Ebook: New Tools to Enhance Posttraumatic Stress Disorder Diagnosis and Treatment

The organizers and attendees of the NATO-funded “Wounds of War” Advanced Research Workshop series realized the need for the 2012 NATO Advanced Study Institute: Invisible Wounds – New Tools to Enhance PTSD Diagnosis and Treatment (IW2012) due to the increased rates of PTSD in combat veterans and survivors of armed conflict. Exposure to traumatic events have led to this increased risk of PTSD and often, the serious consequences of this disorder lead to impulsive and destructive behaviours such as drug abuse, uncontrollable anger, and even suicide. Combat-related PTSD is one of the strongest contributing factors to high suicide risk in returning troops. IW2012 disseminated knowledge, emboldened skill sets, fostered collaborations and trained attendees to help counter this aforementioned internal threat to our countries' security.

In comparison to a traditional conference, IW2012 allowed for greater collaboration among established and emerging research leaders in the field of PTSD, and provided an in depth presentation of this unique material. IW2012 afforded participants a solid grounding in the latest PTSD research; review of the latest science related to theoretical constructs and associated neuroscience; and presentation of the latest psychotherapy and pharmacotherapy for intervention, treatment, and management of this disorder.

Brenda K. Wiederhold, Ph.D, MBA, BCIA

One of the goals in research in the clinical neuroscience of trauma-related disorders is to apply findings related to the effects of traumatic stress in the brain on animals and patients with trauma and stressor-related disorders, e.g. PTSD. The paradigm of translational neuroscience has been an avenue that has contributed much to a model of the neural circuitry of PTSD that is currently used in studies. In general, the neural circuits and systems mediating symptoms of all PTSD, trauma and stressor-related disorders can be studied by registering en assessing behavioral and biochemical responses to environmental/pharmacological challenge to specific neurochemical systems measuring neurotransmitters and hormone levels in blood, urine, and saliva; measuring key brain structures with neuroimaging (Magnetic Resonance Imaging, MRI); provoking disease-specific symptoms in conjunction with (functional) neuroimaging (functional MRI, fMRI), or using imaging (Positron Emission Tomography, PET) to measure neuroreceptors. The findings of the studies (research designs, methodologies, and some of the techniques) will be discussed in this chapter varying to a great extent. Three key mechanisms seen in PTSD are: stress sensitization, fear conditioning and failure of extinction. This chapter further focuses on the functional neuroimaging research conducted in PTSD. It covers various techniques (SPECT, PET and fMRI) that are used in different kinds of paradigms (resting, active tasks and stimulus presentation) and provides a global overview of the brain circuits that currently are used to explain the phenomenology in PTSD. The disorder showed remarkable heterogeneity in some recent studies. These give consideration to speculate on two models for the disorder that can alternate and coexist together. These two models will be presented, one, in which the amygdala is hyperactive, in line with fear circuitry, being the most common and dominant situation. In another model the amygdala is hypoactive, in line with predominance of symptoms of derealisation and depersonalization symptoms that are accompanying the other PTSD symptoms. Finally, the need for longitudinal studies is emphasized. Studies that assess patients before as well as after treatment are the paradigm that will be new and promising.

PTSD is a serious and debilitating psychiatric disorder that can develop in individuals who were exposed to one or more intense traumatic event(s). Since not all people exposed to traumatic experience develop PTSD, it is assumed that different neurobiological, genetic and environmental risk factors are involved in the vulnerability and/or resilience to PTSD. PTSD biomarkers, defined as characteristics that objectively measure and evaluate normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention, might improve the diagnosis and treatment of PTSD. Determined biomarkers were peripheral biochemical markers such as platelet serotonin (5-HT) concentration, platelet monoamine oxidase type B (MAO-B) activity, plasma dopamine-beta-hydroxylase (DBH) activity, and genetic markers /MAO-B intron 13, -1021C/T DBH, catechol-o-methyltransferase (COMT) val158/108met, brain-derived neurotrophic factor (BDNF) val66met, 102T/C serotonin receptor type 2A gene (5HT2A) polymorphism and serotonin transporter (5HTT) gene-linked polymorphic region (5HTTLPR)/. Study participants were Croatian male war veterans with or without current and chronic combat-related PTSD, recruited from the Referral Centre for the Stress-related Disorders of the University Hospital Dubrava, Zagreb. Only plasma DBH activity, but not other markers, differed significantly between war veterans with or without PTSD. When veterans were subdivided according to the narrow clinical symptoms (such as psychotic features, sleep disturbances, suicidal behavior), platelet 5-HT concentration, platelet MAO-B activity, and val66met BDNF were significantly different among these groups. The results indicate that specific PTSD biomarkers, associated with the narrow clinical features, might be indicators of PTSD traits, state or progression, and might be used to improve the diagnosis and treatment of PTSD.

PTSD is common after combat, but onset is frequently delayed until months after return. This “honeymoon effect” affords opportunities to prevent PTSD if high-risk individuals can be identified. We report our iterative effort to educate military family members to recognize symptoms and facilitate intervention, along with preliminary results from direct longitudinal assessment of returning service members for development of PTSD. We conducted focus groups with military families and incorporated their feedback into an educational website which we piloted before evaluating PTSD-related knowledge with a 25-item questionnaire in 497 military family members before and after their use of the website. We also documented interventions reported by 217 of the family members, who, subsequently, returned to the site. In a separate ongoing study, we are assessing 100 service members within 2 months of return from combat with novel brain imaging, psychophysiology, genetic and neuroendocrine measures, followed by serial evaluations to identify the baseline measures that best predict subsequent PTSD. Our educational website improved PTSD-related knowledge from a mean 13.9 correct responses beforehand to 18.7 after (p < .001; effect size 1.2). Nearly 60% of family members returning to the site had intervened with a service member; 74% of them reported discussion with the service member about their symptoms was helpful, as did 91% who persuaded them to see a healthcare provider. Preliminary analysis of the direct assessment of service members indicates that psychophysiologic measures are significantly different between those with subthreshold symptoms of PTSD versus those with very few PTSD symptoms. A web-based intervention can improve PTSD-related knowledge and foster behavioral changes in military family members. Risk stratification of service members via assessment upon their return from deployment also has the potential to facilitate targeted interventions. While others have developed PTSD-related educational websites, we believe we are the first to document their efficacy, both with regard to knowledge and behavioral enhancement. Our direct assessment of service members is unique in its comprehensiveness, and holds great promise for risk stratification.

Posttraumatic stress disorder (PTSD) and other stress related disorders are characterized by prominent psychophysiological symptoms, which are measured through changes mediated by the autonomous nervous system. Psychophysiological procedures in studies of acute and chronic trauma phase such as: baseline resting studies, startle reactivity studies, standardized trauma-related cues and idiographic-trauma cues have tried to gain insight into the neurobiology of the disorder. Psychophysiological parameters in PTSD are also considered as an additional method in diagnostics of PTSD. We will present results of previous studies as well as our research in search for psychophysiological indicators of PTSD. Our experience with applied psychophysiology (biofeedback) as an add-on therapy for psychiatric disorders will be discussed since it seems promising.

Multimodal paradigm for cognitive-emotional elicitation, estimation and regulation may strengthen military training and enhance selection process. It includes multiple sessions involving mission-relevant audio-visual stimulation and simultaneous measurement of the trainee's multimodal physiological, facial and vocal response. The initial audio-visual adaptive stimulation screening sequence contains personalized mission-relevant semantically and emotionally congruent static pictures and sounds, based on the initial interview with the soldier conducted by military psychologists. After each stimulus as well as the entire sequence, the soldier provides subjective emotional ratings in terms of valence, arousal and discrete emotions. These subjective ratings and recorded multimodal response (physiology, voice, and facial expressions) represent initial information regarding the soldier's appraisal of mission-relevant stimuli. Subsequent sessions use dynamic stressful video clips captured in real missions, with soldier's entire multimodal response measurements. To maximize training relevance, video clips are personalized and can be mixed with instructions of the commander and potentially other unit members. Additionally, mission-relevant audio-visual interactive tasks are delivered separately and in conjunction with stressful video clips, to strengthen the soldier's cognitive-emotional capabilities. Offline analysis of the soldier's multimodal response can be additionally enhanced by fMRI to the presented pictures, sounds, video clips, and interactive tasks, to reveal changes that occur as a consequence of training. Parameters of the soldier's cognitive-emotional state estimators are tuned continuously in real-time based on physiology, voice, and facial expressions. Aggregate information from these cognitive-emotional state estimators may assist instructors during real-time decision-making when striving to present the most appropriate stimuli for the trainee's current multimodal response. Such stimuli generation based on expert knowledge and experience in cognitive-behavioral stress inoculation training is implemented in our closed-loop audio-visual adaptive stimulation system.

Group based dominant emotional maps characterized by long lasting negatively valenced emotions, such as fear, anger, hatred or humiliation may elicit strong extreme political attitudes, actions and behaviors, as well as massive posttraumatic stress disorders. The impact of these dominant negatively valenced emotions on political attitudes, actions and group behavior can be referred as toxic power of negatively valenced emotions. Persistent negatively valenced group based dominant emotions may be also used as quantitative statistical measure and the most relevant early warning indicator of potential terrorism and violence among respected group members. The toxic power of extreme political attitudes, actions and behavior might be reduced by Emotionally Based Strategic Communications (EBSC) as a communication method for transforming negative dominant emotional maps into more positive ones. EBSC is conceptualized as the positively valenced stimulation of a negatively emotionally affected group by an appropriate communications strategy, in order to influence extreme political behavior of a targeted group. We argue for significant potential of EBSC to prevent the arousal of intense negative emotions within human collectives and groups, as well as mitigate the toxic power of negatively valenced emotions. Prevention and reduction of negative emotions may ease social and security tensions in politically polarized, culturally fragmented, or economically stratified social settings, and prevent political terrorism by facilitating harmonization of diversified communities. The extreme political attitudes, and related dominant negatively valenced emotions have their neural representation in specific changes on biochemical and molecular levels of related limbic and prefrontal cortical structures of affected brains. Societal enrichment based on positively valenced EBSC might have positive social impact eliciting various positive neuronal responses and changes in the brains of affected people, ranging from different biochemical to neural structural changes like neurogenesis, synaptic plasticity, dendritic arborization, increase of synapse-to-neuron ratios, axonal growth, neurotransmitter changes etc. We regard EBSC “soft power” as important contribution to prevention of extremist action tendencies and radicalized behaviors in afflicted societies. EBSC policy can be also viewed as a large-scale strategy of emotion regulation that might decrease destructive power of extreme political behavior and terrorism.

This paper is a report on 5-year partnership between the Department of Psychiatry and Combat Stress (DP&CS) of the Military Institute of Medicine in Warsaw with the Virtual Reality Medical Center (VRMC) of San Diego, USA in implementation of VR technology in the area of protection of mental health of Polish Military Contingent's (PMC) soldiers and veterans who participated in Operation Iraqi Freedom (OIF) and Operation Enduring Freedom (OEF). The partnership was initiated by the VRMC that transferred free of charge to the DP&CS computer hardware along with dedicated software and provided training to the personnel in the field of the Graded-Exposure, Virtual-Reality-Facilitated, Biofeedback-Guided Treatment for Combat-PTSD. Initially this method was applied to all patients with combat related stress disorders, hospitalised in our clinic. Later on it was limited to PTSD and the VR therapy was based on a therapeutic link and patient's trust to the therapist. Control of arousal by a proper breathing pattern restored to those patients a sense of control over their emotions and facilitated deepened psychotherapeutic work. A strong point of the VR therapy was a possibility of grading the difficulty level of the VR exposed scenes. An excessively technical nature of this method was a source of reserve of the therapists towards this approach. Because of this the VR therapy should be used for treatment of PTSD patients only as additional and supporting one. Good results in PTSD treatment were obtained by a combination of the VR therapy with behavioural training.

Another area of cooperation between the DP&CS and the VRMC was an implementation of a short-term, collective VR Computer-Assisted Stress Inoculation Training for soldiers preparing for a deployment to Afghanistan. The results obtained indicate a short-term effectiveness of the training as a method of tension reduction. However, in the long-term perspective these results are ambiguous and they suggest a need of further research.

The latest chapter of research on application of VR technologies in activities of the DP&CS is utilisation of exposure to virtual war stressors to assess changes in the central nervous system, observed by means of PET-imaging, used as a predicator of resistance to battlefield stress in special forces' soldiers. This research is in progress.

Abstract. The aim of this study was to evaluate the results of VR Stress Inoculation Training (SIT) for 4 soldiers preparing for their first mission in Afghanistan (ISAF) and to assess if their temperamental structure was related to successful training.

Method. For 5 days, 4 soldiers took part in 10 SIT sessions, in accordance with the Virtual Reality Medical Center, San Diego methodology (Training of Physiological Control Exposure to Virtual Stressor while Maintaining Physiological Control). The initial and final arousal/relaxation in response to VR exposition were assessed using Heart Rate Variability: Very Low Frequency (VLF) and Low Frequency (LF) Ratio as an indicator of relaxation/arousal. The temperament traits and structure were assessed using the Formal Characteristics of Behavior – Temperament Inventory (FCB-TI).

Results. The analysis of VLF and LF Ratio graphs showed that 3 soldiers succeeded in reducing their arousal during final session. Two of them achieved better results in relaxation during final exposition, when compared to the initial session. Three of them could effectively reduce the arousal after the exposition as the effect of training. We found their temperament structure more harmonized than the soldier's who has achieved weaker results in training.

Conclusions. Due to the preliminary nature of our findings, replication is necessary on a larger group.

Abstract. The aim of this study was to evaluate the influence of Stress Inoculation Training (SIT) on the anxiety level measured by State-Trait Anxiety Inventory (STAI) both as temporary/emotional state anxiety (X1) and stable personality trait anxiety (X2) in soldiers preparing for their mission in Afghanistan (ISAF).

Method. 118 soldiers were randomly selected from the contingent that consisted of 1500 soldiers and split into two, equinumerable groups - experimental (E) and control (C). Both groups listened to a lecture on the nature of stress, its symptoms and coping with stress. They also filled in the following inventories: STAI, PCL-M, BDI-2, CISS, NEO-PI-R, FCB-TI and TAS. Soldiers from the E group - split into four subgroups - took part during the next 5 days in 10 SIT sessions according to the methodology of Virtual Reality Medical Centre, San Diego. At the same time soldiers from the C group took part in their scheduled training in their military area. After completing the SIT both groups filled in STAI. After the end of their deployment in Afghanistan the soldiers filled in STAI, PCL-M and took part in a structured interview.

Results. The statistical analysis of STAI results shows that: 1) Before SIT, there were no statistically significant differences in STAI and other tests results in both E and C groups. 2) After SIT, both X1 and X2 values in E group were significantly lower (p = 0.04). 3) In the C group which did not take part in SIT, there were no statistically significant differences in X1 value after 5 days; however, there was a statistically significant decrease in X2 value (p = 0.01). 4) After deployment, both X1 and X2 values in the E and C group were significantly lower comparing to X1 and X2 values before SIT (p < 0,05) 5) After deployment, X2 values in the E and C group were significantly lower comparing X2 values measured after SIT (p < 0.01) 6) There were no statistically significant differences in X1 values after deployment compared to values measured after SIT in the E and C group 7) There were no statistically significant differences in X1 and X2 values between the E and C group before, after the experiment and after deployment.

Conclusions. Given the equivocal results of the experiment there is a need for a further study or a deeper analysis.

Abstract. The main goal of this study was to evaluate the impact of personality, temperament and stress coping factors in Stress Inoculation Training (SIT) in soldiers preparing for their first deployment to Afghanistan (ISAF).

Method. 120 soldiers were randomly selected from the contingent that consisted of 2000 soldiers and split into two groups of 60 people each - the experimental (E) and control (C) ones. Soldiers from the E group - split into subgroups of 15 - took part during the next 5 days in ten SIT sessions according to the methodology of the Virtual Reality Medical Center, San Diego (Training of Physiological Control Exposure to Virtual Stressor while Maintaining Physiological Control). Both groups filled in inventories such as: Coping Inventory for Stressful Situations (CISS), Revised NEO Personality Inventory (NEO PI-R), and The Formal Characteristics of Behaviour – Temperament Inventory (FCB-TI). Both before and after the training they filled in the STAI inventory. Having returned from the deployment the soldiers filled STAI once again as well as the PCL-M inventory.

Results. The statistical analysis results show: 1) Before SIT, in E group there was a negative correlation between X1 value in STAI and briskness, sensory threshold and endurance and positive correlation between X1 value in STAI and emotional reactivity; 2) After SIT In the E group there was a correlation between X1 value in STAI and emotional reactivity; 3) After deployment In the E group there was a correlation between X1 value and emotional reactivity as well as between X2 values and the emotions-based, avoidance style and conscientiousness.

Conclusions. Results could be taken into account when analyzing individual susceptibility to SIT.

Comorbidity between posttraumatic stress disorder (PTSD) and substance use disorder (SUD) is common. As a result, the development of integrated treatments addressing both PTSD and SUD are needed. Although there are effective pharmacotherapies for the treatment of PTSD and SUD, there are no proven medications that will treat both conditions. We have conducted two clinical trials testing the safety and efficacy of medication treatments for comorbid PTSD and alcohol dependence (AD). In a 12-week clinical trial enrolling 254 patients with AD and comorbid psychiatric disorders, we compared four treatment conditions: (1) disulfiram and placebo, (2) naltrexone alone, (3) placebo alone, and (4) disulfiram and naltrexone. Patients with PTSD (n = 93) had fewer heavy drinking days and more consecutive days of abstinence when treated with naltrexone, disulfiram, or combination, as compared to placebo. This study demonstrated the efficacy of both disulfiram and naltrexone for the treatment of AD in individuals with PTSD. In the second 12-week study, a total of 88 predominantly male veterans with current diagnosis of AD and PTSD were randomly assigned one of four groups: paroxetine plus naltrexone; paroxetine plus placebo; desipramine plus naltrexone; desipramine plus placebo. Paroxetine was equivalent to desipramine for the treatment of PTSD symptoms. However, desipramine was superior to paroxetine with respect to study retention and alcohol use outcomes. Naltrexone reduced alcohol craving relative to placebo, but did not improve drinking behavior. This study suggests that norepinephrine uptake inhibitors may have efficacy for the treatment of comborbid PTSD and AD.

Previous studies have shown that some wives of war veterans with PTSD develop symptoms of secondary traumatic stress (STS). The aim of this study was to compare the level of present psychological symptoms and perceived quality of life between the wives of veterans with PTSD, without PTSD, and wives of non-veterans. Wives of veterans with PTSD (N = 50) were recruited through their partners and war veterans treated for combat related PTSD in Referent Center for Psychotrauma Rijeka, Croatia. Wives of veterans without PTSD (N = 50) and wives of non-veterans (N = 50) were recruited using the snowballing method. We administrated Sociodemographic questionnaire, Brief symptom inventory, Manchester Short Assessment of Quality of Life and Modified Questionnaire for Secondary Traumatization. Obtained results show that wives of veterans with PTSD have significantly higher level of STS symptoms than wives of veterans without PTSD, and higher level of psychological symptoms and lower perceived quality of life compared to other two groups. Level of STS symptoms is positively correlated with psychological symptoms and negatively with perceived quality of life. Main effect on STS symptoms has the wives' knowledge of partner's war traumatic event while the main effect on wives' psychological symptoms has the presence of PTSD in their husbands. In conclusion, when planning the future interventions for PTSD affected veterans, systemic approach should be considered not only to prevent secondary traumatic stress in partners of war veterans but also to enhance individual functioning of each partner and functioning as a couple.