Ebook: Novel Approaches to the Diagnosis and Treatment of Posttraumatic Stress Disorder

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 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.

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.

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: j.gruzelier@imperial.ac.uk

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 stress-related 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.

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.

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 Extra-Pyramidal 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.

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.

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.

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 post-deployment. 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 post-deployment. Future research will examine scale refinement and the use of sleep problem questions in subsequent screening efforts.

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.

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.

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.

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.

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.

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.

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: gianluca.castelnuovo@auxologico.it

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.

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.

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.

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.