Catecholamine responses to virtual combat: implications for post-traumatic stress and dimensions of functioning

PTSD symptoms can result in functional impairment among service members (SMs), even in those without a clinical diagnosis. The variability in outcomes may be related to underlying catecholamine mechanisms. Individuals with PTSD tend to have elevated basal catecholamine levels, though less is known regarding catecholamine responses to trauma-related stimuli. We assessed whether catecholamine responses to a virtual combat environment impact the relationship between PTSD symptom clusters and elements of functioning. Eighty-seven clinically healthy SMs, within 2 months after deployment to Iraq or Afghanistan, completed self-report measures, viewed virtual-reality (VR) combat sequences, and had sequential blood draws. Norepinephrine responses to VR combat exposure moderated the relationship between avoidance symptoms and scales of functioning including physical functioning, physical-role functioning, and vitality. Among those with high levels of avoidance, norepinephrine change was inversely associated with functional status, whereas a positive correlation was observed for those with low levels of avoidance. Our findings represent a novel use of a virtual environment to display combat-related stimuli to returning SMs to elucidate mind-body connections inherent in their responses. The insight gained improves our understanding of post-deployment symptoms and quality of life in SMs and may facilitate enhancements in treatment. Further research is needed to validate these findings in other populations and to define the implications for treatment effectiveness

Habituation Trajectory During Exposure Therapy: Comparing Trauma Frequency and Trauma Type

The current DSM-5 criteria for Posttraumatic Stress Disorder (PTSD) affords heterogeneous symptom presentations; however, current treatment fails to consider differences in trauma frequency and trauma type. These different symptom profiles that exist within the PTSD framework lead to questions about the generalizability of treatment outcomes from one group to another group. One group of interest is those that experience multiple traumatic events and report multiple index traumas (trauma frequency). The second group of interest is those with a PTSD diagnosis from occupational exposure to traumatic events (trauma type). Appreciation of the reinforcement schedule may be particularly crucial for understanding treatment response. The current study aims to investigate habituation responses during exposure therapy to inform treatment modifications and decisions. Exposure therapy process variables, session variables, and PTSD severity were examined for a sample of 128 participants that sought treatment for combat-related PTSD or occupation-related PTSD, some of whom endorsed multiple index traumas, and some of whom endorsed a single index trauma. Results revealed no significant differences based on trauma frequency or trauma type for within-session and between-session habituation. This suggests that the effectiveness of a flooding approach to extinguish avoidance behavior may overcome the impact of reinforcement schedule on fear habituation. The results of the present study contribute to the growing body of literature that suggests the exclusion of patients based on the pre-treatment characteristics of trauma frequency and trauma type is unfounded

Acquisition and extinction across multiple virtual reality contexts: implications for specific phobias and current treatment methods

Victor Wong studied human acquisition learning over multiple contexts using virtual reality. He found that learning an association over multiple contexts can impact subsequent extinction training. This suggests that fears acquired over multiple contexts may be more difficult to treat using exposure-based therapies and will need to be augmented for effectiveness

Diverse therapeutic developments for post-traumatic stress disorder (PTSD) indicate common mechanisms of memory modulation

Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for treatment of PTSD. These drugs have limited efficacy as they only reduce symptoms related to depression and anxietywithout producing permanent remission. PTSD remains a significant public health problem with high morbidity and mortality requiring major advances in therapeutics. Early evidence has emerged for the beneficial effects of psychedelics particularly in combination with psychotherapy for management of PTSD, including psilocybin,MDMA, LSD, cannabinoids, ayahuasca and ketamine. MDMA and psilocybin reduce barrier to therapy by increasing trust between therapist and patient, thus allowing for modification of trauma related memories. Furthermore, research into the memory reconsolidation mechanisms has allowed for identification of various pharmacological targets to disrupt abnormally persistent memories. A number of preclinical and clinical studies have investigated novel and re-purposed pharmacological agents to disrupt fear memory in PTSD. Novel therapeutic approaches like neuropeptide Y, oxytocin, cannabinoids and neuroactive steroids have also shown potential for PTSD treatment. Here,we focus on the role of fear memory in the pathophysiology of PTSD and propose that many of these newtherapeutic strategies produce benefits through the effect on fear memory. Evaluation of recent research findings suggests that while a number of drugs have shown promising results in preclinical studies and pilot clinical trials, the evidence from large scale clinical trials would be needed for these drugs to be incorporated in clinical practice

Testing a Brief Treatment to Reduce the Frequency of Panic Attacks in a Clinical Outpatient Population

Panic attacks, the key symptom of panic disorder and an associated feature of various anxiety disorders, are extremely distressing events that can negatively impact an individual’s mental health, physical health, and quality of life. This study validated a brief treatment for panic attacks, designed to reduce the frequency of panic attacks after the first session, in an outpatient clinical population. One participant was recruited to participate in this single case experimental ABA design with follow-up, where a reversal was not expected, due to the maintenance of positive effects. The treatment included both cognitive and behavioral techniques. The results were analyzed using simulation modeling analysis, as well as visual analysis. This treatment produced clinically significant effects by reducing the frequency and severity of panic attacks, reducing symptoms of anxiety and panic, decreasing the frequency of cognitive distortions, and increasing the level of functioning. Additionally, these gains were maintained at a 3- month follow-up. It is hoped that this intervention can help clinicians treat panic disorder and improve their effectiveness and efficiency by reducing the time needed to significantly decrease panic attacks. It is also hoped that this intervention might be expanded for use with other panic-related anxiety disorders. Finally, it is possible that this study will encourage efforts toward briefer treatments for other disorders

Traumatic Brain Injury Service, Walter Reed National Military Medical Center 4. National Intrepid Center of Excellence, Walter Reed National Military Medical Center 5. National Institute of Nursing Research , National Institutes of Health 6. RTI Internati

Abstract Traumatic brain injury, depression and posttraumatic stress disorder (PTSD) are neurocognitive syndromes often associated with impairment of physical and mental health, as well as functional status. These syndromes are also frequent in military service members (SMs) after combat, although their presentation is often delayed until months after their return. The objective of this prospective cohort study was the identification of independent predictors of neurocognitive syndromes upon return from deployment could facilitate early intervention to prevent disability. We completed a comprehensive baseline assessment, followed by serial evaluations at three, six, and 12 months, to assess for new-onset PTSD, depression, or postconcussive syndrome (PCS) in order to identify baseline factors most strongly associated with subsequent neurocognitive syndromes. On serial follow-up, seven participants developed at least one neurocognitive syndrome: five with PTSD, one with depression and PTSD, and one with PCS. On univariate analysis, 60 items were associated with syndrome development at p < 0.15. Decision trees and ensemble tree multivariate models yielded four common independent predictors of PTSD: right superior longitudinal fasciculus tract volume on MRI; resting state connectivity between the right amygdala and left superior temporal gyrus (BA41/42) on functional MRI; and single nucleotide polymorphisms in the genes coding for myelin basic protein as well as brain-derived neurotrophic factor. Our findings require follow-up studies with greater sample size and suggest that neuroimaging and molecular biomarkers may help distinguish those at high risk for post-deployment neurocognitive syndromes

Post Traumatic Stress Disorders in a Global Context

If, as a health care or social service provider, one was called upon to help someone who has experienced terror in the hands of a hostage taker, an irate and chronically abusive spouse or parent, or a has survived a motor vehicle accident, landslide, earthquake, hurricane or even a massive flood, what would be one's priority response? What would be considered as the most pressing need of the individual requiring care? Whatever the answer to each of these questions, people who have experienced terror, suffer considerable psychological injury. Post-Traumatic Stress Disorder in a Global Context offers some answers to meet the needs of health care and socials service providers in all settings, whether in a hospital emergency room, at the war front, or natural disaster site. The take home message is, after providing emergency care, there is always a pressing need to provide mental health care to all victims of traumatic stress

Traumatic Brain Injury Service, Walter Reed National Military Medical Center 4. National Intrepid Center of Excellence, Walter Reed National Military Medical Center 5. National Institute of Nursing Research , National Institutes of Health 6. RTI Internati

Abstract Traumatic brain injury, depression and posttraumatic stress disorder (PTSD) are neurocognitive syndromes often associated with impairment of physical and mental health, as well as functional status. These syndromes are also frequent in military service members (SMs) after combat, although their presentation is often delayed until months after their return. The objective of this prospective cohort study was the identification of independent predictors of neurocognitive syndromes upon return from deployment could facilitate early intervention to prevent disability. We completed a comprehensive baseline assessment, followed by serial evaluations at three, six, and 12 months, to assess for new-onset PTSD, depression, or postconcussive syndrome (PCS) in order to identify baseline factors most strongly associated with subsequent neurocognitive syndromes. On serial follow-up, seven participants developed at least one neurocognitive syndrome: five with PTSD, one with depression and PTSD, and one with PCS. On univariate analysis, 60 items were associated with syndrome development at p < 0.15. Decision trees and ensemble tree multivariate models yielded four common independent predictors of PTSD: right superior longitudinal fasciculus tract volume on MRI; resting state connectivity between the right amygdala and left superior temporal gyrus (BA41/42) on functional MRI; and single nucleotide polymorphisms in the genes coding for myelin basic protein as well as brain-derived neurotrophic factor. Our findings require follow-up studies with greater sample size and suggest that neuroimaging and molecular biomarkers may help distinguish those at high risk for post-deployment neurocognitive syndromes

International meta-analysis of PTSD genome-wide association studies identifies sex- and ancestry-specific genetic risk loci.

The risk of posttraumatic stress disorder (PTSD) following trauma is heritable, but robust common variants have yet to be identified. In a multi-ethnic cohort including over 30,000 PTSD cases and 170,000 controls we conduct a genome-wide association study of PTSD. We demonstrate SNP-based heritability estimates of 5-20%, varying by sex. Three genome-wide significant loci are identified, 2 in European and 1 in African-ancestry analyses. Analyses stratified by sex implicate 3 additional loci in men. Along with other novel genes and non-coding RNAs, a Parkinson's disease gene involved in dopamine regulation, PARK2, is associated with PTSD. Finally, we demonstrate that polygenic risk for PTSD is significantly predictive of re-experiencing symptoms in the Million Veteran Program dataset, although specific loci did not replicate. These results demonstrate the role of genetic variation in the biology of risk for PTSD and highlight the necessity of conducting sex-stratified analyses and expanding GWAS beyond European ancestry populations

Aufmerksamkeitsverzerrungen in militärischen Einsatzkräften mit posttraumatischer Belastungsstörung und deren Veränderlichkeit nach Bereitstellung einer internet-basierten kognitiv-behavioralen Intervention

Posttraumatic stress disorder (PTSD) is a prevalent and highly disturbing mental health condition that occurs in response to extremely distressing events during the lifetime. First, military personnel represent a high-risk population for the development of posttraumatic stress symptoms (PTSS) or the full-diagnostic spectrum of the disorder due to deployment- and combat-related stressors during their military career. Despite the existence of well established and efficacious psychotherapy treatments for PTSD, access to trauma-focused psychotherapy is limited and veterans in particular experience high barriers to accessing help from the mental health care system. A substantial proportion of affected veterans receive no or inadequate treatment, increasing the risk of secondary adverse mental and somatic health outcomes, reduced social and occupational functioning, and of the condition becoming chronic. Second, internet-based interventions (IBI), particularly internet-based cognitive behavioral therapies (iCBT), have been shown to be efficacious and widely accepted for the treatment of a range of psychiatric disorders, including PTSD. IBI can already be seen as playing a potentially important role in supplementing the landscape and provision of psychotherapeutic interventions, and this is set to grow further in the future. Indeed, IBI should be particularly beneficial for patients in rural areas with a restricted psychotherapy infrastructure, for patients with restricted mobility, and for patients who desire greater anonymity and more independence regarding the time and location of psychotherapy access. Third, the systematic and reliable assessment of objective indicators of symptom expression and symptom change is of increasing interest and relevance for psychotherapy research. This dissertation thesis aims at incorporating these three pillars in four studies: First, a diagnostic identification of PTSD in veterans of the German Armed Forces (GAF) according to the main diagnostic manuals the International Classification of Diseases and Related Health Problems (ICD) and the Diagnostic and Statistical Manual of Mental Disorders (DSM); second, a meta-analytical evaluation of the efficacy of IBI in PTSD; third, an assessment of patterns of visual attentional bias in (traumatized) veterans (with PTSS); and fourth, an exploration of the modifiability of attentional bias in veterans after receiving iCBT. STUDY 1 investigated the concordance of PTSD prevalence rates when transiting between the diagnostic criteria of the DSM-IV, DSM-5, ICD-10, and proposed ICD-11 in a sample of service members of the GAF. High levels of agreement emerged between the DSM-IV and the DSM-5, and between the DSM-5 and the proposed ICD-11. Prevalence rates were significantly higher according to the proposed ICD-11 compared to the ICD-10, mainly due to the deletion of the time criterion. STUDY 1 provides support for the identification of six ‘core’ PTSD symptoms according to the proposed ICD-11, presenting a high agreement rate with the set of twenty qualifiers according to the DSM-5. STUDY 2 provided meta-analytical evidence for the efficacy of IBI for the treatment of PTSD. Twenty randomized controlled trials (RCT) encompassing 21 comparisons were included, evaluating either iCBT or internet-based expressive writing (iEW) with passive or active control conditions. The results revealed that iCBT was more efficacious than passive control conditions at post-treatment assessment (0.66 ≤ g ≤ 0.83). No superiority of either iCBT or iEW was found in contrast to active control conditions. Subgroup analyses revealed no significant moderators of iCBT efficacy. More research is needed to prove the efficacy of IBI in contrast to active control treatments and further explore the impact of moderators on treatment efficacy. STUDY 3 measured patterns of attentional bias in GAF veterans with PTSS, traumatized veterans without PTSS, and unexposed healthy veterans. In a free-viewing task, participants were presented with pairs of combat-related and neutral pictures, of more general threat-related and neutral pictures, and of emotional and neutral faces, while their eye gazes were tracked. Further, the internal consistency of attentional bias indicators was calculated. The findings provide support for the maintenance hypothesis in PTSS. There was no robust evidence to support the hypothesis of hypervigilant behavior in PTSS. Findings on attentional bias variability remain unclear. Internal consistency varied across attentional bias indicators, highlighting the need for future research in this regard. STUDY 4 investigated the modifiability of attentional bias in veterans with PTSS through the provision of iCBT. In a free-viewing task, participants were presented with combat-related, general threat-related, and neutral pictures, and with faces with negative emotional valence and neutral facial expressions while their eye gazes were tracked. Attentional bias was examined pre- and post-intervention and at a three-month follow-up. No modifications in attentional bias were observable over time. Future investigations are warranted to systematically investigate objective measures of symptom expression and symptom change together with subjective symptom reporting and symptom change in response to psychotherapeutic treatment options. In summary, this dissertation thesis provides a threefold contribution to the current landscape of psychotherapy research: First, it supports the concordance between the DSM-5 and the ICD-11 diagnostic criteria for PTSD. Second, it proves the efficacy of IBI for PTSD. In view of the growing relevance of IBI as a supplement to psychotherapeutic care, future research needs to examine its long-term efficacy, whether it shows equal or superior efficacy compared to other active (control) treatments, potential side effects, and whether it may lead to a deterioration of symptoms. Moreover, studies should focus on tailoring IBI to the specific needs of different patient populations to ensure patients’ safety and satisfaction with IBI. Third, the present thesis underlines the need for systematic and reliable assessments of objective indicators of symptom presentation and of symptom change, in addition to subjective reports. Moreover, methodological approaches need to be extended to measure diverse dimensions of symptom presentation and symptom change and gain a better understanding of their interplay. A multidimensional diagnostic approach and treatment evaluation will be of key relevance for future intervention research and evidence-based practice