanced Technologies in Military Medicine Brenda K. Wiederhold, Ph.D., MBA a,b 1, Alex H. Bullinger, M.D., MBAc, and Mark D. Wiederhold, M.D., Ph.D., FACPb a Interactive Media Institute, San Diego, CA b Virtual Reality Medical Center, San Diego, CA c Center of Applied Technologies in Neuroscience (COAT-Basel), Switzerland

Abstract. Controlled studies by groups throughout the world have proven the efficacy of virtual reality (VR) exposure for “mental rehabilitation,” including treatment of Specific Phobias (SP), Social Phobia (SoP), and Panic Disorder with Agoraphobia (PDA). In addition, many are now showing the power of adding VR to protocols to treat individuals with Posttraumatic Stress Disorder (PTSD) as well as to prevent PTSD by “inoculating” individuals against stressful situations they may encounter (Stress Inoculation Training). Others have shown how VR can be added to protocols for those needing “physical rehabilitation” to improve patient compliance and outcomes. In addition, studies have shown the addition of physiological monitoring and feedback to the VR protocol can have added benefit, both in terms of short term effectiveness and in terms of lowering recidivism in the long term. VR allows stimuli to be presented in a systematic, controlled fashion, and physiology provides objective evidence of when the stimuli are eliciting appropriate responses in the patient or trainee. This enables treatment and training to be individualized, focusing in on those specific parts of the experience which cause the individual the most difficulty. By combining such measures as subjective ratings, physiological data, personality type, and self-report questionnaire scores, with expert clinical observations; it is possible to further refine and improve clinical and research-based protocols. Decades after the first simulators were used to train fighter pilots, advanced technologies and simulations are now impacting military medicine. This paper highlights illustrative studies to introduce the reader to this area. Keywords. Physiology, anxiety, phobias, posttraumatic stress disorder, stress inoculation training, panic disorder, virtual reality, rehabilitation.

Introduction The first studies indicating the possibility of VR as a useful tool in behavioral healthcare were published over a decade ago. Since then, controlled studies from around the world 1 Corresponding Author: Brenda K. Wiederhold, Interactive Media Institute, 6160 Cornerstone Court East, Suite 161, San Diego, CA 92121; E-mail: [email protected].

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have continued to show the value of adding VR as an adjunct to traditional cognitivebehavioral therapy protocols. Prior to VR, most anxiety disorder treatment protocols included exposure as 1 of the components. This was either done in the unpredictable realworld environment (in vivo exposure), or relied on the imaginal skills (visualization) of the patient. VR is an appropriate middle ground and allows the patient and therapist to control the pace of exposure more precisely and focus in on those specific areas significant to the individual patient. It is less overwhelming as a starting point than in vivo and more realistic for most individuals than visualization. The addition of physiological monitoring helps in determining objectively what parts of the simulation are triggering anxiety in the patient, and the physiological feedback helps the patient learn to recognize both arousal and relaxation and develop physiological control which may be useful in real-life situations. While it is clear that self-report measures do not produce the desired level of accuracy for measurement of treatment effectiveness, and may be influenced by numerous patient and event-specific confounds, studies have shown that heart rate variability, skin conductance, and EEG are useful analogs of absorption and presence. A high level of presence and immersion seems to be correlated with faster movement through therapy, a higher level of therapeutic success, and less recidivism [1]. At present, 2 systems are necessary to both present visual VR stimuli and to measure physiology. We hope to create future systems that will combine both tasks into an easy-touse product that makes this form of therapy easier to deliver. An integrated system incorporating a virtual world and physiological monitoring may allow real-time data analysis to occur. The ultimate goal may be to have virtual reality systems that are driven by the patient's own physiology. This will likely include intelligent software that would automatically control the level of difficulty the patient experiences in achieving desired parameters in training. Newer and less invasive methods to measure patient physiology also need to be developed as the current methods are intrusive to some patients and may affect their levels of immersion in the virtual environment. This paper will focus on advanced technologies and how they are being applied in military medicine. It is clear that these same procedures can be translated to the civilian population.

1. Medical Training In 1995, we were given the unique opportunity to become involved in several military medical training exercises in Southern California. These exercises are very important to provide personnel with hands-on training of a mock-up of a war-time triage scenario. Those involved do, however, realize that there are some deficits. One of the things often used is “moulage,” which allows for “fake wounds” to be applied to soldiers so that the medical personnel can practice procedures on various wounds. Realizing the importance of increasing the realism, however, and using the power of advanced technologies, we are now funded by the Telemedicine and Advanced Technology Research Center (TATRC) to utilize “Hollywood” make-up techniques to create realistic wounds, applied to actors and actresses who are coached by medical and psychological personnel to react appropriately

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based on the “wounds” they have received. These “wounded soldiers” can then be imbedded in realistically created computer simulations, allowing personnel to practice and “overlearn” skills. After the appropriate level of skills are attained, personnel can then be tested to see if those simulation training skills then transfer to the near real-world setting in a Hollywood style studio with all the special effects, including exploding bombs, gunfire, smoke and all the confusion one would normally associate with battlefield scenarios. Controlled studies are being conducted to determine if this more realistic training, combining both VR/computer simulation training and real-world training will contribute to attainment of skills. In addition, by creating these simulations on laptop computers, anytime/anywhere refresher training will be able to be performed so that skill decrements may be lessened. VRMC is also developing a number of adjunctive training programs for combat casualty care. To fill a gap in simulation training that exists for Echelon 1 and Echelon 2, we are working with special effects artists, and make-up professionals who prepare lifelike wounds that allow role players or selected troops to appear as casualties during tactical training exercises. Training exercises combine: casualty care, evacuations, and tactical decision making combine with appropriate battlefield stressors and confusion to provide a realistic experience. VRMC is working to produce simulation tools that will allow medical personnel to perform actual procedures on live actors or troops safely but with a high degree of realism and clinical accuracy.

2. Student State Training For optimal learning to occur, it is imperative to keep the student in the proper mental state while training is under way. We were funded by the Defense Advanced Research Projects Agency (DARPA) to test military personnel while they were learning skills on a computer simulation. Physiology was monitored in real time to provide an objective measure of arousal state. Using an off-the-shelf game, 2 training groups were assessed. One group was trained while having a stressor applied (having to return enemy fire while treating wounded patients). Another group was trained while having no real stressor (only treating the patients but not having to return enemy fire). Both groups were then tested in a new, novel simulation environment. As one would expect, those trained with stress were able to perform better in the new test environment than those who were trained without high stress. In addition, subjectively, individuals were unaware when they were becoming too physiologically aroused and perhaps not in the optimum training state. We also were able to see changes in HR, brain wave activity, and skin conductance that correlated with peak performance. We are now performing a follow-on study in which VR worlds are being developed to train and test skills more effectively. The military has at its disposal many new technologies for the purpose of training personnel in new and updated procedures. These technologies are complex and varied, and they require a process by which to compare and assess the diverse capabilities of one technology vs. another. We have prepared a testing protocol that makes use of not only standard examination processes to determine learning, but brain wave measurements to

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ensure that the student using the simulation is sufficiently immersed to maintain focus. This process may then be applied to objectively compare differing simulator technologies and confidently invest military funding into products with tested results. 2.1. Anticipated Benefits/Potential Commercial Applications Because this testing process can easily and efficiently compare very different types of instructional technology, it can be adapted to comparisons of many teaching materials and devices. Training programs throughout the military, beyond medicine, may all benefit from this protocol.

3. Stress Inoculation Training Rates of PTSD in those returning from the Vietnam War have been reported at 15.2% for males and 8.5% for females. Percentages for those returning from Iraq have been estimated at 15.6% for both males and females, with the equal numbers being attributed to an increasing number of females in combat zones. These rates are higher than those reported for Somalia (8% for males and females) and the Gulf War (8% for males and 16% for females). We realize from past studies in other areas such as phobias, anger management, and peak performance training for athletes; that by providing “stress hardening” or stress inoculation training prior to sending individuals into potentially stressful situations, we may be able to provide some protection from the development of posttraumatic stress disorder (PTSD) [2-5]. To encapsulate, on the military medicine side of the house, our mission is to develop, test, validate and deliver a highly effective training experience using innovative technology integrated with medical science, which can successfully train, prepare, and produce stress hardened troops. We have extensive experience in the creation of three-dimensional environments. Our graphics and software groups are skilled in the creation of tactical training facilities both real and idealized. We have developed a number of training protocols in which tactical decision making in virtual environments can be tested at real Military Operations on Urban Terrain (MOUT) facilities. This unique combination of real and virtual spaces allows for the objective evaluation and quantification of simulation training transfer efficiency. The simulated worlds are also useful as mission planning tools, or as an after action/debriefing adjunct. VRMC has developed stress inoculation training protocols for both tactical military training and training for casualty care. Traning in both simulated and real environments can be conducted while personnel wear non-invasive, wireless physiological monitors. The real time assessment of heart rate, electrocardiogram, respiration rate, peripheral skin temperature, and other vital signs allows trainers to assess levels of stress and anxiety during training exercises. The ability to train under stress and achieve mastery of important skills has been associated with successful stress hardening and potential reduction in the incidence of PTSD. Simulations can be viewed on desktops, laptops, through a head-

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mounted display (HMD), or as a 3-wall cave projection system depending on the needs of the specific population to be trained. High fidelity virtual environments, combined with 3D sound, smell, and tactile feedback enhance the training experience. These graphical environments become “The Future of Reality.” Current training scenarios are unable to meet existing and future demands for homeland security. Many investigators have shown that training skills acquired in a static classroom environment do not prepare the individual for the stressful and often unpredictable situations encountered in real-life missions or during wartime. Because of these findings, training must be implemented under stressful conditions and under those conditions that allow the individual to benefit from exposure to maximal variation in outcomes. In general, many training systems today are static and to a certain extent can be “gamed” by the user so that training sessions often become laborious and result in a disinterested and less qualified first responder or warfighter. Today, many younger members who are entering the armed forces and law enforcement are not only computer literate, but quite proficient at Internet and videogame usage. In addition, many younger people are bored with educational programs presented on the blackboard, since they are accustomed to wide-screen televisions, full color graphic videogames, and Internet access. We would like to be able to offer the trainee an experience that is engaging and enjoyable, but more importantly the training should challenge the student and truly build skills that can be fully implemented in real-life wartime situations. To a certain extent, Special Forces and the Army have been using videogames for combat training with some success. These pilot studies provide an initial example of how inexpensive and easy-to-use systems can be of benefit during training. Ideally, these kinds of training scenarios should be available to the first responder and warfighter whenever, wherever, and under the circumstances necessary to provide them what they need at the time. One of the major challenges to training is to provide developers and directors a system of objective measurements and metrics that not only track performance during the training session, but provide a realistic predictor of real-life performance. In addition, because knowledge and skill decrement continue to be a problem with current methods of training, the next generation of training systems should be designed in such a way that the user is drawn into the learning process and provided with a compelling environment that immerses them in their tasks. We are interested in providing an assessment structure that relies on both subjective and objective measurement tools. We have extensive experience over the past 9 years using analysis protocols while patients learn skills in virtual environments for the treatment of certain clinical disorders. We have conducted an in-depth study of the methods that we have used in our clinic and compared them to lessons learned from the stress inoculation training protocols of the Tactical Decision Making under Stress (TADMUS) program, as shown in the table below [6]. (The TADMUS project is sponsored by the Office of Naval Research and was spawned by the 1998 USS Vincennes incident in which an Aegis cruiser engaged in a peace-keeping mission shot down an Iranian Airbus. The resulting investigation suggested that stress may have effects on decision making. TADMUS was designed to address this concern.)

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TADMUS

VRMC

Stress Exposure Training

153

Education

Information provision

Cognitive Behavioral Therapy (CBT) Patient education

Skill Building

Skill acquisition and practice

Physiological feedback and training

Cognitive Schema

Confidence building –

Cognitive coping techniques,

application and practice

desensitization in virtual reality then in vivo (real life)

Over-learn

Over-learn

Training

Training generalizes to real-

Therapy generalizes to real-life

Generalization

life missions

situations

Content

Skills generalize to novel

Other phobias not specifically

Generalization

tasks and novel stressors

trained show improvement

Method of

Gradual increase in stressors

Gradual exposure is important

Exposure

results in skill building

VR Advantages

Virtual reality simulations

Virtual reality simulations allow

crucial in allowing for a

for over-learning and gradual

gradual increase in stressors

exposure to more and more

Degree of Exposure

intense situations Internal Belief

Ongoing Support

Pace of Exposure

A sense of control and

Self-efficacy and a sense of

mastery occurs

mastery occurs

Refresher sessions provide

Booster sessions provide

maintenance of skills

maintenance of skills

Initial exposure to high-

Flooding does not result in

demand/high-stress

development of skills

conditions does not result in skill development and generalization

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Order of Exposure

TADMUS

VRMC

Develop basic physiological

Teach physiological control first

control strategies first to control stress/reduce attention allocated to emotions Quality of

Absolute fidelity is not

Virtual reality simulations better

Exposure

necessary or desirable

than real video

Lessons Learned

Take-home message:

Take-home message: CBT

(pg 213): “an effective

reduces anxiety, results in higher

method for reducing anxiety

levels of functioning, and

and enhancing performance

increases quality of life.

in stressful environments. The results of this analysis should clearly encourage further application and research." TADMUS vs. VRMC: a 1-to-1 correlation

TADMUS highlights several very important facts about training and the lack of appropriate training, which can have very serious consequences. In general, training tasks must be performed under an equal or higher level of stress in order for effective training to take place. Second, the training environment does not necessarily need to replicate the reallife scenario in true fidelity. Third, before training skills can be learned, basic coping mechanisms must be mastered in order to build confidence and self-efficacy in trainees. This preparation allows the trainee to completely focus attention on the tasks at hand and avoids a major problem of training, which is distraction. Although not generally used in training, the measurement of real-time physiology during the training program can provide invaluable information as to the level of engagement, anxiety, or boredom during training. We have found that by measuring selfreported anxiety in combination with EEG brainwaves, skin conductance, and heart rate variability from the EKG, we can not only assess performance during training (or therapy), but also predict who will perform well and who may need additional training or remediation.

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As the photos below illustrate, our teaming strategy is to combine the flexibility afforded by simulation and virtual training with the realism enabled by the Strategic Operations Tactical Training Laboratory.

Uses of virtual environments and simulations for training, although pioneered by the military, are finding increased applications in clinical psychology and executive training in the private sector. Studies have shown that training of skills in a non-stress condition does not transfer to improved task performance when those same skills are then performed in a stressful situation. Therefore, it would be advantageous to employ more real-world stress simulations to allow for more generalizability of skill sets. In 1988, a National Research Council study on enhancing military performance found that when a person is given knowledge of future events, stress surrounding those events is then reduced [7]. In general, this occurs because stress is viewed as a new, novel task. Stress training therefore renders

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the task less novel and improves the trainee’s self-efficacy, which in turn improves performance. At the Virtual Reality Medical Center (VRMC), we have used a combination of cognitive-behavioral therapy and physiological monitoring for the treatment of a variety of psychological disorders. We have evaluated over 5,000 sessions in virtual environments and have noted that successful treatment of stress and anxiety-related disorders requires gradual exposure to more and more stressful situations, which allows the patient to overlearn coping skills and renders the task less novel, which allows for a sense of mastery and an increase in self-efficacy.

4. Post Traumatic Stress Disorder The DSM-IV classifies Posttraumatic Stress Disorder as a heterogeneous disorder that develops following exposure to traumatic events such as a serious injury or threat of injury or death to the self or others. Symptoms of PTSD, which must persist for at least 1 month, include increased anxiety or arousal, dissociation, avoidance of stimuli associated with the trauma and numbing of general responsiveness, as well as flashbacks to the traumatic experience [8]. Both anxiety-reducing medication as well as CBT can help in recovery. In recent years, VR has been shown to improve treatment efficacy for PTSD in survivors of motor vehicle accidents (MVA), war veterans, and those involved in the 9/11 World Trade Center attacks, as well as in other areas [9-15]. 4.1. VR Training/Therapy for Pre-Deployment/Post-Deployment in U.S. Military Personnel The Virtual Reality Medical Center has been funded by the Office of Naval Research (ONR) to develop virtual reality worlds and test them, using our established clinical protocols in combination with physiological monitoring and feedback, to treat noncombatants (including SeaBees and medical personnel) returning from Iraq who are diagnosed with PTSD. The systems will be tested at Balboa Naval Hospital and Camp Pendleton. In addition, we are investigating treatment protocols at both facilities with combatants returning from Iraq utilizing software developed by USC’s Institute for Creative Technologies. Initial results indicate that the worlds do elicit arousal, physiologically and subjectively, in those reporting PTSD symptoms. After treatment, individuals tested thus far no longer meet criteria for PTSD. In a second study funded by ONR, Stress Inoculation Training (SIT) protocols are being tested to determine if providing stress hardening skills prior to deployment can decrease incidence of PTSD. And a third project, funded by the Telemedicine and Technology Research Center, is allowing us the opportunity to ship a VR system to Iraq in August 2005. This will allow us to receive crucial feedback from troops in theater on how the software might need to be adjusted to better meet their needs. Having the end user in the development loop has been an important attribute we have encouraged over the past decade and provides for quicker iterations in the development cycle and a more useful end product.

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Hyperarousal to presentation of combat-related stimuli has been shown in several physiological measurements, including heart rate [16] and electrodermal activity [17-18]. Veterans with PTSD clearly show an increased physiological response as compared to veterans without PTSD. To build on this research, a 1996 article measured visual eventrelated potentials (ERPs) in both a control group and PTSD patients [19]. Event-related potentials reflect neural activity associated with information processing. The P3 component of the ERP reflects stimulus relevance, and its amplitude and latency are thought to be determined by the subjective value of a stimulus [20]. The N1 component of the ERP reflects early-stage selection and its amplitude is dependent on the physical attributes of a stimulus [21]. PTSD patients showed increased P3 and N1 amplitudes in response to combat-related pictures, and also earlier P3 and N1 components for combat-related pictures. They did not show these increases when presented with neutral pictures. The control group of combat veterans who did not have PTSD did not show these patterns. It is important to further explore these measures as virtual reality graded exposure therapy (VRGET) begins to be used to treat this population. It has been hypothesized that the ERP paradigm could possibly be used as a diagnostic tool for PTSD. The 3-dimensional nature of the VR stimuli could allow for more accurate representation of stimuli and would allow for systematic presentation of the relevant stimuli [19]. Dr. Alex Bullinger from the University of Basel has been engaged to provide consulting on these measures. He has been an industry leader in this area of research over the past decade, having published results of several studies indicating the usefulness of 3-dimensional stimuli and its direct effect on physiology. 4.2. Discussion VR has proven an effective method of exposure for those suffering from PTSD, whether it is due to a MVA, natural disaster, terrorism, or war-related trauma. Often in PTSD treatment it is not practical or advisable to re-expose the patient to the trauma in a realworld setting. VR, however, can effectively place the patient back into that scenario so that the necessary processing of memories can occur, allowing the individual to move through the trauma and on to recovery. In order to provide a more time-sensitive solution to those who have been exposed to recent combat situations, several groups are now developing VR worlds and have begun initial testing to treat those returning from Iraq who are suffering from PTSD and Acute Stress Disorder. It is hoped that by providing treatment earlier, many of the co-morbid conditions which often occur, such as substance abuse, can be avoided. Treatment response is also hoped to be greater since the PTSD is not as long-standing.

5. Physical Rehabilitation VRMC is developing advanced computer-assisted rehabilitation systems specifically designed to improve the treatment of the physical and cognitive injuries resulting from battle-related trauma. By employing recent advances in simulation and measurement

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technology, as well as improved rehabilitation paradigms that leverage the brain’s ability to relearn after an injury (neuro-plasticity), it is possible to bring next-generation rehabilitation technology to bear upon the immediate needs of injured military personal . A funded project by DARPA to test inexpensive off-the-shelf videogame environments, such as the EyeToy, as an adjunct to traditional physical therapy protocols will begin pilot testing in September 2005 at the Walter Reed Hospital in Bethesda, Maryland. It is hypothesized that the adjunctive treatment will increase compliance, while decreasing depression and anxiety rates. It is also anticipated that many of the amputees may be experiencing PTSD symptoms due to their physical trauma. These amputees will also be potential participants for an additional arm of our PTSD study. The long-term benefit of this project will be the development and deployment of advanced rehabilitation technologies and strategies. While these technologies will have immediate benefit for injured military personal, their development will also serve to catalyze improvement and change within clinical rehabilitation at large.

6. Conclusion After more than a decade of using VR to treat anxiety disorders, a database of thousands of sessions with patients in virtual worlds has been accumulated. What began with the controlled studies and protocols for the treatment of specific phobias (flying, driving, public speaking, claustrophobia, heights, and spiders) has now expanded to include, amongst others, PDA, PTSD, and SoP. Perhaps the lesson that has been learned above anything else is that there is no “one-size-fits-all” treatment. Responses to virtual worlds vary not only between phobic and non-phobic groups, but also from individual to individual. There is a great deal of variance in the pace at which each patient progresses, as well as their personal feeling of presence in the world. As study results indicate that such variables as personality characteristics and previous VR experience can affect one’s level of immersion (measured through subjective, emotional, and physiological responses), researchers and clinicians, working together in multidisciplinary teams, must continue to create more complex virtual worlds, providing richer and more realistic experiences that can be customized to suit the needs of individual users. Further, as we have learned that this sense of immersion may need to vary among the different phobias being treated, we must continuously refine our protocols. While a person with a specific fear may need to become deeply immersed in the world and ignore his/her surroundings, a patient with PTSD or SoP may feel the need to verbalize feelings during exposure. Finally, we are learning there is a wide range of new technology available, which can be utilized for our common goal of improving the behavioral healthcare field. All studies presented in this paper, whether they were conducted in a million-dollar immersive chamber, HMD, the Internet, or a modified videogame, have shown positive results that point to a promising future for the healthcare application of VR. In developing new virtual reality tools, it is important to keep several concepts in mind. Existing therapeutic concepts should form the basis for the construction of virtual worlds. Virtual reality technology must be understood in light of existing science and

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established paradigms. The application of virtual reality in relation to existing therapeutic approaches and a consideration of the costs of using this technology need to be central in assessing the clinical applications of virtual reality. Multi-disciplinary teams of experts can be very helpful in the development and delivery of virtual reality systems.

References [1]

Wiederhold, B.K. & Wiederhold, M.D. (2003). Three-year follow-up for virtual reality exposure for fear of flying. CyberPsychology & Behavior, 6(4), 441-445. [2] Hoge, C.W., Castro, C.A., Messer, S.C., McGurk, D., Cotting, D.I., & Koffman, R.L. (2004). Combat duty in Iraq and Afghanistan, mental health problems, and barriers to care. New England Journal of Medicine, 351(1), 13-22. [3] Wolfe, J., Erickson, D.J., Sharkansky, E.J., King, D.W., & King, L.A. (1999). Course and predictors of posttraumatic stress disorder among Gulf War veterans: A prospective analysis. J Consult Clin Psychol, 67(4), 520-528. [4] Litz, B.T., Orsillo, S.M., Friedman, M., Ehlich, P., & Batres, A. (1997) Posttraumatic stress disorder associated with peacekeeping duty in Somalia for U.S. military personnel. American Journal of Psychiatry, 154, 178-184. [5] Price, J.L. (2005). Findings from the National Vietnam Veterans’ Readjustment Study. National Center for PTSD, Department of Veterans Affairs. Retrieved June 28, 2005 from http://www.ncptsd.va.gov/facts/ veterans/fs_NVVRS.html [6] Cannon-Bowers, J.A., & Salas, E. (Eds.) (1998). Making Decisions Under Stress: Implications for Individual and Team Training. Washington, DC: American Psychological Association. [7] Druckman, D., & Swets, J. (1988). Enhancing Human Performance: Issues, Theories, and Techniques. Washington, D.C.: National Academy Press. [8] American Psychiatric Association: APA. (2000). Diagnostic and Statistical Manual of Mental Disorders 4th Edition, Text Revision. Washington, DC: American Psychiatric Association. [9] Difede, J. & Hoffman, H.G. (2002). Virtual reality exposure therapy for World Trade Center post-traumatic stress disorder: A case report. CyberPsychology and Behavior, 5(6), 529-535. [104] Rothbaum, B.O., Hodges, L., Alarcon, R., Ready, D., Shahar, F., Graap, K., Pair, J., Hebert, P., Gotz, D., Wills, B., & Baltzell, D. (1999). Virtual reality exposure therapy for PTSD Vietnam veterans: A case study. J Trauma Stress, 12(2), 263-271. [11] Walshe, D.G., Lewis, E.J., Kim, S.I., O’Sullivan, K., & Wiederhold, B.K. (2003). Exploring the use of computer games and virtual reality in exposure therapy for fear of driving following a motor vehicle accident. CyberPsychology & Behavior, 6(3), 329-334. [12] Wiederhold, B.K., Jang, D.P., Gervitz, R.G., Kim, S.I., Kim, I.Y., & Wiederhold, M.D. (2002). The treatment of fear of flying: A controlled study of imaginal and virtual reality graded exposure therapy. IEEE Transactions on Information Technology in Biomedicine, 6(3), 218-223. [13] Wiederhold, B.K., Jang, D., Kim, S., & Wiederhold, M.D. (2001). Using advanced technologies to treat fear of driving. Proceedings of the 9th Annual Medicine Meets Virtual Reality Conference. January 24-27, 2001, Newport Beach, California. [14] Wiederhold, B.K., & Wiederhold, M.D. (2000). Lessons learned from 600 virtual reality sessions. CyberPsychology & Behavior, 3(3), 393-400. [15] Wiederhold, B.K. & Wiederhold, M.D. (2005). Virtual Reality Therapy for Anxiety Disorders – Advances in Evaluation and Treatment. Washington, DC: American Psychological Association. [16] Blanchard, E., Kolb, L., & Prins, A. (1991). Psychophysiological responses in the diagnosis of posttraumatic stress disorder in Vietnam veterans. Journal of Nervous and Mental Disease, 179, 97-101. [17] Brenda, J. (1982). Electrodermal responses in post-traumatic syndromes. A pilot study of cerebral hemisphere functioning in Vietnam veterans. Journal of Nervous and Mental Disease, 170, 352-361. [18] Pitman, R.K., Orr, S.P., Forgue, D.F., de Jong, J., & Claiborn, J.M. (1987). Psychophysiologic assessment of posttraumatic stress disorder imagery in Vietnam combat veterans. Archives of General Psychiatry, 44, 970975.

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[19] Attias, J., Bleich, A., Furman, V., & Zinger, Y. (1996). Event-related potentials in post-traumatic stress disorder of combat origin. Society of Biological Psychiatry, 40(5), 373-381. [20] Donchin, E., & Coles, M. (1988). Is the P300 component a manifestation of context updating? Behavioral Brain Sciences, 11, 357-374. [21] Duncan-Johnson, C.C., & Donchin, M. (1982). The P300 component of the event-related brain potential as an index of informational processing. Biological Psychiatry, 14, 1-52.

Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Indications provided by the Eating Disorder Module of the VEPSY Updated Project: towards a new generation of virtual environments for clinical applications Gianluca CASTELNUOVO, Ph.D.1abc, Gianluca CESA, M.S. ac, Andrea GAGGIOLI, Ph.D. ad, Fabrizia MANTOVANI, Ph.D. ae, Mauro MANZONI, M.S. ac, Enrico MOLINARI, Ph.D. bc, Giuseppe RIVA, Ph.D. abc a Applied Technology for Neuro-Psychology Istituto Auxologico Italiano, Milan, Italy b Clinical Psychology Lab, Catholic University, Milan, Italy c Clinical Psychology Lab, Istituto Auxologico Italiano, Verbania, Italy d Laboratory of Psychology, Department of Preclinical Sciences LITA Vialba, University of Milan, Milan, Italy e Centre for Studies in Communication Sciences (CESCOM), University of Milan Bicocca, Milan, Italy Abstract. This chapter stresses in particular some clinical observations obtained in the eating disorder module of the VEPSY Updated Project and it also proposes some clinical considerations to take into account during the development of new virtual environments for mental health care purposes. For further information, please contact Gianluca Castelnuovo: [email protected] Keywords. e-health, cybertherapy, eating disorders, obesity, clinical psychology, psychotherapy, virtual reality

Introduction In recent years, clinical applications of virtual reality (VR) and telemedicine have been rapidly developing both in medicine and in clinical and rehabilitation psychology [1]. Many 1

Corresponding author: Gianluca Castelnuovo. San Giuseppe Hospital, Istituto Auxologico Italiano, Casello Postale 1-2892, Intra (Verbania) Italy Telephone: +39 0323514339-4278 Fax: +39-0323514338 Email: [email protected]

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terms have been coined to denote this newly developed match between technology and care: cybertherapy and e-health, the integration of telehealth technologies with the Internet and shared virtual reality, are only two examples. This chapter stresses in particular some clinical observations of the eating disorder module of the European funded project VEPSY Updated Project also proposing some clinical considerations to take into account in the development of new virtual environments for mental health care purposes.

1. The VEPSY Updated Project and the Eating Disorder Module The main goal of the "Telemedicine and Portable Virtual Environment in Clinical Psychology"--VEPSY UPDATED--a European Community-funded research project (IST2000-25323, www.cybertherapy.info) was to study the technical and clinical viability of using portable and shared Virtual Reality systems (shared care) in clinical psychology. The selected disorders were anxiety, male sexual disorders and obesity and eating disorders [2, 3]. Particularly its specific goal was the development of different PC-based virtual reality modules to be used in clinical assessment and treatment of social phobia, panic disorders, male sexual disorders, obesity, and eating disorders. About the Eating Disorder Module in the VEPSY Project, the ATN-P Lab – Istituto Auxologico Italiano, the leading partner in this module, has developed the Experiential Cognitive Therapy (ECT), an integrated inpatient/outpatient (4 weeks) and telemedicine approach (24 weeks) that tries to enhance the classical cognitive-behavioral method used in the treatment of eating disorders, through VR sessions and telemedicine support in the follow-up stage. Particularly, using VR and telemedicine, ECT is able to address body experience disturbances, interpersonal relationships, self efficacy and motivation to change, key issues for the development and maintenance of eating disorders that are somehow neglected by actual clinical guidelines [4-9]. Distorted body image, negative emotions, difficulty in maintaining positive outcomes in the long term and lack of faith in the therapy are typical features of obesity and eating disorders treatment. To target these issues different groups are trying to enhance traditional cognitive-behavioral therapy (CBT) with the use of a virtual environment [1, 10-12]. ECT shares with the Cognitive Behavioral Therapy (CBT) the use of a combination of cognitive and behavioral procedures to help the patient identify and change the maintaining mechanisms. However it is different for: • • •

Its use of Virtual Reality (VR): 10 VR sessions. Its focus on the negative emotions related to the body, a major reason patients want to lose weight. Its focus on supporting the empowerment process. VR has the right features to support the empowerment process, since it is a special, sheltered setting where patients can start to explore and act without feeling threatened.

The VR session can approximate natural settings, providing an alternative for exposure and desensitization exercises as well as a more general enhancement to therapy.

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Specifically, VR is believed to increase motivation by allowing individuals to virtually witness changes in their behavior and shape and reach their own conclusions based on actual experience. During typical VR sessions, patients are asked to wear a head mounted VR display system. An approach similar to guided imagery is used to lead the subject through various zones over the course of ten sessions. Stimuli that contribute to abnormal eating behaviors are identified, and associated anxiety and body experiences are targeted for modification. Subjects are also asked to identify figures that most closely resemble their current and ideal body sizes. They are also confronted with a photograph of their actual body. This approach was validated through different case studies [13] and trials. In the first one, uncontrolled, three groups of patients were used [14]: patients with Binge Eating Disorders (BED), patients with Eating Disorders Not Otherwise Specified (EDNOS), and obese patients with a body mass index higher than 35. All patients participated in five biweekly therapy sessions. All the groups showed improvements in overall body satisfaction, disordered eating, and related social behaviors, although these changes were less noticeable in the EDNOS group. This approach was recently tested in further controlled studies. The first one involved twenty women with BED who were seeking residential treatment [15]. The sample was assigned randomly to ECT or to CBT based nutritional therapy. Both groups were prescribed a 1,200-calorie per day diet and minimal physical activity. Analyses revealed that although both groups were binge free at 1-month follow-up, ECT was significantly better at increasing body satisfaction. In addition, ECT participants were more likely to report increased self-efficacy and motivation to change. In a second one, the same randomized approach was used with a sample of 36 women with BED [16]. The results showed that 77% of the ECT group quit binging after 6 months versus 56% for the CBT sample and 22% for the nutritional group sample. Moreover, the ECT sample reported better scores in most psychometric tests including EDI-2 and body image scores. In the final one ECT was compared with nutritional and cognitive-behavioral treatments, using a randomized controlled trial, in a sample of 211 female obese patients. Both ECT and CBT produced a better weight loss than NT after a 6-month follow-up. However, ECT, as compared with CBT and NT, was able to significantly improve both body image satisfaction and self-efficacy. This in turn resulted in a reduction in the number of avoidance behaviors as well as an improvement in adaptive behaviors. In the VEPSY Updated Project the Spanish research group, led by Cristina Botella, worked also as second centre of investigation in the eating disorder module. This group has compared the effectiveness of VR to traditional CBT for body image improvement (based on Cash [17] in a controlled study with a clinical population [18]. In particular, they developed six different virtual environments including a 3D figure whose body parts (arms, thighs, legs, breasts, stomach, buttocks, etc.) could be enlarged or diminished. The proposed approach addressed several of the body image dimensions: the body can be evaluated wholly or in parts; the body can be placed in different contexts (for instance, in the kitchen, before eating, after eating, facing attractive persons, etc.); behavioural tests can be performed in these contexts, and several discrepancy indices related to weight and figure

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can be combined (actual weight, subjective weight, desired weight, healthy weight, how the person thinks others see her/him, etc.). In the published trial eighteen outpatients, who had been diagnosed as suffering from eating disorders (anorexia nervosa or bulimia nervosa) according to the DSM-IV criteria, were randomly assigned to one of the two treatment conditions: the VR condition (cognitive-behavioural treatment plus VR) and the standard body image treatment condition (cognitive-behavioural treatment plus relaxation). Thirteen of the initial 18 participants completed the treatment. Results showed that following treatment, all patients had improved significantly. However, those who had been treated with the VR component showed a significantly greater improvement in general psychopathology, eating disorders psychopathology, and specific body image variables. Since then, the group has also developed a VR simulator of food and eating [19] actually under evaluation with patients. In summary, the data from both Italian and Spanish trials suggest that VR can help in addressing two key features of eating disorders and obesity not always adequately addressed by existing approaches: body experience disturbances and self-efficacy.

2. Why to use VR in clinical psychology: added value and limits 2.1 Advantages The advantages that VR has over traditional approaches have been repeatedly underlined by different studies, overall all in comparison with standard exposure therapies [20-25]. This is understandable given that the majority of the studies about VR-based psychological treatments have used this tool as a new procedure of applying the exposure technique. From this perspective, the following advantages have been pointed out: 2.1.1. VR exposure allows an almost total control of everything occurring in the situation experienced by the person in the virtual world If a patient fears being trapped in a lift, or the turbulences and bad weather during a flight, we can assure him/her that these threats are not going to occur until he/she feels prepared to cope with them and, in fact, he/she accepts them to happen in the virtual world. The same can be said for numerous elements that are present in the situation and can make it more or less threatening. For instance, number of feared persons, animals or objects, size and degree of closing/opening of virtual spaces, the height of the spaces, if there is or not protecting elements, the time a determined situation last, etc. This makes it possible a personalized construction of the exposure hierarchy enabling the user to cope with the feared situation or context at his/her own pace. A VR system can generate as many audiences and social situations as the person requires and such situations can be at his/her disposal when is needed and as many times as the person desires. The only mission of the avatars and the whole virtual world is to be there in order to help. Therefore, VR provides valuable opportunities regarding training and self-training. A person with fear of driving following a motor vehicle accident can practice as many times as needed different feared elements

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(overtaking a track, driving with rain, entering a tunnel, or passing over a bridge) in the virtual world. This possibility of continuous practice in many diverse contexts may help to generalize the therapy achievements to the real world. 2.1.2. VR helps the person to feel present and judge the situation as real In fact, a central element of VR is that it provides the person a place where he/she can be placed and live the experience. Furthermore, the therapist is able to know what is always happening in the situation, what elements are being faced by the patient and what is disturbing to him/her. Obviously, this also contributes to the control of the situation and the protection of the patient. 2.1.3. VR allows going beyond reality We have seen many times in therapy (and also in the real world) the importance of certain situations considered extreme in order to definitely overcome a problem. There would be different thresholds of difficulty/threat; once a very high threshold is overcome, to cope with the remaining ones is much easier. Virtual worlds allow the creation of situations or elements so “difficult or threatening” that they are not expected to happen in the real world. For instance, in our claustrophobia application one of the walls can be displaced (producing a loud noise) reducing the room to a very small space. The first patient who was treated with this application indicated precisely this: “If I am able to cope with that wall I can confront everything” [26]. The same can be made in other virtual worlds; a person with spider phobia unexpectedly has to cope with thousands of spiders, or spiders whose size increases so much that they turn into monsters. 2.1.4.VR is an important source of personal efficacy [21, 26, 27] According to Bandura [28], from all possible sources of personal efficacy, performance achievements are especially useful. We think that VR is an excellent source of information concerning personal efficacy. VR allows the construction of “virtual adventures” in which the person experiences him/herself as competent and efficacious. VR is flexible enough to permit the design of different scenarios in which the patient can develop personal efficacy expectations of highest magnitude (including from easy performances to very difficult ones) generalization (referred to very different domains) and, strength (difficult to extinguish, to achieve the patient perseveres regardless of difficulties). The goal is that the person finds out that the obstacles and feared situations can be overcome through the confrontation and effort. 2.1.5. VR offers privacy and confidentiality The possibility offered by VR of confronting many fears inside the consulting room, without the necessity of in-vivo exposure, represents a significant advantage.

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2.2. Limitations Besides these advantages that VR has over the traditional exposure technique, from a more braoder treatment perspective, VR also has limitations that should be mentioned. The first barrier is the lack of standardization in VR devices and software. The PC-based systems, while inexpensive and easy-to-use, still suffer from a lack of flexibility and capabilities necessary to individualize environments for each patient [29]. To date, very few of the various VR systems available are interoperable. This makes difficult their use in contexts other than those in which they were developed. The second one is the lack of standardized protocols that can be shared by the community of researchers. In reviewing two clinical databases – Medline and PsycInfo - we found only five published clinical protocols: for the treatment of eating disorders [30], fear of flying [31, 32], fear of public speaking [33] and panic disorders [34]. A third limitation is the expense required for to set up trials. As we have just seen, the lack of interoperable systems added to the lack of clinical protocols force most researchers to spend a lot of time and money in designing and developing their own VR application: many of them can be considered "one-off" creations tied to proprietary hardware and software, which have been tuned by a process of trial and error. According to the VEPSY Updated studies [35] the cost required for designing a clinical VR application from scratch and testing it on clinical patients using controlled trials may range between 150000 and 200000 €. Finally, the introduction of patients and clinicians to VEs raises particular safety and ethical issues [36]. In fact, despite developments in VR technology, some users still experience health and safety problems associated with VR use. It is however true that for a large proportion of VR users these effects are mild and subside quickly [37].

3. Conclusion To close this chapter it is important to point out some questions that each VR developer has to take into consideration in designing virtual environments for clinical applications (see Table 1).

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Table 1. Issues to consider in designing virtual environments in clinical applications.

Key questions

→

Possible answers

→

Applications and indications for VR designers

1) Are VEs useful, effective and efficient in clinical applications?

Evaluation of possible advantages and limits. Cost/benefit analysis.

Development of VEs that have to ensure only the factors of presence requested by each application.

2) Do VEs reproduce the physical and perceptual characteristics of real environments?

Attention on graphics and technical characteristics. Focus on realism and graphical issues.

Development of VEs that have to ensure realism and a level of presence as non-mediation and immersion.

3) Do VEs allow users to function in an ecologically valid way?

Attention on cultural and social aspects. Focus on interaction, interactivity. Importance of relationships and context.

Development of VEs that have to ensure ecological situations of interaction, interactivity.

4) Do VEs allow users to experience optimal experiences (flow) during virtual sessions?

Evaluation of qualitative aspects in virtual experiences. Attention on users’ psychological state.

Development of VEs in order to allow optimal experiences, good compliance and high motivation

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[33] C. Botella, R. M. Baños, H. Villa, C. Perpiña, and A. Garcia-Palacios, Telepsychology: Public speaking fear treatment on the internet, CyberPsychology and Behavior 3 (2000) 959-968. [34] F. Vincelli, Y. H. Choi, E. Molinari, B. K. Wiederhold, and G. Riva, A VR-based multicomponent treatment for panic disorders with agoraphobia, Stud Health Technol Inform 81 (2001) 544-550. [35] G. Riva, M. Alcañiz, L. Anolli, M. Bacchetta, R. M. Baños, F. Beltrame, C. Botella, C. Galimberti, L. Gamberini, A. Gaggioli, E. Molinari, G. Mantovani, P. Nugues, G. Optale, G. Orsi, C. Perpiña, and R. Troiani, The VEPSY Updated project: Virtual reality in clinical psychology, CyberPsychology and Behavior 4 (2001) 449-455. [36] N. I. Durlach, and A. S. E. Mavor, Virtual reality: scientific and technological challenges, ed., National Academy Press. Online: http://www.nap.edu/books/0309051355/html/index.html, Washington, D.C. 1995. [37] S. Nichols, and H. Patel, Health and safety implications of virtual reality: a review of empirical evidence, Appl Ergon 33 (2002) 251-271.

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

Treatment of Mental disorders with Virtual Reality Azucena GARCIA-PALACIOSa1 , Cristina BOTELLAa, Hunter HOFFMANb, Rosa M BAÑOSc, Jorge OSMAa, Verónica GUILLÉNa & Conxa PERPINAc a Jaume I University, Castellon, Spain b HITLab, University of Washington, Seattle, WA, USA c Universidad de Valencia, Spain

Abstract. Virtual reality is a new technology that has been applied to the treatment of several mental disorders. The first case study using this new tool was published in 1995. After ten years, several studies have been conducted in the field of Clinical Psychology, mainly in the application of VR for the treatment of anxiety disorders. The present work is a review of the use of Virtual Reality in the treatment of mental disorders. The advantages and limitations of virtual reality are discussed and the findings to date are reviewed. Keywords. Virtual reality, Clinical Psychology, Psychological treatments, Anxiety disorders, PTSD, phobias, eating disorders.

Introduction Immersive Virtual Reality (VR) utilizes technology that enables the creation of 3D computer-generated environments. To have a VR experience we need a computer, software to create the environment, a Head Mounted Display (HMD) or other mean for the user to visualize the VR environment, and a device to move around the environment, such as a mouse or a joystick. The essence of VR is that it allows the simulation of reality in which the user has the illusion of “being” in the computergenerated environment and interacting with the VR objects. This is what we call sense of “presence”. This is a unique feature of VR that is very relevant for use in clinical psychology. Some researchers in this field of psychology initiated studies intended to design and test VR applications for the treatment of mental disorders. The main goal was to explore whether the use of this new tool could help to enhance the efficacy of psychological treatments or to overcome some or their limitations. The first work describing the application of a VR program in the treatment of a mental disorder was published ten years ago by Rothbaum, Hodges, Kooper, Opdyke, Williford, & North (1995). Since then the VR research community has been growing all over the world, facilitating additional efficacy studies exploring the utility of this new tool for various psychological treatments. The aim of this paper is to review the studies exploring the efficacy of VR in the treatment of mental disorders. We will limit our review to Immersive Virtual Reality, and will not include other new technology approaches like 1 Corresponding Author: Azucena Garcia-Palacios. Jaume I University, Dept. Psicologia Basica, Clinica y Psicobiologia, Avola Vincent Sos, Baynat s/n, 12071Castellon, Spain, email: [email protected].

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telepsychology or non-VR computer-assisted treatment programs. First we will review the use of VR as a tool to apply exposure therapy. This has been the main application of VR in clinical psychology, and we can say that the history of VR exposure is the history of the more general field of VR and clinical psychology. Then we will review the application of VR to other mental disorders like eating disorders or addictions, and we will mention other applications of VR like Health Psychology. The final section will be devoted to drawing some conclusions.

1. Virtual reality and anxiety disorders Anxiety disorders are among the most prevalent of all mental disorders (Kessler et al., 1994). Exposure is one of the most effective therapeutic techniques to treat these problems. One of the essential features of anxiety disorders is avoidance. For example, people suffering social phobia avoid social situations because they fear a negative evaluation from others; panic disorder and agoraphobia sufferers avoid public transportation, crowded spaces, etc., because they think if they have a panic attack in those situations it will be difficult to escape or to get help. The essence of exposure is to confront the feared situation in a repeated, gradual, and systematic way. One of the processes involved in the efficacy of exposure is emotional processing (Rachman, 1980). Foa & Kozak (1986) used this concept to explain fear reduction during exposure. This approach assumes Lang’s bio-information theory of emotion in which fear is a cognitive structure that includes representations of stimuli, responses, and their meaning (Lang, 1979). Foa & Kozak suggested that exposure to feared stimuli allows the activation of the fear structure and the presentation of corrective information incompatible with the pathological elements of the fear structure. This process is especially relevant in the case of PTSD. Foa and collegues (e.g. Foa & Riggs, 1993) developed an emotional processing theory to explain PTSD. In order to develop new patterns of acting, thinking, and feeling toward the feared stimuli, exposure therapy requires the practice of new beliefs and actions in the presence of stimuli that elicit the anxiety. Exposure may occur through imagining the anxiety-provoking stimuli, or in vivo, where there is exposure to the real life situation that arouses the anxiety. The therapeutic strategies involve identification of the cues that activate anxiety associated with the feared situation. The individual is then exposed to those cues through imaginal or in vivo exposure. The individual can also receive training in other therapeutic skills including relaxation and cognitive restructuring in order to use these strategies during exposure. With the help of a therapist, the individual learns how to self-manage the anxiety response in the presence of the feared cues. When some clinicians learned about virtual reality they saw a new way of applying exposure. Virtual reality allows simulating reality in a controlled way, but it goes beyond other technological means like video or pictures. Virtual reality gives the user the illusion of “being” in a 3D environment. From a clinical point of view this means having a tool that can make exposure easier to apply. I can expose a patient to fly without leaving the consultation room, and repeat the exact same task once and again in the same session: that is, the patient can take off many times in the same session. Or, I can expose an agoraphobic patient to different situations without leaving the office. I can have a virtual bus, a virtual mall, and a virtual tunnel in the consultation room and I don’t have to wait until it is Saturday afternoon to have the mall crowded, I can just press a key on the computer keyboard and my virtual mall will

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be crowded. I can control every single element to make exposure more gradual if needed. I can expose a patient to fly without turbulences until he overcomes that situation and then progress to fly with turbulence; I do not have that possibility in real flights. VR also allows going beyond reality. For example, in a VR environment for the treatment of claustrophobia we have a room where, pushing a key on the computer, we can make one of the walls move toward the patient with a sound effect to create a sense of closure. Overcoming this kind of exposure enhances the sense of self-efficacy in the patients. On the other hand, as a therapist I can play with the fact that VR situations are “not real”. Because of avoidance, some patients are very afraid of confronting the feared situations, even in a therapeutic setting. In fact, although exposure is very effective, around 25% of phobics refuse enrolment or drop out during the course of treatment. In a study with people with high fear of spiders we found that when making them choose between being involved in a VR exposure program vs. an in vivo exposure program, most of the sample chose VR exposure (Garcia-Palacios et al. 2001). We replicated this finding with a sample of clinical phobics (Fabregat, 2004). In summary, some clinicians and researchers had the idea that VR exposure could help to overcome some of the limitations of in vivo exposure: a) It could be more accepted by some patients; b) It allows graduating the exposure tasks with high accuracy; c) It allows repetitions of the same exposure tasks, promoting overlearning; d) It provides an opportunity to go beyond reality, enhancing self-efficacy; e) .We can expose the patient to different situations without leaving the office, saving time in trips to the feared situations; f) Finally, the fact that we can conduct exposure at the consultation room assures confidentiality. These potential advantages made a group of researchers start to explore the efficacy of VR exposure in the field of anxiety disorders. The first approaches were aimed to treat specific phobias and in the most recent years VR has taken a step forward to study its efficacy in more complex anxiety disorders like panic disorder and agoraphobia, social phobia, and Posttraumatic stress disorder (PTSD). In the next paragraphs we will review the findings up to date in the field of phobias and we will pay special attention to the application of VR to the treatment of PTSD. 1.1. Specific phobias, social phobia, and panic disorder and agoraphobia The application of VR to the treatment of phobias is the most developed field of research in the study of VR and Clinical Psychology. Phobias have provided a wide number of efficacy results in this area of research. The pioneer work testing the utility of VR for the treatment of a phobia was carried out by Rothbaum and collegues (Rothbaum, Hodges, Kooper, Opdyke, Williford, & North, 1995) in a case of acrophobia. Apart from this first experience, six case studies and four controlled studies have been reported to date in acrophobia. All case studies and one non-controlled study (Bouchard, St-Jacques, Robillard, Coté & Renaurd, 2003; Choi, Jang, Ku, Shin & Kim, 2001; Jang et al., 2002; North, North & Coble, 1996a,b,c; Rothbaum et al., 1995) showed positive efficacy results. One case study, however, (Kamphuis, Emmelkamp & Krijn, 2002) reported no efficacy of VR exposure. The controlled studies have shown VR to be more effective than no treatment (Rothbaum, Hodges, Kooper, Opdyke, Williford & North 1995), as effective as in vivo exposure at post-test and six-month follow-up (Emmelkamp, Krijn, Hulsbosch, de Vries, Schuemie & van der Mast, 2002), and as effective at six-month follow-up if using either a head-mounted display (HMD), that is, low presence or a computer

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automatic virtual environment (CAVE), that is, high presence (Krijn et al., 2004). In conclusion, the four controlled studies and most of the case studies show that VR exposure is effective in treating fear of heights. Flying phobia is the specific phobia where most studies have been carried out. Several case studies have reported results of the efficacy of VR therapy (Baños, Botella, Perpiñá & Quero, 2001; Klein, 2000; North, North & Coble, 1997; Rothbaum, Hodges, Watson, Kessler & Opdyke, 1996; Wiederhold, Gervitz & Wiederhold, 1998). Seven more studies, which differ in the degree of methodological control, support the effectiveness of VR for the treatment of flying phobia. Wiederhold (1999) found that VR exposure with physiological feedback was more effective than imaginal exposure at three-month follow-up. Mühlberger, Herrmann, Wiedemann, Ellgring & Pauli (2001) showed that VR was more effective than relaxation. These authors also found that motion simulation did not enhance VR treatment effectiveness (Mühlberger, Wiedemann & Pauli, 2003). Rothbaum, Hodges, Smith, Lee & Price (2000) demonstrated in a well-designed controlled study that VR was more effective than a waiting list condition and as effective as in vivo exposure. These authors reported that these results were maintained at 12-months follow-up (Rothbaum, Hodges, Anderson, Price & Smith, 2002). Maltby, Kirsch, Mayers & Allen (2002) found VR to be more effective than an attention-placebo condition at post-test and at six month follow-up. Finally, Botella, Osma, García-Palacios, Quero & Baños (2004) reported effectiveness at 12-month follow-up using a multiple baseline design. Similar results have been found in spider phobia, although there are no studies comparing VR exposure with in vivo exposure or offering long-term effectiveness. Hoffman’s research group has reported three studies examining the effectiveness of VR exposure for the treatment of spider phobia: a case report (Carlin, Hoffman & Weghorst, 1997) showed the efficacy of immersive virtual reality and mixed reality (consisting of touching real objects which patients also saw in VR) in a 37-year old female with severe and incapacitating fear of spiders. Later, this promising result was supported by two controlled studies. In the first one García-Palacios, Hoffman, Carlin, Furness & Botella (2002) compared VR exposure therapy with a waiting list condition. Results showed that 83% of patients in the VR treatment group improved using strict criteria of clinically significant improvement compared with 0% in the waiting list. The second work (Hoffman, García-Palacios, Carlin & Botella, 2003) found that VR treatment effectiveness was increased by providing the patient the illusion of physically touching the virtual spider, using a real tactile cue (toy spider). There are some preliminary results from a case study, a case series study and an open trial (Wald & Taylor, 2000, 2003; Walshe, Lewis, Kim, O’Sullivan & Wiederhold, 2003) addressing the effectiveness of VR exposure in the treatment of driving phobia. There are also studies using VR in the treatment of social phobia. The first preliminary studies were designed for the treatment of specific social phobia, that is, public speaking fear (North, North & Coble, 1998; Anderson, Rothbaum & Hodges, 2003). Harris, Kemmerling and North (2002) conducted a study with subclinical population comparing VR exposure therapy and waiting list control group. Participants in the VR condition showed an improvement on several questionnaires after treatment.There has been also a preliminary between-subject study testing the efficacy of VR exposure in social anxiety disorder (Klinger et al., 2005). A VR exposure therapy group was compared with a CBT group. The results showed that both groups improved significantly.

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Positive results about for the effectiveness of VR exposure in the treatment of claustrophobic fear have been reported in the three studies carried out by Botella’s research group: A case report (Botella, Baños, Perpiñá, Villa, Alcañiz & Rey, 1998a), a single case study (Botella, Villa, Baños, Perpiñá & García-Palacios, 1999) and a multiple baseline design study (Botella, Baños, Villa, Perpiñá & García-Palacios, 2000). In these studies, VR was effective in the reduction of claustrophobic fear, and results were maintained at three-month follow-up. However, the most important result from these studies was that a generalization of improvement to other agoraphobic situations not specifically treated was observed. This result led the researchers to design a VR environment for the treatment of a more complex disorder, panic disorder with agoraphobia. VR has been used to conduct exposure as one of several components in a Cognitive Behavioral Therapy (CBT) approach to panic disorder with agoraphobia. In the first study, published in 1996, North et al. reported good efficacy data of VR exposure in a sample of subclinical panic compared with no treatment. Data from Jang, Ku, Shin, Choi & Kim (2000) failed to support the efficacy of VR therapy since most of the seven participants were not able to feel present in the virtual environment (tunnel with traffic jam). More recently, Vincelli, Anolli, Bouchard, Wiederhold, Zurloni & Riva (2003) compared two CBT programs, one of which included VR exposure. The results showed that both conditions were equally effective. Another study was conducted by Botella, Villa, García-Palacios, Baños, Quero, Alcañiz and Riva (submitted). Randomization to one of three experimental conditions was employed: VR exposure that permits exposure to external stimuli and interoceptive stimuli; in vivo exposure; and waiting list). Thirty-six participants were randomly assigned to one of the three experimental conditions. The results showed that VR exposure and in vivo exposure were equally effective, with both treatment arms superior to waiting list status. In short, results obtained so far in the field of VR exposure and phobias suggest that VR is efficacious in the treatment of specific phobias. First, several controlled studies support that VR exposure therapy seems to be more effective than control conditions, and as effective as in vivo exposure. One important aspect to highlight is the fact that the skills learned in VR environments generalize to real situations. One of the concerns about the use of VR exposure was that patients would overcome their fears in the virtual environments but that achievement would not transfer to the real situation. The results from empirical studies support the fact that patients are able to confront real situations after going through a VR exposure program. We know this because most studies included a Behavioral Avoidance Test (that involves confronting the real situations) as an outcome measure. Second, we have some evidence from follow-ups confirming the maintenance of treatment gains at long-term. Third, we also have some evidence of the preference of VR exposure vs. in vivo exposure before starting treatment in subclinical and clinical samples of phobics (Fabregat, 2004, GarcíaPalacios et al., 2001). With regard to other more complex phobias like panic disorder with agoraphobia, and social phobia, preliminary results are promising but still scarce. More controlled studies, with larger sample sizes, are needed in order to test long-term efficacy.

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1.2. Post-traumatic stress disorder CBT has been demonstrated to be an effective approach for the treatment of Posttraumatic Stress Disorder (PTSD) (Foa, Keane & Friedman, 2000). A central feature of these interventions is the exposure-based technique providing participants with opportunities to confront the thoughts, situations and emotions related with the traumatic experience, and to learn to control their own emotional responses, correcting the misinterpretations regarding the traumatic event and its consequences. The treatment program for PTSD with the most empirical support is Prolonged Exposure (PE), developed by Foa & Rothbaum (1998), which involves imaginal exposure to the traumatic experience. VR offers a promising alternative to imaginal exposure. VR can help to overcome some of the limitations of imaginal exposure. This type of exposure relies upon the individual’s imagination and memory to recall the traumatic experience. Some patients have difficulties in their ability to imagine. Others may resist or refuse to recall the traumatic event, particularly since one of the PTSD features is avoidance of thoughts and memories related to the trauma. Finally some individuals are able to think about the trauma, but at the same time they are emotionally detached from it. Lack of emotional engagement has been associated with poor treatment outcomes (Jaycox et al., 1998). Reliance upon imagination makes it easier for the patient to use avoidant strategies that interfere with the success of treatment. As previously noted, VR has the capacity to draw the individual into the virtual world, creating “presence”(Hoffman et al., 1998). The virtual environment can recreate the situation where the trauma occurred. The patient is exposed to the trauma not only through imagining what happened, but seeing and “being” in the situation. On the other hand, the possibilities of the computergenerated environment allow graduated exposure to the traumatic situation in a careful way (for example, in a victim of the September 11th attack in New York we can start by exposing the patient of being at the World Trade Center before the attack, just being around the Twin Towers, then we can progress to more stressful parts of the traumatic event). As a result, VR therapy experiences may increase a patient’s feelings of selfefficacy and of being an active agent of their own progress. Rothbaum et al. (1999) published the first case study in the use of VR exposure in the treatment of PTSD for a Vietnam veteran using exposure to virtual environments recreating combat scenarios in the Vietnam War. Lately, in 2001 these researchers conducted an open trial with ten Vietnam veterans (Rothbaum, Hodges, Ready, Graap & Alarcon, 2001). Results showed an important reduction in some PTSD symptoms. In a recent book, Rothbaum, Ruef, Litz, Han & Hodges (2004) published a case study describing the use of VR exposure and psycho-physiological monitoring in PTSD with a Vietnam veteran. One important feature of the work of these researchers is that they are working with severe PTSD patients who suffered the trauma many years ago. This makes the results achieved more promising. Another team has published a case report of the use of VR exposure for the treatment of PTSD in a survivor of the September 11th attack in New York (Difede & Hoffman, 2002). In this case, they showed that VR could be an alternative for those patients who present problems with imaginal exposure. They successfully treated a patient who did not respond to the traditional CBT program that includes imaginal exposure. This is the first study in which VR is an effective alternative to the standard of care for an anxiety disorder—in this case, PTSD. We believe this is an extremely important finding in which VR helps to overcome the limitations of other types of

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exposure. At the present time, these researchers are conducting an open trial with more individuals who did not respond to imaginal exposure. Finally, another approach is the one designed by Dr. Botella in Spain. In earlier studies, VR has been used to simulate traumatic events with high realism in order to expose participants to feared aspects of the trauma. In Dr. Botella’s approach, the aim is to design clinically significant environments for each participant, attending to the meaning of the trauma without the simulation of the physical characteristics of the traumatic event. The aim is not realism, but using customized symbols and aspects that help to process the trauma in a safe and protective environment. We believe that VR technology may provide a useful means to treat PTSD, mainly in those cases where imaginal exposure is not efficacious. The results until now are preliminary but encouraging. On the other hand, there is still a long way to go. We need to conduct controlled studies comparing the efficacy of VR exposure vs. imaginal exposure. We also need studies demonstrating the long-term efficacy of VR exposure and studies exploring the acceptance and satisfaction of patients and therapist regarding the use of this technology.

2. VR and Eating disorders Another field of application of VR is the treatment of distorted body image in eating disorders. One of the essential features of eating disorders is a distorted body image. The treatment of this psychopathology involves confronting the patient with her body image and correcting misconceptions about her own figure, weight, etc. In recent years, researchers in the field of eating disorders are paying increasing attention to body image (e.g., Cash, 1996). However, body image is an abstract concept that is difficult to define and to apply. This is where VR can help—it can be used to confront the patient with a mental image, such as in the case of body image. VR can help to “give reality" to that mental image, creating a representation of it and therefore facilitating the communication between patient and therapist. Also, VR could be helpful in placing the patient into virtual situations that s/he would refuse to recognize as being "real", such as eating "forbidden" food. Finally, facing the patient with his/her fears by means of VR could help to make the individual less reluctant, increasing his/her motivation. There are two groups in Europe that have conducted studies testing the efficacy of VR environments in the treatment of body image. In Spain, the research group led by Cristina Botella designed a VR environment including a 3D figure representing the patient body image whose body parts (arms, breasts, stomach, thighs, legs, etc.) could be enlarged or diminished. The body can be placed in different contexts (for instance, in a kitchen, before eating, after eating, facing people with different complexions, etc.); behavioural tests can be performed in these contexts, and several discrepancy indices related to weight and figure can be combined (actual weight, subjective weight, desired weight, healthy weight, etc.). Dr. Botella’s team has compared the effectiveness of VR to traditional CBT for body image improvement (based on Cash, 1996) in a controlled study with a clinical population offering long-term efficacy at one-year follow-up in patients suffering bulimia and anorexia nervosa (Perpiñà et al., 1999, 2004). The results showed improvement in body image measures as well as in eating and general psychopathology. In Italy, Dr. Riva and his team designed and tested a unique approach that includes VR: Integrated Experiential Therapy. They conducted several uncontrolled and

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controlled studies with good efficacy results in measures related with body image and other eating psychopathology (Riva et al., 1999, Riva et al., 2002, Riva et al., 2003). These studies included mainly patients with Binge Eating Disorder and the results support the efficacy of this approach in body image compared with CBT-based nutritional therapy. In summary, the data from both Italian and Spanish teams suggest that VR can help in addressing an essential feature of eating disorders, body image disturbances. VR have an enormous potential in the field of other disorders related to eating disorders, like obesity. VR can be used to train the patients in healthy eating habits or other skills in the treatment of this condition

3. VR in the treatment of other mental disorders As we have already mentioned the main applications of VR to Clinical Psychology have been done in anxiety disorders. In this section we will summarized the use of VR for the treatment of other psychiatric conditions. Dr. Botella’s team in Spain has developed a virtual environment called EMMA for the treatment of adjustment disorders, concretely pathological bereavement. At this moment the efficacy of that environment is being tested. This virtual environment uses virtual tools to work with symbols that represent the loss. VR has also been applied to childhood disorders like autism (Strickland, 1997). A useful tool is a virtual classroom developed by Dr. Rizzo for the assessment and rehabilitation of attention deficits in Attention Deficit and Hyperactivity Disorder (Rizzo et al., 2000). An emerging field is the use of VR for the treatment of addictions, mainly for the delivery of cue exposure. Several research teams are developing virtual worlds for the assessment and treatment of toxic addictions like nicotine or heroine, and non-toxic addictions like pathological gambling (i.e. Botella, 2004; Kuntze et al., 2001, Lee et al., 2003; Nemire, Beil & Swan, 1999). Another field of application is health psychology. The aim of this paper is to review the use of VR in the treatment of mental disorders, so we will not detail the potential for the use of VR in the treatment of medical conditions. However, we believe it is worthwhile to mention the main lines of research in VR and health psychology. One of them is rehabilitation. Riva and colleagues edited two books with the aim of establishing theoretical and practical issues in the use of VR for the assessment and treatment in neuro-psycho-physiology (Riva, 1997; Riva, Wiederhold & Molinari, 1998). The field has been growing until now with good and promising results. Another line of research is the use of VR as a distraction technique in the treatment of acute pain associated with medical procedures. Researchers from the University of Washington pioneered the use of VR analgesia in acute pain caused by procedures like wound care and physical therapy in burn patients (Hoffman, Doctor, Patterson, Carrougher & Furness III, 2000; Hoffman, Patterson & Carrougher, 2000; Hoffman et al., 2001). The results of VR analgesia are also encouraging in the field of procedural pain related to medical procedures such as the treatment of cancer with chemotherapy (i.e. Gershon, Zimand, Lemos, Rothbaum & Hodges, 2003; Gershon, Zimand, Pickering, Rothbaum & Hodges, 2004; Schneider & Workman, 1999). These results suggest that VR is a promising technique for adjunctive pain reduction during medical procedures. Its unique characteristics, such as the possibility of full immersion and interaction, make

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VR a powerful distractor. The future of VR analgesia is open to the application of this technique to treat acute pain in many other medical procedures.

4. Conclusions and future directions The field of VR and Clinical Psychology has provided evidence of the utility of VR in the treatment of psychological disorders. In some disorders the results are very preliminary, as in the case of addictions. The findings are very promising in eating disorders where VR has proven to be a very useful tool in the treatment of body image disturbances. However, more efficacy studies are needed. The field of anxiety disorders is the most developed. We can state now that VR exposure is as efficacious as in vivo exposure in the treatment of specific phobias, including long-term efficacy. However, we still cannot say that in the treatment of other anxiety disorders like social phobia or panic disorder. Studies are still scarce, and controlled studies are needed. As for PTSD we only have results from case studies and open trials. However, the findings are promising. It is in the treatment of PTSD where we have preliminary evidence that VR can be an alternative for those patients who do not respond to imaginal exposure (Difede & Hoffman, 2002). We believe we need more studies in that line. If VR can help to increase the number of patients who could benefit from CBT treatment, the effort of the VR community will have been worthwhile. This leads us to an important aspect. The APA Task force on Psychological Intervention Guidelines (1995) set two axes to establish the criteria to consider a treatment to be empirically validated. Axis one refers to efficacy and axis two to the therapeutic effectiveness, or clinical utility. The studies in VR until now have provided results regarding axis one, for example comparing VR exposure to control conditions and to in vivo exposure. However, we believe that VR is better understood if we consider axis two. VR is a tool to apply well-established CBT programs and we have to demonstrate that this tool contribute to the improvement of those well-established techniques. If VR is proven to enhance the acceptance of exposure, for example by demonstrating a preference of VR vs. in vivo exposure, that means contributing to the clinical utility of exposure (axis two). If VR is efficacious in those PTSD patients who do not benefit from imaginal exposure, that means contributing to the clinical utility of exposure because with this tool we reach a higher number of patients. The fact that the VR research community is international (there are research groups in America, Europe, and Asia), and that the findings are similar across different countries and cultures, is a result that support axis two. We believe that VR can contribute to the enhancement of the effectiveness and clinical utility of CBT techniques, and we recommend that researchers in this field work along this line. Finally, we would like to make some comments about the limitations that VR presents. One concern ten years ago was cybersickness. Researchers were concerned about patients not being able to complete VR sessions because of cybersickness. However, after ten years of experience treating patients with VR, this has not been a problem in the efficacy studies published. Another limitation that is being overcome is the cost of VR equipments. Ten years ago they were very expensive but now the prices have dropped dramatically. The cost of VR equipment now is around 5,000 Euros (7,000 US$). A problem still remaining is the lack of standardization of VR software and hardware, as well as a lack of standardization of the VR treatment protocols. Technical and clinical researchers should make an effort to standardize hardware,

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software and clinical protocols in order to disseminate VR programs and facilitate its use in daily clinical practice. The application of VR to Clinical Psychology has a short but fruitful history. We believe that VR is a valuable tool to enhance the clinical utility of well-established CBT techniques. The aim is to provide the help needed to all who suffer from mental disorders. There are many challenges and important studies to conduct to contribute to that goal.

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Clinical Issues in the Application of Virtual Reality to Treatment of PTSD Cristina BOTELLA, PhD.a1 , Soledad QUERO, PhD.a, Nuria LASSO DE LA VEGAa, Rosa BAÑOS, PhD.b, Verónica GUILLÉNb, Azucena GARCÍA-PALACIOS, PhD.a and Diana CASTILLAa a Universitat Jaume I, Castellon (Spain) b Universitat de Valencia (Spain)

Abstract. In this chapter the potential for using new technologies (virtual reality) with the aim of treating Posttraumatic Stress Disorder (PTSD) is examined. We have developed a VR application (“EMMA’s room” and “EMMA’s world”) where the therapist and the patient can represent the experience suffered by the patient according to the specific therapeutic needs. The goal of the Emma’s virtual environments is to work with emotions related to the participants’ psychological problem. The specific emotions depend on the specific ways in which the problem is symbolized in each of the scenarios. EMMA tools are used to maximize the effect of these new strategies. EMMA is designed to help the person experience the emotions and experiences which he/she is going through, to touch them and feel them; in short, to accept them and to live with them from another perspective. In this work we present the EMMA environment and the clinical treatment protocol for PTSD in a case study. Keywords. Posttraumatic Stress Disorder, Virtual Reality, Emotional Disorders, Psychological Treatments, Clinical Psychology.

Introduction Since the introduction of Posttraumatic Stress Disorder (PTSD) in 1980 [1], there has been an increased emphasis on the identification and treatment of this disorder because of the significant personal distress, negative consequences, interpersonal and work impairment (marital problems, loss of job, etc.), and the co morbidity with other mental disorders that it entails. Unfortunately, PTSD is related to a very common human condition: reaction to adversity [2]. Human beings have always tried to confront adversity by using multiple strategies. At this moment good approaches for the treatment of this condition are available: Cognitive Behaviour Therapy (CBT) and Proximity, Immediacy, and Expectancy strategies (PIE). 1

Corresponding Author: Cristina Botella. Jaume I University, Dept. Psicologia Basica, Clinica y

Psicobiologia, Avola Vincent Sos, Baynat s/n, 12071Castellon, Spain, email: [email protected]

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CBT is considered an effective approach for the treatment of PTSD [3]. One of the central features of these interventions is exposure-based techniques that provide participants with opportunities to learn to control their own responses when confronted with stimuli related to the traumatic experience. The use of CBT programs that include exposure-based techniques currently represents the treatment of choice for PTSD. The treatment program for PTSD with the most empirical support is Prolonged Exposure (PE), developed by Foa and Rothbaum [4], which involves imaginal exposure to the traumatic experience. The aim of this intervention is to evoke the stressful event and to work on processing it in an adaptive way. The therapeutic strategy involves identification of the stimulus cues or triggers that activate fears associated with the traumatic events. The individual is then exposed to those cues. Exposure may also involve real life situations, objects or individuals that arouse the anxiety. The individual can also receive training in self-regulation skills including relaxation, cognitive awareness (self-monitoring), and reframing interpretations of events (cognitive restructuring or attributional retraining) in order to use these strategies during exposure. Several meta-analytic reviews pointed out that there is strong empirical support for the efficacy of CBT interventions for improving PTSD symptomatology [5, 6]. Despite these encouraging findings, exposure appears to be under-utilized in clinical practice. Becker, Zayfert and Anderson [7] found that only a small minority of a sample of 852 psychologists used exposure to treat PTSD. Avoidance of the feared stimuli is a central diagnostic feature of PTSD and the need to confront the trauma in therapy can present a significant challenge for these patients. They may resist or refuse to recall the traumatic event as well as situations, objects, or people that remind them of it. Some patients are able to think about their trauma, but are emotionally detached from the experience. The lack of emotional engagement can hinder anxiety reduction, resulting in poor treatment outcomes [8]. Potential negative effects on treatment response can also occur as a result of the patient’s inability to imagine. Finally, Orsillo and Batten [9] reported limitations regarding the disseminability and acceptability of exposure in the treatment of PTSD. Some individuals may be unwilling to emotionally engage with their traumatic memories because they find this task too aversive. Regarding PIE strategies, Herbert and Sageman [2] remind us in their work entitled “First do not harm”: emerging guidelines for the treatment of posttraumatic reactions” of the classic aphorism: “Primum non nocere”. The thesis Herbert and Sageman defend is the central influence of the healer-patient dynamic in raising or lowering expectancy of recovering. These authors point out that Babinski, one of Charcot’s disciples, stated that hysteria was the result of iatrogenic suggestions which were inadvertently made to the patient. From this perspective, Babinski [10] proposed “persuasion” as a cure and called the attention of his colleagues to the great importance of not eliciting or suggesting possible pathological symptoms. During World War I the French were the first to adopt Babinski’s ideas on how to confront and treat emotional casualties. The recommendation was not to suggest morbid ideas to the victims. On the contrary, the focus was that they were treated as though they were experiencing a normal reaction to extreme events. Additionally, the recommendation was that the treatment should take place close to the front, with the aim of not giving great importance to the situation. This same approach was adopted by Salmon [11] regarding American casualties in World War I. The victims had to be immediately treated somewhere close to the front, and they had to be given the expectation of a quick improvement and recovery. The same approach was also

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adopted in War World II and “combat stress” (under whatever label) was not a significant problem at that moment [12]. Later, the acronym PIE was coined with the purpose of emphasizing the following three prongs: Proximity, Immediacy, and Expectancy. Herbert and Sageman [2] underline that the experience from the two World Wars was very extensive. This experience led to an emphasis on expectancies, (the “E” in Salomon’s PIE strategy), an emphasis consistent with findings on expectancy effects in psychotherapy. However, in modern approaches to treating posttraumatic reactions the deserved importance to these strategies has unfortunately not been given. Although these two perspectives are interested in treating the same problem, they are focused on different aspects: CBT is mainly focused on the trauma (processing the traumatic experience), whereas PIE strategies are mainly focused on expectancies, on the possibility of recovering, (that is, on future life). Virtual Reality (VR) can improve both approaches. Regarding CBT, VR can help overcome some limitations of this therapy. VR can simulate the stressful event with a high degree of realism and, therefore, help the patients regardless of their ability to imagine. It also permits to have precise control in presenting the feared stimuli or situations to the patient. This may prevent cognitive avoidance and therefore enhance emotional engagement, an essential issue in the efficacy of exposure. VR can also improve PIE strategies by providing a timeless space where the person can rest and recover resilience in order to confront the future. Rothbaum’s team [13] published the first case study where VR exposure was used in the treatment of PTSD. Later this group also reported data from an open trial in which VR with ten Vietnam veterans was used [14], revealing a trend towards reduction in some PTSD symptoms. Recently, Rothbaum, Ruef, Litz, Han & Hodges [15] described a case study highlighting the use of VR exposure in PTSD. In addition, Difede and Hoffman [16] presented a case study on the use of VR exposure for the treatment of PTSD in a victim of the September 11th attack with positive results. It must be underlined that these authors were treating patients who did not respond to the traditional imaginal exposure. Therefore, they show that VR could be an alternative for those patients who have problems with imaginal exposure. Also, an application for the treatment of Iraq war victims has been designed, derived from the X-Box game entitled Full Spectrum Warrior, although data regarding its efficacy have not been offered yet [17]. In summary, VR technology may provide a useful means to treat PTSD. These results are preliminary, but encouraging. However, these studies usually have been addressed to very specific populations that have gone through the same traumatic event. The virtual scenario was very similar for all patients. Furthermore, in these studies the approach was to simulate the traumatic events with high realism. Although this can be an important aim, a possible limitation of this approach is that it could be difficult to reach all patients suffering different traumatic experiences. Nevertheless, if we want to treat different trauma populations (for example, rape victims, assault victims, terrorism victims, pathological grief, etc.) we need more flexible virtual scenarios that can evoke the different stressful events. One possible means of doing so is the use of symbols that represent the trauma. This approach is addressed by Botella’s team in Spain. The aim is to design clinically significant environments for each participant, while attending to the meaning of the trauma for the individual and not merely the simulation of the physical characteristics of the traumatic event with high realism. The focus is not on realism, but on using customized symbols and aspects that provoke and evoke an emotional reaction in the participant that helps

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achieve the emotional processing of the trauma. At the same time, the process creates a safe and protective environment that helps him/her to recover and go on with his/her life. This study has been conducted within the EMMA project, a research project funded by the European Union. In the EMMA project we have developed a VR application (EMMA’s room and EMMA’s world) where the therapist and the patient can represent the experience suffered by the patient according to the specific therapeutic needs. The goal of the EMMA’s virtual environments is to work with negative emotions related to the participants’ psychological problem (anger, anxiety, sadness). In EMMA’s room it is also possible to work with positive emotions (joy, relaxation). The specific emotions depend on the therapy moment and patients needs. EMMA is designed to help the patient experience the emotions and the experiences which he/she is going through, to touch them and to feel them. In short, EMMA is designed to help patients accept their emotions and to live with them from another perspective.

1. Method 1.1. Participant The patient was a 33-year-old single woman who came to the Emotional Disorders Clinic at Jaume I University of Castellón. She presented a Posttraumatic Stress Disorder (PTSD), according to DSM-IV criteria [18, 19], developed from a very conflictive couple relationship. A month after starting to date her boyfriend, they decided to live together. In May 2004 the first slight physical aggression took place after an argument. He apologized, and the patient decided to continue the relationship. In August 2004 she got pregnant and he asked her to abort, but she decided to wait until he changed his opinion. Shortly later, a second aggression episode occurred after a domestic argument. He threw her to the ground and tried to suffocate her by gripping her neck. She escaped, but her aggressor enclosed her in the house. Finally, the patient managed to be heard by a neighbour, who called the police. After this episode, she denounced her aggressor and soon after decided to abort. When she came to seek help, the patient presented low mood, anxiety, hypervigilance (she practically did not go out of her house, she made safety behaviours when she was out at the street, had excessively fearful responses to noises …), nightmares (about abortion and situations of the relationship with her aggressor), distressing recurrent and intrusive memories of the trauma, restricted range of affect (she was not capable of feeling love or expressing affection, emotional detachment regarding friends and relatives), and avoidance of multiple situations (having social relations with men, meeting new people, seeing children…). The clinical history revealed personal antecedents of a major depressive episode two years prior, after the break up of a 9-year relationship. She received psychiatric treatment for this problem with good results. She defined this relationship as satisfactory, although with “excessive dependence towards him”. Another important antecedent was a previous abortion she had when she was 16, which was dictated by her parents.

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Relevant problems in the social or labour areas were not observed. The patient showed a good level of general functioning and demonstrated a high motivation to initiate the psychological treatment. 1.2. Measures 1.2.1. Diagnostic Instrument: Clinician-Administered PTSD Scale (CAPS) [20, 21]. This is a clinician-rated scale which assesses the presence of traumatizing events in the life of the individual and the symptoms associated to those events. This instrument also determines the diagnosis of posttraumatic stress disorder following the DSM-IV [18, 19] criteria. It includes a checklist of possible traumatizing events. The three most traumatizing events are chosen and the individual is asked for a description of the event and his/her emotional response. This instrument also assesses associated features of PTSD like feelings of guilt and dissociative symptoms. Several studies have reported good reliability (internal consistency and interrater reliability) [e.g., 20, 22] and convergent validity [20, 22, 23] for this measure. Treatment sensitivity has also been reported [e.g., 24]. The mean score of the CAPS for a clinical sample was 45.9 (SD = 29.1) [25]. 1.2.2. Self-report measures: x Measures directly related to the problem: - Fear/emotional distress and avoidance scales [Adapted from 26]. The patient and the therapist established three target behaviours or situations that the patient avoided because of the traumatic experience and that he/she would like to overcome at the end of the treatment. The patient rated the level of avoidance in a 0-10 scale where 0 is “I never avoid it” and 10 is “I always avoid it”; and the level of fear/emotional distress in another 0-10 scale, where 0 is “No fear” and 10 is “Extreme fear/emotional distress”. The patient and the therapist also established three target memories, thoughts and emotions related with the traumatic experience that he/she avoided and rated the degree of fear/emotional distress and avoidance using the same 0-10 scales. - Catastrophic thoughts. The main catastrophic thoughts related to the traumatic experience in the target behaviours or situations were specified. The degree of belief in these thoughts was assessed in a scale ranged from 0% to 100%: where 0% means that the patient did not believe the content of the thought at all, and 100% meant that the patient believed that the thought was totally true. x Measures related to anxiety, depression: - Positive and Negative Affect Scales (PANAS) [27]. This is a 20-item questionnaire to assess two dimensions of affect: positive and negative. Positive affect ranges from enthusiasm and activation to sluggishness and lethargy; negative affect ranges from subjective distress and aversive arousal to calmness and serenity. The items are rated in 5-point scales related to what extent they have felt a list of adjectives describing mood states over a specified time frame. This scale is administered in 5 minutes and it offers separate scores for the two subscales. Good internal consistency and test-retest reliability has been reported for the PANAS [27]. The factor structure is supported by several studies [e.g., 27-29]. The mean for the Positive affect subscale in

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a normal sample was 29.7 (SD = 7.9) and for the Negative affect subscale 14.8 (SD = 5.4). - Beck Depression Inventory (BDI) [30]. This is one of the most widely used instruments to assess depression symptoms. It includes 21 items. Each item offers four possible answers. The participant has to choose the statement that best describes his/her mood state. This instrument assesses mainly cognitive aspects of depression, as well as behavioural and physiological symptoms. x Measures related with impairment and improvement: - Maladjustment Scale (MS) [Adapted from 31]. This instrument assesses the level of impairment that the problem causes in different life areas (work, social life, leisure, partner, family, and global impairment) using 0-8 scales where 0 is “Not impaired” and 8 is “severely impaired”. This scale offers good psychometric properties and is sensitive to the effects of the treatment. In this study only data concerning the global scale are provided. - Impairment/Severity rated by the therapist [Adapted from 32]: The therapist assessed the global severity and impairment of the patient weekly in a scale from 0 to 8 where 0 is “free of symptoms” and 8 is “extremely severe and disabling, all aspects of normal life affected by the problem”. x Measures regarding expectations and satisfaction about the treatment: - Participant’s expectations and satisfaction. An instrument was designed in order to obtain information about the respondents’ expectations with regard to the treatment before starting it and about the respondents’ satisfaction at the end of it. Following Borkovec & Nau [Adapted from 33], several questions to measure expectations for the treatment were included. The questions were about how logical the treatment seemed, to what extend it could satisfy the respondent, if the respondent would recommend this treatment to other people suffering from the same problem, if it could be useful to treat other problems, its usefulness for the respondent’s problem, and to what extent it could be aversive. The respondents fill out the same questions at the end of the treatment in order to assess the satisfaction with the treatment. 1.3. Procedure A complete assessment was carried out at pre-treatment to evaluate the problem that the participant suffered. The same assessment was carried out at post-treatment to evaluate the effect of the treatment. Both assessments included the measures described previously. The pre-treatment assessment was conducted in two sessions. The first session lasted about 90 minutes and was dedicated to the assessment of the psychological crisis that the individual was suffering. The participant went through the CAPS and filled out the Davidson Trauma Scale (DTS). This first session was videotaped so an independent clinician could make a clinical judgment about the diagnosis of the individual. In the second session, which lasted about 60 minutes, the therapist and the participant established and rated avoidance and fear regarding the target behaviours and catastrophic thoughts. The patient rated impairment caused by his/her problem using the Maladjustment Scale. The patient also filled out the Positive and Negative Affect Scales and the Beck Depression Inventory. In the second assessment session the patient chose 3D objects and images available on the list in EMMA’s room that, according to her, reflected her emotions with regard to the traumatic events (aggression and abortion). Before finishing this session, an

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initial VR training session was carried out in which the patient had a first contact with the EMMA environment and learned how to manage the VR system. She could also choose a piece of music related to the emotions she experienced with regard to the traumatic events. After being informed about the treatment program for PTSD using VR, the patient signed an Informed Consent form to take part in the study. 1.4. Treatment protocol For the treatment of PTSD, an adaptation of Foa and Rothbaum’s [4] treatment program for this disorder was made. The treatment program consisted of 10-12 sessions, each of which lasted approximately 90 minutes. The components used were: In vivo exposure, Breathing training, and Exposure to the trauma. The virtual environments and EMMA’s tools were used to provide exposure and processing of the negative emotions associated with the trauma. The goal of the strategies included in the treatment programs was to help the patient build a new way of experiencing negative and positive emotions in order to overcome her psychological problems and improve her mental health. Following is a brief description of EMMA environment. 1.4.1. Description of EMMA virtual environment The main elements in the virtual environment are EMMA’s room and EMMA’s world. EMMA’s room is an architectonic structure, a protecting space that contains very important elements. There is a database screen, a listing of icons showing all the elements that a user can manipulate, including three-dimensional objects, music, sounds, images, colored lights, movies and texts. The “book of life” has an index and several chapters defined by the user, and in each chapter he/she can describe any idea or story. It is represented by a virtual book. Different elements can be copied to the living book from the database screen. A virtual keyboard allows the user to label elements or chapters in the book of life. Titles can be added to the different chapters. The purpose is to help the user relive the past as it happened with family photographs and home videos. The second main element is EMMA’s world. The VR environment also has different scenarios or ‘landscapes’ available (a “beach”, a “field”, a “desert”, a “forest”, a “solitary and snow-covered place”). In EMMA’s world it is possible to modify the scenario and to graduate the intensity of these modifications in order to reflect and enhance the emotion that the user is experiencing or to induce certain emotions. The patient can choose to be placed in a landscape that symbolizes his/her feelings and emotions. EMMA allows real-time modifications of the virtual environments; the use of different realistic natural effects (fog, rain, change from night to day, earthquake, rainbow, etc.); the use of specific objects and significant symbols (from 3D objects to real photographs of something/someone significant to the person) to anchor the virtual experience to the personal history. The appearance of EMMA’s world can be dynamically controlled by the therapist, depending on the emotions that the user is feeling at each moment. The aim is to reflect and enhance the emotion that the user is experiencing or to induce certain emotions. It is possible to include modifications in the scenario and to graduate the intensity of these modifications in order to reflect the changes in the

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participants’ mood states. For example, in the “field” landscape, EMMA’s room is surrounded by green hills and trees. It is a beautiful sunny day. We can change the environment, covering the sky with clouds or making it become gradually sunny. Also, we can make the landscape more colourful (with flowers) and livelier (butterflies and birds). The “forest” landscape is a deep wood with bushes, blackthorns and big grey threatening and twisted trees. It is a dark night full of shadows. We can graduate the environment making the wood invade the space of EMMA’s room, or we can include strange or unrecognizable sounds that are usually associated with threats (e.g., animals, or a baby crying). The “desert” landscape is surrounded by rocks. We can graduate the environment making the sky become red and cloudy as if volcanoes were exploding on the horizon. Also, there could be a big storm in that red landscape, with clouds, heavy rain, lightning, and noisy thunder. The ground shakes. The “beach” landscape is a calm blue sea. It is a beautiful sunny day. EMMA’s room is located in a beach with white sand. We can graduate the environment making the sky become more blue and bright or the day can become a beautiful sunset. Finally, the “solitary and snow-covered” landscape is a winter landscape with a pale light and a grey sky. We can graduate the environment with heavy rain, fog or a darker sky. Besides the specific variations for each emotional scenario it is possible to modify the environment according to time, that is, we can establish day or night in each scenario. In summary, the different three-dimensional objects, the sounds, the colours, the lights, the images, the symbols... all of them are designed to reflect or enhance the participant’s mood state in order to help the person to confront, accept and manage the emotions and experiences that he/she has gone through previously in his/her life and is going to experience in the therapy environment. Several images of the EMMA environment are available at http://www.emma.upv.es 1.4.2. Treatment procedure In this particular case, treatment was carried out in 12 weekly sessions of approximately an hour and a half. The first two sessions were devoted to the following components: logic of the treatment program, guidelines for training in slow breathing, education about the common reactions to a traumatic event, and in vivo exposure to traumatic memories about the aggression episode. In the third session, the cognitive restructuring component was introduced. Sessions using EMMA´s tools began at the fourth treatment session. In the first session with EMMA, the patient chose the beach environment (at night) which reflected her feelings with regard to the aggression (loneliness, sadness…). Later, exposure to this traumatic event was carried out using some of the objects selected by the patient and following the general guidelines used for imaginal exposure to traumatic events. The patient was asked to remember the aggression episode as vividly as possible and to narrate the event in present time in 3060 minutes, watching the selected object/s and environment chosen. At the end of the exposure session the patient could choose to make changes in the EMMA environment to reflect her emotions at that time. During all VR sessions the same procedure was followed, using the objects described below: x Sessions 4 and 5: pictures of “plates” and a piece of sad music. According to the patient, this picture was reflecting the place where the aggression episode occurred (kitchen) and also the sensation of “chaos” associated with this day.

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x

Sessions 6, 7 and 8: picture of “man-woman aggression”, the object “bulb” and a piece of sad music. The bulb was representing the diffuse image that the patient had of her ex-boyfriend during the aggression, since she could not remember his face (“I see it blurry”). x Sessions 9, 10 and 11: picture of her ex-boyfriend with her, the object “bulb” and a piece of sad music. In addition, the beach environment on a sunny day was used to practice slow breathing before finishing some especially anxiety-provoking sessions (e.g., session 7), but after the exposure task was over. Session 12 was devoted to working with the traumatic event of abortion, following the same procedure as was used in previous sessions. In this case a photo of “mother with baby” jointly with another piece of sad music was used. After this last exposure session, the main measures of the assessment protocol were again administered. 1.5. Hardware A detailed description of the EMMA technical characteristics is not presented here since a full description can be found in other chapter of the present book [34]. Different devices were used: two PCs, a big screen where the environment was projected, two projectors, a wireless pad and a system of speakers. Brainstorm eStudio software was used for developing the application. Brainstorm eStudio is an European software that is sold worldwide. Until now, it has been used mostly for virtual sets in television. In the EMMA project, we have been the first to use it for virtual reality applications. These devices were placed in a room with dimensions of 5x9 m. PC1 had the graphical outputs from its graphic card connected to two projectors, which were used to project the environment on a metacrilate screen that was placed in the mid part of the room. A wireless pad was placed on a table on the other side of the room, and the patient was seated next to it to interact and navigate in the environment. The therapist was seated next to PC2, and from there she could control the application and the features of the virtual environment that were shown to the patient. The sound system was composed of several speakers distributed in the room to conform to a 5.1 configuration.

2. Results 2.1. Diagnostic Instrument As can be observed in Table 1, at pre-treatment the patient obtained higher scores in the Davidson scales measuring the DSM-IV criteria for PTSD (Criterion B, C and D) than the clinical population. However, at post-treatment a notable reduction of the scores was produced and they were closer to the normal population mean than the clinical one, compared to pre-treatment assessment. Davidson Scale frequency and severity scores are also included. Table 1. Davidson scores compared with normal and clinical populations. Participant Normal population mean PRE POST

Clinical population mean

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Criterion B Criterion C Criterion D Total Frequency Scale Severity Scale

28 43 31 102 55 47

12 16 12 40 22 18

4.17 (3.16) 3.65 (9.53) 4 (8.01) 11.83 (22.24)

22.89 (9.35) 29 (11.46) 24.31 (9.44) 76.48 (27.01)

2.2. Self-report measures In table 2 scores obtained by the measures directly related to the problem, measures related to anxiety and depression, and measures related to impairment and improvement, are presented. As can be seen, the participant showed a reduction in all measures after treatment: the degree of fear and avoidance of the target-behaviours (situations or activities), the thoughts, images and emotions related to her trauma, the degree of belief in the catastrophic thoughts regarding the trauma, the level of anxiety (PANAS) and depression (BDI), the level of impairment that the problem causes in the participant’s life according to her (Maladjustment Scale), and the interference and severity of the problem assessed by the therapist. Table 2. Scores obtained in the measures related to the problem, with anxiety and depression and with impairment and improvement. Situations or activities Having sexual relations with men Relating to men in general (friends, known people…) Seeing children Going out of house Thoughts or images Abortion Image of her ex-boyfriend’s face Emotions Affect towards other persons (friends and especially men) Degree of belief in the negative thoughts “You never know who is going to hurt you” “Nothing good happens to me” Other measures related to anxiety and depression Panas negative scale Panas positive scale BDI Measures related to impairment and improvement Maladjustment Scale Interference assessed by the therapist Severity assessed by the therapist

PRE Fear 9 8

Avoidance 10 8

POST Fear 2 0

Avoidance 0 0

8 6 Fear 10 8 Fear 9

7 6 Avoidance 10 10 Avoidance 9

2 0 Fear 3 2 Fear 2

0 0 Avoidance 4 0 Avoidance 0

PRE 10 10 PRE

POST 4 2 POST

45 21 23 PRE

21 22 10 POST

42 5 5

15 2 2

Lastly, in Table 3 results regarding expectations and satisfaction about the treatment are shown. The patient had positive expectations about the treatment before receiving it and after treatment she had a good opinion of it (she thought the treatment was logical, she was satisfied with it, she would recommend it to another person suffering from the same problem, she thought it could be useful for other problems, she thought it was useful to her and, significantly, she evaluated it as less aversive at posttreatment).

C. Botella et al. / Clinical Issues in the Application of Virtual Reality to Treatment of PTSD Table 3. Treatment expectations and satisfaction scores. PRE To what extent does it seem logical to you? 7 To what extent are you are satisfied with it? 8 To what extent would you recommend it to other 8 people with the same problem? To what extent do you think it could be useful to 8 treat other problems? To what extent do you think it is useful in your 9 case? To what extent you think it is aversive? 7

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POST 8 8 8

8 8 5

3. Discussion Considering the obtained data the treatment seems to offer efficacious and effective tools for the treatment of this patient. Furthermore, the patient’s opinion regarding EMMA was very positive. Regarding specific questions about the utility of EMMA’s tools, the patient noted that she found the possibility of introducing her ex-boyfriend’s photograph into the VR system especially useful since this enabled her to recognize angry feelings towards the aggressor. She explained that it helped her to locate her exboyfriend as the subject of the aggression (before that, she avoided seeing him when she was reminded the aggression episode). She thought the system was immersive and that it helped her to deepen her emotions. She valued the use of the different environments to reflect her emotions very positively (“some times it is easier to express what I am feeling like this than with words”). These are only very preliminary results. This is just a case study. Now, we are applying this treatment in a between-subjects controlled study comparing this procedure with the traditional protocol for the treatment of PTSD by Foa and Rothbaum. As has been said before, there exist different approaches for the treatment of PTSD using VR. One possibility is to develop different virtual environments for each traumatic situation, some of which are very difficult to develop (for instance, regarding sexual abuse in children). Our design follows a different approach. The goal is not to “recreate” the reality, but to achieve virtual environments relevant and significant to the person. The important point is to develop therapeutic contexts and devices which help people to confront their problems, and to open their future and the possibility of living their lives in a more satisfactory way. EMMA’s virtual environment is an “open VR system”. It provides a “timeless space” where the traumatic events are activated and people can live these experiences again but in a safe way. In this timeless space the person is supported by the therapist and the global space reflects her/his emotions and the possibilities of the future. Basically, what we have tried with this work is to structure “creative engineering” of exposure such as is recommended by Becker et al. [7], with the aim of improving these treatment programs for PTSD. Preliminary results of the application of this system to persons with PTSD or pathological grief are very promising [35, 36]. Perhaps these new “open” VR systems which consider the relevance and meaning of virtual environments to be very important permit future additional advances in the field of psychological treatments.

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The aim is to potentate positive expectancies about the future, that is, the “E” from PIE. This is one of the main objectives of EMMA treatment and it is consistent with the evidence that support the idea of “creative engineering” exposure to reach a broader number of individuals suffering stress related disorders [7]. In any case, we must not forget that, as Summerfield [37] reminds us, human nature is basically sturdy and resourceful and is able to respond to the different trials of life.

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Acknowledgements This research was funded through the EMMA project (IST-2001-39192), funded by the European Community: V Framework Programme (IST Programme, 8th call, “Future and Emerging Technologies”).

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Virtual Reality in the Treatment of Survivors of Terrorism in Israel Naomi Josmana1 , Azucena Garcia-Palaciosb, Ayelet Reisberga Eli Somerc, Patrice L. (Tamar) Weissa and Hunter Hoffmand a Department of Occupational therapy, University of Haifa, Haifa Israel b Jaume I University, Castellon, Spain c School of Social work University of Haifa, Haifa, Israel d HITLab, University of Washington, Seattle, WA, USA

Abstract. Due to the numerous terrorist attacks that have occurred in Israel during the last five years there are many people suffering from PTSD who are seeking therapeutic help. Previous studies support the role of virtual reality (VR) as an effective tool for the treatment of PTSD. This chapter describes the development of a VR environment for the treatment of PTSD for people who were traumatized by suicide bus bombings in Israel. We present an overview of the simulation software and the study design including the clinical protocol and outcome measures. Included in these measures is the client’s occupational performance which, to date, has received less attention by those investigating PTSD. Keywords. PTSD, terror, Virtual reality

Introduction Over 1,000 Israelis have been killed in a series of attacks over the last five years, including: shooting incidents, car bombings and suicide bomb attacks which have frequently targeted public transport. Many more people have been physically wounded, and an uncountable number of people have become psychological casualties; these "silent" victims do not assume a special status or become heroes, are frequently ashamed of their disability, and moreover are destined to suffer for prolonged periods, possibly for the rest of their lives Since the beginning of the Palestinian "Intifada", or uprising, in September 2000, 6979 Israeli civilians have been treated for trauma in the aftermath of deadly terrorist attacks. On the Palestinian side, between September 29, 2000 and July 8, 2003, 2,572 Palestinians have been killed, and more than 41,000 injured. An initial telephone survey conducted in Israel examined the impact of terrorism on a nation-wide representative sample [1]. Using a stratified sampling method, 512 participants responded to the survey aimed at assessing the psychological impact of 1

Corresponding author: Naomi Josman. Department of Occupational therapy, Faculty of Social Welfare & Health Studies University of Haifa, Mount Carmel Haifa, 31905 Israel, Phone # 972-4-8240610 Fax # 972-48249753 Email: [email protected]

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ongoing terrorism in Israel. Survey results revealed that 45% of the sample had been impacted by terror. Six percent of the sample experienced personal exposure or had relatives or friends who were wounded or killed. An additional 3.3% had personal exposure or relatives or friends who were exposed but not wounded, and 7% had been personally exposed but did not have relatives or friends who were exposed. Sixteen percent had no personal exposure but had relatives or friends wounded and/or killed, while 12% had no personal exposure but had relatives or friends who were exposed but not wounded. Nothing in life can prepare a citizen for the horror of an act of terrorism. Even in Israel, despite the statistics presented above, few expect such a thing to happen to them. Reactions to the abnormal events of terrorism include a wide range of powerful feelings that may feel abnormal to the person having them or seem strange to those who have not gone through such a disaster. Terrorism evokes a fundamental fear that is a manifestation of helplessness. The violent actions are random, intentional, unprovoked by the individuals attacked, and often targeted at defenseless citizens. This chapter describes the development of a VR environment for the treatment of PTSD as an alternative to conventional imaginal exposure therapy. We present an overview of the simulation software, developed especially to represent bus-bombings in Israel, and the study design including the clinical protocol and outcome measures. Included in these measures is the client’s occupational performance which, to date, has received less attention by others investigating PTSD.

1. The effects of terrorism Victims of terror, including those who have not been physically injured, frequently manifest a severe emotional reaction. People who have experienced the trauma often fall into the following categories: x Survivors of past traumatic events (e.g. veterans, survivors of wars, terrorism, or torture, and survivors of domestic violence, child abuse or street crime); these individuals may have a heightened sense of vulnerability. x People who personally witnessed or were victims of the terrorist attack. x People who experience traumatization from learning of relatives, friends and acquaintances that were subject to the violence, or from exposure to repeated media accounts of the trauma. x People who provide aid and assistance to terror victims [2-3]. Timely secondary prevention may reduce the risk for ASD or PTSD. Posttraumatic distress may include one or all of the following symptoms: x shock and numbness x intense emotion x fear x guilt x anger and resentment x depression and loneliness x isolation x physical symptoms of distress x panic x inability to resume normal activity.

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The DSM-IV-TR [4] groups PTSD symptoms in three categories: re-experience of the trauma, avoidance, and increased arousal. A delayed reaction may occur in some individuals. They may indeed be energized by the initial stressful situation and not react until weeks or months later. Mental health professionals need to educate the public and community physicians about this risk [2, 5]. A number of therapeutic approaches have been developed for the treatment of PTSD. These include Exposure Therapy, Pharmacotherapy, Eye Movement Desensitization and Reprocessing (EMDR), Group treatment, and Brief Psychodynamic Psychotherapy. Exposure therapy, often regarded as the gold standard for successful treatment of PTSD, focuses primarily on evoking self-generated images to facilitate the recreation of the client’s traumatic memories. This approach, however, poses a major difficulty since the clients' natural inclination is to avoid thinking about or imagining the traumatic event thereby preventing or hampering subsequent treatment improvement.

2. Virtual Reality as an intervention tool for PTSD VR-based therapy has been shown to be highly effective for the treatment of phobias [6-7] and for the reduction of pain during burn care [8] and venipuncture [9]. More recently, VR has been successfully used to treat PTSD in case studies and a non-controlled trial. Until the recent introduction of VR based therapies, imaginal exposure therapies relied primarily on the imaginative and memory capacity of patients. Virtual reality affords opportunities not only to capitalize on the patient’s imagery ability, but also to supplement them with visual and auditory computersimulated experiences. For patients who are hesitant or unable to recall the traumatic events, the sensory-rich virtual environment engenders an evocative therapeutic experience which may nurture the patient’s emotional engagement. Since the patient encounters the virtual environment at a self-determined pace, it is easier to distinguish between the act of remembering (and staying in control) and the act of reliving (becoming overwhelmed by the re-experience) [10]. Additionally, VR technology allows for graded exposure to increasingly feared virtual environments/objects/events that can be carefully monitored and tailored to the individual patient. As a result, VR therapy experiences may increase a patient’s feelings of self-efficacy and of being an active agent of his or her own therapeutic experience. VR based therapy for PTSD was introduced by Rothbaum and colleagues. Based theories of Foa and colleagues, Rothbaum and colleagues proposed that the illusion of going into the computer-generated virtual environmemt facilitates emotional processing of memories associated with the traumatic event. They developed and evaluated the therapeutic effectiveness of VR exposure (Virtual Vietnam), for the treatment of combat-related PTSD experienced by soldiers who had been in Vietnam, as one component of a comprehensive treatment program [11]. In a case study, Vietnam veterans exposed to a helicopter environment and an open field environment had strong emotional responses. Results suggested that being immersed in Virtual Vietnam can effectively assist PTSD sufferers in imagining, visualizing and describing their traumatic experiences. This participant had a 34% decrease in symptoms on clinician-rated PTSD and a 45% decrease on self-rated PTSD. Treatment gains were maintained at the 6-month follow-up examination [11]. In an uncontrolled study, 10

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males with PTSD were treated with Virtual Vietnam for eight to 16 sessions. Results indicated that in the clinician-rated PTSD scale at 6-month follow-up, there was a statistically significant reduction (p=.0021) in symptoms associated with specific reported traumatic experiences. Although chronic PTSD in Vietnam Veterans is notoriously difficult to treat successfully, all eight participants reported reductions in PTSD symptoms ranging from 15% to 67%, with significant decreases in all three symptoms clusters (p<.02). Participants’ self-reported intrusion symptoms as measured by the Impact of Event Scale [33] were significantly lower (p<.05) at 3 months than at baseline but not at 6 months, although there was a clear trend toward fewer intrusive thoughts and somewhat less avoidance. The researchers concluded that VR exposure therapy holds promise for treating PTSD in Vietnam veterans [12]. Difede & Hoffman [10] developed the first virtual environment to treat civilian PTSD following the terrorist attack on the World Trade Center Twin Towers in 2001. Using a course of only six one-hour VR exposure therapy sessions involved cognitive behavioral therapy with VR exposure, a PTSD patient who had previously failed to respond to traditional PTSD therapy with imaginal exposure was gradually and systematically exposed to increasingly realistic VR simulations of September 11th. In her first VR session, the patient put on a VR helmet and looked at the towers with no attack. Then, virtual planes flew over the World Trade Center without crashing. As the patient habituated, she was able to tolerate more eventful simulations until in the final sessions, planes crashed into the buildings with animated explosions and sound effects, virtual people jumped to their deaths from the burning buildings, the towers collapsed into dust clouds accompanied by sound effects (screaming, sirens, etc). Depression and PTSD symptoms as measured by the Beck Depression Inventory [13] and Clinician Administered PTSD Scale indicated a large (83%) reduction in depression, and large (90%) reduction in PTSD symptoms In summary, the results of these preliminary studies indicate that VR exposure is a promising tool in the field of PTSD. Controlled trials are needed to establish the efficacy of VR exposure in comparison with imaginal exposure and control conditions.

3. The essence of a client’s occupation Despite the search for effective interventions for PTSD, no study has as yet examined the impact that this condition has on the sufferer’s inability to continue participation in daily occupations and their subsequent rehabilitation to pre-trauma occupational life. Occupations are what we do for a living. They provide the basis for feelings about ourselves. Our jobs help engage us in the world around us, and in so doing, enable us to survive and maintain ourselves. They develop our abilities and skills, allow us to pursue our interests, relate with other people, and express our values [14]. One of the major goals of occupational therapy is to enable the client to achieve a satisfying and productive life by the development or rehabilitation of occupationrelated skills, which facilitate functioning at a satisfactory personal and interpersonal level. The desired outcome of intervention is for the client to be able to meet his own needs, as far as possible, and to have the motivation to continue working towards achieving his full potential. Sub-goals which lead to this major goal are to: x assess client needs in terms of the occupations which are important to him; x identify the skills needed to support those occupations;

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x x x

remove or minimize barriers to successful occupational performance; assist the client to develop, relearn or maintain skills to a level of competence that will allow him to perform occupations to his own satisfaction; and help the client to achieve a satisfactory balance of activities in his daily life.

Most interventions that have reported for PTSD clients focus on decreasing the number and severity of symptoms, and the occupational component is not mentioned in the literature. We propose adding this component both in our evaluation and intervention of the PTSD clients.

4. BusWorld: Bus Bomb Survivor PTSD Therapy A typical immersive virtual reality system consists of a virtual reality helmet that positions miniature computer displays near the participants eyes, and blocks their view of the real world. An electromagnetic xyz coordinate position tracking system attached to the helmet sends information to the computer. When users look around in the virtual world by moving their head orientation, the computer correspondingly changes what they see in VR. Clients put on a VR helmet and experience a virtual world designed to give them the illusion of being on a sidewalk in Israel, across the street from a bus stop (see Figures 1-4 below). There are a number of different levels in this graded exposure, which the therapist controls by pressing a button on the keyboard. For the first level, no bus ever appears at the bus stop (see Figure 1 below). For the second level, a bus comes around the corner and stops at the bus stop but there is no attack (see Figure 2). For the third level, a bus pulls up, and breaks in half as if exploding, but there are no sound effects and no explosion or fire. Additional levels add explosion sound effects, visual special effects of an explosion and the bus on fire (see Figure 4), sounds of people screaming and crying in Hebrew, police sirens and flashing lights that represent the arrival of rescue vehicles. BusWorld was designed by several members of our team, based on interviews with Israeli PTSD victims, therapists. BusWorld was programmed by Worldbuilder Ari Hollander (www.imprintit.com) using sound effects made available by DaneTracks, audio clips created by sound engineer Commnander. Russ Shilling, and texture maps from digitized photos taken in Israel. Photos of actual terrorist bus bomb scenes were used to guide the special effects used in BusWorld (e.g., the geometry of the bus and exploded bus frameworks). A video clip showing the full simulation experienced by the patient on their final therapy session is appended on CD.

N. Josman et al. / Virtual Reality in the Treatment of Survivors of Terrorism in Israel Figure 1

Figure 3

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Figure 2

Figure 4

All images copyrighted by Ari Hollander, www.imprintit.com, used with permission.

5. Clinical Protocol The treatment program is virtual reality exposure therapy [12] which is an adaptation of an empirically validated CBT program, Prolonged Exposure (PE) developed by Foa & Rothbaum [15] and upgraded by Foa, Hembree & Dancu, [16]. The main component of the traditional PE program, exposure to the trauma memories, is usually conducted using imagination. In this study we use a new tool, virtual reality exposure. Exposure to the trauma is conducted by gradually exposing the clients to the different sequences of a VR program simulating a bus bombing attack (described in the previous section). The therapists who apply the PE program with the VR treatment have been previously trained in the application of the traditional PE program and in the use of VR exposure. VR therapy is a powerful tool, so it is especially important that therapists are well trained and experienced in treating PTSD before using it. The length of the treatment is 10 weekly sessions that last 90-120 minutes each. The components of the treatment program are the following: x x x

Education about the common reactions to trauma (Sessions 1 and 2). Breathing retraining (sessions 1 and 2). In vivo exposure to situations related to the traumatic event (Session 2 through 9).

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x

VR exposure to the traumatic event (Sessions 3 through 9). Homework for VR exposure: The Clients will use a DVD of the VR session conducted with the therapist in the consultation room to conduct exposure at home.

To test the efficacy and effectiveness of this VR program an assessment protocol including PTSD measures, as well as general psychopathology measures, and compliance and satisfaction measures is administered at pre-treatment, post-treatment and follow-ups.

6. Outcome measures Six different assessment tools are used in this study; all questionnaires are standardized with Hebrew translations: 1. Clinician Administered PTSD Scale (CAPS): a standardized diagnostic interview to determine DSM-IV criteria for the PTSD questionnaire [17]. 2. Post Traumatic Diagnostic Scale (PDS): a standardized self-report questionnaire to measure PTSD symptoms [18]. 3. Beck Depression Inventory (BDI): a standardized questionnaire measuring symptoms of depression [13]. 4. Brief Symptom Inventory (BSI): a standardized questionnaire measuring general psychopathology symptoms [19]. 5. Presence Questionnaire (PQ): a standardized questionnaire to investigate perceptions and feelings of presence in the VR environment [20]. 6. Activity Card Sort (ACS): a standardized measure of activity participation [21]. The ACS employs pictures of people involved in real-life activities and thus can elicit vivid responses from participants. This instrument was adapted to Israeli culture through several in-depth studies [22-23].

7. Progress to date The software was first tested with more than 30 non-symptomatic users who viewed and interacted with it while wearing an HMD at various demonstration events. Overall these users found the environment to be realistic and evocative of a suicide bombing. It was clear that key features such as the trademark green bus, palm trees and distant sight of the Mediterranean were in accordance with a true Haifa city view. There were no reports of cybersickness-like side effects although some users requested to stop the simulation due to feelings of distress. Feedback from these non-PTSD sufferers provided strong support for the ecological validity of BusWorld.

8. Conclusions This chapter describes the development of BusWorld, a VR environment for the treatment of PTSD as an alternative to conventional imaginal exposure therapy. We presented an overview of the simulation software, developed especially to represent bus-bombings in Israel. Feedback from non-PTSD sufferers provided initial support for

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the ecological validity of BusWorld. We are currently recruiting five subjects with PTSD due to suicide bus bombings to test the feasibility and effectiveness of VR-based exposure therapy.

References [1]

Bleich, A., Gelkopf, M. & Solomon, Z (2003). Exposure to terrorism, stress-related mental health symptoms, and coping behaviors among a nationally representative sample in Israel. Journal of the American Medical Association, 290, 612-620. [2] Shalev, A. Y. (1996). Stress versus traumatic stress: From acute homeostasic reactions to chronic psychopathology. In B. A. van der Kolk, A. C. McFarlane, & Weisaeth, L. (Eds.), Traumatic Stress: The effects of overwhelmigng experience on mind, body, and society. New York: Guliford, pp 77-101. [3] Somer, E., Keinan, G., & Carmil, D. (1996). Psychological adaptation of anxiety disorder patients following repeated exposure to emergency situations. Journal of Traumatic Stress, 9(2), 207-221. [4] American Psychiatric Association (2000). Diagnostic and Statistical Manual of mental Disorders. Washington DC: APA. [5] Schlenger, W. E., Caddell, J. M., Ebert, L., Jordan, B. K., Rourke, K. M., Wilson, D., Thalji, L., Dennis, J. M., Fairbank, J. A. & Kulka, R. A. (2002). Psychological reactions to terrorist attacks: Findings from the National Study of Americans' Reactions to September 11. Journal of the American Medical Association, 288(5), 581-588. [6] Anderson, P., Jacobs, C. & Rothbaum, B. A. (2004). Computer-supported cognitive behavioral treatment of anxiety disorders. Journal of Clinical Psychology, 60, 253-267. [7] Hodges, L.F., Anderson, P., Burdea, G., Hoffman, H.G., & Rothbaum, B.O. (2001). VR as a tool in the treatment of psychological and physical disorders. IEEE Computer Graphics and Applications, 21, 2533. [8] Hoffman H.G, Patterson D.R., & Carrougher, G.J. (2000). Use of virtual reality for adjunctive treatment of adult burn pain during physical therapy: a controlled study. Clinical Journal of Pain, 16, 244-50. [9] Reger, G.M., Rizzo, A.A., Buckwalter, J.G., Gold, J., Allen, R., Augustine, R., & Mendelowitz, E. (2003). Effectiveness of virtual realty for attentional control to reduce children's pain during venipuncture. Proceedings of the 2nd International Workshop on Virtual Reality, Piscattaway, NJ. [10] Difede, J. & Hoffman, H. G. (2002).Virtual reality exposure therapy for World Trade Center Posttraumatic Stress Disorder: A case report. CyberPsychology & Behavior, 5, 529-535. [11] Rothbaum, B. O., Hodges, L., Alarcon, R, D., Shahar, F., Graap, K., Pair, J., Hebert, P., Gottz, D., Willis, B., & Baltzell, D. (1999). Virtual reality exposure therapy for PTSD Vietnam veterans: A case study. Journal of Traumatic Stress, 12, 263- 271. [12] Rothbaum, B. O., Hodges, L., Ready, D., Graap, K., & Alarcon, R, D. (2001). Virtual reality exposure therapy for Vietnam veterans with posttraumatic stress disorder. Journal of Clinical Psychiatry, 62, 617-622. [13] Beck, A. T. & Steer, R. A., (1987). Beck Depression Inventory Manual. San Antonio, TX: The psychological Corporation. [14] Baum, C., & Christiansen, C. (2004). The person environment occupational performance model: A conceptual model for practice. In C. Christiansen & C. Baum (Eds.). Enabling Function and Well-Being (3rd ed.). Thorofare, NJ: SLACK. [15] Foa, E. B., & Rothbaum, B. O. (1998). Treating the trauma of rape. New York: Guilford. [16] Foa, E. B., Hembree, E. A. & Dancu, C. V. (2002). Prolonged Exposure (PE) Manual Revised Version. University Of Pennsylvania. [17] Blake, D., Weathers, F., Ngy, L., Klauminzer, G., Charney, D., & Keane, T. (1990). Clinical Administered PTSD Scale (CAPS). Boston, MA: National center for posttraumatic Stress Disorder, Behavioral Science Division. [18]Foa, E. B., (1995). Posttraumatic Stress Diagnostic Scale Manual. USA: National Computer Systems. [19] Derogatis, L. R. (1983). SCL-90-R administration, scoring, and procedures manual-II. Towson, MD: Clinical Psychometric Research. [20] Witmer, B. G., & Singer, M. J. (1998) Measuring presence in virtual environment: A presence questionnaire. Presence, 7, 225-240. [21] Baum, C. M., & Edwards, D. (2001). Activity Card Sort (ACS). Test Manual. St. Louis: Program in Occupational Therapy, Washington University School of Medicine.

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[22]Katz, N., Karpin, H., Lak, A., Furman, T., Hatrman-Maeir, A. Participation in occupational performance: Reliability and validity of the Activity Card Sort. Occupational Therapy Journal of Research: Occupation, Participation and Health,23, 10-17. [23] Sachs, D. & Josman, N. (2003). The Activity Card Sort: A Factor Analysis. Occupational Therapy Journal of Research: Occupation, Participation and Health, 23, 165-174.

Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Virtual Vietnam: Virtual Reality Exposure Therapy Barbara Olasov Rothbaum, Ph.D. 1 Department of Psychiatry, Emory University School of Medicine, Atlanta, Georgia

Abstract. Virtual reality (VR) offers a new human-computer interaction paradigm in which users are no longer simply external observers of images on a computer screen but are active participants within a computer-generated three-dimensional virtual world. Posttraumatic stress disorder (PTSD) is a severe and often chronic and disabling anxiety disorder, which can develop following exposure to a traumatic event that involves actual or threatened injury to self or others. The term exposure therapy refers to several behavioral and cognitive behavioral treatment programs that involve confronting feared but safe thoughts, images, objects, situations, or activities in order to reduce pathological (unrealistic) fear, anxiety, and anxiety disorder symptoms. In the treatment of PTSD, exposure therapy usually involves prolonged, imaginal exposure to the patient’s memory of the trauma and in vivo exposure to various reminders of the trauma. There is substantial evidence that exposure programs are highly effective in the treatment of PTSD. A Virtual Vietnam environment was created to explore the efficacy of VR Exposure therapy with Vietnam combat veterans with PTSD. Two virtual environments, a virtual Huey helicopter and a virtual clearing surrounded by jungle were created. Patients were exposed to their most traumatic Vietnam memories while immersed within the virtual environments following a standard treatment manual. Data are presented, and other applications of VR exposure therapy in the treatment of PTSD are discussed. Keywords. Virtual reality, exposure therapy, PTSD, posttraumatic stress disorder, virtual reality exposure therapy, Vietnam veterans

Introduction Virtual reality (VR) offers a new human-computer interaction paradigm in which users are no longer simply external observers of images on a computer screen but are active participants within a computer-generated three-dimensional virtual world. Virtual environments differ from traditional displays in that computer graphics, various display and input technologies are integrated to give the user a sense of presence or immersion in the virtual environment. Virtually BetterTM (www.virtuallybetter.com) is intended to be a 1

Corresponding Author: Barbara Rothbaum, Department of Psychiatry, Emory Univerrsity School of Medicine, 1365 Clifton Road, Atlanta, Georgia 30322. Tel.: 404-778-3875; fax 404-778-3875. Email: [email protected].

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component of a comprehensive treatment package. It is recommended at the point in therapy when exposure therapy would be introduced. Virtual reality exposure (VRE) has the advantages of conducting time-consuming exposure therapy without leaving the therapist's office, with more control over exposure stimuli and less exposure of the patient to possible harm or embarrassment.

1. Literature review: VRE A thorough review of the literature on the efficacy of virtual reality exposure therapy (VRET) is beyond the scope of this chapter; the reader is referred to Rothbaum [20]. In general, VRET has been shown to be effective in the treatment of specific phobias such as arachnophobia, [7] claustrophobia [3], acrophobia [25], social phobia including the fear of public speaking [1], and fear of flying [12]; [23]; [20], among others. The latter study represents the largest controlled study of VRE to date with 87 patients enrolled.

2. Introduction to exposure therapy for PTSD: Theoretical Perspectives Posttraumatic stress disorder (PTSD) is a severe and often chronic and disabling anxiety disorder, which can develop following exposure to a traumatic event that involves actual or threatened injury to self or others. Symptoms include re-experiencing the traumatic event through intrusive unwanted memories of the event, flashbacks of the event, nightmares, and intense emotional and physiologic reactions to trauma-related cues, persistent avoidance of the trauma related cues and emotional numbing, and increased physiological arousal manifested by sleep problems, hyper vigilance, increased anger or irritability, and exaggerated startle. Prospective studies indicate that most traumatized individuals experience symptoms of PTSD immediately after the trauma. In a prospective study of rape victims, 94% met symptom criteria for PTSD in the first week following the assault [21]. Therefore, the symptoms of PTSD are part of the normal reaction to trauma. The majority of trauma victims naturally recover from the trauma as indicated by a gradual decrease in PTSD symptom severity over time. However, many continue to exhibit severe PTSD symptoms. Therefore, PTSD can be viewed as a failure of natural recovery which reflects in part a failure of fear extinction following trauma. Consequently, several theorists have proposed that conditioning processes are involved in the etiology and maintenance of PTSD. These theorists invoke Mowrer’s [16] two-factor theory, which posits that both Pavlovian and instrumental conditioning are involved in the acquisition of fear and avoidance behavior. Through a generalization process many stimuli come to elicit fear and avoidance. Consistent with this hypothesis, emotional and physiological reactivity to stimuli resembling the original traumatic event even years after the event’s occurrence is a prominent characteristic of PTSD and has been reliably replicated in the laboratory [2, 18]. Cognitive and behavioral avoidance strategies are further hypothesized to develop in an attempt to avoid or escape these distressing conditioned

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emotional reactions. The presence of extensive avoidance responses can interfere with extinction by limiting the amount of exposure to the CS in the absence of the UCS. Conceptualizing PTSD within the framework of emotional processing theory, Foa, Steketee and Rothbaum [11] suggested that the traumatic memory could be conceived as a mental fear structure comprising a network of information about the feared stimuli; information about verbal, physiological, and overt behavioral responses; and interpretative information about the meaning of the various stimuli and responses contained in the network. Foa and Kozak [8] suggested that two conditions are required for the reduction of fear. First, the fear memory must be activated. That is, as suggested by Lang [15], if the fear structure remains unaccessed in storage, it will not be available for modification. Second, they proposed that information must be provided which includes elements "incompatible with some of those that exist in the fear structure, so that a new memory can be formed. This new information, which is at once cognitive and affective, has to be integrated into the evoked information structure for an emotional change to occur" (p.22). Therapy is aimed at reducing fear presumably by changing this fear structure. Exposure therapy is notoriously good at accessing the fear structure. Then, information incompatible with associations between stimuli and anxiety responses must be provided during therapy. The term exposure therapy refers to several behavioral and cognitive behavioral treatment programs that involve confronting feared but safe thoughts, images, objects, situations, or activities in order to reduce pathological (unrealistic) fear, anxiety, and anxiety disorder symptoms. In the treatment of PTSD, exposure therapy usually involves prolonged, imaginal exposure to the patient’s memory of the trauma and in vivo exposure to various reminders of the trauma. Prolonged exposure (PE) is a specific exposure therapy program that typically consists of four components administered in 9-12 sessions lasting 90-120 minutes each: (1) psychoeducation about the symptoms of PTSD and factors that maintain PTSD along with a thorough rationale for exposure therapy, (2) training in controlled breathing that patients may use as a stress management skill, although patients are discouraged from using it during exposure exercises, (3) prolonged imaginal exposure to the trauma memory conducted in therapy sessions and repeated as homework, and (4) prolonged in vivo exposure implemented as homework. There is substantial evidence that exposure programs are highly effective in the treatment of PTSD, no compelling evidence that any CBT program is more effective than exposure therapy, and no evidence for the usefulness of adding other components to exposure therapy [10].

3. Applying Exposure Therapy to PTSD in Vietnam Veterans PTSD is one of the most disabling psychopathological conditions affecting the veteran population. Approximately 15.2% of the men and 8.5% of the women who fought in Vietnam were found to be suffering from PTSD 15 or more years after their service. An estimated 830,000 veterans currently have symptoms of chronic combat-related PTSD [31]. Evidence suggests that behavioral therapies with an imaginal exposure component have been more effective than most other types of treatment for combat-related PTSD [28, 30], although the effects are not robust in veterans.

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Both exposure in imagination and exposure in vivo to trauma related events appear to be therapeutic. The exposure treatment that has been developed by Foa and her colleagues typically incorporated imaginal exposure that has the patient recall the traumatic memories in the therapist's office. The patient is asked to relive the trauma in his or her imagination. The patient is asked to close his or her eyes and to describe it out loud in the present tense, as if it were happening now. Very often, this narrative is tape recorded (audiotaped) and that tape is sent home with the patient so that s/he may practice imaginal exposure at home, usually daily, between therapy sessions. Although this reliving is often painful for the patient initially, it quickly becomes less painful as exposure is repeated. The idea behind this type of treatment is that the trauma needs to be emotionally processed, or digested, so that it can become less painful. The process is similar to the grief process: when a loved one dies, it is extremely painful, but by expressing that pain, it gradually becomes less painful. Also, many patients with PTSD mistakenly view the process of remembering their trauma as dangerous and therefore devote much effort to avoiding thinking or processing the trauma. Imaginal reliving serves to disconfirm this mistaken belief and thus helps reduce the PTSD symptoms associated with this belief. For the sake of brevity, only the literature on exposure therapy for PTSD in Vietnam veterans is briefly reviewed below. Imaginal exposure was successfully applied to PTSD in a case study by Keane and Kaloupek [14]. Only three controlled studies have examined the utility of prolonged imaginal exposure (PE) for reducing PTSD and related pathology in male Vietnam veterans. Treatment was conducted over 6 to 16 sessions. In one study, all clients received the "standard" PTSD treatment (weekly individual and group therapies) in addition to exposure [6]. In the second study by Keane et al., [13], PE was compared to a waiting-list control group. During each session, patients were initially instructed to relax. The patients then received 45 minutes of imaginal flooding, followed by relaxation. In the third study, all patients received a group treatment milieu program; one-half received additional PE and the remaining patients received weekly individual traditional psychotherapy [4-5]. All three studies found some benefit from the PE compared to the control groups, but the effects were small. In the Cooper and Clum [6] study, PE reduced the PTSD symptoms, but had little effect on depression or trait anxiety. A mixed picture emerged from the Keane et al. [13] study: therapists rated exposure clients as more improved on PTSD symptoms than control clients, but on self-report measures of these symptoms no differences were detected. However, exposure patients did rate themselves as more improved on general psychopathology measures than those in the waitlist control. Boudewyns and Hyer [5] found no group differences on psychophysiological measures, but at the three-month follow-up, the exposure group improved more on the Veterans Adjustment Scale (VAS). In further analysis of the data with additional patients, a higher percentage of the exposure-treated clients were classified as successes when compared with those receiving traditional therapy [4]. An uncontrolled report found that flooding benefited Vietnam veterans with PTSD only on avoidance symptoms as measured by the IES and self-recorded number of daily intrusions [17].

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4. Virtual Reality Exposure Therapy for Vietnam Veterans with PTSD Obviously, in vivo exposure to combat situations is not a viable option. Thus, a Virtual Vietnam environment was created to explore the efficacy of VRE with Vietnam combat veterans with PTSD. Two virtual environments, a virtual Huey helicopter (see Figures 1-4) and a virtual clearing surrounded by jungle were created. In the virtual jungle clearing, the audio effects include recordings of jungle sounds i.e., crickets, gunfire, helicopters, mine explosions, and men yelling “Move out! Move out!” which can be increased in intensity. Visual effects include muzzle flashes from the jungle, helicopters flying overhead, landing and taking off, and fog. In the virtual helicopter, audio effects include the sound of the rotors, gunfire, bombs, B52s, engine sounds, radio chatter, and men yelling “Move out! Move out!” Visual effects include the interior of a Huey helicopter in which the backs of the pilot’s and copilot’s heads with patches are visible, instruments, controls, as well as the view out of the helicopter side door.

Figure 1. The landing zone (clearing) of the Virtual Vietnam.2

2

Figures reprinted with permission from Virtually Better, Inc (www.virtuallybetter.com).

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Figure 2. The view out of the virtual helicopter in the Virtual Vietnam. 3

This view includes aerial shots of other helicopters flying past, clouds, and the terrain below which included rice paddies, jungle, and a river. Patients were exposed to their most traumatic Vietnam memories while immersed within the virtual environments following a standard treatment manual. The therapist attempts to match what the patient is describing for imaginal exposure (e.g., “The chopper is landing now and I hear explosions all around me.”) with what the patient sees and hears and feels in the virtual reality (e.g., landing the helicopter amid explosions and gunfire). A difference between standard Prolonged Exposure for PTSD [9] and virtual reality exposure for PTSD is that in VR, patients’ eyes are open to see the stimuli.

3

Figures reprinted with permission from Virtually Better, Inc (www.virtuallybetter.com).

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Figure 3. The landing zone (clearing) of the helicopter Virtual Vietnam 4

Figure 4. The view inside of the virtual in the Virtual Vietnam. 5

During virtual reality exposure sessions patients wear the head-mounted display with stereo earphones that provide visual and audio cues consistent with looking out over Vietnam terrain from a Huey helicopter and walking around a swampy clearing. To increase the effectiveness of the illusion of actually being in a helicopter, patients are seated in a "Thunder seat" similar in structure to an airplane seat with a woofer below the seat that adds vibrations. Metal may interfere with the position sensors, so wood or plastic chairs should be 4-5

Figures reprinted with permission from Virtually Better, Inc (www.virtuallybetter.com).

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used. In all the environments the patient experiences only computer-generated audio and visual stimuli while "real-world" stimuli are shut out. The therapist communicates with the patient with a microphone connected through the computer to the headphones. The therapist is able to control the apparent closeness of the stimuli with the audio effects and volume control. The patient should be encouraged to expose him or herself to traumatic memories triggered by the virtual environments, following guidelines for standard exposure therapy. As most Vietnam veterans have several traumatic memories, it is important to address each in a separate session per incident unless they are naturally tied together by the patient. The therapist asks the patient to give a SUDs (Subjective Units of Discomfort, 0= no anxiety and 100=maximum anxiety) rating approximately every five minutes during all exposures as an indication of level of anxiety. The therapist makes appropriate comments and encourages continued exposure until anxiety has habituated. The patient is allowed to progress at his/her own pace (see below for the Summary Treatment Outline). The therapist simultaneously views on a video monitor all of the virtual environments in which patients are interacting and therefore is able to comment appropriately. Therapist's comments are identical to what would be expected for conventional exposure. Treatment is terminated when the patient indicates no anxiety associated with the exposures or after the predetermined last session, whichever is first. Session 1 is devoted to information gathering by the therapist, explaining the rationale for treatment, building rapport, and acquainting the patient with virtual reality using a neutral virtual environment (VE). Information can be gathered on the patient's Vietnam service and combat experience. Information is collected on the 3 most traumatic experiences in Vietnam. The rationale for treatment centers on emotional processing theoretical account of the helpfulness of exposure therapy and briefly reviewing the efficacy of VRE therapy. The patient is given a handout explaining the rationale for treatment. At the end of the session, the patient is familiarized with VR using a neutral VE. Any questions are answered and discussed. Exposure treatment begins in Session 2. Treatment proceeds in an additive manner. The first sessions expose the patient to the virtual environments of Vietnam only without incorporating any imaginal exposure to his own traumatic memories. This VE only exposure continues until the patient has demonstrated habituation as evidenced by a decrease in SUDs and clinical judgment. Once habituated to VE only exposure, the next step is exposure to triggered memories. The patient is asked what memories are triggered by the VE. The therapist focuses on one memory at a time and asks the patient to repeat it until he has habituated. The patient describes the memory in the present tense with eyes open to view the VE. When the patient has habituated to the first memory, he is asked what other memories the VE triggers and continues in the same manner through that memory and others that arise. Once the patient has habituated to these triggered memories, he is asked to recount his most traumatic memories that had been discussed in Session 1. He is asked to recount that experience in the present tense, making sure to include stimuli, responses, and meaning, repeatedly until anxiety has habituated to that memory. Then the next traumatic memory will be recounted for exposure, and so on, until anxiety has habituated to the 3 to 5 most traumatic memories. These sessions should be tape recorded (audio) and the tapes given to

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the patient to practice imaginal exposure as homework. It is very important to audiotape all imaginal exposure to the traumatic memories and assign imaginal exposure (obviously without virtual reality) with the audiotape at home daily. Simply turn on the tape recorder during the session as the imaginal exposure is begun. The therapist should inquire at the beginning of each session about how the imaginal exposure at home is going. The therapist should attempt to match the virtual stimuli to the patient’s description of his traumatic experience, for example by landing the helicopter at the appropriate time in the memory, or by having gunfire, bombs, fog, or night time to match the memory. This is only attempted during the phase of treatment in which the patient is exposed to his most traumatic memories while in the VR. The therapist should make appropriate comments and encourage continued exposure until anxiety has habituated. Some sample comments include: "You are doing great! You see, by staying with it your anxiety is coming down."

"Make sure your eyes are open." "It's okay to feel anxiety. That's what we're here for." "If you didn't feel any anxiety, this wouldn't be working." "We'll stay at this level as long as you like. We're not in any hurry." "Let me know when you feel ready for the next step." "What scares you now? Tell me what you fear." The patient is allowed to progress at his own pace in the preset order of the hierarchy of exposures. It may be helpful to inform the patient’s significant other (e.g., wife or girlfriend) of the need for the patient to listen to the tape daily and that this may be upsetting for him and the need for understanding and support. It is important to warn the patient and his significant others that it will seem as if he is getting worse before he gets better, and that this is actually a good sign that he is emotionally processing his traumatic experiences. The entire course of treatment should last 8 to 12 sessions and may proceed as follows twice weekly: The first use of VRE for a Vietnam veteran with PTSD was reported in a case study [22]. The veteran was a 50-year-old, Caucasian male meeting DSM-IV criteria for PTSD, major depressive disorder and past alcohol abuse. He served as a helicopter pilot in Vietnam approximately 26 years prior to the study. Treatment consisted of fourteen, 90-minute individual sessions conducted over a 7-week period. Results indicated post-treatment improvement on all measures of PTSD and maintenance of these gains at a 6-month follow-up.

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An interesting case report describes the treatment by exposure therapy of a Vietnam veteran for PTSD related to his war experiences using the Virtual Vietnam. There are several unique features of this particular treatment and case report. One, the nature of several of these traumatic memories included guilt over acts that the patient committed in Vietnam, a sort of history which frequently indicates a poor candidate for exposure therapy. Two, psychophysiological monitoring occurred throughout the treatment as well as at preand post-treatment. His response to treatment, in terms of guilt, anger, and anxiety, measured at pre- and post-treatment and follow-ups of 3- and 6-months, and psychophysiological responding, indicated a successful treatment [29]. This case study was followed by an open clinical trial of VRE for Vietnam veterans [26]. In this study, 16 male patients who met DSM-IV criteria for PTSD were entered and 10 completed VRE. An average of 10, 90-minute exposure therapy sessions delivered over five to seven weeks resulted in a significant reduction in PTSD and related symptoms. The average age of the group was 51 years (SD 3.16). Fourteen of 16 were taking one or more psychotropic medications for PTSD symptoms. Persons who were actively addicted, had serious heart conditions, psychosis, bipolar disorder, unstable medication regimes, planned departures from the Atlanta area, uncontrolled suicidal intention and/or lack of approval from their treating physicians were excluded. All had served in combat operations in Vietnam and the group averaged heavy combat exposure. The majority was being compensated through the VA system for disabilities. Follow up in this population proved difficult, as many of the participants live in remote areas. Ten completed the required treatment sessions, however one did not attend any post-treatment assessments. Table 1 contains the means and standard deviations on the primary measures at pre-treatment, posttreatment, and 3- and 6-month follow-ups. Table 1. Pre- and Post-Treatment, and 3- and 6-month Follow-up (FU) Means (SD) Measure CAPS Total Score

% Decrease Range CAPS Cluster B Reexperiencing CAPS Cluster C Avoidance CAPS Cluster D Arousal IES Total Score IES Intrusion

IES Avoidance Beck Depression Inventory

Baseline (N=9) 68.00 (15.26)

16.33 (6.06) 28.22 (8.18) 23.44 (4.47)

42.89 (10.20) 20.33 (6.10) 22.55 (7.88) 26.11 (11.36)

Post-Tx (N=9) 57.78 (20.61) p=.0727

3 Mo FU (N=5) 54.6 (17.47) p=.0256*

6-Mo FU (N=8) 47.12 (17.04) p=.0021*

–15% +41% to –38% 13.89 (6.33) p=.2812 24.78 (10.74) p=.2814 19.11 (8.91) p=.1163 36.11 (21.64) p=.3988 16.11 (8.56) p=.2126

–27% –13% to –48% 9.40 (6.99) p=.0231* 23.20 (7.33) p=.0507 22.00 (4.69) p=.0777 19.4 (14.71) p=.0327* 8.00 (9.07) p=.0135*

–31% –15% to –67% 11.12 (4.45) p=.0103 17.25 (9.35) p=.0116* 18.75 (5.31) p=.0021* 29.88 (19.39) p=.0912 13.88 (10.48) p=.0949

20.00 (15.43) p=.6259 21.77 (10.12) p=.09

11.40 (5.86) p=.1585 25.6 (12.28) p=.38

16.00 (10.61) p=.1412 17.85 (11.01) p=.01*

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After treatment, the majority of patients’ ratings of their global improvement indicated improvement. At 6 months, 6 of 8 reported improvement. Clinician’s ratings of patients’ global improvement as measured by the CGI indicated that 5 of 6 showed improvement immediately after the study while one appeared unchanged. At 6 months, 7 of 8 were rated as demonstrating some improvement. Clinician-rated PTSD symptoms as measured by the CAPS, the primary outcome measure, at 6 month follow-up indicated an overall statistically significant reduction from baseline in symptoms associated with specific reported traumatic experiences. Eight of 8 participants at the six-month follow up reported reductions in PTSD symptoms ranging from 15 to 67%. Significant decreases were seen in all three symptom clusters. Patient self-reported intrusion and avoidance symptoms as measured by the IES were significantly lower at 3 months than at baseline but not at 6 months, although there was a clear trend toward fewer intrusive thoughts and somewhat less avoidance.

Clinicia n Adminis te re d P TS D S ca le 70 60 50 40 30 20 10 0

PRE

POST

3 mo FU

6 mo FU

Figure 5. Clinician Administered PTSD Scale

Impa ct of Eve nts S ca le 45 40 35 30 25 20 15 10 5 0

PRE

POST

3 mo FU

Figure 6. Impact of Events Scale.

6 mo.FU

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In conclusion, VRET led to significant reductions in PTSD and related symptoms and was well tolerated. None of our worst fears were realized. No person de-compensated due to exposure to the VREs. No participant was hospitalized during the study for complications related to the treatment. Most of those who dropped out of the study were provided opportunities for other treatment within the PTSD Clinical Team clinic at the Atlanta VA Medical Center and did not appear to suffer any long-term problems attributable to their participation. This preliminary evidence suggests that VRE may be a promising component of a comprehensive treatment approach for veterans with combat-related PTSD. 4.1 VRE Combined with Medication Some very recent data suggest that medication may facilitate VRET [19]. D-Cycloserine, a partial agonist at the N-methyl-D-aspartate receptor, has previously been shown to improve extinction of fear in rodents. This study utilized a precisely controlled VR exposure paradigm to examine the ability of D-Cycloserine to facilitate the emotional learning that occurs in behavioral exposure therapy. Participants with a fear of heights underwent two therapy sessions, which is considered a suboptimal amount of exposure therapy for acrophobia. Single doses of placebo or D-Cycloserine were taken prior to each of the two sessions of VRE. Patients returned at one week and 3 months for post-treatment measures to determine the presence and severity of acrophobia symptoms. The group receiving DCycloserine during VRE demonstrated significantly greater improvements on general measures of real-world acrophobia symptoms that was evident early in treatment and was maintained at 3 months and on measures of anxiety, attitudes towards heights, clinical global improvement, and number of self-exposures to real-world heights for the DCS group that was related to improvement. There was also evidence of decreased physiological responding within the virtual environment. This may have implications for PTSD and the exposure therapy for other anxiety disorders.

References [1] [2]

[3] [4]

[5]

[6] [7]

Anderson, P., Rothbaum, B.O., & Hodges, L. F. (2003). Virtual reality exposure in the treatment of social anxiety: Two case reports. Cognitive and Behavioral Practice, 10 Blanchard, E. B., Kolb, L. C., Gerardi, R. J., Ryan, D., & Pallmeyer, T. P. (1986). Cardiac response to relevant stimuli as an adjunctive tool for diagnosing post-traumatic stress disorder in Vietnam veterans. Behavior Therapy, 17, 592-606. Botella, C., Banos, R. M., Perpina, C., Villa, H., Alcaniz, M., & Rey, A. (1998). Virtual reality treatment of claustrophobia: A case report. Behaviour Research & Therapy, 36(2), 239-246. Boudewyns, P.A. & Hyer, L. (1990). Physiological response to combat memories and preliminary treatment outcome in Vietnam veteran PTSD patients treated with direct therapeutic exposure, Behavior Therapy, 20, 381-391. Boudewyns, P.A., Hyer, L., Woods, M.G., Harrison, W.R., McCranie, E. (1990). PTSD among Vietnam veterans: An early look at treatment outcome using direct therapeutic exposure. Journal of Traumatic Stress, 3, 359-368. Cooper, N. & Clum, G.A. (1989). Imaginal flooding as a supplementary treatment for PTSD in combat veterans: A controlled study. Behavior Therapy, 20, 381-391. Carlin, A. S., Hoffman, H. G., & Weghorst, S. (1997). Virtual reality and tactile augmentation in the treatment of spider phobia: A case report. Behaviour Research & Therapy, 35(2), 153-158.

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Foa, E. B., & Kozak, M. J. (1986). Emotional processing of fear: Exposure to corrective information. Psychological Bulletin, 99, 20-35. Foa, E. B. & Rothbaum, B. O. (1998). Treating the Trauma of Rape: A Cognitive- Behavioral Therapy for PTSD. Guilford: New York. Foa, E.B., Rothbaum, B.O. & Furr. (2003). Is the Efficacy of Exposure Therapy for Posttraumatic Stress Disorder augmented with the Addition of Other Cognitive Behavior Therapy Procedures? Psychiatric Annals, 33 (1), 47-53. [Foa, E. B., Steketee, G., & Rothbaum, B. O. (1989). Behavioral/cognitive conceptualizations of posttraumatic stress disorder. Behavior Therapy, 20, 155-176. Kahan, M., Tanzer, J., Darvin, D., & Borer, F. (2000). Virtual reality-assisted cognitive-behavioral treatment for fear of flying: Acute treatment and follow-up. Cyberpsychology & Behavior, 3(3), 387-392. Keane, T.M., Fairbank, J.A., Caddell, J.M., & Zimering, R.T. (1989). Implosive (flooding) therapy reduces symptoms of PTSD in Vietnam combat veterans. Behavior Therapy, 20, 245-260. Keane, T.M., & Kaloupek, D.G. (1982). Imaginal flooding in the treatment of post-traumatic stress disorder. Journal of Consulting and Clinical Psychology, 50, 138-140. Lang, P.J. (1977). Imagery in therapy: An information processing analysis of fear. Behavior Therapy, 8, 862866. Mowrer, O.A. (1960). Learning and behavior. New York: Wiley. Pitman, R.K., Orr, S.P., Altman, B., & Longpre, R.E. (1996). Emotional processing and outcome of imaginal flooding therapy in Vietnam veterans with chronic posttraumatic stress disorder. Comprehensive Psychiatry, 37, 409-418. Pitman, R.K., Orr, S.P., Forgue, D.F., de Jong, J.B., & Claiborn, J.M. (1987). Psychophysiologic assessment of post-traumatic stress disorder imagery in Vietnam combat veterans. Archives of General Psychiatry, 44, 970-975. Ressler KJ, Rothbaum BO, Tannenbaum L, Anderson P, Zimand E, Hodges L & Davis M (2004). Cognitive enhancers as adjuncts to psychotherapy: Use of D-cycloserine in phobic individuals to facilitate extinction of fear. Archives of General Psychiatry, 61, 1136-1144. Rothbaum, B. (in press). Virtual Reality Exposure Therapy. In Rothbaum, B. O., (Ed.). The Nature and Treatment of Pathological Anxiety. Guilford: New York. Rothbaum, B. O., Foa, E. B., Riggs, D., Murdock, T., & Walsh, W. (1992). A Prospective Examination of Post-traumatic Stress Disorder in Rape Victims, Journal of Traumatic Stress, 5, 455-475. Rothbaum, B.O., Hodges, L., Alarcon, R., Ready, D., Shahar, F., Graap, K., Pair, J., Hebert, P., Gotz, D., Wills, B., & Baltzell, D. (1999a). Virtual reality exposure therapy for PTSD Vietnam veterans: A case study. Journal of Traumatic Stress, 12(2), 263-271. Rothbaum, B.O., Hodges, L., Anderson, P.L., Price, L. & Smith, S. (2002). 12-Month Follow-Up of Virtual Reality Exposure Therapy for the Fear of Flying. Journal of Consulting and Clinical Psychology, 70, 428-432. Rothbaum BO, Hodges L, Anderson P, Zimand E, Lang D, & Wilson J (in press). Virtual Reality Exposure Therapy and Standard (In Vivo) Exposure Therapy in the Treatment of Fear of Flying. Accepted for publication Behavior Therapy February, 2005. Rothbaum, B.O., Hodges, L.F., Kooper, R., Opdyke, D., Williford, J. and North, M.M. (1995). Effectiveness of virtual reality graded exposure in the treatment of acrophobia. American Journal of Psychiatry, 152, 626628. Rothbaum, B.O., Hodges, L., Ready, D., Graap, K., & Alarcon, R. (2001). Virtual Reality Exposure Therapy for Vietnam Veterans with Posttraumatic Stress Disorder. Journal of Clinical Psychiatry, 62, 617-622. Rothbaum, B. O., Hodges, L., Smith, S., Lee, J. H., & Price, L. (2000). A controlled study of virtual reality exposure therapy for the fear of flying. Journal of Consulting and Clinical Psychology, 68(6), 1020-1026. Rothbaum, B.O., Meadows, E.A., Resick, P., & Foy, D.W. (2000). Cognitive-Behavioral Treatment Position Paper Summary for the ISTSS Treatment Guidelines Committee. Journal of Traumatic Stress, 13, 558-563. Rothbaum BO, Ruef AM, Litz BT, Han H, Hodges L (2003). Virtual Reality Exposure therapy of combatrelated PTSD: A case study using psychophysiological indicators of outcome. Journal of Cognitive Psychotherapy: An International Quarterly, 17. 163-178. VanEtten M & Taylor S(1998).Comparative efficacy of treatments for posttraumatic stress disorder: A metaanalysis. Clinical Psychology and Psychotherapy, 5, 126-145. Weiss, D. S., Marmar, C. R., Schlenger, W. E., Fairbank, J. A., Jordan, B. K., Hough, R. L., & Kulka, R. A. (1992). The prevalence of lifetime and partial post-traumatic stress disorder in Vietnam theater veterans. Journal of Traumatic Stress, 5, 365-376.

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Acknowledgements This research was supported by NIMH grant #5 R21 MH55555-02 awarded to Dr. Rothbaum. Disclosure Statement: Dr. Rothbaum receives research funding and is entitled to sales royalty from and owns equity in Virtually Better, Inc, which is developing products related to the research described in this paper. The terms of this arrangement have been reviewed and approved by Emory University in accordance with its conflict of interest policies.

Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Developing A Virtual Reality Treatment Protocol for Posttraumatic Stress Disorder following the World Trade Center Attack JoAnn DIFEDE1ab, Judith CUKOR ab, Nimali JAYASINGHEab and Hunter HOFFMANcd a Weill Medical College of Cornell University, New York, New York b The New York Presbyterian Hospital, New York, New York c Human Interface Technology Laboratory, University of Washington, Seattle, Washington d Department of Psychology, University of Washington, Seattle, Washington

Keywords. PTSD, Virtual reality exposure therapy, terrorism

Introduction Posttraumatic stress disorder (PTSD) represents a significant burden for individuals and their communities in the U.S. General population surveys suggest that anywhere between 39% and 90% of adult civilians are exposed to at least one traumatic event during their lifetime and that between 15% and 24% of affected individuals will go on to develop PTSD [1-3]. Based on such findings, researchers estimate that 8-9% of individuals in the population to be at risk for at least one episode of PTSD at some point in their lives [1-3]. People who suffer from this condition are at high risk for developing other psychological conditions – especially mood disorders, anxiety disorders, and substance abuse disorders [4]. In addition, PTSD is associated with adverse outcomes such as marital discord and unemployment [4] and results in a productivity loss of about US$ three billion per year for the nation’s economy [4]. Without treatment, PTSD symptoms, once established, are often persistent [5]: the National Comorbidity Survey indicates that more than one-third of PTSD cases never fully remit after many years, independent of receiving treatment [5]. The terrorist attacks of September 11, 2001 on the WTC claimed the lives of an estimated 2,948 people in New York City [6]. Tens of thousands of others who were in the WTC that day escaped. Those who survived exposure to the attacks, however, face the possibility that PTSD will affect their lives in other ways. Those persons at high risk include individuals who were working in the towers that morning but escaped, 1

Corresponding Author: JoAnn Difede. Associate Professor of Psychology in Psychiatry Director, Program for Anxiety and Traumatic Stress Studies Weill Medical College of Cornell University, New York Presbyterian Hospital525 East 68th Street, Box 200 New York, New York 10021 212-746-3079

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either injured or physically unharmed; eyewitnesses in the area surrounding the towers that morning who watched large numbers of people jumping hundreds of stories to their deaths on the sidewalks as the towers were hit, burned, and finally fell; disaster workers who rushed to the scene or were involved in recovery efforts; and residents of the downtown area, many of whom were displaced from their homes. A telephone survey of selected residents throughout Manhattan conducted between five and eight weeks after September 11 indicated that some 7.5% of respondents complained of symptoms consistent with a diagnosis of PTSD and researchers estimated on this basis that some 67,000 persons in Manhattan alone were suffering from PTSD at the time [7]. Meanwhile, a door-to-door screening of selected residents in the area immediately surrounding the WTC conducted at the end of October 2001 indicated that almost 40% of respondents endorsed symptoms consistent with a diagnosis of PTSD [8]. With regard to disaster workers, another study indicated that nearly 20% of civilian medical volunteers reported acute PTSD symptoms [9]. These figures provide a glimpse of the challenge that mental health services professionals face in addressing the needs of survivors in New York. Expert treatment guidelines for PTSD were published for the first time in 1999, recommending that cognitive-behavioral treatment with exposure therapy should be the first-line therapy for PTSD [10]. For the exposure component of the therapy, most treatments employ imaginal exposure, in which the patient either listens to the therapist recounting a vivid description of the traumatic event or the patient selfgenerates/recounts their own trauma memories themselves repeatedly with gradually increasing detail. [11]. In a recent and extensive review of extant research, Rothbaum, Meadows, Resick, and Foy write that some 12 controlled studies show positive outcomes for exposure treatment for PTSD[11]. They note, for instance, that studies have demonstrated the effectiveness of exposure in treating Vietnam combat veterans [12-17], female victims of sexual assault [18-20], and mixed trauma populations who have experienced both military and civilian traumas [21-24]. In addition, at least two preliminary studies have revealed positive results for interventions including exposure in treating survivors of terrorism [25-26]. Emotional engagement or fear activation plays a critical role in exposure therapy. Foa and Kozak [27] propose that in order for fear reduction to occur, fear relevant information associated with the patient’s memory for the traumatic event (i.e., the fear structure) must be accessed and activated through emotional engagement. In addition, after the fear structure is aroused through emotional engagement, new or corrective information is incorporated into the patient’s memory structure. The authors argue that repeated safe contact with a feared stimulus is necessary for fear structures to change, thereby allowing long-term habituation to take place. Though the efficacy of exposure therapy has been established in multiple studies with diverse trauma populations [11], imaginal exposure presents an impossible dilemma for some patients: effective imaginal exposure, according to standard protocols used in PTSD treatment outcome research [25], requires that the patient tell his/her trauma in the present tense to their therapist, over and over again; yet avoidance of reminders (e.g., thoughts, emotions, places) of the trauma, is inherent in PTSD. Hence, most people with PTSD never seek treatment, some patients who seek treatment refuse to engage in the treatment, and others, though they express willingness are unable to engage their emotions or senses, retelling a flat emotionless tale, reflecting their numbness. Such patients typically fail to improve.

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This is consistent with the few studies that have addressed the question of treatment failures, and which conclude that failure to engage emotionally predicts a poor treatment outcome. One of the first and only studies to examine treatment variables that mediate outcome in the treatment of PTSD investigated the impact of the variables emotional engagement and habituation on successful outcome of exposure therapy for chronic PTSD in female assault victims [28]. Results showed that although all participants made treatment gains, those with high emotional engagement in the treatment and habituation to emotion-eliciting stimuli were eight times more likely to meet stringent criteria for good end-state functioning, (e.g., a 50% reduction in PTSD symptom scores and normal scores on measures of depression and anxiety). Thus, while imaginal exposure therapy offers considerable promise as an effective tool in reducing the suffering associated with PTSD, barriers to effective treatment remain to be addressed. Studies of treatment failure highlight the importance of finding means to motivate patients and facilitate their emotional engagement in therapy. Recent developments in Virtual Reality (VR) technologies open new vistas for the treatment of anxiety disorders, including PTSD. The essence of immersive virtual reality is the illusion it gives users that they are inside the 3-D computer-generated virtual world, as if it is a place they are visiting, an illusion known as “presence” in the virtual world. Virtual Reality affords opportunities not only to capitalize on the patient’s imaginative and memories capacities, but also to augment them with visual, auditory, and even haptic computer-generated experiences [29-31]. For patients who are reluctant to engage in recollections of feared memories, VR provides a sensory-rich and evocative therapeutic environment, which may allow patients to experience a “sense of presence” in the Virtual Environment [29]. In addition, VR technology allows for graded exposure to increasingly feared virtual simulations of traumatic events that can be carefully monitored and tailored to the individual patient’s needs [29]. VR environments can be manipulated above and beyond the constraints of the everyday world, thus creating new possibilities for therapeutic action [29-30,32]. As a result, VR therapy experiences can increase patients’ feelings of self-efficacy and their sense of being active agents of their own therapeutic progress. In addition, patients have been found to be more willing to consider VR therapy than other forms of exposure therapy [29-32]. For example, in one survey, people with fear of spiders were asked to choose between in vivo exposure vs. VR exposure therapy, 81% chose VR, suggesting that VR exposure therapy may eventually prove valuable for increasing the number of patients who seek treatment for anxiety disorders. The VR world often does not include the same risks as returning to the feared real world environment or event. Because therapists view on a computer monitor what the patient is seeing in the helmet, patients can feel supported in knowing that the therapist is sharing in the patient’s experiences in the virtual world [29-32]. Hence, in the treatment of PTSD, VR technologies can offer patients who are fearful or unable to recount their experiences an external setting a computer-generated environment in which to encounter and master their trauma. The multiplicity of sensory cues that VR affords also provides a greater possibility of generating patient involvement and a sense of presence that can facilitate processing of the traumatic experience. And, because the Virtual Environment can be encountered at the patient’s own pace, a firm distinction can be created between remembering and reliving. Several case reports and controlled research studies attest to the utility of VR exposure in the treatment of anxiety disorders including acrophobia, fear of flying, spider phobia, claustrophobia, and PTSD [31, 34-42]. In two published reports, VR

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graded exposure has been successfully employed in treatment of combat-related PTSD. Rothbaum and colleagues conducted a 14-session VR treatment of a man who had served in Vietnam 26 years earlier and suffered from chronic PTSD and Major Depression at the time of treatment [41]. The patient’s clinician-rated level of PTSD dropped by 34% (from the severe to moderate range) and his self-reported levels of PTSD decreased by 45%. Furthermore, these notable clinical gains were maintained at six-month follow-up. The success of VR treatment for PTSD was further bolstered by a study of 10 Vietnam veterans [42]. In this study, patients participated in twiceweekly sessions, with treatment ranging from 8 to 16 sessions. Patients in this study demonstrated a 15% to 67% decrease in PTSD at six-month follow up. In summary, VR exposure has been proven to be an effective treatment for a variety of phobias and although randomized controlled studies have not yet been published using VR for PTSD, preliminary results have shown that VR can be helpful for treating PTSD. We recently published the first case report on the use of VR therapy to treat PTSD following the World Trade Center attacks of September 11, 2001 [50]. The civilian patient, who witnessed the attack from outside the buildings and had to escape as the Towers collapsed, was diagnosed with PTSD and a co-morbid depression. She had been previously unable to engage in imaginal exposure therapy. According to the standardized treatment outcome measures (Beck Depression Inventory and the Clinician Administered PTSD Scale), the patient showed a large reduction in both PTSD (90% reduction) symptoms and depression (83% reduction) after six VR sessions. Although conclusions cannot be based on the outcome of one patient, the fact that the patient responded so well to VR therapy after failing to respond to imaginal exposure therapy provided enough encouraging preliminary evidence to suggest that more controlled studies were warranted. The goal of our study is to evaluate the efficacy of the use of virtual reality exposure therapy in the treatment of PTSD resulting from terrorism in individuals who directly witnessed the World Trade Center attacks on September 11, 2001. As the data from the clinical trial are currently being prepared for publication, the following sections outline the methods and offer commentary on the rationale for our choices. We also present some discussion of problems in implementation that we thought would be useful information for others who are thinking about implementing virtual reality research protocols.

1. Materials and Methods 1.1. Participants and Measures Enrolled subjects met diagnostic criteria for PTSD and directly witnessed at least part of the attacks of September 11. Subjects in the treatment group received treatment based upon a 14–week protocol that integrates virtual reality exposure with other cognitive-behavioral techniques. Symptoms of PTSD and other significant indicators of psychopathology were assessed using structured clinical interviews and self-report measures with well-established psychometric properties at three time points: pretreatment, immediately post-treatment, and at six-month follow-up. All clinical assessments were conducted by an independent assessor. In addition, VR participants completed self-report measures prior to every treatment session. All VR sessions were

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videotaped and reviewed weekly in supervisions with the senior psychologist associated with the project. Exclusion criteria were: (1) presence of current organic mental disorder (2) schizophrenia (3) bipolar disorder (4) depression with psychotic features (5) current substance dependence (6) delusional disorder (7) active suicidal ideation, intent, or plan (8) active homicidal ideation, intent, or plan (9) history of chronic childhood sexual abuse and (10) use of pacemaker. Participants who met the broad inclusion criteria of the study were assessed by a doctoral-level clinician with the Clinician Administered PTSD Scale (CAPS) [43], Trauma History Questionnaire [44], and the full SCID (non-patient version) [45]. The self-report questionnaires include the Posttraumatic Symptom Checklist (PCL) [46], Beck Depression Inventory, [47], State-Trait Anger Inventory [48], and Brief Symptom Inventory [49]. 1.2. Training All psychologists conducting treatment had been trained to conduct imaginal exposure in a diverse trauma sample including civilian and disaster worker survivors of the WTC attack. All VR exposure sessions were videotaped and reviewed with the senior psychologist (J.D.) who has fifteen years experience assessing and treating PTSD in diverse trauma populations. New therapists participated in group supervision with the clinicians who were already treating patients to learn the structure of the protocol and to become familiar with issues in implementing cognitive behavioral therapy with imaginal and VR exposure therapy. 1.3. Equipment A Dell (www.dell.com) 530 workstation with dual 2-gig CPUs, 2 gigs of RAM, a Wildcat 5110 video card, Windows 2000 operating system, and MultiGen-Paradigm Inc Vega VR software (www.multigen.com) was coupled with a 1,024 2 X 768 resolution Kaiser XL-50 VR helmet, with 40 degrees horizontal field of view (www.keo.com/proviewxl3550.htm). A PolhemusTM Fastrak position tracking system was used to measure the position of the user’s head (www.polhemus.com). During VR exposure therapy, the patient wore a head-mounted virtual reality helmet that positioned two goggle-sized miniature LCD computer screens close to the patient’s eyes. Position tracking devices kept the computer informed of changes in the patient’s head location. An electro-magnetic head orientation device fed the x,y,z coordinates of the patients head to the computer, which could quickly change what the patient saw in virtual reality accordingly (e.g. the patient saw the streets and buildings if they looked straight ahead, they saw the WTC towers and sky if they looked up, etc). The scenery in VR changed as the patient moved her head orientation (e.g., virtual objects in front of the patient in VR got closer as the patient, wearing the VR helmet, leaned forward in the real world). The essence of immersive virtual reality is the illusion it gives patients that they are have gone inside the 3-D computer generated environment/virtual world.—as if they are “there” in the virtual world. In the present study, the place the patients visited was lower Manhattan, and the event re-experienced was a computer simulation of the September 11th attack on the WTC. After the therapist helped the patient put on their VR helmet, the patient saw the twin WTC towers from a distance, with no sound effects, with a sunny blue sky, as it

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appeared the morning of September 11, 2001. Over the course of the exposure sessions, the patient progressed through a series of sequences that increased in intensity and detail. The virtual world was programmed such that the therapist was able to control what the patient experienced in VR by touching pre-programmed keys on the keyboard. During the exposure segments, the therapist simultaneously viewed the virtual environments on a video monitor and provided comments and encouragement to ensure that the patient is able to continue with exposure until anxiety is sufficiently reduced. . The therapist monitored the patient’s self-reported Subjective Units of Distress (SUDS) on a scale of 0 to 100 every five minutes. The following is a list of the sequences viewed by the patient: a) A jet flies over the WTC towers, but doesn’t crash, normal New York city street sounds. b) Then a jet flies over, hits building, but no explosion c) Then a jet flies over, crashes with explosion, but no sound effects d) Then a jet flies over, crashes with explosion, and explosion sound effects e) Burning and smoking building (with hole where jet crashed), no screaming f) Burning and smoking building (with hole where jet crashed) and screaming g) Burning and smoking building (with hole where jet crashed), screaming, and people jumping (see Figure 1) h) Second jet crashes into second tower with explosion and sound effects i) Second tower collapses with dust cloud j) First tower collapses with dust cloud k) The full sequence

Figure 1. A computer-generated avatar (virtual human) falling from the WTC. Patients were exposed to such images only during the final stages of therapy, when they could tolerate the VR experience without excessive distress (image created and copyrighted by Hunter Hoffman, U.W.).

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1.4. Procedure The WTC virtual environment was constructed to allow for a graded hierarchical exposure to the stimuli in the world. The program was carefully constructed in this fashion to prevent overwhelming or flooding the patient. The treatment followed the principles of imaginal exposure. The pace was individualized and patient-driven. For the sequences in the WTC world that were relevant to the patient’s experience, each sequence in the VR menu was repeated until the Subjective Units of Distress level decreased by at least 50% . Each sequence was repeated a number of times before habituation occurred. The next sequence was not approached without the patient’s verbal assent. This procedure was designed to evoke a level of response that created discomfort, but was tolerable. Gradually, as the patient habituated to their experience, they were able to approach sequences that more nearly approximated the traumatic event. In addition to the virtual reality exposure therapy, the treatment included common components of other exposure therapies including: (1) psychoeducation, in which the patient learned about common reactions to trauma and related these to their experience; (2) relaxation training, in which the patient learned relaxation and breathing techniques valuable in the management of anxiety and stress; (3) cognitive restructuring, in which the patient challenges his thoughts and beliefs about himself, the world and his trauma experience. Components of each of the sessions are outlined in Table 1. Table 1. Outline of VR Exposure Therapy Treatment Sessions Session

Components of VR Exposure Treatment

1

• Psychoeducation – patient learns about common reactions to trauma and rationale of treatment and recounts their trauma experience to therapist to begin to build foundation for exposure therapy in future sessions • Stress management – patient learns and practices controlled-breathing and relaxation techniques

2

• Relaxation – patient is instructed in controlled breathing and commonly-used relaxation techniques • Imaginal Exposure – patient participates in imaginal exposure: target 30 minutes in exposure

3

• Relaxation - techniques and uses are reviewed • In vivo exposure – patient and therapist discuss avoidance symptoms. The technique of in vivo exposure is introduced and graded hierarchies are drawn up and assigned to be completed outside of the session • VR Exposure – patient is familiarized with VR equipment with a target of 30 minutes in VR

4

• Relaxation - techniques and uses are reviewed • In vivo exposure – assignment is reviewed and the next step in the hierarchy is assigned for homework • Planning for Pleasure – patient is instructed in importance of scheduling pleasurable activities and plans pleasurable activities for week •VR Exposure target 45-60 minutes

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• Relaxation - techniques and uses are reviewed • In vivo exposure – assignment is reviewed and the next step in the hierarchy is assigned for homework • Planning for Pleasure – assignment is reviewed and patient plans for activities for upcoming week • Cognitive restructuring – patient learns rationale for CR and examines changes in beliefs about self/world •VR Exposure target 45-60 minutes

6-9

• Relaxation, In vivo exposure, Planning for Pleasure – uses reviewed and upcoming assignments planned • Cognitive restructuring – patient examines changes in beliefs about self/world • VR Exposure to triggered memories target 45-60

10-13

• Relaxation, In vivo exposure, Planning for Pleasure – uses reviewed and upcoming assignments planned • Cognitive restructuring – patient examines changes in beliefs about self/world as well as existential issues such as meaning of life/death • VR Exposure- while in the VR world, exposure to most traumatic memories VR target 45-60 minutes

14

• Wrap-up - Patient review skills learned and change in symptom picture • Discussion of schedule for post-treatment assessment and follow-up

2. Clinical Profiles of Our PTSD Treatment Population To date, nine patients have successfully completed our virtual reality treatment protocol. Three were utility workers, three New York City firefighters, and three civilians. Seven of the nine patients entered the VR exposure therapy study only after failing to respond to traditional PTSD treatment! That makes these results especially important since there are currently few treatment options available for patients who do not respond to imaginal exposure therapy. It is possible that VR could become an effective option for some “non-responders” who fail to respond to imaginal exposure therapy. The following clinical vignettes are provided so that the reader may have a more vivid picture of the types of clinical presentations we deemed appropriate for our virtual reality treatment. Individuals with PTSD from direct exposure to the WTC usually presented with anxiety, irritability, and sleep problems, (i.e., sleep latency and continuity), as their most common complaints [52]. Those in this group usually had direct and prolonged exposure to the attack beginning on September 11, 2001, as illustrated by Mr. G, a utility manager. He responded within minutes of the attack, with sufficient time to observe the Towers fall. His usual responsibilities included responding to emergencies and assessing safety factors. Thus, he had the burden of knowing his decisions would affect the safety of his employees and the community. Mr. G. grew up in the same neighborhood where he currently resided and was a well-respected community leader. The community was home to scores of firefighters, police, and utility workers. As a consequence of his stable community ties, he knew countless men who died at the WTC on September 11, 2001, many of them since their childhood. He continued to work at the WTC site supervising operations until the site closed in May, 2002 thus he had ongoing exposure to the carnage of human remains and the pervasive destruction.

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Upon presentation, he was anxious and tearful and could no longer control his irritability. He accepted treatment because he believed that he would be more effective in his quest to help others, if he was able to accept treatment for himself, and in so doing serve as a role model to others who could benefit from treatment. In contrast, the experience and profile of one of our civilian patients’, whose case has been previously published [50] was quite different. The patient, a 26-year-old single African American female, was diagnosed with post-traumatic stress disorder approximately four months after the attack on the WTC. Prior to Sept 11th, she served as an executive for a large financial institution located near the WTC, she had functioned well in a very competitive industry. She described herself as optimistic and ambitious prior to the WTC attacks. Arriving to work near the World Trade Center on Sept 11th, she was across the street from the North tower when the first plane hit. During her initial evaluation she described what happened to her on Sept 11th with little emotion and denied feeling terror. Her re-experiencing symptoms included frequent unbidden intrusive imagery of the plane striking the tower, and the building collapsing, being distressed when confronted with reminders, and occasional flashbacks. The patient’s avoidant symptoms were extensive, and included avoiding thoughts of the attack, avoiding reminders of the attack (e.g., refusal to watch TV news or read newspapers) and avoiding situations where she perceived herself to be especially vulnerable (e.g., she would not stay in her boyfriend’s apartment because it was on a high floor of a tall tower). Although she was raised in a close extended family, she described feeling distant, and cut-off from her family and friends after September 11th. Her symptoms of hyperarousal included difficulty falling asleep and staying asleep, difficulty concentrating, an exaggerated startle response and intense anger. Her hypervigilance extended to sleeping with the lights on and keeping a pair of eyeglasses near the door. She reported being very irritable and angry with those closest to her. She repeatedly lost her temper and yelled at her mother and others in her family. She had “no patience” for them. She noted that this was unlike her. Indeed it was her mother who initially called the first author to ask for help, noting that she was very worried about her daughter who “was not herself, and was unusually irritable.” Using DSM-IV criteria, the patient was diagnosed with PTSD and a co-morbid major depression. The patient reported moderate to severe symptoms in each of the three DSM-IV cluster areas for PTSD, but did not have any other Axis I or II disorder. She had no trauma history. These two patients illustrate the diverse profiles of patients who have presented to our clinical research program as eligible for the virtual reality treatment. While the first patient had multiple previous traumas and pervasive exposure to the WTC attack and its aftermath, the second patient had no trauma history and experienced the WTC attack as more of a discrete event without subsequent exposure to the rescue and recovery site. These cases illustrate that the world was sufficiently flexible and rich in sensory detail to provide adequate sensory cues to emotionally engage those with widely disparate experiences of the WTC attack.

3. Issues in the Development of the Study Design In the following paragraphs we will discuss some issues in the design of the study regarding patient eligibility criteria as well as discussion of some issues in treatment

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implementation that we anticipated would occur in future VR treatment studies. While this is by no means a complete list of all the issues faced in the design of the study and in treatment implementation, it addresses questions that have often arisen when we present our work at professional meetings. 3.1. Patient Eligibility Criteria: Epidemiological studies estimate that between forty and ninety percent of the United States population has had a trauma that would place them at risk for PTSD [1-3]. Thus the simple case of PTSD is more likely a myth than a clinical reality. In light of the rates of trauma in the United States, we chose not to exclude those with a significant adult trauma history from the virtual reality exposure protocol. However, those with a childhood history of chronic sexual abuse were excluded. It was not uncommon across our research protocols and clinical program [52] to have patients report that memories from their prior traumas had become activated following the WTC (i.e., a Vietnam Veteran reporting that he was having a resurgence of intrusive imagery of his Vietnam experience that had been dormant for decades, as well as his WTC experience). This was consistent with our experience of another terrorist incident, the 1993 attack on the WTC, as previously reported [53]. Such a clinical picture can be daunting, especially in the early stages of treatment when there is so much uncertainty regarding the patient’s clinical presentation. While prior trauma is often perceived as an obstacle to treating PTSD related to the current trauma, and indeed sometimes is so, it need not always be the case. In our clinical program, we have observed a temptation on the part of our trainees to construct their treatment plans to address the traumas in historical order on the premise that the existence of the prior trauma shaped the patient’s experience of subsequent trauma and therefore must be dealt with first to effectively address the subsequent experience. However, in our research protocol we instructed patients to simply inform us when they had memories or symptoms related to their prior trauma both in and outside of the VR WTC simulation, but the treatment remained focused on their WTC experience. The clinician would record the memories and imagery and tell the patient that they would return to it later. While we were initially worried as to how the processing of the WTC trauma would impact the patient’s experience of their prior trauma, we found that our strategy was effective. For the most part, as our patient’s processed their WTC experience their memories and symptoms related to their prior traumas remitted. So for example, a Vietnam Veteran who arrived at the WTC in time to witness the towers collapse presented with flashbacks and intrusive imagery about the WTC as well as a recurrent intrusive image of what he described as his worst experience in Vietnam. The Vietnam memory had not intruded on a regular basis for many years but was now occurring several times a week. By the end of treatment, the Vietnam memory had receded with minimal processing in session. Why might this be so? Studies suggest that memory is mood congruent [54-55] i.e., that we are more likely to recall memories consistent with our current mood state. These studies have shown for example that when people are sad they are more likely to remember sad memories than happy ones. Similarly, a person who develops PTSD usually feels terror, anxiety, sadness and guilt. Thus recalling memories that are consistent with these mood states seems more likely. By processing these mood states regarding the current trauma in the context of the exposure therapy, the affective link to the prior traumas may be broken allowing for the formation of a discreet memory

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regarding the present trauma. The current trauma no longer provides the emotional “fuel” to sustain the activity of the prior trauma memory. 3.2. Substance Abuse and Dependence as Exclusion Criteria In the context of the VR research protocol, we chose to exclude substance dependence but not substance abuse. Studies show that the co-morbidity of substance abuse with PTSD may be as high as fifty percent [5, 56]. Substance use, especially alcohol use, is common among disaster workers who comprise the bulk of the patients seen in our larger clinical program from which the VR sample was drawn. Though the prevailing clinical wisdom is to engage the patient in a plan to quit their substance use, premature adoption of this strategy may lead to treatment failures [57]. It was our impression that as undesirable as the excessive alcohol consumption was, we would have lost many patients to further treatment if we had been insistent on an immediate sobriety plan because we did not have an adequate substitute to offer that would ease their suffering. Many refused to consider psychotropic medication as a palliative measure, despite our urging. There is some debate in the clinical literature as to how to approach the dual problem of PTSD and substance use. Recent evidence suggests that the PTSD should be treated concurrently. Otherwise if the substance problem is ignored, any gains made in the treatment hour might be mitigated by substance abuse. If the substance abuse is treated first, the patient is likely to relapse because their PTSD symptoms, such as intrusive imagery, are cues for drinking [58]. A challenge for future virtual reality studies will be to integrate PTSD and co-morbid substance abuse/dependence treatment.

4. Treatment Implementation The development and implementation of virtual reality into our treatment protocol was not without its challenges. Based upon the principles of exposure therapy and the theory behind the use of virtual reality, we were able to create a clear set of guidelines for use of the VR. However, as with any other therapeutic tool, the success of the VR was based upon applying the general principles to fit the needs of the individual patient. In the case of VR this challenge was manifested in a number of ways. As with imaginal exposure therapy, the clinicians had to determine when it was best to allow the patient to speak without interruption and when it was appropriate to offer encouraging remarks or prompt the patient with questions. This was an especially important determination in the virtual reality protocol since VR aims to engage the patient through the involvement of all of his senses. The clinician had to be sensitive to the role of his comments and questions and determine whether the interaction would draw the patient out of the environment, or whether it would help in engaging the patient within the environment. This may be illustrated by the following example. One patient was engaged in the exposure exercise as evidenced by his elevated SUDS score and visible signs of distress. In his recounting of his experience, a significant time gap in the patient’s story was noted. The therapist thought it would be beneficial to make the patient aware of this gap, and elicit the missing information. It was especially noteworthy to find out if the patient was able to remember what had happened or if avoidance of something too distressing had caused him to omit it. However, the therapist had to consider that asking the patient a direct question might distract the

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patient from the environment and thereby disengage him from the exposure exercise. Weighing the most beneficial course of action in this situation depended on clinical skill and experience. There were two ways to use the VR sequences in this protocol. The clinician could play a sequence and ask the patient what came to mind and to recount their experience. Alternately, the patient could begin to describe his experience while the clinician would match the virtual environment to what the patient described. It was left to the clinician’s judgment to use each technique when it was best. This knowledge, however, only came with practice and an understanding of the benefits of each technique. This was difficult to relay in training and depended mostly on clinical expertise. Finally, distinguishing between numbing and habituation was at times a challenge. Most of the patients seen in the VR protocol were individuals who had been unsuccessfully engaged in prior treatment. Numbing was common. Virtual reality was utilized to further engage the patient in the exposure exercise in an effort to access his emotions. It proved to be a challenge, especially for less experienced clinicians, to distinguish between scores that were low as a result of numbing and those that were low due to habituation. Clinical judgment was vital in determining if a patient’s low SUDS scores indicated that they had habituated to a particular part of their exposure or were numb. Clinical supervision played a crucial role in the decision-making process with regard to this issue.

5. Clinical Indicators of Treatment Success As noted above we used standardized clinical and self-report measures to assess our patients’ progress. However, it is useful to have early indicators of treatment success that might predate improvements on objective assessments. The single best early indicator of prognosis in our clinical experience was the spontaneous recollection of aspects of the patient’s experience that had been forgotten. To illustrate the point, one patient, a fifty-five year old New York City Fire Chief and former Navy pilot, who had a central role in establishing and running the command center at the WTC before it collapsed. He escaped from the North Tower as it was collapsing. Many around him died while they were trying to escape with him. He recalled ducking behind a car for safety and then running through the debris. However, he still did not believe that he was going to die. After a few VR sessions, while in the VR world, he spontaneously recalled running past a building near the WTC site where he heard a man, who was wearing a jacket that said FBI (Federal Bureau of Investigation), say into a walkietalkie “There is a third plane coming in”. The patient, a former Navy pilot, concluded that if there was a third plane coming in that the country must be at war. He thought to himself for the first time “we are all going to die,” and then had a panic attack. This memory came as a complete surprise to the patient. (Indeed, he sounded and looked surprised as he recounted the memory). He had had no recollection of it until that point, so it was also not possible for the clinician treating him to have been aware of a gap in his memory. The memory appeared to be triggered by the sight of a building in the WTC world (i.e. a specific sensory cue) that reminded the patient of the building he was running past when he saw the FBI agent. This spontaneous recollection served as pivotal point in the patient’s treatment.

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6. Future Directions Though much research remains to be done on the efficacy of VR exposure to treat PTSD, preliminary data from our research group and Rothbaum and colleagues leads us to consider empirical questions that build upon these results. First, can the efficacy of VR exposure be enhanced with a pharmacologic agent? To that end we are currently examining the efficacy of VR exposure in combination with d-cycloserine (DCS, seromycin) in a randomized placebo controlled clinical trial. D-Cycloserine (DCS; Seromycin) is a broad-spectrum antibiotic that has been used in clinical trials over the last decade as a cognitive enhancer. It is a partial agonist at the N-methyl-D-aspartate receptor, which is known to play an essential role in learning and memory. Both fear learning and extinction are blocked by antagonists at the glutamatergic NMDA receptor. D-cycloserine has been shown to facilitate extinction learning in animal models of conditioned fear and in some human trials of other types of learning. Preliminary data from Rothbaum and colleagues has demonstrated that DCS when combined with VR exposure treatment accelerated the learning processes thereby significantly reducing the number of therapy sessions needed to complete treatment of fear of heights from six sessions to two [59]. A second question has implications for more efficient world building and is also germane to an exploration of the efficacy of exposure therapy itself. What is the role of each sensory modality in the efficacy of VR exposure? How do sensory cues from each sensory modality differentially affect a patient’s sense of presence and immersion? To date, much attention has been focused on creating accurate visual worlds to enhance presence and immersion. Additionally, in VR exposure treatment, attention has been focused on the verbal processing of the trauma. Little or no attention has been given to the role of each sensory modality as variables in the creation of presence and immersion or in the efficacy of VR exposure therapy. Yet the experience of trauma begins as a multi-sensory experience. Several studies regarding the phenomenology of trauma memories have suggested that these memories are usually more fragmented and characterized by sensory-perceptual qualities than non-trauma memories [60-61]. VR may prove to be a uniquely effective environment in which to process these memories because of the multi-sensory capacity of the VR simulations. The sensory cues in the VR world may serve as triggers for the patient’s memory fragments thereby facilitating both the patient’s emotional engagement and the sensory and emotional processing of the memory fragment. Though many have postulated that the multi-sensory nature of VR worlds enhances the patient’s emotional engagement thereby facilitating treatment, studies have yet to investigate the role of each sensory modality in emotional engagement or immersion and presence. Though anecdotal, we were impressed that most of our patient’s identified the sounds from the WTC VR world as the most powerful sensory cue and credited it with enhancing their engagement in the treatment. Basic research is needed to examine the role of each sensory modality in the efficacy of VR trauma worlds. References [1] [2]

Breslau N. The epidemiology of posttraumatic stress disorder: What is the extent of the problem? Journal of Clinical Psychiatry, 62(suppl 17): 16-22, 2001. Hidalgo RB & Davidson JRT. Posttraumatic stress disorder: Epidemiology and health-related considerations. Journal of Clinical Psychiatry, 61(suppl 7): 5-12, 2000.

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[54] Clark, DM, Teasdale, JD. Diurnal variation in clinical depression and accessibility of memories of positive and negative experiences. Journal of Abnormal Psychology 91, 87-95, 1982. [55] Teasdale JD, Taylor R, Fogarty S J. Effects of induced elation- depression on the accessibility of memories of happy and unhappy experiences. Behaviour Research & Therapy, 18:339-49, 1980. [56] Stewart SH, Pihl RO, Conrod PJ, Dongier, M: Functional associations among trauma, PTSD, and substance-related disorders. Addictive Behaviors, 23: 797-812, 1998. [57] Ouimette PC, Brown PJ, Najavits LM. Course and treatment of patients with both substance use and posttraumatic stress disorder. Addictive Behaviors, 23:785-795, 1998. [58] Najavits, L.M. (2002). Seeking safety: A treatment manual for PTSD and substance abuse. New York, NY: Guilford Press. [59] Ressler, K.J., Rothbaum, B.O., Anderson, P., Zimand, E., Tannenbaum, L., Hodges, L., and Davis, M. (2004) D-Cycloserine, a Putative Cognitive Enhancer, Accelerates Extinction of Fear in Humans. Archives of General Psychiatry, 61:1136-44. [60] Hackmann A, Ehlers A, Speckens A, Clark DM. Characteristics and content of intrusive memories in PTSD and their changes with treatment. Journal of Traumatic Stress 17:231-40, 2004. [61] van der Kolk BA, Fisler R. Dissociation and the fragmentary nature of traumatic memories: overview and exploratory study. Journal of Traumatic Stress 4: 505-25, 1995.

Acknowledgements This research was funded by a NIDA supplement to to J.D. Pfizer Pharmaceuticals provided a grant (J.D.) to purchase the high quality VR helmet, and head position tracking system. Dell Computers donated the high-performance PC computer. WTC world software was created with funding to Dave Patterson, Ph.D. from the Paul Allen Family Foundation. Creation of WTC world involved MultiGenparadigm VEGA programming by Howard Abrams, custom 3-D models, and animations by cyberartist Duff Hendrickson, and use of a 3-D model of Manhattan donated by www. 3dcafe.com, and Digimation. The authors would like to thank Dave Thomas, Ph.D. for his advice and encouragement.

Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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A Virtual Reality Exposure Therapy Application for Iraq War Military Personnel with Post Traumatic Stress Disorder: From Training to Toy to Treatment Albert RIZZO a1, Jarrell PAIR a, Ken GRAAP, Brian MANSON a, Peter J. MCNERNEY a, Brenda WIEDERHOLD c, Mark WIEDERHOLD c, & James SPIRA d a University of Southern California Institute for Creative Technologies, Marina del Rey, California b Virtually Better Inc. Decatur, Georgia c Virtual Reality Medical Center, San Diego, California d Naval Medical Center San Diego, San Diego, California

Abstract. Post Traumatic Stress Disorder is reported to be caused by traumatic events that are outside the range of usual human experiences including (but not limited to) military combat, violent personal assault, being kidnapped or taken hostage and terrorist attacks. Initial data suggests that 1 out of 6 Iraq War veterans are exhibiting symptoms of depression, anxiety and PTSD. Virtual Reality (VR) exposure treatment has been used in previous treatments of PTSD patients with reports of positive outcomes. The aim of the current paper is to specify the rationale, design and development of a Virtual Iraq PTSD VR application that has been created from the virtual assets that were initially developed for a combat tactical training simulation, which then served as the inspiration for the XBox game entitled Full Spectrum Warrior. Keywords: Virtual Reality, PTSD, Exposure Therapy, Full Spectrum Warrior

Introduction In 1997, researchers at Georgia Tech released the first version of the Virtual Vietnam VR scenario for use as a graduated exposure therapy treatment for Post Traumatic Stress Disorder (PTSD) with Vietnam veterans. This occurred over 20 years following the end of the Vietnam War. During that interval, in spite of valiant efforts to develop and apply 1 University of Southern California Institute for Creative Technologies 13274 Fiji Way, Marina del Rey, California 90292; Email: [email protected]

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traditional psychotherapeutic approaches to PTSD, the progression of the disorder in some veterans severely impaired their functional abilities and quality of life, as well as that of their family members and friends. The tragic nature of this disorder also had significant ramifications for the U.S. Veteran’s Administration healthcare delivery system often leading to designations of lifelong service connected disability status. In mid-2004, the first systematic study of mental health problems due to the Iraq conflict revealed that “…The percentage of study subjects whose responses met the screening criteria for major depression, generalized anxiety, or PTSD was significantly higher after duty in Iraq (15.6 to 17.1 percent) than after duty in Afghanistan (11.2 percent) or before deployment to Iraq (9.3 percent)” [3]. With this history in mind, the USC Institute for Creative Technologies (ICT) has initiated a project that is creating an immersive virtual environment system for the treatment of Iraq War veterans diagnosed with combat-related PTSD. This project has now been funded as part of a larger multi-year effort by the U.S. Office of Naval Research that brings together the technical, clinical and creative forces of ICT, Virtually Better, Inc. and the Virtual Reality Medical Center. The VR treatment environment is based on a cost effective approach to recycling virtual graphic assets that were initially built for a combat tactical simulation scenario entitled Full Spectrum Command, which later inspired the creation of the commercially successful X-Box game, Full Spectrum Warrior. This paper will present the vision, rationale, technical specifications, clinical interface design, and development status of the Full Spectrum PTSD treatment system that is currently in progress at the ICT.

1. Post Traumatic Stress Disorder According to the DSM-IV [1], Post Traumatic Stress Disorder is caused by traumatic events that are outside the range of usual human experiences such as military combat, violent personal assault, being kidnapped or taken hostage, terrorist attack, torture, incarceration as a prisoner of war, natural or man-made disasters, automobile accidents, or being diagnosed with a life-threatening illness. The disorder also appears to be more severe and longer lasting when the event is caused by human means and design (bombings, shootings, combat, etc.). Such incidents would be distressing to almost anyone, and is usually experienced with intense fear, terror, and helplessness. Typically, the initiating event involves actual or threatened death or serious injury, or other threat to one's physical integrity; or witnessing an event that involves death, injury, or a threat to the physical integrity of another person. Symptoms of PTSD are often intensified when the person is exposed to situations or stimulus cues that resemble or symbolize the original trauma in a non-therapeutic setting. Such uncontrolled cue exposure may lead the person to react with a survival mentality and mode of response that could put the patient and others at considerable risk. The essential feature of PTSD is the development of characteristic symptoms that may include:

● Intrusive thoughts and flashbacks ● Anger ● Isolation ● Emotional numbing and

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constriction ● Anxiety ● Depression ● Substance abuse ● Survivor guilt ● Hyper-alertness ● Suicidal feelings and thoughts ● Alienation ● Negative self-image ● Memory impairment ● Problems with intimate relationships ● Emotional distance from family and others ● Denial of social problems

2. Rationale for Virtual Reality Therapy Applications for PTSD Prior to the availability of VR therapy applications, the existing standard of care for PTSD was imaginal exposure therapy. Such treatment typically involves the graded and repeated imaginal reliving of the traumatic event within the therapeutic setting. This approach is believed to provide a low-threat context where the patient can begin to therapeutically process the emotions that are relevant to the traumatic event as well as de-condition the learning cycle of the disorder via a habituation/extinction process. While the efficacy of imaginal exposure has been established in multiple studies with diverse trauma populations [10, 12], many patients are unwilling or unable to effectively visualize the traumatic event. In fact, avoidance of reminders of the trauma is inherent in PTSD, and is one of the defining symptoms of the disorder. It is often reported that, “…some patients refuse to engage in the treatment, and others, though they express willingness, are unable to engage their emotions or senses.” [1]. Research on this aspect of PTSD treatment suggests that the inability to emotionally engage (in imagination) is a predictor for negative treatment outcomes [4]. The use and value of Virtual Reality for the treatment of cognitive, emotional, psychological and physical disorders has been well specified [2, 8]. The first use of VR for a Vietnam veteran with PTSD was reported in a case study of a 50-year-old, Caucasian male veteran meeting DSM-IV criteria for PTSD [9]. Results indicated post-treatment improvement on all measures of PTSD and maintenance of these gains at a 6-month followup. This case study was followed by an open clinical trial of VR for Vietnam veterans [11]. In this study, 16 male PTSD patients were exposed to two HMD-delivered virtual environments, a virtual clearing surrounded by jungle scenery and a virtual Huey helicopter, in which the therapist controlled various visual and auditory effects (e.g. rockets, explosions, day/night, yelling). After an average of 13 exposure therapy sessions over 5-7 weeks, there was a significant reduction in PTSD and related symptoms. Similar positive results have also recently been reported for VR applied to PTSD resulting from the attack on the World Trade Center [1]. In this report, a case study was presented using VR to provide re-exposure to the trauma with a patient who had failed to improve with traditional exposure therapy. The authors reported significant reduction of PTSD symptoms by exposing the patient to explosions, sound effects, virtual people jumping from the burning buildings, towers collapsing, and dust clouds and attributed this success partly due to the increased realism of the VR images as compared to the mental images the patient could generate in imagination. Positive treatment outcomes from a wait-list controlled VR study with patients who were not successful in previous imaginal therapy are currently in press by this group (Joanne Difede, personal communication, March 17, 2005). Such early results suggest that VR may be a valuable technology to apply for the treatment of PTSD and that it may be a

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promising component of a comprehensive treatment approach for persons with combatrelated PTSD.

3. The Full Spectrum Virtual Iraq PTSD Therapy Application 3.1. Background and Development History The primary aim of the current project is to use the already existing ICT Full Spectrum Warrior graphic assets (go to: ftp://imsc.usc.edu/pub/uploads/Skips%20Stuff/PTSD%20 Stuff/ for video demos of the content) as the basis for creating a clinical VR application for the treatment of PTSD in returning Iraq War military service personnel. The ICT games project has created two training tools for the U.S. Army to teach leadership and decision making skills. Full Spectrum Command (FSC) is a PC application that simulates the experience of commanding a light infantry company. FSC teaches resource management, adaptive thinking, and tactical decision-making. Developed for the Xbox game console, Full Spectrum Warrior puts the trainee in command of a nine person squad. Trainees learn small unit tactics as they direct fire teams through a variety of immersive urban combat scenarios. These tools were developed through collaboration between ICT, entertainment software companies, the U.S. Army Training and Doctrine Command (TRADOC), and the Research, Development, and Engineering Command, Simulation Technology Center (RDECOM STC). Additionally, Subject Matter Experts from the Army’s Infantry School contributed to the design of these training tools. 3.2. Technical Specifications The current VR PTSD application is designed to run on two Pentium 4 notebook computers each with 1 GB RAM, and a 128 MB DirectX 9 compatible graphics cards. The two computers are linked using a null Ethernet cable. One notebook runs the therapist’s control application while the second notebook drives the user’s head mounted display (HMD) and orientation tracker. We are exploring the usability of three different Head Mounted Displays (HMDs) for use in this application aiming to find the best instrument available to conduct deliver this treatment at the lowest cost. This design goal is important in order to promote maximum accessibility to this system in the future. The three HMDs that are being tested for this purpose are: 1. The 5DT HMD 800 capable of 800x600 (SVGA) resolution (see for specs: http://www.5dt.com/products/phmd.html); 2. The Icuiti v920 HMD capable of 640x480 (VGA) resolution (see for specs: http://www.icuiti.com/); and 3. The eMagin OLED z800 HMD capable of 800x600 (SVGA) resolution (see for specs: http://www. emagin.com/). The Intersense InertiaCube2 tracker is being used for 3DOF head orientation tracking and the user navigates through the scenario using a USB gamepad device. It should also be noted that while we believe that the HMD display approach will provide the optimal level of immersion and interaction characteristics for this application, the system is be fully configurable to be delivered on a standard PC monitor or within a large screen projection display format. The application is built on ICT’s FlatWorld Simulation Control Architecture

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(FSCA). The FSCA enables a network-centric system of client displays driven by a single controller application. The controller application broadcasts user triggered or scripted event data to the display client. The client’s real-time 3D scenes are presented using Numerical Design Limited’s (NDL) Gamebryo graphics engine. The content originally used in Full Spectrum Warrior was edited and exported to the engine using Alias’ Maya software. We are also adding olfactory and tactile stimuli to the experience of the environment. Scent is delivered into the VR scenario through the use of a Scent Palette (Envirodine Studios, Canton, GA). This machine interfaces with the VR program through the computer’s USB port and is activated by triggers programmed into the environment via the FlatWorld Simulation Control Architecture. This allows for the simultaneous delivery of these stimuli with visual and audio events to create a more realistic multi-modal experience for the user in order to enhance the sense of presence in the environment. The amount of scent to be released is specified in seconds. For example, one could have a one second burst of concentrated scent delivered which would provide a subtle hint of the scent as when passing by a flower garden while moving between scenes. Conversely, the machine could be programmed to deliver a longer bust of scent such as might be experienced when approaching someone wearing cologne. The scents are concentrated and gelled much like an air freshener cartridge and enclosed within the Scent Palette in an airtight chamber that fills with compressed air. When activated, the scent is released into an air stream provided by 4 electric fans inside the Scent Palette so that it moves past the user and then dissipates into the volume of the room. The scents that have been selected for this application thus far include burning rubber, cordite, garbage, body odor, smoke, diesel fuel, Iraqi spices and gun powder. The addition of tactile input in the form of vibration is designed to add another sensory modality to the virtual environment, again to enhance presence. Vibration is obtained through the use of sound transducers (Aura Bass Shakers, Aura Sound, Inc. Santa Fe Springs, CA) driven by an audio amplifier. The sound files embedded in the software are customized to provide vibration consistent with relevant visual and audio stimuli in the scenario. For example, explosions and gunfire can be accompanied by this additive sensation and the vibration can also be varied as when a virtual vehicle moves across seemingly uneven ground. 3.3. Scenario Settings, User Perspective Options & Clinical Interface Design and Development In parallel with our efforts to seek the funding required to create a comprehensive VR application to address a wide range of possible combat-related PTSD experiences, we created a prototype virtual environment designed to resemble a middle-eastern city (see Figures 1-5). This VE was designed as a proof of concept demonstrator and as a tool for initial user testing to gather feedback from both Iraq War military personnel and clinical professionals in order to refine the city scenario and to seek guidance for options needed for the future expansion of the system to include other relevant scenario settings. Current ONR funding has now allowed us to evolve this existing prototype into a full-featured version 1.2 application that is currently undergoing user-centered design feedback trials with non-PTSD soldiers at the Naval Medical Center - San Diego (NMCSD) who have returned from an Iraq

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tour of duty. The vision for the project includes not only the design of a series of diverse scenario settings (i.e. city, outlying village and desert scenes), but as well, the creation of options for providing the user with different first person user perspective options. These choice options when combined with real time clinician input via the “Wizard of Oz” clinical interface is envisioned to allow for the creation of a user experience that is specifically customized to the needs of the patient participating in treatment. This is an essential component for giving therapist the capacity to modulate patient anxiety as is required for an exposure therapy approach. Experience customization and flexibility are key elements for these types of VR exposure applications. 3.4. Scenario Settings The software is being designed such that clinical users can be teleported to specific scenario settings based on a determination as to which environment most closely matches the patient’s needs, relevant to their individual combat related experiences. All scenario settings are adjustable for time of day or night, weather conditions and lighting illumination. The following are the scenario settings that are being created for the application: 1. City Scenes – In this setting, we envision two variations. The first city setting (currently developed in our prototype version 1.2) has the appearance of a desolate set of low populated streets comprising of old buildings, ramshackle apartments, warehouses, a mosque, factories and junkyards (see Figures 1-5). The second city setting will have similar street characteristics and buildings, but will be more highly populated and have more traffic activity, marketplace scenes and monuments. 2. Checkpoint – This area of the City Scenario will be constructed to resemble a traffic checkpoint with a variety of moving vehicles arriving, stopping and then moving onward into the city. 3. City Building Interiors – Some of the City Scenario buildings will have interiors modeled that will allow the user to navigate through them. These interiors will have the option of being vacant (see Figure 5) or have various levels of populated virtual characters inhabiting them. 4. Small Rural Village – This setting will consist of a more spread out rural area containing ramshackle structures, a village center and much decay in the form of garbage, junk and wrecked or battle-damaged vehicles. It will also contain more vegetation and have a view of a desert landscape in the distance that is visible as the user passes by gaps between structures near the periphery of the village. 5. Desert Base – This scenario will be designed to appear as a desert military base of operations consisting of tents, soldiers and an array of military hardware. 6. Desert Road – This scenario has been constructed and consists of a paved roadway which will eventually connect the City, Desert Base and Village scenarios. The view from the road currently consists of desert scenery and sand dunes (see Figure 6) with occasional areas of vegetation, ramshackle structures, battle wreckage, debris and an occasional virtual human figure standing by the side of the road.

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3.5. User Perspective Options The system is designed such that once the scenario setting is selected, it will be possible to select from a variety of user perspective and navigation options. These are being designed in order to again provide flexibility in how the interaction in the scenario settings can be customized to suit the clinical user’s needs.

Figure 1. City View

Figure 2. City View

Figure 3. “Flocking” Patrol

Figure 4. “Flocking” Patrol

Figure 5. Interior View

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Figure 6. Desert Road View

Figure 7. HUMVEE View

Figure 8. Helicopter View

Figure 9. Clinical Interface

User perspective options will include: 1. User walking alone on patrol from a first person perspective (see Figures 1-2). 2. User walking with one soldier companion on patrol. The accompanying soldier will be animated with a “flocking” algorithm that will place them always within a 5-meter radius of the user and will adjust position based on collision detection with objects and structures to support a perception of realistic movement.

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3. User walking with a patrol consisting of a number of companion soldiers using a similar “flocking” approach as in #2 above (see Figures 3-4). 4. User view from the perspective of being either inside of the cab of a HUMVEE or other moving vehicle or from a more exposed position in a gun turret above the roof of the vehicle. Options are provide for automated travel as a passenger through the various setting scenarios (see Figure 7) or at the driving column that allow for user control of the vehicle via the gamepad controls. The interior view will also have options for other occupant passengers that will have ambient movement. This view is also adjustable to support the perception of travel within a convoy or as a lone vehicle. 5. User view from the perspective of being in a helicopter hovering above or moving over any of the scenario settings (see Figure 8). In each of these user perspective options, we are considering the wisdom of having the user possess a weapon. This will necessitate decisions as to whether the weapon will be usable to return fire when it is determined by the clinician that this would be a relevant component for the therapeutic process. Those decisions will be made based on the initial user and clinician feedback from the version 1.2 application. 3.6. Clinical Interface We have created a “wizard of oz” type clinical interface (see Figure 9) to control all of the above features in the system. This interface is a key element in the application, as it needs to provide a clinician with a usable tool for placing the user in VE locations that resemble the setting and context in which the traumatic events initially occurred. As important, the clinical interface must also allow the clinician to further customize the therapy experience to the patient’s individual needs via the systematic real-time delivery and control of “trigger” stimuli in the environment. This is essential for fostering the anxiety modulation needed for therapeutic habituation. In our initial configuration, the clinician can use a separate computer monitor or tablet laptop to display and actuate the clinical interface controls. While the results from our initial user feedback trials is currently guiding the interface design modifications, our initial candidate setup provides four quadrants in which the clinician can monitor ongoing user status information, while simultaneously directing trigger stimulus delivery. The upper left quadrant will contain basic interface menu buttons used for placement of the patient (and immediate removal if needed) in the appropriate scenario setting and user perspective. This quadrant also contains menu keys for the control of time of day or night, atmospheric illumination, weather conditions and initial ambient sound characteristics. The lower left quadrant will provide space for real-time display of the patients’ heart rate and GSR readings for monitoring of physiological status when that feature is integrated. The upper right quadrant contains a window that displays the imagery that is present in the user’s field of view in real-time. And the lower right quadrant contains the control panel for the realtime delivery of specific trigger stimuli that are actuated by the clinician in an effort to modulate appropriate levels of anxiety as required by the theory and methodology of exposure-based therapy.

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The specification, creation and addition of such trigger stimuli will likely be an evolving process throughout the life of the application based on relevant patient feedback. We began this part of the design process by including options that have been reported to be relevant by returning soldiers and military subject matter experts. For example, Hoge et al., [3], in their study of self-reported anxiety, depression and PTSD-related symptomatology in returning Iraq War veterans, present a useful listing of combat related events that were commonly experienced in their sample. These events provided a useful starting point for conceptualizing how relevant trigger stimuli could be presented in a VR environment. Such commonly reported events included: “Being attacked or ambushed, Receiving incoming artillery, rocket, or mortar fire, Being shot at or receiving small-arms fire, Shooting or directing fire at the enemy, Being responsible for the death of an enemy combatant, Being responsible for the death of a noncombatant, Seeing dead bodies or human remains, Handling or uncovering human remains, Seeing dead or seriously injured Americans, Knowing someone seriously injured or killed, Participating in de-mining operations, Seeing ill or injured women or children whom you were unable to help, Being wounded or injured, Had a close call, was shot or hit, but protective gear saved you, Had a buddy shot or hit who was near you, Clearing or searching homes or buildings, Engaging in hand-to-hand combat, Saved the life of a soldier or civilian.” (p. 18). From this and other sources, we have begun with our initial effort to conceptualize what is both functionally relevant and pragmatically possible to include as trigger stimuli in our current clinical interface. There appear to be at least four general classes of trigger stimuli that are relevant for this application: 1. Auditory (i.e., weapons fire, explosions, vehicle noise, wind, human voices), 2. Static Visual (i.e., human remains, wounded civilians and combatants, wrecked vehicles), 3. Dynamic Visual (i.e., distant views of human and vehicle movement), 4. Dynamic Audiovisual (i.e., nearby human and vehicle movement, battlefield engagement with enemy combatants). Thus far in the Version 1.2 prototype, we have created a variety of auditory trigger stimuli (i.e., incoming mortars, weapons fire, voices, wind, etc.) that can be actuated by mouse clicks. We can also similarly trigger dynamic audiovisual events such as helicopter flyovers above the user’s position and verbal orders from a commanding officer who is gesturing in an excited manner. The creation of more complex events that can be intuitively delivered from the clinicians interface while providing a user with options to interact or respond in a meaningful manner is one of the ongoing focuses in this project. Perhaps it may be of value to actually immerse the user in varying degrees of combat in which they may see members of their patrol (or themselves) get wounded or in fact have the capability to fire a weapon back at enemy combatants. However, such trigger options will require not only interface design expertise, but also clinical wisdom as to how much and what type of exposure is needed to produce a positive clinical effect. These issues will be keenly attended to in our initial clinical trials. 4. Conclusions War is perhaps one of the most challenging situations that a human being can experience.The physical, emotional, cognitive and psychological demands of a combat

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environment place enormous stress on even the best-prepared military personnel. In this regard, one of the more foreboding findings in the recent Hoge et al., [3] report, was the observation that among Iraq War veterans, “…those whose responses were positive for a mental disorder, only 23 to 40 percent sought mental health care. Those whose responses were positive for a mental disorder were twice as likely as those whose responses were negative to report concern about possible stigmatization and other barriers to seeking mental health care.” (p. 13). While military training methodology has better prepared soldiers for combat in recent years, such hesitancy to seek treatment for difficulties that emerge upon return from combat, especially by those who may need it most, suggests an area of military mental healthcare that is in need of attention. To address this concern, perhaps a VR system for PTSD treatment could serve as a component within a reconceptualized approach to how treatment is accessed by veterans returning from combat. One option would be to integrate VR-delivered combat exposure as part of a comprehensive “assessment” program administered upon return from a tour of duty. Since past research is suggestive of differential patterns of physiological reactivity in soldiers with PTSD when exposed to combat-related stimuli [6, 5] an initial procedure that integrates our VR PTSD application with psychophysiological monitoring could be of value. If indicators of such physiological reactivity are present during an initial VR exposure, a referral for continued care could be negotiated and/or prescribed. This could be provided in a format whereby the perceived stigma of independently seeking treatment could be lessened as the soldier would be simply involved in “non-combat reintegration training” in similar fashion to other designated duties to which they would participate. As well, current generation military personnel, having grown up with digital gaming technology, may actually be more attracted to and comfortable with participation in a VR application approach as an alternative to what is viewed as traditional “talk therapy” (even though such talk therapy would obviously occur in the course of a recommended multi-component approach for this disorder). This potential for a reduction in the perceived stigma surrounding treatment has been anecdotally reported by practitioners who treat civilians with aerophobia (fear of flying) using VR [13]. These observations indicate that some patients have reported that prior to treatment, they had “just lived with problem” and never considered seeking professional treatment. Upon hearing of VR therapy for fear of flying, often via popular media reports, they then sought out VR exposure treatment, typically with resulting positive outcomes. In addition to the ethical factors that make an unequivocal case for the importance of exploring new options for assessment and treatment of combat-related PTSD, economic drivers for the Department of Veterans Affairs healthcare system and the military also provide incentives for investigating novel approaches in this area. Currently there are 13,524 Gulf War Veterans who are receiving compensation for PTSD from the Department of Veterans Affairs as of September 2004 (VA Fact Sheet, 12/2004). In addition to the direct costs for benefit compensation, medical care usage by persons with PTSD is estimated to be 60% higher than average [7] and lost income-based tax revenues raise the “hidden” costs even higher. These data make the initial development and continuing infrastructure costs for running PC-based VR systems pale by comparison. The military could also benefit economically by way of reduced “turnover” of soldiers with mild PTSD. These personnel

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might be more likely to reenlist if their mental health needs were addressed soon after combat in a progressive manner via early VR assessment and treatment. As well, such a VR tool initially developed for exposure therapy purposes, offers the potential to be “recycled” for use both in the areas of combat readiness assessment and for stress inoculation. Both of these approaches could provide measures of who might be better prepared for the emotional stress of combat. For example, novice soldiers could be pre-exposed to challenging VR combat stress scenarios delivered via hybrid VR/Real World stress inoculation training protocols as has been reported by [14] with combat medics. Finally, one of the guiding principles in our development work concerns how VR can extend the skills of a well-trained clinician. This VR approach is not intended to be an automated treatment protocol that could be administered in a “self-help” format. The presentation of such emotionally evocative VR combat-related scenarios, while providing treatment options not possible until recently, will most likely produce therapeutic benefits when administered within the context of appropriate care via a thoughtful professional appreciation of the complexity and impact of this disorder.

References [1]

Hoge, C.W., Castro, C.A., Messer, S.C., McGurk, D., Cotting, D.I. and Koffman, R.L. (2004). Combat Duty in Iraq and Afghanistan, Mental Health Problems, and Barriers to Care. New England Journal of Medicine, 351 (1):13-22. [2] Difede, J. & Hoffman, H. (2002). Virtual reality exposure therapy for World Trade Center Post Traumatic Stress Disorder. Cyberpsychology and Behavior, 5:6, 529-535. DSM-IV. (1994). American Psychiatric Association, Washington, D.C. [3] Rothbaum, B.O., Meadows, E.A., Resick, P., et al. (2000). Cognitive-behavioral therapy. In: Foa, E.B., Keane, T.M., Friedman, M.J. (eds.), Effective treatments for PTSD. New York: Guilford, pp. 60–83. [4] Rothbaum, B.O., & Schwartz, A.C. (2002). Exposure therapy for posttraumatic stress disorder. American Journal of Psychotherapy 56:59–75. [5] Jaycox, L.H., Foa, E.B., & Morral, A.R. (1998). Influence of emotional engagement and habituation on exposure therapy for PTSD. Journal of Consulting and Clinical Psychology 66, 186–192. [6] Glantz, K., Rizzo, A.A. & Graap, K. (2003). Virtual Reality for Psychotherapy: Current Reality and Future Possibilities. Psychotherapy: Theory, Research, Practice, Training, 40, 1/2, 55–67. [7] Rizzo, A.A., Schultheis, M.T., Kerns, K. & Mateer, C. (2004). Analysis of Assets for Virtual Reality Applications in Neuropsychology. Neuropsychological Rehabilitation. 14(1) 207-239. [8] Rothbaum B., Hodges, L., Alarcon, R., Ready, D., Shahar, F., Graap, K., Pair, J., Hebert, P., Gotz, D., Wills, B., & Baltzell, D. (1999). Virtual reality exposure therapy for PTSD Vietnam veterans: A case study. Journal of Traumatic Stress 12, 263-271. [9] Rothbaum, B., Hodges, L., Ready, D., Graap, K. & Alarcon, R. (2001) Virtual reality exposure therapy for Vietnam veterans with posttraumatic stress disorder. Journal of Clinical Psychiatry 62, 617-622. [10] Laor, N., Wolmer, L., Wiener, Z., Reiss, A., Muller, U., Weizman, R. & Ron, S. (1998). The function of image control in the psychophysiology of posttraumatic stress disorder. Journal of Traumatic Stress, 11, 679696. [11] Keane, T. M., Kaloupek, D. G., Blanchard, E. B., Hsieh, F. Y., Kolb, L. C., Orr, S. P., Thomas, R. G. & Lavori, P. W. (1998). Utility of psychophysiological measurement in the diagnosis of posttraumatic stress disorder: Results from a Department of veterans affairs cooperative study. Journal of Consulting and Clinical Psychology, 66, 914-923. [12] Wiederhold, B.K., & Wiederhold, M.D. (2004). Virtual-Reality Therapy for Anxiety Disorders: Advances in Education and Treatment. American Psychological Association Press: New York.

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[13] Marshall R.P., Jorm, A.F., Grayson D.A. & O’Toole B.I. (2000). Medical-care costs associated with posttraumatic stress disorder in Vietnam veterans. Australian and New Zealand Journal of Psychiatry, December 2000, vol. 34, no. 6, pp. 954-962. [14] Wiederhold, M.D & Wiederhold, B.K. (2005). Military mental health applications. The 13th Annual Medicine Meets Virtual Reality Conference. January 29, 2005, Long Beach, CA.

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Section V Other Aspects of Military Healthcare

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

Advanced 3D Computer-Assisted Technologies in Improving Patient Telecare Ivica KLAPANa,b,c1 , Ljubimko ŠIMIýIûc, Sven LONýARIûd-e University Department of ENT, Head & Neck Surgery, Division of Plastic and Reconstructive Head & Neck Surgery and Rhinosinusology, Zagreb University School of Medicine, b Zagreb University Hospital Center, Zagreb, Croatia, c Reference Center for Computer Aided Surgery and Telesurgery, Ministry of Health, Republic of Croatia, Zagreb, Croatia, d Professor of Electrical Engineering and Computing, Faculty of Electrical Engineering and Computing, University of Zagreb, Croatia, e Department of Electrical and Computer Engineering, New Jersey Institute of Technology, Newark, USA a

This work was in part supported by an unrestricted grant by the Ministry of Science and Technology, Republic of Croatia, No. 5-01-543

Abstract. Fast development of computer and information technology enables realization and application of new methods and systems that were not feasible in the past century. One example of such development is the area of virtual reality (VR), virtual surgery (VS), virtual endoscopy (VE), computer assisted surgery (CAS), 3D-CAS, robotic/telerobotic surgery, and Tele-3D-CAS. The real visual, auditory, and tactile cues are replaced by computer-generated sensory cues, therefore giving the user a sense of presence in a virtual world. CAS and VR have found many applications in the field of medicine. Advances in high performance computing, graphics, and networking, together with new humanmachine interfaces form a technological basis for VR/3D-CAS/Tele-3D-CAS applications. Related fields and terminology such as augmented reality, full and partial immersion, wearable computers, telepresence, and telemedicine will be introduced in the paper. The aims of the paper are to present VR, 3D-CAS, and Tele-3D-CAS technology, to provide an overview of some mentioned research activities, information and research resources. An overview of the current research activities in the field of medicine of the 21st century includes: education, surgical planning and simulation, visualization, telemedicine/telesurgery, computer-aided surgery, human-machine interfaces, and rehabilitation and therapy. Keywords. Computer assisted surgery, Telesurgery, Three-dimensional visualization, Endoscopy, Telemedicine, Virtual reality, Virtual endoscopy.

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Corresponding Author: Ivica Klapan. University Hospital Center Gojka Šuška 12, HR-10000 Zagreb, Croatia.

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Introduction Research in the area of 3-D image analysis, visualization, tissue modelling, and humanmachine interfaces provides scientific expertise necessary for developing successful 3D-CAS, Tele-3D-CAS, and VR applications. These technologies represent a basis for realistic simulations that are useful in many areas of human activity, including medicine, and can create an impression of immersion of a physician in a non-existing, virtual environment. Such an impression of immersion can be realized in any medical institution using advanced computers and computer networks that are required for interaction between a person and a remote environment, with the goal of realizing telepresence. In human medicine, extremely valuable information on anatomic relationships in particular regions, while planning and performing endoscopic surgery, is provided by high quality CT or MRI diagnosis[1] (Fig. 1), thus contributing greatly to the safety of this kind of surgery[2].

Figure 1. CT of the Nose and Paranasal Sinuses

To understand the concept of virtual reality (VR), it is necessary to recognize that the perception of the surrounding world created in our brain is based on information perceived by each of the human senses, along with the help of knowledge that is stored in our brain. The usual definition says that the impression of being present in a virtual

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environment (VE), such as virtual endoscopy of the patient’s head, which does not exist in reality, is called VR. The user/physician, has an impression of presence in the virtual world and can navigate through it to manipulate virtual objects. A VR system may be designed in such a way that the user/physician is completely immersed in the VE. The basic requirement in human medicine, resulting from the above mentioned needs, refers to the use of a computer system for visualization of anatomic 3Dstructures and an integral operative field upon to operate. The mode of computer visualization of anatomic structures[3] of the human body that has been used prior to the present day could only provide diagnostic information, and possibly to assist in the preoperative preparation. Intraoperative use of the computer generated operative field 3D-model has not been widely adopted to date. The intraoperative use of the computer in real time requires development of appropriate hardware and software to connect medical instruments with the computer, and to operate the computer via these instruments and sophisticated multimedia interfaces

1. High Quality Diagnosis (DICOM Standard) High quality diagnostic imaging is the main prerequisite for appropriate utilization of computer systems during the preparation, performance and analysis of an operative procedure. Development of a system for data exchange between multiple medical diagnostic devices as well as between diagnostic devices and computer networks has led to the establishment of DICOM (Digital Imaging and Communication in Medicine) standards describing the forms and modes of data exchange. Before the introduction of DICOM standards, image recordings were stored on films, where the information obtained from the diagnostic device was in part lost. Under ideal conditions, sixteen different image levels could be distinguished on films at best. When film images were to be stored in computer systems, films had to be scanned, thus inevitably losing significant data and often introducing some undesirable artifacts. The setting level and window width to be observed on the images could not be subsequently changed. Visualization of the image on the diagnostic device monitor was of a considerably higher quality, thus it was quite naturally used for record receipt and storage in computer media. Video imaging allows for the receipt of 256 different levels at best. It is not possible to subsequently modify the setting level and window width to be observed on the images that have already been stored in the computer system. When stored in computer systems by use of DICOM protocol, images are stored in the form generated by the diagnostic device detector. These image recordings can then be properly explored through the use of powerful computer systems. This is of special relevance when data in the form of images are to be used for complex examinations and testing, or in preoperative preparation where rapid and precise demarcation between the disease involved and intact tissue is required. It is also very important for the images to be visualized in various forms and from different perspectives and then – which is most demanding indeed – to develop spatial models to aid the surgeon in preparing and performing the procedure, as well as in postoperative analysis of the course of the procedure. The entire operative procedure can be simulated, and critical areas avoided during the real procedure, by employing real patient images in the operation preparatory phase

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using complex spatial models and simulated operative field entry (Virtual Endoscopy, or Virtual Surgery)[4,5]

2. Preoperative Preparation The real-time requirement means that the simulation must be able to follow the actions of the user that may be moving in the virtual environment. The computer system must also store in its memory a 3-D model of the virtual environment (3D-CAS models). In that case a real-time VR system will update the 3-D graphical visualization as the user moves, so that up-to-date visualization is always shown on the computer screen. For realistic simulations it is necessary for the computer to generate at least 30 such images per second, which imposes stringent requirements regarding computer processing power. Use of the latest programs enables development of 3D spatial models, exploration in various projections, simultaneous presentation of multiple model sections and, most importantly, model development according to open computer standards ( e.g., Open Inventor). Such a preoperative preparation can be applied in a variety of program systems that can be transmitted to distant collaborating radiologic and surgical work sites for preoperative consultation as well as during the operative procedure in real time[6] (telesurgery) (Fig. 2). Such a model in medical applications will enable simulation of changes that the tissue undergoes when compressed, stretched, cut, or palpated. The computer must then generate, in real-time, an appropriate visualization of the tissue as it is deformed by the user. Biological tissue modeling represents an important research area with applications in many medical areas. In this context, physics-based deformable models represent a powerful simulation tool. In the context of VR applications, real-time 3-D visualization techniques are particularly important. The goal here is to develop methods for rapid and realistic visualization of 3-D objects that are in the VE.

Figure 2. Our 3D models of the human head in different projections. VR systems may be used for medical visualization in several medical areas: 3-D stereo visualization of anatomical structures, 3-D data fusion of multiple imaging modalities, VE, visualization of individual patient anatomy for surgical planning and

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rehearsal, visualization for image-guided surgery procedures, and visualization of anatomy in radiation therapy planning

Three-dimensional spatial models developed via advanced technologies facilitate simulation of endoscopic surgery, making it possible to plan the course of future procedures (Virtual Endoscopy) or telesurgery (Tele-Virtual Endoscopy). By entering the models and navigating through the operable regions, the surgeon becomes aware of the problems he will encounter during the real operation. In this way, preparation for an operation can be conducted, including identification of the shortest and safest method for carrying out the real operation[6,7] (Fig. 3).

Figure 3. An example of 3D computer-assisted microsurgery of the nose and paranasal sinuses (3D-C-FESS) with simulation and planning of the course of subsequent endoscopic operation (VE). Virtual endoscopy overcomes some difficulties of conventional endoscopy. In classical endoscopy an endoscope is inserted into the patient to examine the internal organs or spaces. The physician uses an optical system to view interior spaces of the body.

The two main approaches to visualization are surface rendering and volume rendering. Surface rendering is a classical visualization method where object surfaces are approximated using a set of polygonal shapes such as triangles. Most generalpurposed computers use this approach and their wide availability represents an important advantage of surface rendering. A disadvantage is that surface rendering cannot represent volume interior. Volume rendering can create appealing representations of volume interiors, but a disadvantage is that special hardware is required for acceleration because of computational complexity. During the course of our Three-Dimensional Computer Assisted Functional Endoscopic Sinus Surgery (3D-C-FESS) method development, a variety of program systems were employed to design an operative field model through spatial volume rendering techniques (www.mef.hr/3D-CFESS). Initially, the modeling was conducted with the VolVis, Volpack/Vprender, GL Ware programs on a DEC Station 3100

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computer. With the advent of 3D Viewnix V1.0 software, we employed this program, followed by the 3D Viewnix V1.1 system, AnalyzeAVW system, T-Vox system and OmniPro 2 system on Silicon Graphics O2, Origin200 and Origin2000 computers (Fig. 4).

Figure 4. 3D Viewnix V1.0 and AnalyzeAVW (OmniPro 2 is shown in Fig. 3)

3. Computer Assisted Diagnosis and Surgery VR, 3D-CAS and Tele-3D-CAS systems can be used for education, assessment of work skills, training, simulation, 3-D visualization, computer-aided design, teleoperation, and telemanipulation. If we look at various application areas, we see that one of the more popular VR applicaton areas is medicine. A potentially useful application is for minimally invasive surgery (MIS). The learning of MIS techniques is more difficult than learning open surgery techniques because there is no tactile information, only an indirect field of view is available, and there are difficulties with hand-eye coordination. Training is therefore usually conducted either on animals or in the OR with live patients. More modern computer-based systems for surgical training may prove superior. The use of computers during surgery or telesurgery requires highly reliable, stable and fast computer systems. Computer work stations with UNIX compatible operative systems are most commonly used. During the procedure, the surgeon is engaged in performing the surgery, so he cannot operate the computer. Therefore, the presence of a computer system expert within the operative theater is essential to the conduct of computer-aided operative procedures. VR systems may be used to aid the delivery of surgical procedures. In fact, the most useful systems are augmented reality systems, which combine a patient image with images obtained using various medical imaging modalities such as CT, MR, and ultrasound. Such systems for surgical delivery are used for neurosurgery, knee surgery, endoscopic ENT surgery, and breast biopsy. During such procedures, the surgeon can voice-operate the computer system (Voice Navigation). Model movements, various projections and sections can all be brought up on the monitor with simple and short voice instructions during the surgery. The system fuses computer-generated images with endoscopic images in real time. The surgical instruments have 3-D tracking sensors and the instrument position is superimposed on the video image and CT image of the patient head. The system

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provides guidance according to the surgically planned trajectory. The advantages of the system include reduced time for procedures, reduced training time, greater accuracy, and reduced trauma for patients. On initial computer-aided operative procedures, spatial orientation within the operative field of a 3D computer model, as well as transfer of the particular point to the real operative field of the patient, were performed by arbitrary approximation of the known reference points of the operative field anatomy[8]. In this way, the given entities were recognized on the model and in the real operative field[9]. The use of 3D spatial modeling of the operative field during surgery has highlighted the need to delineate the instrument (endoscope, forceps, etc.) position tip within the computer model. The major problem is transmission of the real patient operative field co-ordinate system to the co-ordinate system of the computer 3D spatial model of the patient, which has been previously designed from a series of CT images during preoperative preparation[10] (Fig. 5).

Figure 5. An example of our 3D computer assisted surgery. Advantages of virtual endoscopy and/or televirtual endoscopy are that there are no restrictions on the movement of the virtual endoscope (it can be moved anywhere through the body), it avoids insertion of an instrument into a natural body opening or minimally invasive opening, and requires no hospitalization. However, virtual endoscopy also has some disadvantages such as the fact that current virtual endoscopy techniques do not reveal the look of the tissue surface (3D imaging techniques do not reveal surface properties).

The modes of instrument localization within the operative field include electromagnetic, optic and mechanical methods. The electromagnetic method is very sensitive to environmental electromagnetic fields (electrical devices, lighting) and large amounts of metal (cabinets, table, instruments), and the basic, ideal precision of localization within the field is inadequate for surgery performance. Optic locators have proven suitable but are relatively expensive and less precise than mechanical locators. Mechanical locators are virtually 3D digitalizers sending their shifts within six degrees of freedom to the computer, which then converts them to shifts within the co-ordinate system of the operative field 3D model. The main problem and shortcoming of current mechanical locators is the inability to reach deep regions within the operative field. This could be solved by replacing current tips with thinner and longer endings, or even better by the original surgical instrument (e.g., forceps or endoscope) (www.mef.hr/MODERNRHINOLOGY). The endoscope is mounted at the end of the 3D digitalizer instead of the existing ending or outside the existing ending axis. The depth of the reachable entity is identical to the depth attainable by the standard endoscope or pump (Fig. 6).

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Figure 6. The primary problem encountered in 3D-CA-surgery is how to transmit the real patient operative field co-ordinate system to the co-ordinate system of the computer 3D spatial model of the same patient, previously developed from a series of CT images during preoperative preparation

Using a special digitalizer (endoscope simulation) model and computer model, the preoperative preparation and simulation of the entire procedure can be done on the computer model of the real patient. Employing a 3D digitalizer during the real procedure, the tip of the instrument (simulated endoscope) can be precisely identified in

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the real operative field and visualized on the computer model[5,11]The freedom of endoscope manipulation during the procedure is not reduced because the connection is realized at the instrument handle and endocamera link sites.

4. Computer Assisted Telesurgery The purpose of a tele-presence system is to create a sense of physical presence at a remote location. Tele-presence is achieved by generating sensory stimuli so that the operator has an illusion of being present at a location distant from the location of their actual physical presence. A tele-presence system extends the operator’s sensory-motor facilities and problem solving abilities to a remote environment. A tele-operation system enables operation at a distant remote site by providing the local operator with necessary sensory information to simulate the operator’s presence at the remote location. Tele-operation is a special case of tele-presence where, in addition to the illusion of presence at a remote location, the operator also has the ability to perform certain actions or manipulations at the remote site. In this way it is possible to perform various actions at distant locations, where it is not possible to go due to a danger, prohibitive price, or a large distance. Realization of VR systems requires software (design of the VE) for running VR applications in real-time. Simulations in real-time require powerful computers that can perform real-time computations required for generation of visual displays. Telemedicine attempts to break down the distance barrier between the provider and the patient in health-care delivery. VR is able to simulate remote environments and can therefore be applied to telemedicine. Physicians can have a VR-produced copy of a remote environment, including the patient, at their physical location. One of the simplest telemedical applications is medical teleconsultation, where physicians exchange medical information over computer networks with other physicians, in the form of image, video, audio, and text. Teleconsultations can be used in radiology, pathology, surgery, and other medical specialties. One of the most interesting telemedical applications is tele-surgery. Telesurgery is a telepresence application in medicine where the surgeon and the patient are at different locations, but such systems are still in an early phase of research. Patients, who are too ill or injured to be transported to a hospital may be operated on remotely. Such cases typically represent the need for a surgical specialist who is located at some distance. Computer technologies allow for computer-assisted surgery to be performed at distance. The most basic form of telesurgery can be realized by using audio and video consultations during the procedure. Sophisticated endoscopic cameras show the operative field on a monitor mounted within the operating theater; however, the same image can also be transmitted to a remote location through video transmission. The latest computer technology enables receipt of CT images from a remote location, examination of these images, development of 3D spatial models, and transfer of these models back to the remote location12. This can be accomplished nearly within real time. These procedures imply preoperative consultation. During the surgery, those in the operating theater and remote consultants follow on the patient computer model the procedure images, the 'live' video image generated by the endoscopic camera, and instrument movements made by the remote surgeon[6]. Simultaneous movement of the 3D spatial model on the computers

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connected to the system providing consultation is enabled[6,12]. It should be noted that in most cases, intraoperative consultation can be realized from two or more locations, though the utmost care is required to establish a proper network among them. The extreme usage of computer networks and telesurgery implies the use of robotic technologies operated by remote control. In such a way, complicated operative procedures could be carried out from distant locations. The main idea behind considering the use of computer networks in medicine is: IT IS PREFERABLE TO MOVE THE DATA RATHER THAN THE PATIENT (Fig. 7). In the future, we can expect more applications of VR in medicine. Advances in computer science will make possible more realistic simulations. VR, 3D-CAS, and Tele-3D-CAS systems of the future will find many applications in both medical diagnostics and computer-aided intervention.

Figure 7. An example of our Tele-3D-computer assisted surgery of the nose and paranasal sinuses. The virtual endoscopic procedure has several steps, such as: 3-D imaging of the organ of interest (e.g using CT, or MRI), 3-D preprocessing of the acquired image data (interpolation, registration), 3-D image analysis to create the model of the desired anatomical structures (segmentation), computation of the 3-D camera-target path for automatic fly-through or manual path selection, and rendering of multiple views along the computed path to create the animation (either surface or volume rendering).

5. Postoperative Analysis The surgical workstation should include 3-D vision, dexterous precision surgical instrument manipulation, and input of force feedback sensory information. The surgeon

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operates in a virtual world. The use of computer technology during preoperative preparation and the actual conduct of surgery enables the storage of all relevant patient data throughout the process. CT images, results of other tests and examinations, computer images, 3D spatial models, and both computer and video records of the course of the operation or teleoperation are stored in the computer and in CD-R devices for subsequent analysis7 (www.mef.hr/MODERNRHINOLOGY). This can prove tremendously useful for education as well as in the practice of different surgical approaches for students, residents, fellows, and even staff physicians. VR has many applications in computer-aided surgery [13]. The four main application areas are a) surgical training and rehearsal (for education of surgeons, for rehearsal of complex surgical procedures), b) surgical planning, c) surgical rehearsal, and d) surgical delivery Statistical studies show that physicians are more likely to make errors during their first several to few dozen surgical procedures. Surgical training may be done on cadavers, but the problem is a chronic shortage of cadavers for medical research. It would be helpful if medical training could be performed using a realistic imitation of a human body inside the computer. Such computer-based training can be used for minimally invasive surgery, and for open surgery. Training on cadavers has several drawbacks: a) if a trainee cuts a nerve or a blood vessel in a cadaver nothing will happen, b) no action can be reversed on cadavers (what is cut is cut), c) dead tissue is harder, color is altered, and arteries do not pulsate. Advantages of computer simulations are that the procedures can be repeated many times with no damage to the virtual body, the virtual body does not have to be dead (many functions of living body can be simulated for realistic visualizations), and organs can be made transparent and modeled. The trainee may be informed of mistakes either during or after the surgical procedure using a multimedia-based context-sensitive help. In this way, the real surgery and telesurgery procedures can be subsequently analyzed and possible shortcomings defined in order to further improve operative treatment. The use of the latest computer technologies enables connection between the computer 3D spatial model of the surgical field and video recording of the course of surgery to observe all critical points during the procedure, with the ultimate goal to improve future procedures and to develop an expert system that will facilitate computer assisted surgery and telesurgery, with due account of all the experience acquired on previous procedures. Also, using the computer recorded co-ordinate shifts of a 3D digitalizer during the telesurgery procedure, an animated image of the course of surgery can be created in the form of navigation, i.e. the real patient operative field fly-through, as we have done from the very begining (1998) in our telesurgeries [14].

6. Computer Networks A component that is essential to the realization of 3D-CAS, Tele-3D-CAS, and VR systems is a fast computer network. The network is the basis for teleoperation. Fast computer networks are also the basis for telemedical applications, which may also be viewed as a kind of teleoperation system. Following the application of computers to surgery and the connection of diagnostic devices with computer networks through DICOM protocol, the next step is directed toward connecting local computer networks with broad range networks, i.e. within a

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clinical center, city, country, or even internationally. The establishment of complex, widespread computer networks across the country offers another significant application of computer networks in medicine, i.e. telemedicine (distant medical consultation in the diagnosis and treatment). Current computer networks using ATM technology allow for very fast and simultaneous communication among a number of physicians for joint diagnostic or therapeutic consultation. Textual, image, audio and video communication as well as exchange of operative field spatial models are thus enabled. Patient images and 3D spatial models can be simultaneously examined by a number of phyisicans, who can then outline and describe image segments through textual messages, indicator devices, voice or live image. The course and conclusions of such a consultation can be stored in computer systems and subsequently explored, employed or forwarded to other users of the computer assisted diagnostic system. The use of computer networks in medicine allows for high quality emergency interventions and consultations requested from remote and less equipped medical centers in order to achieve the best possible diagnosis and treatment (e.g., surgery). In addition to this, through consultation with a surgeon, a physician in a remote diagnostic center can perform appropriate imaging of a given anatomic region, which is of utmost importance for subsequent operation to be carried out by the consultant surgeon from the remote hospital center.

7. System Implementation In 1992, a scientific research rhinosurgical team was organized at the University Department of ENT, Head & Neck Surgery, Zagreb University School of Medicine and Zagreb University Hospital Center in Zagreb, and developed the idea of a novel approach in head surgery. This computer aided functional endoscopic sinus microsurgery has been named 3D-C-FESS. The first 3D-C-FESS operation in Croatia was carried out at the Šalata University Department of ENT, Head & Neck Surgery in May 1994, when a 12-year-old child suffered a gunshot wound in the region of the left eye. The gunshot wound of the left orbit injured the lower eyelid and conjunctiva of the left eye bulb, with massive subretinal, retinal and preretinal hemorrhage. The vitreous chamber was diffusely blurred with blood, and the child was blinded in the injured eye. Six years after the 3D C-FESS surgery, the left eye function was completely normal, with normal vision bilaterally. With support from the University Department of ENT, Head & Neck Surgery, Zagreb University Hospital Center; Merkur University Hospital; as well as T-Com Company; InfoNET; and SiliconMaster, in May 1996 the scientific research rhinosurgical team from the Šalata University Department of ENT, Head & Neck Surgery organized and successfully conducted the first distant radiologic-surgical consultation (teleradiology) within the frame of the 3D-C-FESS project. The consultation was performed before the operative procedure between two distant clinical work posts in Zagreb (Šalata University Department of ENT, Head & Neck Surgery and Merkur University Hospital) (outline/network topology). In 1998, and on several occasions thereafter, the team conducted a number of firsttime tele-3D-computer assisted operations (Fig. 8)—unique procedures not previously conducted elsewhere in the world [6,12] (www.mef.hr/MODERNRHINOLOGY).

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Figure 8. An example of our Tele-3D-C-FESS surgery initially performed in 1998

References [1] Mladina R, Hat J, Klapan I, Heinzel B. An endoscopic approach to metallic foreign bodies of the nose and paranasal sinuses. Am J Otolaryngol 16(4) (1995), 276-279. [2] Rišavi R, Klapan I, Handžiü-ûuk J, Barþan T. Our experience with FESS in children. Int J Pediatric Otolaryngol 43 (1998), 271-275. [3] Elolf E, Tatagiba M, Samii M. 3D-computer tomographic reconstruction: planning tool for surgery of skull base pathologies. Comput Aided Surg 3 (1998), 89-94. [4] Holtel MR, Burgess LP, Jones SB. Virtual reality and technologic solutions in otolaryngology. Otolaryngol Head Neck Surg 121 (1999), 181. [5] Klapan I, Šimiþiü Lj, Rišavi R, Bešenski N, Bumber Ž, Stiglmajer N, Janjanin S. Dynamic 3D computer-assisted reconstruction of metallic retrobulbar foreign body for diagnostic and surgical purposes. Case report: orbital injury with ethmoid bone involvement. Orbit 20 (2001), 35-49. [6] Klapan I, Šimiþiü Lj, Rišavi R, Pasari K, Sruk V, Schwarz D, Barišiü J. Real time transfer of live video images in parallel with three-dimensional modeling of the surgical field in computer-assisted telesurgery. J Telemed Telecare 8 (2002), 125-130. [7] Klapan I, Šimiþiü Lj, Bešenski N Bumber Ž, Janjanin S, Rišavi R, Mladina R. Application of 3Dcomputer assisted techniques to sinonasal pathology. Case report: war wounds of paranasal sinuses with metallic foreign bodies. Am J Otolaryngol 23 (2002), 27-34. [8] Klimek L, Mosges M, Schlondorff G, Mann W. Development of computer-aided surgery for otorhinolaryngology. Comput Aided Surg 3 (1998), 194-201. [9] Mann W, Klimek L. Indications for computer-assisted surgery in otorhinolaryngology. Comput Aided Surg 3 (1998), 202-204. [10] Anon J. Computer-aided endoscopic sinus surgery. Laryngoscope 108 (1998), 949-961. [11] Olson G, Citardi M. Image-guided functional endoscopic sinus surgery. Otolaryngol Head Neck Surg 121 (1999), 187. [12] Klapan I, Šimiþiü Lj, Rišavi R, Bešenski N, Pasariü K, Gortan D, Janjanin S, Paviü D, Vranješ Ž. Tele3D computer assisted functional endoscopic sinus surgery: new dimension in the surgery of the nose and paranasal sinuses. Otolaryngol Head Neck Surg 127 (2002) 549-557. [13] Burdea G. Virtual Reality Technology, Wiley, 1994 [14] Klapan I, Vranješ Ž, Rišavi R, Šimiþiü Lj, Klapan D. Computer assisted surgery and telesurgery in otorhinolaryngology. Ear Nose Throat J, 2005 (in press).

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

War Related Stress George NANEISHVILI 1 , Nino OKRIBELASHVILI and Ketevan GIGOLASHVILI M.Asatiani Research Institute of Psychiatry, Tbilisi Georgia

Abstract. Background. Prolonged armed conflicts in Georgia (1991-93) took place against a background of extreme social-political tension and economic decline of the country. Teams for Crisis Assistance investigated the wounded participants of war actions, who were located in military hospitals. Methods. A general questionnaire was administered to the wounded, to ascertain socio-demographic and medical background information. A mental status examination was conducted. Each subject was given time to talk about physical and psychological impacts of a traumatic event. Results. Among 1400 wounded the range of immediate reactions were considerable: 79.3% of those investigated met criteria for Acute Stress Reaction (ASR), with 8.9% meeting full criteria for Post-traumatic Stress Disorder (PTSD). Prompt treatment of trauma survivors with psychotherapy and medication caused the considerable diminution of separate symptoms (i.e., anxiety, nightmares, flash backs, intrusive thoughts) in 47% of cases, and the total reduction in 31% of observed cases, while 22% dropped out from the treatment plans. Conclusions: Our findings support the efficacy of early intervention in war-related stress morbidity. Key words: Acute Stress Reactions, PTSD, War-Related Stress

Introduction Each person has an individual threshold for responding to various types of stressors [1]. The range of psychological reactions caused by a traumatic event depends on the type, magnitude, duration and severity of the stressors, as well as ethno-cultural peculiarities. 1

M.Asatiani Research Institute of Psychiatry, 10 Asatiani St., Tbilisi 0177, Georgia

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Extreme traumatic experience, leading to the impairment of defense mechanisms, can impact all levels of psychological and social functioning and disturbs the individual bio-psycho-social balance. In 1993, the IFRC in the World Disaster Report proposed the taxonomy of disasters, in which armed conflicts and displacement are recognized as long-term man-made disasters. Therefore, armed conflicts, which agitated Georgia in 1991-93 and resulted in the forcible migration of approximately 286,000 people, could be considered a complex multidimensional phenomenon. So called “civil war” could be considered a universal complex of stressors that impacts every individual in the society, and at one end of the continuum of possible responses are manifest acute and chronic traumatic reactions.

1. Methods/Patients The study was conducted in a highly selected and vulnerable population. Teams for Crisis Assistance investigated almost 1400 wounded participants of war actions in the military hospitals of Tbilisi (Georgia). A general questionnaire for the wounded assessed socio-demographic factors and medical histories. Socio-demographic variables included age, gender, marital status, education, occupation, military history, and trauma history. Medical information collected included medical/surgical history, substance use, mental status examination, and a Brief Psychiatric Rating Scale. Trained psychiatrists and clinical psychologists administered the instruments. Observations also included open-ended psychiatric interviews. Each subject was provided sufficient time to talk about the physical and psychological impacts of a traumatic event.

2. Results Most of those studied presented various psycho-pathological symptoms, both neurotic and psychotic. The range of immediate reactions was considerable: 79.3% met criteria for acute stress reactions (ASR), while the separate symptoms of Post-traumatic Stress Disorder (PTSD) were reported in 8.9% of cases. Non-pathological situational reactions sometimes were manifest as deviant behavior, adaptive-situational reactions, and psychological crisis. The team members faced definite obstacles: wards were overloaded, no separate rooms were available for psychotherapy, and patients were demanding pills. (It is ingrained in the Georgian cultural milieu that every visit to the doctor must result in “getting pills”), and working hours were unlimited. During the initial therapeutic sessions, the investigators had to cope with patients’ dissimulation of the extent of psychological disturbances because of cultural socialization patterns that reinforce silent endurance as a manifestation of courage in men. By making immediate decisions, taking into account personal/social resources and skills, and in accordance with the professional qualification of the observer, patients with acute traumatic reactions received individualized treatment plans (education about the process of trauma recovery, individual rational psychotherapy and psycho-correction with elements of catharsis, axio- and logotherapy) [2,3]. Medication was administered on occasion. About 53% of the wounded received problem-oriented short-term group therapy, which was provided to wards of 6-8 patients. Due to the shortage of psychiatric medication, medicinal treatment was provided at minimal doses with frequent substitution of drugs. The most common medications offered to the wounded

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included antidepressants, benzodiazepines and carbamazepine [4]. Follow-up assessments at 8 weeks indicate that the immediate attention to trauma survivors with psychotherapy and medication was associated with considerable, though gradual, diminution of separate symptoms (i.e., anxiety, nightmares, flash backs, intrusive thoughts) in 47% of cases, and the total reduction in 31% of observed cases, while 22% failed to follow up with treatment when the crisis period passed.

3. Discussion We believe that early intervention in psychological trauma and, particular, in war related stress, reduces post-traumatic stress morbidity and provides an opportunity to prevent the progression of conditions into chronic forms of PTSD. Prompt assistance may well prevent later manifestations and help to lessen potential complications. We hypothesize that a number of factors might be associated with the high rate of acute stress reactions (ASR): 1. The investigations were provided among the wounded – the physical trauma, as a direct mortality threat, and the exposure to the dead destroy a myth of invulnerability that is the major risk for the development of ASR [5, 6, 7, 8]. 2. The military conflict in Georgia occurred against a background of political destabilization and an unstable military position. Prolonged political conflicts, the indistinctness of enemy's territory, unclear identification of the enemy, and frequent rotation of military units, maximizes the destructive impact on personality and promotes the development of ASR and PTSD. 3. Physical emaciation: The difficulty in delivery of food or inferior nourishment (in 78% of cases), loss of weight about 8-10 kg (reported 46%), disturbances in sleep stereotype (92% - responded positively) – also creates vulnerability for ASR and PTSD development [9]. 4. Frequent use of drugs (24%) and alcohol for relief of tension reduces the adaptive potential of the individual [10, 11]. 5. The moral situation: During the ethnic conflicts, each soldier has to make his own decisions, which he has to defend in future. Among those studied, 64% volunteered, and their motivation for participation in war actions was: "I fight, because”others” were taking away my motherland". It was a "civil war," requiring very difficult decisions – on the other side were relatives, ex-neighbors, ex-friends or simply compatriots. In 75% of individuals, we observed an agonizing feeling regarding an unwarranted, unjustified war. 6. Lack of life experience: We found that 72% received only secondary education, 56% were single, and 36% were 18-25 years old. The young age, low level of education [12], and lack of life experience foster difficulties in orientation in new situations, where one can encounter many unfamiliar feelings to which the brain is not oriented [13]. 7. Lack of military experience: Forty-four percent of those studied went into battle without any military training. This intensified feelings of being uncertainty, vulnerability and, lack of protection, as a result, and in turn, future anxiety [14], uneasiness, and feelings of terror. While our investigation has many salient findings, it should be noted that this represents an uncontrolled study, so it may be that some individuals would have

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gradually improved over time without our intervention, but the medical literature is replete with documentation of worsening of stress-related symptoms over time in the absence of symptoms.

References [1] F. Neuner, M.Schauer, U. Karunakara, C. Klaschik, C. Robert, Thomas Elbert. Psychological trauma and evidence for enhanced vulnerability for posttraumatic stress disorder through previous trauma among West Nile refugees. BMC Psychiatry. 2004; 4: 34. [2] Onyut LP, Neuner F, Schauer E, Ertl V, Odenwald M, Schauer M, Elbert T. The Nakivale camp mental health project: building local competency for psychological assistance to traumatised refugees. Intervention 2004;2:90–107. [3] Neuner F, Schauer M, Klaschik C, Karunakara U, Elbert T. A comparison of narrative exposure therapy, supportive counseling, and psychoeducation for treating posttraumatic stress disorder in an african refugee settlement. J Consult Clin Psychol 2004;72:579–587. doi: 10.1037/0022-006X.72.4.579. [4] Stein DJ, Zungu-Dirwayi N, van der Linden GJH, Seedat S. Pharmacotherapy for post traumatic stress disorder (PTSD). The Cochrane Database of Systematic Reviews 2000, Issue 4. Art. No.: CD002795. DOI: 10.1002/14651858.CD002795. [5] I.D. Yalom. Existential Psychotherapy. New York: Basic Books, 1980 [6] D. Foy et al. Etiology of PTSD in Vietnam veterans: Analysis of preliminary, military and combat exposure influences. J Consult Clin Psychol 1987; 43: 643-649 [7] Pitnam R. et al. Prevalence of PTSD in wounded Vietnam Veterans. Am J Psychiatry 1989;146: 667-669 [8] Green BL, Lindy JD, Grace MC, Gleser GC: Multiple diagnosis in posttraumatic stress disorder: the role of war stressors. J Nerv Ment Dis 1989; 177:329-335 [9] Titchner JL. Post-traumatic decline: A consequence of unresolved destructive drives. In: Figley CR (ed.) Trauma and Its Wake vol. New York: Brunner/Mazel, 1987 [10] Bond TC. The why of fragging. Am J Psychiatry 1976; 133:1328-1331 [11] Khantzian EJ. The self-medication hypothesis of addictive disorders: Focus on heroin and cocaine dependence. Am J Psychiatry 1985; 142:1259-1264 [12] Pilisuk M. The legacy of the Vietnam Veterans. J Soc. Issues 1975; 31:3-12 [13] Solomon Z. et al. Exposure to recurrent combat stress: combat stress reactions among Israeli Soldiers in the Lebanon war. Psychol Med. 1987;17:433-440 [14] SM Southwick, A Morgan, LM Nagy, Bremner D, Nicolaou AL, Johnson DR, Rosenheck R, Charney DS: Trauma-related symptoms in veterans of Operation Desert Storm: a preliminary report. Am J Psychiatry 1993; 150:1524-1528

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PTSD – Hungarian Lessons Learned in Afghanistan and Iraq LTC Zoltan VEKERDI, a1 , LTC Laszlo SCHANDL, Ph.D.b Operational Division, Medical Command, Hungarian Defence Forces, Budapest Hungary b First Department of Internal Medicine, Central Military Hospital, Hungarian Defence Forces, Budapest, Hungary

a

Abstract. The authors review conditions of establishment of the Hungarian Military Medical Contingent. They discuss problems met during the preparation phase, and briefly describe the curriculum of a pre-deployment training program, during which mission-oriented foreign language medical training appears as a new element. They describe the work done by the Contingent and its successful integration into the multinational medical support system of International Security Assistance Forces (ISAF) in Afghanistan. They give details on the role of Hungarian military medical personnel in providing medical support after a terrorist act against German forces on June 7, 2003, and also the Hungarian role played in elaboration of a new Mass Casualty Plan of the German Field Hospital deployed in Kabul, Afghanistan. They focus on stress factors affecting Hungarian soldiers (both regular ones and medical personnel) deployed in Afghanistan and Iraq, and coping methods to prevent Post Traumatic Stress Disorders. Finally, the authors describe opportunities to improve multinational medical co-operation. Key words. Hungarian Military Medical Contingent, ISAF, Afghanistan, German Field Hospital, Terror Act, Mass Casualty Care

Introduction This article gives an overview of the goals and structure of the Hungarian Military Medical Contingent that was deployed in Kabul, Afghanistan to augment German and Dutch Medical Treatment Facilities. The authors describe the process of its integration into Level-2 and Level-3 elements of the mission’s medical support system. A pivotal motive of these Medical Treatment Facilities, aside from routine medical support to the troops, is improving readiness, capability and adequate capacity to cope with possible MASCAL (Mass Casualty) situations. The operational plan of the German Field Hospital that is summarized here serves this goal. This plan is based on risk analysis, limitations of capacity, capability and readiness considerations. Readiness must be assured by education and training of all people involved on all levels and services. Implementation periods of the MASCAL Plan of the Bundeswehr 1

Corresponding Author: LTC Dr VEKERDI, Zoltan, Operational Division, Medical Command, Hungarian Defence Forces, 1885 Budapest PO Box 25, Hungary, E-mail: [email protected]

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Field Hospital include: the alert process, preparation, reaction phase, after-action activities, and return to normal work and duty. The authors give summarized lessons learned during implementation of the MASCAL plan in exercises and real events.

2. Activities of the Hungarian Military Medical Contingent 2. 1. Legal background After the overthrow of the Taliban regime, based on United Nations Security Council Resolution 1386/2001, the International Security Assistance Forces (ISAF) mission was launched to foster the stabilization process in Afghanistan. Hungary, based on its Parliament decision 111/2002, decided to contribute to the ISAF mission with a military medical contingent. The size of this contingent was limited to not more than 50 persons at a time, and the Hungarian Parliament mandated the contingent to fulfill its tasks and responsibilities until 31 December 2003. 2.2. Establishment of the contingent Based on traditionally prominent bilateral co-operation with medical services of the Bundeswehr and The Netherlands, it was logic to integrate personnel of the Hungarian Military Medical Contingent (HMMC) into the structure of German and Dutch military medical treatment facilities already deployed and functioning in the theatre f operation. From a military point of view this decision was supported by the fact that Germany and The Netherlands became the lead nations in ISAF mission at the beginning of 2003. Preparatory works started with inspection of the deployment areas in Kabul in early January 2003. The Hungarian delegation visited ISAF Headquarters, the Dutch augmented surgical unit (NATO code: Role2+) at Kabul International Airport, and Bundeswehr Field Hospital at Camp Warehouse (NATO code: Role3). They collected information on the work of these units, on tentative tasks and responsibilities and also on conditions of work, rest, and accommodation of the HMMC personnel to be deployed. Professional consultations with the German and Dutch parties started in January 2003 to finalise technical details of co-operation. As a result, a military technical agreement was signed with Germany. It was mandatory for members of HMMC to be volunteer military people. Since Hungary is heavily involved in different peacekeeping operations all over the world, the number of Hungarian military medical specialists deployed at a time to support Hungarian troops in different missions is approximately 50. Rotation and sustainment of these people lays quite a burden on the Medical Service of the Hungarian Defence Forces. This is the reason why medical specialists also from the civilian sector were recruited for this mission. 2.3. Selection and preparation of the personnel The selection process included analysis of professional training, education and experience, previous mission assignments, military background and language skills as well. Medical

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examination reviewed health status, physical performance and also psychological features of the applicants. After selection, members of HMMC went through normal military training regular for every Hungarian peacekeeping soldier before deployment. This two-week training included also a three-day psychological training lead by a professional psychologist. The aim of the training was to prepare participants to recognise and cope with stress situations, train for conflict management, and prevent lost days of duty due to psychological reasons. The training method included both theoretical and practical training in small groups. Immunization protocol for members of the contingent have followed the matrix used by Bundeswehr in Kabul. Personnel of the HMMC were to integrate separately, as individuals, into the Medical Treatment Facilities deployed and operated by NATO allies. It was this integration by individual members that made mission-oriented pre-deployment foreign language medical training (in English and German languages) necessary. 2.4. Integration into the multinational medical support system The personnel of the HMMC were deployed and rotated by fragments, as positions in the medical treatment facilities offered for the Hungarian party became vacant. The largest number of Hungarian military medical personnel deployed at a time was 21. Most of the Hungarian military medical specialists were assigned to the German Field hospital and Medical Evacuation Company attached to the field hospital. Two qualified nurses worked at the Dutch Role2+ facility deployed at Kabul International Airport. In order to reduce the risk of national donor fatigue during the long sustainment period, the German field hospital integrated medical specialists of several nations. The true multinational character of it can be well described through the national percentage of Medical Officers working in the field hospital and its medical evacuation company (respectively), which in August 2003 was as follows: - German 52%, and 70% in the medical evacuation company - Hungarian 16%, and 30% in the medical evacuation company - French 16% - Lithuanian 8% - Danish 4% - Bulgarian 4% 2.5. Activities during deployment The experience gained during the first weeks after deployment of HMMC personnel proved the correctness of principles followed during the pre-deployment selection process. We experienced the real physiological effects of the extreme continental climate of Kabul situated at 1800 meters above see level. Low air pressure, dust storms and variations in daily temperature combined with heavy fitness programs, without a proper acclimatization period, to lead to some fatalities among allied soldiers. The excellent professional readiness of the Hungarian military medical personnel was a great asset in the process of integration into multinational teams. Daily tasks quickly became routine activities. This monotony, combined with emotional deprivation that resulted from confinement to the camp of deployment, became the main stress factors for the personnel.

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Since well-being is an outcome of combined factors of person, environment and occupation, a variety of measures were recommended and taken to mitigate the abovementioned stress factors: team-building activities (professional, national, international and cultural events), regular physical exercise (a program gradually built up after proper acclimatization), proper relation of rest and work, access to national news and media (via Internet and satellite TV), opportunity to contact relatives via cell phone (so called “morale calls” – calls paid by the Army were introduced later for Hungarian soldiers deployed to Iraq), controlled incentive trips to the city, a 10-day holiday at home during a 6-month mission period (paid by Hungarian Defence Forces), food quality and variety, security measures and conditions of accommodation, meaningful work, etc. For reasons of humanitarian assistance, training purposes, and to keep staff of the field hospital busy, free capacities of the facility under certain conditions were used to treat local patients. This constant and planned flow of patients fostered team-building efforts, served as a training method to conserve the manual skills of specialists with a surgical orientation, helped to establish co-operation between functional areas of the hospital (which is essential in preparation for possible MASCAL situations) and provided a meaningful purpose of work for the people involved. All of the above-mentioned activities fostered successful integration of HMMC personnel. The real test of effective work and co-operation for the multinational and multicultural medical units of the German Field Hospital, German Medical Evacuation Company and the Dutch Surgical Unit deployed at Kabul International Airport was the management of medical consequences of a terrorist act against German troops on June 7, 2003. 2.6. Terrorist act on June 7, 2003 The terrorist act on June 7, 2003 was the bloodiest committed against German soldiers since the end of WW II. That Saturday, Afghani suicide bombers attacked the convoy of German soldiers that were headed to airport after completion of their mission in Afghanistan, killing four and injuring 29 people. At approximately 07.50 hours that day a yellow Toyota cab approaching from the opposite direction crossed the dividing narrow ground stripe of the two-lane road, lined up and exploded beside the second bus of the convoy full of soldiers. The force of the explosion knocked the bus into the field across the opposite lane, near a gas station. The leading car of the convoy alarmed the German Rescue Coordination Centre that activated for mass casualty situation the German Field Hospital, the Medical Evacuation Company and the Dutch Surgical Unit. In addition, American and British allies heard the alarm and joined into rescue operation. A casualty collection point was established to manage ambulatory casualties at the scene. To prevent a possible second wave of attack, an armed guard was set up at the perimeter of the scene. By 09.30 hours all the casualties were evacuated from the scene. Management of casualties has proven the raison d'Ċtre and effectiveness of multinational rescue teams. As a result of activation, in preparation for the mass casualty situation, the field hospital set up the main and reserve triage areas, redirected regular sick call patients, and activated reserve intensive and regular care beds. In addition, mass casualty management areas were set up with the appropriate teams to manage incoming

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casualties, reserve stores of medical materials were activated and emergency blood donation from regular soldiers were organised (“walking blood banks”).

Table 1. The terror act medical consequences in numbers. Total number of casualties 33 German soldiers and 2 Afghani people

35 persons

Number of light and medium severity casualties All German soldiers

25 persons

Number of seriously injured casualties 6 German soldiers and 1Afghani person

7 persons

Casualties with eye injury All German soldiers

25 persons

Enucleation required

3 persons

Lower extremity amputation required German soldier

1 person

Total number of dead 4 German soldiers and 2 Afghani people

6 persons

Died at the scene 4 persons 3 German soldiers and the Afghani suicide bomber Died during evacuation from the scene

-

Died in the German Field Hospital - 1 German soldier and 1 Afghani person

2 persons

Based on the above figures it is obvious that not only the casualties themselves, but also care providers and fellow soldiers required psychological support to cope with consequences of this trauma situation. As dedicated member of the German contingent, a field psychologist and two troop priests worked with the affected personnel. Also a British and an American priest arrived to the field hospital to augment their German colleagues. The personnel background of psychological support was present. At the same time, obviously, this is effective only with efficient language contact (communication capability) between the participants. HMMC personnel contributed to rescue and consequence management operation according to his/her training, education, position and experience from the very first minute of rescue efforts. For security reasons (to avoid panic) the Germans turned the cell phone network off. The commander of the HMMC (the second author of this article) reported to the homeland commander of HMMC via satellite phone before the arrival of the first casualties to the field hospital. During the afternoon, the commander of the HMMC

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also gave a telephone interview to Hungarian Television to reassure Hungarian public. He emphasized that there were no Hungarian victims or casualties, and that consequence management activities were taking place with sustained effort. The first opportunity to call together members of HMMC and talk about the events of the day opened late evening. After this staff meeting HMMC personnel filed past the catafalque of dead fellow German soldiers, and were among the first to sign the book of final tribute. All the above-mentioned measures have helped to control the natural reaction of bereavement and turn it into energy of creativity to augment feeling of group coherence. Unlike the Hungarian contingent in Iraq, due to the small number in this HMMC, no Hungarian psychologist or chaplain were deployed to Afghanistan. If there had been Hungarian victims or casualties, or if emotional reactions necessitated it, duty psychologists from Hungary would have arrived to Kabul to support HMMC personnel. As part of the permanent staff of the Hungarian military transport contingent deployed later in Iraq, there were both a psychologist and a chaplain included (based on pre-deployment risk assessment). During the mission period of this contingent only one soldier was diagnosed and treated for PTSD (after returning to home). His fellow Hungarian soldier died in a mortar attack committed against the Hungarian convoy in Iraq. At the same time -more or less- almost every soldier showed signs of acute stress reaction after terror attacks against their camp in Iraq (regardless weather he/she was injured or not in the incident). 2.7. MASCAL plan update with Hungarian contribution The two pivotal targets of the field hospital mass casualty plan are assurance of adequate medical response to possible mass casualty situations, and sustainment of operability of the medical treatment facility. For a successful operation, and for the survival and sustainment of any military unit deployed in an operational environment, it is essential to turn lessons learned into every day routine as quick as possible. This is also the case for the field hospital, where highly qualified medical personnel are rotated every 3 to 6 months, if not more frequently. It is critical for frresh personnel to achieve familiarization with the lessons learned, to acquire and adapt them in protocols for major incident medical management and to practice them in regular exercises. Lessons learned during the terrorist event were analysed carefully in several professional forums. As a result, pre-deployment training programs and the field hospital MASCAL plan were updated. In August 2003, as the new commander of HMMC, I arrived to Kabul and became the second Hungarian Clinical Director of the German Field Hospital shortly afterwards. For the newly arrived staff of the hospital I compiled a training material in PowerPoint format to familiarise them with the MASCAL plan of the facility (before they start exercising it) that included lessons learned. 2.8. Redeployment

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According to a resolution of the Hungarian Parliament, the HMMC completed its mission and was redeployed in December 2003. Part of the contingent’s materials and equipment remained in the theatre of operation to support Hungarian soldiers who, as individual contributions to the NATO lead ISAF mission and based on bi-lateral agreement with Germany arrived and continued to serve in Afghanistan. After mandatory post-deployment medical examinations, members of HMMC returned to their original military or civilian place of work, however many civilians – based on their favourable mission experience - decided to remain in the Army.

3. Discussion Lessons learned during the organization, establishment and mission activity of the Hungarian Military Medical Contingent can be summarized as follows: - Since 1990 this was the first time when Hungarian military medical personnel, as individuals, separately integrated into a Medical Treatment Facility deployed and operated by a NATO ally. - It was this integration by individual members that made mission-oriented predeployment foreign language medical training necessary. - Successful medical care at a terrorist incident site is considerably influenced by security of the area (to prevent second wave attacks), by effectiveness of first aid and buddy aid provided before arrival of medical rescue teams, by triage, first management and rapid evacuation of casualties. - In a mass casualty situation, both the method and level of medical care provided for the sick, wounded or injured by the field hospital changes. That is, medical care focusing maximally on the needs of individual casualties, and medical support provided on levels as close as possible to peacetime medical standards, is replaced by medical care and support focusing on the needs of casualties as a whole contingent (the best possible care to the largest possible number of casualties) in order to save life, limb and function. - In a mass casualty situation, the key factor to sustain continuous operational capability of the field hospital is rapid, proper, coordinated evacuation of casualties based on flexible adjustment to the operational needs of the Medical Treatment Facility. - Proper trauma management of mass casualty situations has the utmost importance in the prevention of Post Traumatic Stress Disorder. The risk of traumatic events as a result of enemy activity in operations other than war is mainly determined by the mission statement of the force (which depends primarily on levels of political and military ambition). The Hungarian Parliament did not authorize the Hungarian Defence Forces to deploy combat units into different theatres of operation. That determined mission, tasks, responsibilities and consequently –to a great extent- the possible risk exposure to the troops as well. This may be the logic explanation for the extremely low number of combat related PTSD patients among Hungarian soldiers.

4. Conclusion

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The reader is briefed on the medical support system of the ISAF mission, on challenges, on system levels that ensure continuity and progressiveness of medical support. The reader gets an overview of the activation and implementation of the MASCAL Plan of the German Field Hospital in Kabul with an analysis of lessons learned during exercises and real events. After traumatic events (especially after mass casualty situations) acute stress reactions affect almost every soldier of any nationality concerned or just involved in incident management. Proper trauma management of mass casualty situations is of outmost importance in prevention of Post Traumatic Stress Disorder. The German Field Hospital in Kabul, Afghanistan is a living example of successful integration of multinational military medical personnel in a peacekeeping / peaceenforcement operation. Multinational cooperation however does not mitigate the ultimate national responsibility over medical support to entire military formations and individual soldiers, which must include proper psychological and/or psychiatric support as well.

References [1]

ACE Medical Support Principles, Policies and Planning Parameters, ACE Directive 85-8 Supreme Headquarters Allied Powers Europe, Belgium, 1993 [2] Allied Joint Medical Support Doctrine, AJP-4.10 Supreme Headquarters Allied Powers Europe, Belgium, 1999 [3] Guidelines for Medical MASCAL Planning – ISAF, 2002 [4] Kretschmer H, Döller PC, Bialek R, Schüle B: Ratschläge zur Erhaltung der Gesundheit in tropischen und subtropischen Ländern [5] Bundesverwaltungsamt, 1999 [6] Medical Training in First Aid, Basic Hygiene and Emergency Care – NATO STANAG 2122, 1991 [7] NATO Medical Handbook The Committee of the Chiefs of Military Medical Services in NATO (COMEDS) HQ NATO (IMS/LA&R) Brussels, Belgium, 2001 [8] NATO Principles and Policies of Operational Medical Support – Final Decision on MC 326/2, 2004 [9] Principles of Medical Policy in the Management of Mass Casualty Situation - NATO STANAG 2879 MED (EDITION 3), 1998 [10] Servais O: A katonaorvos és a Genfi Egyezmények Magyar Honvédség Egészségügyi SzolgálatfĘnökség, 1990 [11] Schandl L: Das Selbstmordattentat am 7.6.2003 – Zusammenarbeit des medizinischen Personals Wehrmedizin 2003;27(3):22-23 [12] Svéd L, Kopcsó I: A magyar katonaegészségügy a jelenkor válságaiban Honvédelmi Minisztérium Honvéd Vezérkar Egészségügyi CsoportfĘnökség, 2004 [13] Weidringer JW (red): Katastrophenmedizin – Leitfaden für die ärztliche Versorgung im Katastrophenfall Bundesministerium des Innern, 2003

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Section VI Working Groups

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

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Posttraumatic Stress disorder - Diagnostic and Epidemiological Concerns NANEISHVILI G., M.Asatiani Research Institute of Psychiatry, Tbilisi, Georgia

Abstracts. In Cavtat in June, 2005, several international experts convened to address the key issues in the presentation of PTSD, including diagnostic instruments, classification, risk factors and co-morbidity, as well as clinical aspects of secondary and associated posttraumatic symptoms. Here, we summarize the consensus achieved in discussion between working group members of the group focusing on “Diagnostic and Epidemiologic concerns".

Keywords. PTSD, Trauma, Stress, Clinical phenomenology, Classification, Comorbidity, Risk factors, Secondary and associated posttraumatic symptoms.

Introduction Posttraumatic stress disorder (PTSD) has been identified in some individuals who have experienced a physically or emotionally traumatic event that is outside of the range of normal human experience, such as military combat, rape, natural or manmade (artificial) disasters. PTSD is diagnosed when certain pathopsychological symptoms develop after exposure of traumatic events. There are three major symptom categories, which include: 1) reexperiencing the trauma through dreams or recurrent and intrusive thoughts; 2) emotional numbing such as feeling detached from others; and 3) symptoms of arousal such as irritability and exaggerated startle response. The point prevalence of PTSD in the general population has been estimated to be 0.5% among men and 1.2% among women. Most men with PTSD have experienced combat. For women, the most common stressors are rape and physical assault. PTSD may begin within hours or days after a significant stress, or the onset may be delayed for months or even years.

1. Formation of the concept of PTSD Traumatic disorders can arise in response to a large variety of severe stressors. Despite the diversity of stressors, the concept of an extreme psychological reaction to catastrophic events was first demonstrated exclusively in the context of war, specifically as a reaction to combat actions [1]. The concept of traumatic reaction dates back at least to the time of "the birth of nosological psychiatry", when Griezinger [2] identified two forms of psychosis, with the first characterized as psychoses caused by

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emotional turbulence, when “the whole psychic life is accordingly changed ". The second type includes mental disorders based on intellectual and volitional breaches, where there is the organic defeat of brain. In the first group Griezinger includes forms of melancholies caused by heavy emotional influence, in which there is reflected psychic trauma. Sommer [3] and other psychiatrists underlined the relationship between psychogenic reactions and hysteria. They emphasized the existence of a pathological basis in development of this type of psychosis. Accounts World War I described stupor and depressive disorders during hostilities among soldiers [4], as well as attacks of panic and agitation with hallucinations and delusion on the battlefield [5]. Others supplement these observations, including Kraepelin [6], who coined the term "accidental psychosis” or “neurosis caused by accident", and Jaspers [7], who defined psychogenic reactions as "a conflict of personality with ‘unbearable’ reality". Subsequently, extreme agitation, fright and disorientation have been described following a variety of other military conflicts. These accounts gave birth to such terms as "shell shock", "combat neurosis", "battle fatigue", and "traumatic neurosis". More recently, PTSD was formally recognized and codified in DSM-III [8], and many authors have expanded upon the initial reports from combat settings to document similar psychopathology across a wide range of civilian traumas.

2. Clinical Phenomenology and Classification of PTSD. Posttraumatic Stress Disorder is one of several potential sequelae of exposure to traumatic stress, including operational stress. Mood and anxiety disorders, psychotic reactions, sexual disorders, dissociative disorders, and a series of life problems (e.g., relationship, vocational, and social problems) are also more common in those exposed to significant trauma. PTSD is by definition a reaction to exposure to an event which is outside of normal human experience. The symptoms of PTSD may initially be considered a normal human emotional reaction to an abnormal situation, but their persistence, in association with impairment of function, constitutes a disorder. It should also be emphasize that there is a wide range of “normal” with regard to the response of various individuals, and some may even have significant PTSD in response to a trauma that does not pose a significant threat to their lives. The key is for the event to be perceived by the victim as traumatic. PTSD represents emotional and cognitive dysfunction of prolonged duration, but it is well documented that full and complete recovery can be expected, whether spontaneously or aided by treatment. Responses in patients with PTSD may be divided into 4 categories: 1. Emotional: Shock, Irritate, Fear, Sorrow, and Indefensibility. 2. Cognitive: Disorientation, Difficulties with concentration, fixed ideas. 3. Biological: Insomnia, Hyperarousal, and Agitation. 4. Psychological: Progressive restriction of social activities, Interpersonal conflicts, abuse of alcohol or drugs. The disorder features the following tenets: A. Exposure to a traumatic event, B. Response of fear, helplessness, horror, D. Re-experiencing of traumatic events (Flashbacks, Recurrent nightmares),

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E. Avoidance of stimuli associated with trauma, F. Arousal symptoms. They are two further detailed in both the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV), and the International Classification of Mental Disorders (ICD-10). Historically, the first formal criteria for the diagnosis of trauma-related disorders appeared with DSM-I (1952). These disorders initially were characterized as "traumatic neuroses", emphasizing the psychoanalytic concept of unconscious defense mechanisms. DSM-II (1968) supplemented the earlier definition of posttraumatic syndromes with "transient situational disturbances" and "adjustment reactions", while DSM-III (1980) was the first to include PTSD. DSM-IV (1994) represented the provision of clear-cut definitions for the stressor criterion for PTSD. In addition, DSMIV detailed primary and secondary symptoms. PTSD is classified by DSM-IV with code 309.81, as a member of the group of "Anxiety Disorders". The diagnostic criteria for PTSD according of DSM-IV: A. The person has been exposed to a traumatic event in which both of the following were present: 1. the person experienced, witnessed or was confronted with an event or events that involved actual or threatened death or serious injury. 2. person's response involved intensive fear, helplessness or horror. B. The traumatic event is persistently reexperienced in one or more of following ways: 1. recurrent and intrusive distressing recollections of the event, including images, thoughts or perceptions. 2. recurrent distressing dreams of the event. 3. acting or feeling as if the traumatic event were recurring. 4. intense psychological distress at exposure to internal or external cues that symbolize or resemble an aspects of the traumatic event. 5. psychological reactivity on exposure to internal or external cues that symbolize or resemble an aspect of the traumatic event. C. Persistent avoidance of stimuli associated with traumatic event and numbering of general responsiveness: 1. efforts to avoid thoughts, feelings or conversations associated with the trauma, 2. efforts to avoid activities, places or peoples that arouse recollections of the trauma, 3. inability to recall an important aspect of the trauma. 4. markedly diminished interest or participation in significant activities. 5. feeling of detachment from others. 6. restricted range of affect. 7. sense of a foreshortened future D. Persistent symptoms of increased arousal: 1. difficulty falling or staying asleep. 2. irritability or outbursts of anger. 3. difficulty concentrating. 4. hypervigilance. 5. exaggerated startle response E. Duration is more that 1-month.

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F. The disturbance caused clinically significant distress in social, occupational or other important areas of life. The disorder may be further categorized as acute (duration less than 3 months), chronic (duration is 3 month or more) or of delayed onset (onset of symptoms is at least 6 months after the trauma)[9]. PTSD is represented within ICD-10 by the code F43.1 in the group of "Reaction to severe stress, and adjustment disorders"[10]. There are similarities and differences in the diagnostic criteria between DSM-IV and ICD-10. The similarities include the clinical picture of the disorder, although psychogenic amnesia (partial or total) is emphasized only in ICD-10. Duration is less clearly defined in ICD-10. The diagnosis of PTSD accurately describes the symptoms that result when a person experiences a short-lived trauma (car-accident, natural disasters, rape). They are considered traumatic events of time-limited duration. However, chronic traumas may persist for months to years at a time. Clinicians have found that the current PTSD diagnosis often does not capture the severe psychological harm that occurs with such prolonged, repeated trauma. Some investigators believe a new diagnosis, "Complex PTSD", [11] is needed to describe the symptoms of long-term trauma. In many nations, ICD-10 Classification is primarily used for reporting and/or diagnostic purposes, while DSM-IV is used predominantly for research. The working group discussion addressed new information based on recent research, including: –Psychotic features as a subtype of chronic PTSD (particularly based on work done by Kozaric-Kovacic with Croatian Homeland War veterans); –The relative significance of flashbacks vs. re-experiencing symptoms; –The need for future research to address predictors of the risk of mortality; –For military populations, the questionable validity of an emotional response of “fear, helplessness and horror” (to be further studied).

3. Problems of co-morbidity Many studies have documented a high degree of co-morbidity of PTSD with other mental disorders. For example, the NVVRS [12] found the following rates of psychiatric co-morbidity among Vietnam veterans with PTSD: Major depression, 15.7%; Panic disorder, 4.9%; Obsessive-compulsive disorder, 8.7%; Alcohol abuse, 22.2%. The VES, [13] conducted by the Centers for Disease Control and Prevention, also reported high rates of co-morbid depression, GAD and substance abuse among Vietnam veterans with PTSD compared to veterans without this disorder. High comorbidity with somatic disorders suggests a kinship between PTSD and mechanisms of conversion and dissociation.

4. Risk factors of PTSD Many studies [14-16] have found evidence of pre-trauma predictors of risk for PTSD. Such factors include familial psychiatric illnesses, paternal poverty, sexual assault, childhood behavioral disorders, neuroticism, introversion, prior psychiatric disorders, and low socio-economic status. Some studies have found that premorbid risk factors

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both increase the risk of exposure to trauma as well as the subsequent risk of developing disabling symptoms from the event. PTSD rates were three times higher in wounded Vietnam veterans than in nonwounded combat veterans (20% versus 6,3%) [16]. Epidemiological studies found that the frequency and severity of PTSD increased in proportion to proximity to the trauma. The modal form of PTSD for the "on playground" group (i.e./ most exposed) was severe PTSD (48%); for the "in school group" (i.e., less exposed) it was moderate PTSD (50%) and the modal reaction for the "not at school" group was no PTSD (55%) [17]. Debates have continued as to the relative contributions of the trauma itself and the role of potential predisposing or subsequent events as determinants of PTSD. An important finding also arose from the MSH study [18]. It was found that premorbid risk factors became less important as the intensity of the exposure to trauma increased. When the stress factor impact was most severe, the stressor overrode vulnerability factors that, at lower levels of trauma exposure had identified higher risk subgroups. This argument has been important for showing the influence of risk-group variability and different levels of stress exposure on psychiatric morbidity. Several studies have shown that the role of the trauma itself was modest at best and diminished with time. It was overshadowed by premorbid factors as neuroticism, previous psychiatric history, and previous adverse events. The validity of pre-trauma risk factors was the subject of extensive discussion. There is confidence for only two factors: 1. Previous exposure to trauma, 2. Previous history of psychiatric disorders Additional clarification and future research is indicated for: 1. The role of age as a risk factor of PTSD (vs. self-selection), 2. The positive role of social support and cohesion, 3. The importance of psycho-education and stress inoculation training (i.e. using VR)

5. Secondary and associated posttraumatic symptoms. Secondary symptoms are problems that arise because of the posttraumatic reexperiencing and avoidance symptoms. As time passes after a traumatic experience, more secondary symptoms may develop. Over time, secondary symptoms can become more troubling and disabling than the original re-experiencing and avoidance symptoms. Associated symptoms don't come directly from being overwhelmed with fear; they occur because of other things that were going on at the time of the trauma. Depression can develop when a person has loss connected with trauma or when avoidance of other people leads to isolation. Despair and hopelessness can result when a person is afraid that he/she will never feel better again. Patients with PTSD may have their belief system shaken when a traumatic event makes them lose faith that the world is good and safe place. Aggressive behavior toward oneself or others can result from frustration over the inability to control PTSD symptoms. Patients may also become aggressive when other things that happened at the time of trauma make the person angry. Anger and aggression can cause occupational, marital and relationship problems, and loss of active social contacts.

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Self-blame, guilt and shame can arise when PTSD symptoms make it hard to fulfill current responsibilities. Self-blame can cause considerable distress and can prevent a person from reaching out for help. Sometimes society also blames the victim of trauma. Patients with PTSD may have relationship problems, and may feel detached or disconnected from others because they have difficulty feeling or expressing positive feelings. Less interest or participation in things the person previously enjoyed, and social isolation, may result from depression following a trauma and can occur because of social withdrawal and lack of trust in others. Patients may develop problems with identity and self-esteem . Physical health symptoms and medical problems can result from long periods of physical agitation or arousal from anxiety. For example, an increased rate of mortality from cardio-vascular disorders was seen in Israel war veterans with PTSD (information provided by workshop participant Joseph Zohar). Culturally dependent alcohol and drug abuse may occur when patients with PTSD want to avoid the bad feelings that result with the disorder's symptoms. Many patients use alcohol and drugs as a way to try to cope with upsetting trauma symptoms, but it in fact often leads to more problems. Sixty to eighty percent of Vietnam veterans seeking PTSD treatment have alcohol use disorders [19]. Veterans over the age of 65 with PTSD are at increased risk for attempting suicide if they also experience problematic alcohol use or depression [20].

Conclusions Trauma is always a catalyst for human behavior. A complex interaction of environment, biology and mind determines the development of Posttraumatic Stress Disorder. PTSD is a reaction to an event which is outside of normal human experience. Combat, natural or artificial disasters, rape, physical attack, robbery and terrorism are examples of such traumatic events. This type of trauma causes chaos and fills the lives of those exposed with terror of the unexpected and fear of loss, injury and death. The essential feature of PTSD is the development of characteristic symptoms following exposure to an extreme traumatic stressor involving direct personal experience of an event that involves actual or threatened death or serious injury or other threat to one's psychical integrity. The past decade has witnessed dramatic increases in psychiatry's understanding of bio-psycho-social responses to trauma. Psychiatrists assume that early detection and intervention will prevent the development of chronic forms of PTSD.

References [1] Grinker R., Spiegel J. Men Under Stress. Philadelphia, PA, Blakiston, 1945 [2] Griezinger W. Uber psychiatriche Reflexactionen. Berlin, 1874 [3] Sommer R., cit."Handbook of Psychiatry", Moscow 1988 [4] Sheickovich M., cit."Handbook of Psychiatry", Moscow 1988 [5] Christoffer A., cit."Handbook of Psychiatry", Moscow 1988 [6] Kraepelin E., Psychiatrie.-6 aufl. – Leipzig: Bart Verlag, 1899 [7] Jaspers K., Allgemeine Psychopatologie. – Berlin; Heidelberg; New York. Springer Verlag, 1965 [8] Diagnostic and Statistical Manual of Mental Disorders, DSM-III. Published by the APA, Washington, DC, 1980

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[9] Diagnostic and Statistical Manual of Mental Disorders, DSM-IV. Published by the APA, Washington, DC, 1994 [10] The ICD-10 Classification of Mental and Behavioural Disorders, Clinical descriptions and diagnostic guidelines. WHO, Geneva,1992 [11] Herman J., Trauma and recovery: The aftermath of violence from domestic abuse to political terror. NY, Basic Books, 1997 [12] Kulka RA, Schlenger WE, Fairbank JA, et al: Trauma and Vietnam War Generation. NY, Brunner/Mazel, 1990 [13] CDC: Health status of Vietnam veterans: psychological characteristics. JAMA 259:2701-2707, 1988 [14] Card JJ: Epidemiology of PTSD in a national cohort of Vietnam veterans. J Clin. Psychol. 43:6-17, 1987 [15] Davidson JRT, Hudges D, Blazer D, et al: PTSD in the community: an epidemiological study. Psychol Med 21:1-9, 1991 [16] Herzel JE, Robins LN, McEvoy L: PTSD in general population. New Eng J Med 317:1630,1987 [17] Pynoos RS, Frederick C et al: PTSD in school age children. Arch Gen Psychiatry 12:1057-1063, 1987 [18] Shore JH, Tatum MS et al: Evaluation of mental health effects of disaster. Am J Pub Health 76:76-83, 1986 [19] Evans K, Sullivan J.M. Treating addicted survivors of trauma. NY, Guilford Press, 1995 [20] Kofoed L., Friedman M.J., Peck R. Alcoholism and drug abuse in patients with PTSD. Psychiatric Quarterly, 64:2.151-171, 1992

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Technological challenges in the use of Virtual Reality Exposure Therapy Charles VAN DER MAST a,1 , Sinisa POPOVIC b, Dave LAM c, Gianluca CASTELNUOVO d, Pavel KRAL e, Zeljka MIHAJLOVIC b a Delft University of Technology, the Netherlands b University of Zagreb, Faculty of Electrical Engineering and Computing, Croatia c U.S. Army Telemedicine and Advanced Technology Research Center, Ft. Detrick Maryland, and University of Maryland School of Medicine, National Study Center for Trauma and EMS, Baltimore Maryland, USA d ATN-P Lab, Instituto Auxologico Italiano, Milan, Italy; Clinical Psychology Lab, Instituto Auxologico Italiano, Verbania, Italy and Department of Psychology, Catholic University, Milan, Italy e Central Medical Psychology Department, Central Military Hospital, Prague, Czech Republic

Abstract. This paper describes the result of a discussion in a working group and a plenary discussion at the NATO Advanced Research Workshop on Novel approaches to the diagnosis and treatment of posttraumatic stress disorder. Several technological challenges are presented with regard to the basic functions of a VRET system. Most challenges are demand-driven and are focused on better ways to support the therapist, for better and more efficient treatment. Tele-care is one of the most promising but difficult challenges. The results give directions for both fundamental and practical research. Keywords. Virtual reality exposure therapy, agent technology, tele-care, humancomputer interaction., PTSD, Post Traumatic Stress Disorder

Introduction Virtual reality exposure therapy (VRET) is the result of a close collaboration between researchers and practitioners of significantly different disciplines, among others, psychiatry, clinical psychology, psychotherapy, computer science, graphics design, human-computer interaction, and engineering. The traditional cognitive behavioral therapy (CBT) treatment 1 Corresponding Author: C. van der Mast, Delft University of Technology, Mekelweg 4, 2628 CD Delft, The Netherlands; E-mail: [email protected].

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process between therapist and patient has been taken as the main paradigm to be supported by technology in different ways, not in the least by providing interactive immersive worlds to “play” the treatment process in virtual reality instead of in vivo, as in the behavioral approach or by imagination, such as in the cognitive framework. It has proven to be the case that patients are very sensitive to specific multimodal features in the virtual world and the appropriately accompanying sounds [12]. Medium-level resolution and graphics quality has proven sufficient in many cases to trigger the specific phobia-related reactions that are essential in exposure therapy. The effect of locomotion technique on fear has been studied [20]. In one study [11], treatment using a standard head-mounted display (HMD) -gave the same results for the treatment of acrophobia as an advanced CAVE system providing advanced virtual reality systems. Of course this substitutability may be dependent on the specific type of disorder to be treated. It has been proven in many studies that VRET can achieve the same results as traditional CBT, but will not outperform it [8]. However, there are more aspects of CBT which are important other than just exposure. Technology can also support the therapist in changing in real time to other synthetic worlds in which to expose the patient, or in recording and replaying sessions in the virtual world for later analysis and planning the following session [2]. Current VRET systems are mostly developed and used in laboratories where technical support is available. A few systems are available on the market, but evaluation of practical use on a larger scale has not yet been reported. To provide full support in clinical situations, it is essential that VRET systems be feasibly employed in the clinic by several therapists of a team and without strong and expensive technical support. This usability is important to enhance the performance of the treatments on the one hand, while on the other hand we may expect benefits from other support functions besides the VR exposure technique itself [7]. Interesting new technologies are available to extend a VRET system with new functions in order to measure and analyze the details of the treatment process for a better understanding of diagnosis and treatment, as well as for improving the efficiency of the therapist’s work [16]. In this paper we present the results of a structured brainstorming session on technological challenges which might assist in enriching and improving all aspects and functions of VRET we can imagine now. Three of the authors have a technical background in VRET technology and three have a background in clinical treatment. First we present an overview of the essential technical and functional components of VRET systems. Second we present, explain and structure the challenges we found. Finally we will discuss these and give some final conclusions.

1. Essential components of VRET systems Most current VRET systems consist of typical functions and components as summarized below. The system is usually located in one room where both therapist and patient are together so they can communicate by natural means. If for some reason they are not in the same room an audiovisual intercom facility should be provided. See Figure 1 for a typical VRET system in one room with direct communication between therapist and patient.

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This system is equipped for treating fear of flying. The main functions are the following. First a device is needed to present the world visually (in stereo or mono) to the patient [1].

Figure 1. Overview of a typical VRET system in one clinical room [7] and [19].

This computer-generated synthetic world can be presented in an immersive way by a headmounted device or it can be projected on one or more screens. However, some intermediate forms are possible. Augmented reality can be used to superimpose artificial objects, e.g. animals, on the real world you can see through the HMD. Patients should be able to look around. If immersive worlds are being presented a tracker system is needed with a sensor on the patient’s head built in the HMD. Another function is that the patient should be able to navigate in the virtual world, although it may be to prefer that the therapist takes the navigation task over from the patient in some situations [20]. For navigation some other input device is necessary to start and stop navigation in a particular direction. Sometimes the patient should be able to initiate actions or events or choices within the virtual world, e.g. as part of tasks to do selections of virtual objects to improve presence. Then we need stereo sound as an important resource to improve the sense of presence [14] in the virtual environment. This sound may be dependent on the distance and the direction between the source of sound and the patient. Another output channel may be servo-controlled

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mechanical devices, e.g. to move the aircraft chair to simulate air turbulence during the flight.

Figure 2. Example of a therapist user interface of a system for treating fear of flying [7].

This may improve the presence, e.g. for treating fear of flying, significantly. Last but not least we need a user interface for the therapist to control what may or should happen in the world [7], e.g. lighting condition in the world, the occurrence of turbulence in the aircraft, the change of crowds in worlds for agoraphobia, see figure 2. We can summarize all these functions in Figure 3.

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two-way communication

visual audio action

VRETsystem

therapist

other

patient

navigation evaluation look around action measurement

Figure 3. Basic communication functions in a VRET system.

2. Challenges The following challenges were formulated in the workgroup by the authors, and discussed during a plenary meeting with all the participants of the NATO workshop. We decided that it is not reasonable to give a priority to these challenges, as work in many of these areas is currently ongoing simultaneously in different venues, and any or all of these developments may be useful, no matter in which order technological advances are made. 2.1. Personalizing the system A VRET system may be used by many different colleagues from a clinic. Additionally, each therapist may change over time his or her preferences about using the system for some specific phobias. This gives a rationale for implementation of the possibility to personalize the user interface and a part of the main functions of the treatment process by the individual therapist and to store the applicable parameters. It is conceivable that this personalization could be extended to prepare for each patient an individual treatment procedure off-line,

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including some changes in the worlds, specific for each patient to be treated. This kind of personalization is an important research goal sometimes referred to as “adaptive” user interfaces [22]. The possibility of the therapists to “tailor” different versions of the same virtual environment according to the patient’s needs has been underlined by Castelnuovo [5]. 2.2. Automated support for the therapist This challenge was emphasized most highly by the workgroup. The first function of a VRET system is to offer an interactive virtual environment for the patient to experience the feelings that have to be worked on. But beyond that, the most promising challenge is to develop support functions for the therapist [2]. By analyzing the treatment process and composing task models one can recognize and specify steps and modes in the treatment (see Figure 4). This is an example of a task model. New models have to be developed describing the task in terms of treatment steps and specific aspects and levels of the disorder.

Cure Curepatient patient

Goals Procedures

Determine Determinefear fear

Change exposure

Solve patient ambiguity

sim. Ask Askpatient patientto to to report to reportfear fear

Monitor Monitorpatient patient response response

Sound T.Controls T.Screen P.Posture Figure 4. ‘Determine fear’ goal decomposition (see [21] for decomposition and explanation of more details).

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If it is possible to describe a treatment session in terms of steps to be taken under supervision by the therapist it may be possible to develop an electronic agent which provides advice including some rationales to the therapist about the following step(s) in the actual context of the treatment. It would also seem interesting to provide a planning mode to the therapist to specify some sequential steps for a session just before it starts. The general goal is to provide extra explicit knowledge to the therapist about the progress of the treatment. The agent can obtain its information from built-in procedures which may be adjusted by the therapist and by measurements of the patient’s physiological condition, e.g. heart rate and skin conductance. It would be most useful to construct a learning electronic agent which could learn from an experienced therapist. A junior therapist could use this “smart” agent to give better treatment in non-critical sessions, under the responsibility and supervision of an experienced therapist. It would be possible to teach such agents to give good advice by analyzing individual treatment patterns in specific clinical cases. The advice might propose the next procedure step or the next navigation or modification of the virtual world to control the level of fear. Even more measurements can be done by face recognition [15], [25] and voice recognition since these can indicate levels of stress, fear, and other emotions [18], [24]. An additional form of support may be considered procedures of computer-supported self-treatment by the patient. The therapist should be able to specify the procedures and constraints of these modules for self-treatment. Related to section 3.1, easy-to-use tools oriented toward non programmers could be useful for providing greater flexibility and individualization in defining VR scenarios. The therapist could thus individualize homework scenarios for the patients without the need for the programmer to hard code each scenario. Individualization of virtual environments is addressed within a currently ongoing EMMA project [3]. Envisioned VR scenarios driven by the patient’s physiology [23] could also be useful for patient’s self-treatment during homework sessions. 2.3. Computer-based training A completely different challenge is the construction of a VRET system for computer-based training of junior therapists. This could be done using simulated or real patients, or recorded sessions. The learner could be trained to use the system and to treat different types of disorders. Simulated patients could include a combination of computer-generated patients and normal people requested to simulate. Computer-generated patients could model non-visible changes happening in real patients (e.g. physiological changes), and normal people could manifest patients’ visible responses. 2.4. Tele-Care It is both a technical and an organizational challenge to develop a system for tele-treatment of mental disorders using VRET over the internet. The most serious challenge is to have a ratio of therapist: patient of more than 1:1. It should be possible to develop a system and a therapist’s user interface to allow the provision of treatments to more than one patient at the same time, in different rooms in the same clinic or in different clinics. If one senior and one

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junior therapist could treat more than two patients simultaneously, the ratio will improve. Some experience with tele-treatment of agoraphobia without VR has previously been reported [13]. In a more general project on tele-care the possibilities of agent support for tele-care at home has been investigated [8], [17]. 2.5. Eye tracking A challenge that was discussed a lot during the plenary session was the use of an eye tracking to study how the focus of the patient is oriented during VRET sessions. It is expected that this may give better insight into what triggers the emotions during the sessions. This information may be used to adjust the session procedure or the characteristics of the virtual world online. It was noted that the development of such a capability which would not require time-consuming and difficult alignment or standardization for each new patient might be very difficult, but that lessons may be learned from the work previously done in aviation technology with Heads-Up-Displays and helmet-mounted visual devices. 2.6. VRET experience with the MRI/CT scanner The most futuristic challenge is to implement a mechanism to allow the use of MRI or CT scans of the brain during a VRET session. Early steps in this direction have been taken by devising a fiberoptic magnet-friendly high-resolution wide-field-of-view image delivery system [9]. Initial tests with functional MRI (fMRI) offer promising results, showing that the display does not interfere with the brain scans, and that the users can feel the sense of presence in the virtual environment while being inside the scanner [10]. With state-of-theart technology it therefore seems possible to present images of virtual environments to a person who is within a scanner. Further VRET-fMRI research could address brain patterns occurring in patients during VR baseline and exposure sessions, compare brain activities of patients and controls, and so on. The challenge is to conduct research on understanding optimal treatment schedules, not at standard scanner-mediated treatment in the clinic.

3. Discussion Most of these challenges were discussed during the plenary workshop without detailed knowledge about what is going on in other domains. In aviation training and development, interesting progress is being made which should be looked into, especially with regard to heads-up displays and helmet-mounted visual instruments. New visualization techniques in cockpit design using mixed reality may give interesting concepts for improving VRET. In any case, we need to separate the requirements of basic research from those of clinical therapy – they have different requirements, goals, and rationales. In general we need the best clinical feedback during treatment. The goal is to provide the therapist with information and feedback on the changes that occur, so as to allow him to provide the most effective treatment. Tools to detect changes in physiological parameters by external measurement are necessary. Some participants in the plenary session stated that tele-

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treatment could be dangerous because these patients are difficult and fragile, but others reported that tele-care (without VR) of agoraphobia and PTSD [13] works, and is currently being used safely and effectively. It may prove to be that tele-treatment of PTSD or other psychiatric disorders is only feasible in some stages (diagnosis and initial therapy) of the treatment plan. Obviously, all of these alternative potentials require much more research and development in both the clinical and technological realms to determine their feasibility and benefits.

4. Conclusion It is clear that several interesting technological challenges are on the horizon. But we must remain aware that we need fundamental research on how new technologies can improve the very personal treatment process supervised by the therapist. This research must be demand driven by the therapists, and not pushed by technology—The technical ability to do something does not imply that it is either safe or desirable from a clinical standpoint. We are just in the early stages of some very interesting developments. They will both improve our insight in how treatment can be given in the most effective way and how treatment can be deployed on a large scale more efficiently than with the current means. VRET may play an important role in these developments. In our view, an emerging scenario could characterize the future clinical setting: old (and functional) practices could be integrated and enhanced through new (and promising) media such as VR. This framework aims at matching “techno” and “psycho” for clinical purposes [4].

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M. Alcaniz, J.A. Lozano & B. Rey, Technical Background of VR, in G. Riva et al. (Eds.) Cybertherapy, IOS Press Studies in health technology and informatics Vol 99, 2004, 199-214. C. Botella, S. Quero, R.M. Banos, C. Perpina, A. Garcia Palacios & G. Riva, Virtual reality and psychotherapy, in G. Riva et al. (Eds.) Cybertherapy, IOS Press Studies in health technology and informatics Vol 99, 2004, 37-54. C. Botella, Clinical issues in the application of virtual reality to treatment of PTSD. NATO ARW Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder, Cavtat-Dubrovnik, Croatia, 2005 G. Castelnuovo, C. Buselli, R. De Ferrari, A. Gaggioli, F. Mantovani, E. Molinari, M. Villamira, and G. Riva, New tools in cybertherapy: the VEPSY web site, Stud Health Technol Inform 99 (2004) 15-35. G. Castelnuovo, G. Cesa, A. Gaggioli, F. Mantovani, E. Molinari, G. Riva, A new generation of virtual environments for the treatment and rehabilitation of eating disorders, Book of Abstracts, SPR 2005, Ulm: Ulmer Textbank, 2005, 176. A.H.M. Cremers & M.A. Neerincx. Personalization Meets Accessibility: Towards the Design of Individual User Interfaces for All. In: User-Centered Interaction Paradigms for Universal Access in the Information Society. Lecture Notes in Computer Science. Berlin etc.: Springer, 2004, 119-124. L. T. Gunawan, C. van der Mast, M. A. Neerincx, P. Emmelkamp, M. Krijn, Usability of Therapist's User Interface in Virtual Reality Exposure Therapy for Fear of Flying in: Jeanne Schreurs & Rachel Moreau, Proceedings of the Euromedia 2004 Conference, April 19-21 2004, Hasselt, Belgium, 2004, 125-132.

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G. de Haan., C.A.P.G. van der Mast, O.A. Blanson Henkemans and M.A. Neerincx, SUPERASSIST: Personal Assistants for Cooperative Healthcare Treatment, Proceedings Euromedia 2005, ISBN 9077381-17-1, EUROSIS publication, April 2005, 2005, 125-128. H. G. Hoffman, T. L. Richards, J. Magula, E. J. Seibel, C. Hayes, M. Mathis, S. R. Sharar and K. Maravilla, A magnet-friendly virtual reality fiberoptic image delivery system, CyberPsychology & Behavior 2003 Dec;6(6):645-648 H. G. Hoffman, T. Richards, B. Coda, A. Richards and S. R. Sharar, The illusion of presence in immersive virtual reality during an fMRI brain scan, Cyberpsychology & Behavior 2003;6(2):127-131 M. Krijn, P. M. G. Emmelkamp, R. Biemond, C. de Wilde de Ligny, M. J. Schuemie and C. A.P.G. van der Mast, Treatment of acrophobia in Virtual Reality; the role of immersion and presence Behaviour Research and Therapy, 2004 Feb; 42(2):229-239. M. Krijn, P. M. G. Emmelkamp, R.P. Olafsson, R. Biemond, Virtual reality exposure therapy of anxiety disorders: A review, Clinical Psychology Review 24 (2004) 259-281. A. Lange, Schrieken, B.A.L., Ven, J.-P.Q.R. van de., Bredeweg, B., & Emmelkamp, P.M.G., Kolk, J. van der., Lysdottir, L., Massaro, M., & Reuvers, A. INTHERAPY: The effects of a short protocolled treatment of post-traumatic stress and pathological grief through the internet. Behavioral & Cognitive Psychotherapy, 28, 2, 2000, 103-120. K. Nowak, Conceptualizing, Differentiating and Measuring Copresence and Social Presence, 4th Annual International Workshop PRESENCE 2001, Temple University, Philadelphia, PA, USA, 2001. M. Pantic and L.J.M. Rothkrantz, "Machine understanding of facial expression of pain", Int'l Journal of Behavioral and Brain Sciences, vol. 25, no. 4, pp. 469-470, August 2002. B. Rey, M. Alcaniz & J.A. Lozano, New technologies for providing remote psychological treatments, in G. Riva et al. (Eds.) Cybertherapy, IOS Press Studies in health technology and informatics Vol 99, 2004, 181197 G. Riva, F. Morganti & M. Villamira, Immersive virtual Telepresence: virtual reality meets eHealth, in G. Riva et al. (Eds.) Cybertherapy, IOS Press Studies in health technology and informatics Vol 99, 2004, 255270. L.J.M. Rothkrantz, P.Wiggers, J.W.A. van Wees, R.J. van Vark, Voice stress analysis, Proceedings of Text, Speech and Dialogues 2004, 2004. M. Schuemie and C. Van der Mast, VR testbed configuration for phobia treatment research, in: M.E. Domingo, J.C.G. Cebollada & C.P. Salvador (Eds.), Proceedings of the Euromedia 2001 conference, April 18-20 2001, Valencia, Spain, pp. 200-204. M.J. Schuemie, B. Abel, C.A.P.G. van der Mast, M.Krijn and P.M.G. Emmelkamp, The effect of locomotion technique on presence, fear and usability in a virtual environment in: Marwan Al-Akaidi & Leon Rothkrantz (Eds.) Proceedings of Euromedia 2005 Conference, April 11-13, 2005, Toulouse France, 2005, 129-135. M.J. Schuemie (2003). Human-Computer Interaction and Presence in Virtual Reality Exposure Therapy. PhD Dissertation, Delft University of Technology. (available at http://mmi.tudelft.nl/~vrphobia under publications) C. Stephanidis, (2001). Adaptive techniques for universal access. User modeling and user-adapted interaction, 11, 159-179 (20). B. K. Wiederhold and M. D. Wiederhold, The future of Cybertherapy: improved options with advanced technologies, in G. Riva, C. Botella, P. Légeron, G. Optale (Eds.), Cybertherapy: Internet and Virtual Reality as Assessment and Rehabilitation Tools for Clinical Psychology and Neuroscience, Amsterdam: Ios Press, 2004, 263-270. P. Wiggers, L.J.M. Rothkrantz, Integration of speech recognition and automatic lip-reading, Proceedings of Text, Speech and Dialogues 2002, September 2002, 203-212. A. Wojdel, J.C. Wojdel and Leon J.M. Rothkrantz, Dual-view Recognition of Emotional Facial Expressions, Proceedings of 5th annual conference of the Advanced School for Computing and Imaging ASCI'99, pp. 191198, Heijen, The Netherlands, June 15-17 1999, 191-198.

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Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder M.J. Roy (Ed.) IOS Press, 2006 © 2006 IOS Press. All rights reserved.

Novel Approaches for the Integration of Behavioural Therapy and Virtual Reality Mariano R. ALCAÑIZ1, Carmen L. JUAN, Beatriz S. Rey, José Antonio Q. LOZANO Medical Image Computing Laboratory. Technical University of Valencia, Valencia, Spain

Abstract. In this chapter we describe several technological requirements that must be considered in order to achieve a practical, efficient, ecological and usable integration of behavioural therapy and virtual reality (virtual therapy or VT). Some critical aspects are considered regarding the media form and media content of virtual therapy applications. Finally, future trends and promising technological tools used for VT applications are discussed like adaptive displays and augmented reality interfaces. Keywords. cognitive behavioural therapy, virtual reality, exposure therapy, mental disorders

Introduction The use of Virtual Reality (VR) technology for Behavioural Therapy, also known as Virtual Therapy (VT) constitutes nowadays a mature scientific area that is being applied successfully for the treatment of several psychological disorders [1]. Virtual Therapy (VT), as a clinical applications of VR technology, requires a seamlessly integration into the daily clinical routine in order to spread its use inside the clinical community. After a decade of VT development and clinical validation, for achieving that named integration, it is crucial to analyze the major drawbacks of actual VR technology for its use in VT systems and to identify some requirements to be accomplished. In this chapter, we summarize some of these drawbacks and identify new promising technological fields that will facilitate a practical, efficient, ecological and usable integration of behavioural therapy and virtual reality. VR technology for VT can be analyzed from two main perspectives: media form and media content. Media form refers to the way the stimuli are presented to the patient and includes the proprieties of the display medium, the extent of sensory information presented, the degrees of control that users have over positioning their sensors within the environment, etc.). Media content refers to the content of these stimuli and includes the objects, actors and events represented by the media and users’ ability to modify aspects of the virtual environments.

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Corresponding Author: Mariano Alcaniz. Medical Image Computing Laboratory. Technical University of Valencia. Camino vera s/n. 46022 Valencia, Spain.

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1. Media form aspects In a Virtual Therapy (VT) system it is crucial that the user can “live” the virtual reality experience, that is, to achieve a satisfactory and clinically useful sense of presence within the VT application. Media form characteristics have a significant impact on the sense of presence in VT. Nobody doubts about the importance of immersion, interaction and perceptual realism for developing VT applications. However, as a clinical application, instead of trying to maximize the immersion of the patient using the most advanced, and sometimes cumbersome, VR technology, it is more important to establish the drawbacks of VR technology normally used for VT systems and to identify the tools that are being demanded by the clinicians in order to ensure efficient and reliable treatments for their patients.

2. Visual devices Basically, there are two categories of visual devices to be used for VT applications: Head Based Visual Devices and Stationary Visual Devices. 2.1. Head Based Visual Devices The Occlusive Head Based Visual Devices, also know like Head Mounted Device (HMD), is the device that most people associate with Virtual Therapy. These devices isolate completely the user from the real world. Anything the user needs to see will must to be generated by the virtual world, including this own body if this was necessary. These devices have some screens that they move with the movements of the user head. These screens are small and lightweight since they are worn or held by the user. Most of the HMD allow stereoscopic image using, normally, a dual visual output (one for each eye) system. Although these devices display the virtual world through the user’s viewpoint, in these devices it is possible to add some tracking method and, also, some could have it incorporate in the unit. Tracking the location and orientation of the user head, the HMD can to be the most intuitive visual interface because, if a user wants to see another side of an object he will have simply walking to this new side and looking the object. The main advantages of these devices are the following: o Low cost for low resolution models o Can occlude the real world o Great portability The main disadvantages of these devices for routine uses with VT applications are: o Market dependence o Hygiene problems o Usability problems (cables, head fitting, FoV) o Poor ergonomics o Fragility

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2.2. Stationary Visual Devices (Monitor Based and Projection VR) These devices are known as “stationary” because they are fixed in place, and unlike previous systems, they can not be moved with the user head movements in the virtual experience. Basically there are two types: 2.3. Monitor Based Devices Normally, this visual device is an extension of a simple desktop computer (standard computer monitor) setup but it may require other additional components like patient head tracking devices. The main advantages of these devices are the following: o Inexpensive o Easy to use o Higher visual resolution The main disadvantages of these devices are the following: o Less immersive (than most other VR visual devices) o Limited field of view. Although it has been successfully used for some VT applications [2], the above mentioned drawbacks constitute severe limitations for VT applications. 2.4. Projection VR These systems use large screens in order to visualize the virtual experience. This large visual “surface” is normally created using LCD or DLP projectors. With actual PC based graphic cards, it is quite easy to set up a large image, stitching together several images coming from different graphic pipelines. In this sense, it is possible to develop custom-made large immersive systems that produce a strong immersion. The large physical dimensions that are necessary for CAVE-based systems and or rear-projected solutions can be avoided through the use of adequate mirror based set-ups or special optics, which are becoming standards for LCD/DLP projectors. These visual devices constitute very natural interfaces for the patient and are quite suitable for a routine clinical use. The main advantages of these solutions can be summarized as follows: o Low cost solutions o No need for big spaces (mini CAVE concept) o Natural interfaces for the patient. Greater user mobility (few cables) o Ease of use for clinicians o Wider FOV o Better for group viewing Taking into account these characteristics, projection-based VR systems are the most promising visual VR device for VT applications.

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3. Media content aspects 3.1 Critical issues of media contents One of the most important characteristics of VT systems is that they allow the patient to explore and to interact with an artificially created environment. Thus, the patient “has the feeling” of being in a different place from where they physically are, and this feeling has labeled a “sense of presence”. As previously stated, media form characteristics have a significant impact on the sense of presence. Nobody doubts the importance of immersion, interaction and perceptual realism. However, presence research has overemphasized them, and sometimes they have been used erroneously to describe the experience of presence. In some theoretical models, the sense of presence has been seen as the outcome, or a direct function of immersion. As a result, it has been assumed that the more inclusive, extensive, surrounding and vivid the VE, the higher the sense of presence [3]. There have been some attempts to distinguish presence from immersion. Slater [4,5] defined immersion as an objective description of the technology, while the sense of presence is a subjective experience and only quantifiable by the user experiencing it. Presence is essentially a cognitive or perceptual parameter whilst immersion essentially refers to the physical extent of the sensory information and is a function of the enabling technology. Up to now, definitions of presence have been based on cognitive or environmental aspects. However, it has been demonstrated that presence, like all human experiences, is influenced by emotions [6]. Emotions play an important role in the way we make our subjective judgments, we react to the world and we learn things about it. It has been demonstrated that this variable is especially important in order to generate and enhance presence in Mental Health applications of VR, e.g., [7]. In this sense, Hoorn, Konijn & Vand de Veer [8], in a paper entitled “Virtual Reality: Do not augment realism, augment relevance” argue that VR experience gains more from increased emotional relevance than from higher realistic solutions. These authors claim that to design VR, experience instead of technology is the key word, and they recommend that VR designer focuses on developing features that sustain relevance to the goals and concerns of the user. According to them, “The sophisticated technology of VR may be powerful but it is not enough to initiate a reality-experience that is true-to-life. Basic to realityexperiences that are true-to life is that the experience is emotionally loaded (…). The basis of emotion psychology is personal meaning: without relevance no emotion occurs. Thus, VR needs personal relevance for the user to arrive at the intended (total) involvement as manifested in the experiences of immersion and presence”.Taking into account this line of thinking, emotions may play a role on the sense of presence. From this point of view, the focus would lay on designing affectively significant environments. In order to achieve this, it would be necessary to include elements with the potential of activating emotions. This is especially true for Clinical Psychology, because the goal is to achieve important changes in the users. 3.2. Adaptive displays: a key tool for virtual therapy An adaptive display can be defined as a device that autonomously adjusts its presentation and actions to better match the immediate goals and abilities of the user.

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The system has to monitor several variables, such as user status, tasks and context. The possibilities depend on the capabilities of the technology that carries the display. Rothrock et al. [9] identified two types of adaptability depending on the tasks that the user must perform in the system: interaction and knowledge content. If the user’s purpose is to execute and control tasks using the system, interaction adaptability would be required. In this case, a perceptual adaptation is usually made. On the other hand, if the user’s purpose is to acquire knowledge, the focus would be on content adaptability. In recent years, interest in adaptive displays has greatly increased, as it is a technology that can be applied in many different areas. A lot of research has focused on the technical aspects such as improving resolutions and detail of the displays. Other research has focused on cognitive aspects such as analyzing the problem of information overload and the observer’s ability to process the information that is shown. To achieve a truly adaptive display, i.e., one that automatically adjusts its contents to the constantly changing state of the observer, requires that the designer be able to characterize not only the bandwidth required, but also to be able to “impedance match” the display to the observer, ideally by using non-contact (remote) sensing of the observer’s cognitive state. One exciting derivative of the clinical work is an adaptive display that actually shifts within a narrow range of modes according to the physiological/ cognitive state of the user [10]. Currently, there are research groups that are developing new kinds of sensors and algorithms that can detect information related to affect. This could be the basis of a new kind of display that adapts to affect [11]. One of the pioneering works in applying adaptive display technology within VT applications has been performed within the EMMA (Engaging Media for Mental Health Applications), an EU funded project.[2] It is representative of the latest category of adaptive displays. We have developed a virtual reality application whose contents and aspects change dynamically depending on the emotions of the user. It can be described as an adaptive display that reacts to affect. This environment is designed to be used in psychological therapy. The system that has been developed, named “the book of life”, permits customization of the VE with personnel contents of the patient and to change dynamically in real time its contents in order to be adapted to the mood state of the patient. 3.3. The book of life: an adaptive display for virtual therapy 3.3.1. Clinical aspects The application has been designed to help in the treatment of post-traumatic stress disorder, adjustment disorder, and bereavement. In each of these conditions, people have suffered a traumatic experience (e.g. the loss of a loved one, loss of a job, divorce, rape, etc.). To accomplish our therapeutic goals, a series of emotional objects can be used and personalized so that they are meaningful to the user and contain the fundamental elements that the person must confront. The objective is to obtain a physical representation of personal meanings and the emotions that are related to those meanings and to study how this strategy helps the person to change. The set of personal experiences that is created can be used to activate, correct, structure and restructure those previous experiences. By using them as cognitive-emotional structures, the therapist can help the patient to structure a new way of processing and integrating past, present and future experiences.

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3.4. General description of the different tools In the first stages of the therapy, the patient learns how to navigate and interact with the system by practicing in a neutral environment. The treatment environment is a special place where patients can feel free to express their emotions and where emotions are going to have an effect on everything that surrounds them. A series of tools are used in each session. They are always available in the environment and are selected based on the therapist’s instructions. For example, if the patient is asked to relive an experience while speaking to the therapist, the virtual environment will reproduce these feelings in different forms (such as a dark forest with no exit). Another tool provided by the system is “the living book”, which has been designed so that the person can reflect feelings and experiences in it. It contains images, objects and other elements that are also present in the virtual environment. The objective is to represent the most important moments, people and situations in the person’s life. Anything that is meaningful for the patient can be incorporated in the system: photos, drawings, phrases, videos... Both the therapist and the patient are physically present in a room. The patient visualizes the virtual environment in a retro-projected screen. The virtual environment contains a circular room, so the environment outside the room can be visualized from the inside. The user can navigate both inside the virtual room and outside it (Figure 1). The patient can select different objects that can appear in different places of the environment in order to personalize it. The therapist can control the contents that the user views from another computer, and can make the environment change in real time; for example, a beach can be changed to a snow-covered town. The therapist can also create different effects in the environment such as rain, snow, earthquakes... 3.5. Personalization by the patient The environment includes different systems that interact to allow the patient to express ideas through different items. The characteristics and positions of these items can be modified in real time.

4. Object selection The first customization that the user can make in the environment is the selection of different objects and elements that can be added to the environment in real time.

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Fig. 1. Image of the room from the outside.

A database with different elements can be created for each patient. A graphical element, the database screen (Figure 2), provides access to the different categories of objects that can be held and used in the system: sound, video, images, threedimensional objects and colours. Each category is composed of an array of icons that represents objects that are present in the database. When the patient selects them, they are copied to a temporary storage tool called the inventory tool, from where the elements can be copied to different places in the virtual room. In order to identify the parts of the virtual room where objects can be copied, there are special objects, called “object holders”, which are distributed throughout the room. The objects that are in the inventory can be copied into these holders. The effect created is different depending on the object that is copied. If it is a three-dimensional object, it is viewed above the object holder (Figure 3). If it is a sound, it will be heard when the user approaches the object holder. If it is a video, it will be viewed on a small screen above the object holder when the user approaches it. If it is an image, it will be viewed in a small screen above the object holder. An object holder can serve as a mixing tool to combine several elements to form a new more complex element. This is achieved when different elements from different categories are copied to the same object holder; thus, an object holder can simultaneously show a 3D object, a video and an image; the associated sound can be heard when the patient approaches it. Also, if a colour element is copied to an object holder that already has a 3D object, a coloured light will be applied to the object. The size of the different elements that are shown in an object holder can be controlled by the patient.

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Fig. 2. The database screen. The object category is shown in the image. The user can select other categories by pressing the correct tab.

The elements in the object holders can be moved by copying them to the inventory. This makes them disappear from their current location. Then, they can be copied in other object holders of the virtual room. Besides object holders, there are other special elements that are used inside the virtual room. The most important one is the living book (Figure 3).

Fig. 3. The living book. The title can be read on the upper left corner of the first page. There are different slots for placing different objects.

The representation of this element is a book that contains pages that represent different chapters. A title for each chapter can be introduced by using a virtual keyboard. The living book is the instrument that the patient uses put in order and keep all the contents that have been analyzed with the therapist during the session. Initially, the living book is empty. The user can select the elements that will be introduced in each of the chapters directly from the database screen or from an object holder. The elements are copied temporarily to the inventory tool, and from there to the different positions that are available on each page of the living book. The elements are represented in the living book by means of an icon. Once the elements have been copied in the book, their order can be changed at any point during the session.

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Finally, there is another special element that is used to eliminate objects, the drain. It is used to destroy the objects that are no longer needed. The interaction with the drain is similar to the ones that we have described above. When the user drops an element from the inventory to the drain, the element is deleted from the inventory and can no longer be used.

5. Emotional discharge system The emotional discharge system (Figure 4) provides a space that allows the patient to modify and manipulate the characteristics of the virtual environment and the objects that are placed in it in accordance with emotions.

Fig. 4. The discharge area. It is composed of three special object holders that allow the user to modify the objects that are placed above them.

The discharge system has been implemented as three special object holders that are on the balcony of the virtual room. Patients can modify the shape and the aspect of the objects that are placed on them with their voices (shouting in a louder or softer way depending on their emotional state). The size of the objects placed in those special object holders is modified according to the loudness of the input sound. More than one object holder can be active at the same time. In this case, the aspect of all the objects placed over them will change simultaneously. 5.1. Personalization by the therapist The therapist accompanies the patient during the session and can have an important role in the customization of the environment. A special interface has been prepared to allow the therapist to control several aspects of the appearance of the outer part of the virtual room. The application that controls this runs on a different computer from the one with the virtual environment. The commands that the therapist introduces are sent using TCP/IP to the environment computer, and the appearance of the environment changes depending on

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the command that the computer has received. There are five different pre-defined aspects (Figure 5): a desert, an island, a threatening forest, a snow-covered town and meadows. The environments are related to different emotions. For example, the desert can be related to rage. The island can be shown when the therapist wants to induce relaxation in the patient. The threatening forest can be related to anxiety. The snow-covered town can be used during the session when the patient is remembering a sad situation in his / her life. The meadows can be used to induce happiness in the patient. However, the specific use that is given to each environment depends on the context of the session and can be selected by the therapist in real time.

Fig. 5. The different aspects of the virtual environment: the meadows, the desert, the island, the snowcovered town and the threatening forest.

Apart from this large-scale control (changing the entire aspect of the outer part of the virtual environment) the therapist can also make small-scale changes. Different effects can be applied to the environment (Figure 6): a rainbow can appear; it can start to rain or to snow; an earthquake can be generated; the hour of the day (and the corresponding illumination) can change... All these effects can be launched from the same interface, and the therapist can control both the appearance and disappearance of the effect, as well as the intensity with which the effect is shown.

6. Augmented reality: a promising field for virtual therapy Augmented Reality (AR) interfaces suppose a very promising tool for VT applications. With respect to the occlusive VR interfaces traditionally used for VT, AR offers several advantages. In AR, the environment is real and the elements that the patient has to use to interact with the application are real as well. The possibility of an easy integration of tangible interfaces constitutes a strong advantage for enhancing the sense of presence

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(the sensation of being there) and reality judgment (the fact of judging the experience as real) in VT applications. In AR based VT applications, the patient is seeing his/her own hands, feet, etc. This is an important aspect for clinical applications of VR. This situation can be simulated in VR but with more technical difficulties and less effective clinical results.

Fig. 6. Sad environment with a storm, rain, and snow. The therapist can control the appearance of these effects at the relevant moments.

6.1. An example of successful use of Augmented Reality based Virtual Therapy One of the first VT systems using an AR interface has been described in [13]. It consists in an AR system for treating phobia to cockroaches and spiders. The system uses a video-see through HMD visualization interfaces and paper based markers for identification of real elements. The system presents several options for interaction with the patient: Appearance of animals: when the system recognized the animal’s marker, it shows the number of selected animals. The user can increase/reduce the number of animals in 3 or 20. Movement of animals. The user can select that animals start to move. Stop movement. The user can select to stop movement. Initial position. Animals come back to their initial position. Zoom in/ Zoom out. Animals increase/reduce their size with these options. Apart from these options, the system includes the possibility that the patient kills one or several animals. It can be done using two different typical instruments to kill small animals. The first one is a flyswatter, the program identifies when the flyswatter marker and the animal’s marker are near and then it kills one or several animals depends on the number of animals that have been selected. The second instrument is a typical animal killer. Again, the program identifies when the insecticide marker and the

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animal’s marker are near and then it kills one or several animals. In this case the sound is like when you use a real insecticide. Once one or several animals are died and the scraper is near the animal’s marker, only one dead animal appears in the middle of the marker, so the patient or the therapist can take the dead animal to the dustbin. All these options are included so the patient’s treatment can be progressive. The therapist chooses in every moment how many animals have to appear, if they have to move or not, their size, to kill an animal when the patient is prepared and throw it to a dustbin. The published initial clinical results of the system are very promising. The system has helped two patients to overcome the phobia to cockroaches and one patient to overcome the phobia to spiders. Before the exposure session with the system, patients were not able: to approach normally to a bowl with an alive animal or to interact with an alive animal. Following the guidelines of “one-session treatment” from Östtreatment [14] and using the AR system in the exposure session, patients experienced a notable decrease in the degree of fear and avoidance of real animals. After the AR exposure session patients were able to approach to a real animal, to interact with it and to kill it by themselves. This reduction in fear and avoidance is maintained because after two months of the treatment first patient was able to interact and to kill four alive cockroaches. Apart from that, participants manifested their preference to be treated with an AR system instead of a treatment with real animals.These results highlight the importance of AR interfaces for VT applications.

Fig. 7. Two images of the augmented reality system designed for treating phobia to cockroaches and spiders

References [1]

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North, M.M., North, S.M. y Coble, J.R., “Virtual reality therapy: an effective treatment for psychological disorders”, Handbook of Virtual Environments. Design, Implementation and Applications, Kay M. Stanney (Ed.), pp. 1065-1077, 2002. Alcañiz M., Botella C., Bañoz R., Perpiñá C., Rey B., Lozano JA:, Guillén V., Barrea F., Gil JA. Internet-Based Telehealth System for the treatment of Agoraphobia CyberPsychology and Behavior 6:4. (2003), 355-359. Schubert, T. W., Friedmann, F., Regenbrecht, H. T. The experience of presence: factor analytic insights. Presence: Teleoperators & Virtual Environments, 10, (2001), 266–281. Slater, M. Measuring presence: A response to the Witmer and Singer presence questionnaire. Presence: Teleoperators and Virtual Environments, 8(5) (1999), 560-565. Slater, M. Usoh M. and Steed A, Depth of presence in virtual environments. Presence: Teleoperators and Virtual Environments, 3 (2003), 130-144 Baños R. Botella C., Alcañiz M., Liaño V., Guerrero B., Rey B (2004). Immersion and Emotion: Their Impact on the Sense of Presence CyberPsychology and Behavior 7: 734-741

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M.R. Alcañiz et al. / Novel Approaches for the Integration of Behavioural Therapy and VR Baños, R.M., Botella, C., García-Palacios, A., Villa, H., Perpiñá, C. & Alcañiz, M Presence and Reality Judgment in virtual environments: A unitary construct? Cyberpsychology and Behavior, 3 (3), (2000), 327-335. Hoorn, J.F., Konijn, E. & Van der Veer, G.C. Virtual Reality: Do Not Augment Realism, Augment Relevance. UPGRADE - The European Online Magazine for the IT Professional, http://www.upgrade-cepis.org, IV(1), ISSN 1684-5285, . (2003), 18-26. Rothrock, L., Koubek, R., Fuchs, F., Hass, M., & Salvendy, G. Review and reappraisal of adaptive interfaces: towards biologically inspired paradigms. Theoretical Issues in Ergonomic Science 3 (1) (2002) 47-84. Schmeisser E.T. Introduction: Dream of a Display that Pays Attention to the Viewer. CyberPsychology & Behavior. 7:6 (2004), 607-609 Reynolds, C. & Picard, R. Ethical Evaluation of Displays that Adapt to Affect. CyberPsychology & Behavior 7(6): (2004), 662-666. Alcañiz, M., Baños, R., Botella, C., Rey, B. The EMMA Project: Emotions as a Determinant of Presence. Psychnology Journal 1(2): (2003), 141-150. Juan, MC, Botella, C, Baños, R, Guerrero, B., Alcañiz, M. , Monserrat, C., Rey, B. Augmented Reality to the treatment to phobia to small animals. First prototype and firsts treatments. IEEE Trans. Computer Graphics & Applications (2005) (In press) Öst, L., Salkovskis, P. & Hellstroöm, K. One-session therapist directed exposure vs. self-exposure in the treatment of spider phobia, Behavior Therapy, 22, (1999), 407-422.

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Posttraumatic Stress Disorder: Assessment and Follow-up Paul M.G. EMMELKAMP 1 University of Amsterdam, The Netherlands Abstract. Research into posttraumatic stress disorder is discussed from the perspective of clinically relevant measures to be included in future outcome research. It is concluded that studies into the effects of treatment of posttraumatic stress disorder should include measures for co-morbidity, impairment and quality of life. Further, recommendations are made to investigate moderator and mediator variables affecting outcome of treatment in trauma victims, including social support, personality traits, and cognitive characteristics. It is recommended to use theoretically derived variables, rather than available base-line characteristics. Further, these moderators and mediators should be studied in specific groups of trauma patients, rather than in patients who have experienced a variety of traumatic events of varying severity levels Key words. PTSD, co-morbidity, impairment, outcome, prediction

Introduction Research into the treatment of acute stress disorder and posttraumatic stress disorder (PTSD) has accumulated over the past decade. Generally, a number of cognitive behavioral treatments (CBT; e.g. exposure, cognitive interventions and EMDR) have shown promise [1,2]. Further, recent studies suggest that writing assignments to emotionally processing traumatic experiences might be equally effective as CBT [3,4]. Writing assignments have been found to be effective in treating posttraumatic stress when applied through the Internet [5,6]. Similarly, there is some evidence that virtual reality exposure may be used as an adjunct to regular CBT treatment [7], but the evidence is far from conclusive yet [8,9]. Most studies into the effectiveness of psychological treatment have involved patients who had experienced a variety of traumatic events of varying severity levels, making results of these studies difficult to evaluate. Further, the assessment of effectiveness of treatment in these studies is usually limited to posttraumatic stress symptoms. The effectiveness of treatment on a number of other - often co-morbid – disorders is usually not evaluated. In addition, effects of treatment on impairment and quality of life are not established. Finally, most studies evaluate the effectiveness of treatment with at most 6 months’ follow-up. The aim of this paper is to discuss and recommend additional measures in outcome research in addition to measures of posttraumatic stress. It is important to make a distinction between type of measures: some are useful for screening, assessment and treatment planning, whereas other measures are suited to evaluate the effects of treatment, and a few are useful both for treatment planning and 1

Corresponding Author: Paul M.G.Emmelkamp, Department of Clinical Psychology, Roetersstraat 15, 1018 WB Amsterdam; [email protected]. This paper was written while the author was Fellow at The Netherlands Institute for Advanced Research (NIAS), Wassenaar.

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outcome assessment. Further, different measures may be needed to evaluate the process of treatment and to predict treatment outcomes than to evaluate the effects of treatment.

1. Rapid Screening Screening in large populations with an expected low prevalence of PTSD does not seem to be justified given the large number of 'false positives' that would be generated. However, screening might be feasible in cases where high prevalence rates are expected, thus allowing the identification of high-risk individuals who might benefit from evidence-based brief early interventions. Perhaps the most studied screening approach to date is that of diagnosing acute stress disorder (ASD) within 1 month of the traumatic event. Currently, the prevalent view is that the ASD diagnosis does not have adequate predictive power to predict subsequent PTSD. For example, in a review of 10 studies which addressed this issue, the proportion of individuals with acute stress disorder who went on to develop PTSD ranged from 30% to 83% at 6 months follow-up [10]. Further, dissociative symptoms were found to be rarely endorsed and therefore particularly unhelpful in predicting PTSD [11]. In traumatic events involving a large number of people, the gold standard of structured interviews by an experienced clinician may be unrealistic. Similarly, although a number of standardized psychological instruments exist, most are lengthy and cannot be used as a rapid screening device to identify high-risk groups for PTSD, depression and substance abuse. A number of screening instruments, primarily questionnaires, containing traumatic stress symptoms, have been found to be useful in detecting the presence of PTSD. Brewin [12] recently reviewed the literature and concluded that the overall mean diagnostic efficiency was 86.5%. Taken into account the number of items (the fewer, the better) and the eases of administration, the following questionnaires appear to have the greatest potential: the Impact of Event Scale (IES), the Trauma Screening Questionnaire (TSQ) and the SPAN. The IES [13] contains 15 questions about intrusion and avoidance relative to a specified event, which are answered on a four-point scale. A disadvantage of the IES scale is that the extended revision has more items and has not been validated yet. The SPAN test [14] comprises only four questions: the 'startle', 'physiological upset on reminders', 'anger' and 'numbness' questions. These four questions are scored for both frequency and severity during the previous week on scales of 0-4, which scoring is more complicated than is the case for the TSQ. Finally, the TSQ [15] consists of the ten re-experiencing and arousal items from the PSS-SR [16], modified to provide only two response options. Respondents indicate whether or not they have experienced each symptom at least twice in the past week. A disadvantage of the short screening instruments discussed above is that they only focus on posttraumatic stress symptoms. Following the tragic events of 9/11/2001, a short screening instrument was developed that covered important mental health symptom domains, mental health functioning, and possible predictive risk factors: The Pentagon Post Disaster Health Assessment (PPDHA) [17]. The survey consisted of 61 questions, including 17 that were specific to mental health. The survey included 10 questions that pertained to PTSD, depression, anxiety, and alcohol use, as well as 7 additional questions that pertained to key risk or protective factors, functional impairment, and use of mental health services. Although clinical diagnosis of mental

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disorders was not possible with this screen, high-risk groups for mental health outcomes could be established.

2. Criteria for Outcome Posttraumatic stress can be assessed using the Clinician Administered PTSD Scale (CAPS) [18,19]. This is a widely used structured interview for establishing current or retrospective diagnosis of PTSD in accordance with DSM-IV criteria [20]. With adequate training interrater reliability is generally satisfactory [21]. Children's posttraumatic stress symptoms can be assessed using the 17-item Child PTSD Symptom Scale (CPSS), which assesses DSM-IV symptoms of PTSD [22]. The scale can provide measures of both the number and severity of symptoms. In addition, there is a 7-item scale assessing functional impairment in areas such as relationships, schoolwork, chores, and hobbies. A number of studies addressing the effects of treatment in the trauma field rely heavily on the outcome criterion of still fulfilling the criteria of PTSD or not. While this is understandable from the perspective of the medical model (one has a disorder or not), from a psychometric perspective it is hard to defend. As in most other disorders change can better be conceptualized in dimensional rather than in categorical data. Further, especially with the current diagnostic criteria of DSM-IV-R, often only a minor change in one criterion is sufficient to move someone from the PTSD disorder category into the recovered category. However, many of the patients who at post treatment show only a minor change in terms of the DSM-IV-R criteria, but in doing so come into the normal range, will actually still suffer substantially from stress and related complaints. An example of a dimensional measure to assess posttraumatic stress symptoms is the Impact of Events Scale [23]. Further, the Harvard Trauma Questionnaire (HTQ) can also be used to assess posttraumatic stress symptoms in war situations [24].

3. Anxiety, Depression and Suicide Studies of the impact of psychological trauma on mental health have shown that trauma not only results in Post Traumatic Stress Disorder (PTSD) but also in other psychopathology, particularly other anxiety disorders and depression, but this is neglected in most outcome studies. For example, De Jong et al. [25] assessed the prevalence of mood disorder, somatoform disorder, post-traumatic stress disorder, and other anxiety disorders in over 3000 individuals from post conflict communities in Algeria, Cambodia, Ethiopia, and Palestine. In most countries, PTSD was the most prevalent disorder in victims of violence associated with armed conflict, but such violence was a common risk factor for various other disorders (anxiety, depression, and somatoform disorders) as well. Post-traumatic stress disorder (PTSD) is frequently comorbid with depression. One-half to two-thirds of adults with PTSD report a lifetime history of major depression [26-28]; high co-morbidity has been reported in children and adolescents as well [29]. Comorbidity of PTSD and depression is associated with more severe symptoms, higher depression, impulsivity, and more suicide attempts compared to individuals with PTSD alone [30]. There appears to be a strong connection between suicidality and the experience of trauma. In a study by Tarrier & Gregg [31] over half

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of the sample reported some aspect of suicidality, including ideation (38%), and suicide plans ( 8.5%). Nearly ten percent of trauma victims had made suicide attempts since the trauma, which is much higher than in the general population. Both life impairment and depression were independently and significantly associated with suicidality. In children, there is considerable evidence that exposure to a traumatic event may be a major risk for developing not only PTSD [32-34], but other mental disorders as well. For example, direct exposure to different types of mass traumatic events is associated with an increase in somatic symptoms, [35] anxiety, and depression, [36] which are frequently comorbid with posttraumatic stress reactions among youth [37]. Recently, Hoven et al. [38] assessed the prevalence and correlates of probable mental disorders among New York City, NY, public school students 6 months following the September 11, 2001, and World Trade Center attack. One or more of 6 probable anxiety/depressive disorders were identified in 28.6% of all children. The most prevalent were probable agoraphobia (14.8%), probable separation anxiety (12.3%), and probable posttraumatic stress disorder (10.6%). Studies suggest that patients suffering from comorbid PTSD and depression differ clinically and biologically from individuals with PTSD alone or depression alone. Some have suggested that PTSD is the primary disorder, with comorbid depression developing as a secondary reaction [39], but others hold that PTSD is a severe manifestation of depression. Recently, Sher [30] has suggested that individuals diagnosed with comorbid PTSD and depression have a separate psychobiological condition that can be termed “post-traumatic mood disorder”. Nevertheless, most treatment outcome studies have focused mainly on posttraumatic stress disorder (PTSD), and have not assessed other mental disorders as well. Further, in most studies patients with co-morbid psychopathology are often excluded. Thus, it is questionable whether the results of these studies generalize to PTSD patients with co-morbid disorders.

4. Substance Abuse High rates of co-morbid post-traumatic stress disorder (PTSD) and substance abuse have been reported in a number of epidemiological studies. In a community sample of substance-abusing women about 42% reported histories of physical assault, and about 47% reported histories of sexual assault. In substance use disorder populations, rates of 30–58% have been reported for lifetime PTSD, and 20–38% for current PTSD [40]. Some research suggests that men may manifest traumatization in different ways than women, possibly through substance use [41-43]. All too often mental health workers who are confronted with trauma victims are less familiar with substance assessment tools and fail to ask for substance abuse, while a number of short, reliable and valid measures are available. A number of screening instruments for substance use problems have been developed, which are particularly useful. The following screening measures require from 2 to 10 minutes to complete. In screening for alcohol use either the Michigan Alcoholism Screening Test (MAST) [44] or the Alcohol Use Disorder Identification Test (AUDIT) [45] can be used. The Drug Abuse Screening Test (DAST) has been shown to be a valid screener for drug use disorders [46]. The CAGE [47] is a very brief (4-item) screening tool that focuses on subjective negative consequences of alcohol abuse. The Dartmouth Assessment of Lifestyle Instrument (DALI) was specifically

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developed to detect substance use disorder in acute psychiatric care settings [48]. The DALI, derived from other screening questionnaires listed above, has excellent interrater and test-retest reliabilities. The DALI has higher sensitivity and specificity than the MAST, CAGE, or the DAST and can be used as pretreatment and post treatment measure.

5. Impairment, Quality of Life and Social Functioning Impairment and subjective quality of life may be important to assess in trauma victims. PTSD has been shown to be associated not only with poorer mental and physical health but also with lower quality of life [49]. Quality of life has been found to be particularly poor in sexual assault survivors [50,51], war veterans [52], refugees of war [53], and patients who have experienced multiple traumatic events [54]. In this respect it is of note that a number of studies found that individuals with subthreshold PTSD also are severely impaired in social functioning and work [55, 56]. Similarly, children and adolescents who did not meet full diagnostic criteria of PTSD nevertheless had impairment associated with sub-threshold symptoms [57,58]. Social functioning has been studied in a number of studies as well. For example, Bolton et al. [21] assessed young adults who had survived a shipping disaster (the sinking of the Jupiter in 1988) between 5 and 8 years previously. Survivors with diagnosable disorder showed poorer psychosocial functioning as compared to controls. The time course of psychopathology and social functioning remains poorly understood. In adolescent survivors of the Pol Pot regime in Cambodia, Sack et al. [59] found that depression, but not PTSD, was associated with significantly poorer global social functioning. Similarly, in the study of Bolton et al. [21], impaired psychosocial function was more strongly linked to major depression than to PTSD. Given the impairment and deficits in social role functioning associated with PTSD, there is a clear need to assess these domains in treatment outcome studies. In treatment outcome studies, interpersonal and social role performance can be assessed with the Adult Personality Functioning Assessment (APFA) for which high inter-rater reliability and subject-informant agreement have been demonstrated [60], the Manchester Short Assessment of Quality of Life [61], the Social Adjustment Scale [62], or the Work, or the Social Adjustment Scale [63].

6. Moderator and Mediators of Treatment Outcome 6.1. Social Support Social support may offer important protection for mental health in the context of traumatic events, including violent assaults and the trauma of war [64-66]. Among Vietnamese refugees who had experienced traumatic war experiences, low social support was associated with psychiatric disorders [67]. Similarly, in Israeli soldiers during the Gulf war low social support was associated with psychological distress [68]. In PTSD sufferers in general, and refugees in particular material and social support may be at least as important as specific psychological or medical interventions [69,70].

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The effects of social support and traumatic experiences on mental health in conflict situations may be different by gender. In a study two years after the war in Kosovo [71], there remained a high prevalence of posttraumatic stress symptoms, particularly among women with low social support. Women and persons who experienced more traumatic events had higher posttraumatic stress scores. Persons with stronger social support had lower posttraumatic stress scores. Social support had a greater protective effect for women, whereas traumatic events had a greater detrimental effect on men. Given the considerable evidence that social support may act as a moderator in victims of trauma, it might be important to assess social support in victims of trauma in future studies, not only to assess who are particularly at risk to develop psychopathology, but also to investigate its role in treatment and relapse. For example, the finding that debriefing has no or perhaps even a negative effect might be related to the under use of social support facilities by the victims [72]. Also in outcome studies, assessment of social support might be important in order to understand why some patients improve and others do not. After trauma, treatments that facilitate the use of social support in the natural environment might be more effective than treatments which do not. There are a number of social support measures available, but few are brief, and psychometric characteristics have hardly been investigated. Further, different components of social support have not been incorporated in most measures. Timmerman et al. [73] developed a short self-report measure of perceived satisfaction with social support that is easy to administer: the Social Support Inventory (SSI), which has good psychometric properties. The SSI contains 20 items and assesses instrumental support, emotional support, informative support, and social companionship. 6.2. Personality Traits A number of studies have investigated whether personality traits predict the development of PTSD, but personality disorder has not been investigated as predictor of treatment outcome. Generally, neuroticism on its own or in combination with introversion is related to the severity of post-traumatic stress. Most studies, however, are retrospective and it is likely that personality assessment post-trauma may be less reliable and affected by the traumatic experience itself. Not surprisingly, few prospective studies have been reported. Knezevic et al [74] investigated prospectively to what extent post-traumatic stress was influenced in civilians who experienced air attacks in Belgrade, Yugoslavia. Thirteen percent of variance in post-traumatic stress (IES) at one-year follow-up was explained by personality, but only on intrusions, not on avoidance. Openness to Experience, one of the ‘Big Five’ personality traits, was the most significant contributor. Similarly, of the ‘Big Five’ personality traits only Openness to Experience was found to be significantly related to PTS resulting from post-intimate stalking [75]. Whether such personality characteristics are related to treatment outcome deserves to be studied. 6.3. CognitiveChanges To assess the process of change it might be important to include cognitive measures as well. The Posttraumatic Cognitions Inventory [76] is particularly useful in this regard. The PTCI consists of three subscales labeled 'Negative Cognitions About Self (21 items), 'Negative Cognitions About the World' (7 items), and 'Self-Blame' (5 items).

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For this purpose more implicit cognitive measures [77] may also be used, such as the Directed Forgetting Task. It has been suggested that the patient’s memory is fixed on the traumatic event, as a result of a disturbance of the autobiographic memory. To retrieve memories, others have to be inhibited. These inhibition mechanisms have been studied using the Directed Forgetting Paradigm, which measures the capacity to forget recently processed information and to retain the relevant information [77,78]. However, when using the Directed Forgetting Task as pre- and post treatment measure, the instruction should be adapted in that the "remember" or "forget" instruction should be given after each word. Changes in these cognitive characteristics may be related to improvement after treatment. It is particularly interesting to investigate whether patients who improve on post-traumatic stress measures, but do not improve on these cognitive characteristics are particularly vulnerable to relapse after treatment.

7. Prognostic Factors and Follow-up Research on prognostic factors is limited, with different studies often finding different predictors [2]. This might be partially the result of different groups of trauma victims studied. Why should we expect that the same variables moderate the effects of treatment of children who have been sexually abused over the years as those that moderate the effects of treatment of victims of a single traumatic event, such as a motor vehicle accident? Thus there is a clear need of studies investigating predictor variables for specific trauma groups. Another issue that deserves more attention from researchers in the field is the identification of exactly what we want to predict. Prediction of dropout of treatment may be unrelated to prediction of post treatment status, and both may be related only loosely to relapse and long-term follow-up. Although it is often assumed that patients who do not get better tend to dropout, research in other areas suggests that the picture is much more complex and deserves study on its own. Actually, very few studies have investigated long-term effects of the treatment of trauma victims [2]. Further, it might well turn out that variables at posttest are better predictors of long-term outcome than base-line characteristics. The few studies that investigated prediction of treatment outcome used convenient predictor variables, which were at hand (e.g. base-line characteristics). To better understand who will profit from treatment and who will not, other research designs may be needed. The few studies which have addressed prediction in the context of treatment studies concern treatment outcome studies in which the comparative effectiveness of different treatments was evaluated. However, this is not the optimal design for studies of mediator and moderator variables associated with who will profit from treatments and who will not, given the limited number of individuals in each treatment condition and the variety of traumas involved. Given that different factors might be involved in different traumas it may be worthwhile to investigate whether one treatment is more effective for some patients and another treatment for other patients. For example, in ongoing cases of stalking, there seems little use of trauma-focused exposure [79]. Similarly, it is questionable whether treatments, which have proven effective in victims of single traumatic events, are equally effective in polysymptomatic victims of repeated traumatic events.

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8. Malingering PTSD is particularly vulnerable to malingering given the disability benefits often involved. Recently, there is some concern regarding the validity of combat exposure reports of veterans seeking treatment for combat-related post-traumatic stress disorder [80,81]. A significant number of treatment-seeking war veterans may misrepresent their combat involvement, related to secondary gain incentives (e.g. disability claims). Frueh et al. [81] verified combat exposure history for 100 consecutive veterans reporting Vietnam combat in a Veterans Affairs PTSD clinic. Only 41% of the total sample had objective evidence of combat exposure documented in their military record. There was virtually no difference between the Vietnam ‘combat’ and ‘no combat’ groups on relevant clinical variables. Given that malingering might be involved in a substantial number of cases, there is a clear need of assessing potential malingering in treatment outcome studies. Although there is no single or preferred measure to detect malingering among PTSD claimants, diverse assessment instruments can contribute to the overall effort. The fake-bad indices of the MMPI were not particularly useful in this respect, but the MMPI-2 appears to do a better job in discriminating malingering PTSD cases from veterans with combat-related PTSD [82]. Further studies in this area could take into account more implicit measures like the direct forgetting task [78]. 9. Recommendations and Concluding Remarks What implications should the above considerations have for treatment outcome studies? ‰ Be explicit regarding exclusion criteria and do not exclude a priori individuals with co-morbid psychopathology. ‰ Assess malingering and exclude patients from treatment outcome studies who are suspected of malingering. ‰ Assess changes in post traumatic stress symptoms dimensionally, rather than categorically. ‰ Assess co-morbidity pre and post treatment, most notably other anxiety disorders, depression including suicidal ideation, and substance abuse. ‰ In children: assess not only internalizing disorders, but externalizing disorders as well [83]. ‰ Assess impairment and quality of life. ‰ Assess effects of treatment over extended period of time, up to four year. ‰ Investigate treatment matching. ‰ Investigate theoretically derived moderator and mediator variables, including trauma-event related characteristics, premorbid personality characteristics, and cognitive characteristics. There is now some consensus in the field that treatments for combat-related PTSD showed less effect than for PTSD related to other types of trauma. Researchers investigating moderator and mediator variables affecting treatment outcomes in trauma victims would do well to use theoretically derived variables, rather than available baseline characteristics. Further, these moderators and mediators should be studied for specific groups of trauma patients. In doing so we may become more specific about

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Author Index Adler, A.B. Alcañiz, M.R. Baños, R.M. Bliese, P.D. Boddam, R. Botella, C. Brennen, T. Bullinger, A.H. Castelnuovo, G. Castilla, D. Cesa, G. Cosic, K. Cukor, J. Cuvelier, Y. Difede, J.A. Dullea, K. Emmelkamp, P.M.G. Gaggioli, A. García-Palacios, A. Geraerts, E. Gigolashvili, K. Graap, K. Gruzelier, J. Guillén, V. Hacker Hughes, J.G.H. Henigsberg, N. Hoffman, H. Jayasinghe, N. Jehel, L. Josman, N. Jovanović, T. Juan, C.L. Judaš, M. Klapan, I. Kostović, I. Kozarić-Kovačić, D. Kral, P. Kraus, P.L.

78, 121 296 170, 183 78 111 170, 183 31 148 161, 286 183 161 135 219 121 219 67 309 161 170, 183, 196 31 264 235 13 170, 183 121 101 170, 196, 219 219 67 196 87 296 23 251 23 3, 42, 87 286 59

Lam, D. Lasso de la Vega, N. Lončarić, S. Lozano, J.A.Q. Manson, B. Mantovani, F. Manzoni, M. McNerney, P.J. Mihajlovic, Z. Molinari, E. Mück-Šeler, D. Naneishvili, G. Okribelashvili, N. Osma, J. Pair, J. Perpina, C. Pivac, N. Popović, S. Quero, S. Reisberg, A. Rey, B.S. Riva, G. Rizzo, A. Rothbaum, B.O. Roy, M.J. Schandl, L. Šimičić, L. Slamic, M. Somer, E. Spira, J. Thomas, J.L. Tichy, V. van der Mast, C. Vekerdi, Z. Weiss, P.L. Wiederhold, B.K. Wiederhold, M.D. Wright, K.M.

286 183 251 296 235 161 161 235 286 161 3 264, 279 264 170 235 170 3, 42 87, 135, 286 183 196 296 161 235 205 xv, 59 268 251 135 196 235 78 121 286 268 196 148, 235 148, 235 78

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