Abstracts: Posttraumatic Stress Disorder and Traumatic Brain Injury
Neural, Psychophysiological, and Behavioral Markers of Fear Processing in PTSD: A Review of the Literature
. Curr Psychiatry Rep 2013; 15(5):358.
As presently defined, posttraumatic stress disorder (PTSD) is an amalgam of symptoms falling into: re-experiencing of the trauma, avoidance of reminders of it, emotional numbing and hyperarousal. PTSD has a well-known proximate cause, commonly occurring after a life-threatening event that induces a response of intense fear, horror, and helplessness. Much of the advancement in understanding of the neurobiology of PTSD has emerged from conceptualizing the disorder as one that involves substantial dysfunction in fear processing. This article reviews recent knowledge of fear processing markers in PTSD. A systematic search was performed of reports within the specific three-year publication time period of January 2010 to December 2012. We identified a total of 31 studies reporting fear processing markers in PTSD. We further categorized them according to the following classification: (1) neural-activation markers (N=10), (2) psychophysiological markers (N=14), and (3) behavioral markers (N=7). Across most studies reviewed here, significant differences between individuals with PTSD and healthy controls were shown. Methodological, theoretical and clinical implications were discussed.
Current Status on Behavioral and Biological Markers of PTSD: A Search for Clarity in a Conflicting Literature
. Neurosci Biobehav Rev 2013; 37(5):860–895.
Extensive research has identified stereotypic behavioral and biological abnormalities in posttraumatic stress disorder (PTSD), such as heightened autonomic activity, an exaggerated startle response, reduced basal cortisol levels and cognitive impairments. We have reviewed primary research in this area, noting that factors involved in the susceptibility and expression of PTSD symptoms are more complex and heterogeneous than is commonly stated, with extensive findings which are inconsistent with the stereotypic behavioral and biological profile of the PTSD patient. A thorough assessment of the literature indicates that interactions among myriad susceptibility factors, including social support, early life stress, sex, age, peri- and posttraumatic dissociation, cognitive appraisal of trauma, neuroendocrine abnormalities and gene polymorphisms, in conjunction with the inconsistent expression of the disorder across studies, confounds attempts to characterize PTSD as a monolithic disorder. Overall, our assessment of the literature addresses the great challenge in developing a behavioral and biomarker-based diagnosis of PTSD.
Nightmares in Active-Duty Soldiers Returned From Iraq and Afghanistan
. Am J Psychiatry (Epub ahead of print: July 12, 2013)
Objective: The authors conducted a 15-week randomized controlled trial of the alpha−1 adrenoreceptor antagonist prazosin for combat trauma nightmares, sleep quality, global function, and overall symptoms in active-duty soldiers with posttraumatic stress disorder (PTSD) returned from combat deployments to Iraq and Afghanistan. Method: Sixty-seven soldiers were randomly assigned to treatment with prazosin or placebo for 15 weeks. Drug was titrated based on nightmare response over 6 weeks to a possible maximum dose of 5 mg midmorning and 20 mg at bedtime for men and 2 mg midmorning and 10 mg at bedtime for women. Mean achieved bedtime doses were 15.6 mg of prazosin (SD=6.0) and 18.8 mg of placebo (SD=3.3) for men and 7.0 mg of prazosin (SD=3.5) and 10.0 mg of placebo (SD=0.0) for women. Mean achieved midmorning doses were 4.0 mg of prazosin (SD=1.4) and 4.8 mg of placebo (SD=0.8) for men and 1.7mg of prazosin (SD=0.5) and 2.0mg of placebo (SD=0.0) mg for women. Primary outcome measures were the nightmare item of the Clinician-Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index, and the change item of the Clinical Global Impressions Scale anchored to functioning. Secondary outcome measures were the 17-item CAPS, the Hamilton Depression Rating Scale, the Patient Health Questionnaire−9, and the Quality of Life Index. Maintenance psychotropic medications and supportive psychotherapy were held constant. Results: Prazosin was effective for trauma nightmares, sleep quality, global function, CAPS score, and the CAPS hyperarousal symptom cluster. Prazosin was well tolerated, and blood pressure changes did not differ between groups. Conclusions: Prazosin is effective for combat-related PTSD with trauma nightmares in active-duty soldiers, and benefits are clinically meaningful. Substantial residual symptoms suggest that studies combining prazosin with effective psychotherapies might demonstrate further benefit.
Treatment-Seeking Barriers for Veterans of the Iraq and Afghanistan Conflicts Who Screen Positive for PTSD
. Psychiatr Serv 2013; 64(3):280–283.
Objectives: Barriers associated with the decision not to seek treatment for symptoms of combat-related posttraumatic stress disorder (PTSD) were examined. Methods: Participants were 143 military men and women who served in Operation Enduring Freedom or Operation Iraqi Freedom (OEF/OIF) and who screened positive for posttraumatic stress disorder (PTSD), as assessed by the PTSD Checklist-Military Version, and who had not sought treatment for PTSD. During a cognitive-behavioral telephone intervention, participants were asked about their beliefs concerning seeking PTSD treatment. Results: Four categories of beliefs were associated with the decision to seek treatment, including concerns about treatment (40%), emotional readiness for treatment (35%), stigma (16%), and logistical issues (8%). Conclusions: This work suggests areas for intervention efforts to minimize barriers to treatment for PTSD for OEF/OIF veterans.
Implications of Memory Modulation for Post-Traumatic Stress and Fear Disorders
. Nat Neurosci 2013; 16(2):146–153.
Posttraumatic stress disorder, panic disorder and phobia manifest in ways that are consistent with an uncontrollable state of fear. Their development involves heredity, previous sensitizing experiences, association of aversive events with previous neutral stimuli, and inability to inhibit or extinguish fear after it is chronic and disabling. We highlight recent progress in fear learning and memory, differential susceptibility to disorders of fear, and how these findings are being applied to the understanding, treatment and possible prevention of fear disorders. Promising advances are being translated from basic science to the clinic, including approaches to distinguish risk versus resilience before trauma exposure, methods to interfere with fear development during memory consolidation after a trauma, and techniques to inhibit fear reconsolidation and to enhance extinction of chronic fear. It is hoped that this new knowledge will translate to more successful, neuroscientifically informed and rationally designed approaches to disorders of fear regulation.
Pharmacological Innovations for Posttraumatic Stress Disorder and Medication-Enhanced Psychotherapy
. Curr Pharm Des 2012; 18(35):5645–5658.
Posttraumatic stress disorder (PTSD) is a common condition for which existing treatments are ineffective for many patients. Recent discoveries in the neurobiology of learning and memory, along with expanding knowledge of how those systems are impacted by the biology of the stress response, have opened new arenas for potential medication treatments for PTSD. We conducted a review of registered clinical trials investigating the efficacy of new agents for PTSD. The glucocoritcoid and adrenergic signaling systems are the most frequent targets of these investigational approaches to the prevention and treatment of PTSD. Additional trials are evaluating modulation of other CNS targets, including neurosteroids, glutamate, gamma-amino butyric acid, endocannabinoids, oxytocin, neurokinin/Substance P, and dopamine. A particularly exciting area of research is studies examining Medication-Enhanced Psychotherapy (MEP). Medications provided before or after exposure therapy for PTSD can enhance outcomes by: 1) strengthening learning and memory of fear extinction; 2) disrupting reconsolidation, thereby weakening fear memories; or 3) facilitating engagement in psychotherapy by reducing fear and enhancing openness to experience. The next few years promise to produce insight into the neurobiology and clinical efficacy of several novel approaches in the pharmacologic treatment and prevention of PTSD. © 2010 Bentham Science Publishers Ltd.
Review of VA/DOD Clinical Practice Guideline on Management of Acute Stress and Interventions to Prevent Posttraumatic Stress Disorder
. J Rehabil Res Dev 2012; 49(5):637–648.
This article summarizes the recommendations of the Department of Veterans Affairs (VA)/Department of Defense (DOD) VA/DOD Clinical Practice Guideline for Management of Post-Traumatic Stress that pertain to acute stress and the prevention of posttraumatic stress disorder, including screening and early interventions for acute stress states in various settings. Recommended interventions during the first 4 days after a potentially traumatic event include attending to safety and basic needs and providing access to physical, emotional, and social resources. Psychological first aid is recommended for management of acute stress, while psychological debriefing is discouraged. Further medical and psychiatric assessment and provision of brief, trauma-focused cognitive-behavioral therapy are warranted if clinically significant distress or functional impairment persists or worsens after 2 days or if the criteria for a diagnosis of acute stress disorder are met. Follow-up monitoring and rescreening are endorsed for at least 6 months for everyone who experiences significant acute posttraumatic stress. Four interventions that illustrate early intervention principles contained in the VA/DOD Clinical Practice Guideline are described.
Review of Posttraumatic Stress Disorder and Chronic Pain: The Path to Integrated Care
. J Rehabil Res Dev 2012; 49(5):753–776.
With the large number of Veterans experiencing posttraumatic stress disorder (PTSD) and chronic pain, the purpose of this article is to review the prevalence of PTSD and chronic pain, the theoretical models that explain the maintenance of both conditions, and the challenges faced by providers and families who care for these patients. The Department of Veterans Affairs (VA)/Department of Defense (DOD) VA/DOD Clinical Practice Guideline for Management of Post-Traumatic Stress with special attention to chronic pain is presented. Limited scientific evidence supports specific care and treatment of PTSD and chronic pain, and this challenges providers to investigate and research potential treatment options. Integrated care models designed for working with these patients are reviewed, including a focus on the techniques and strategies to address not only PTSD and chronic pain, but other conditions, including substance dependence and depression. A specific focus on headaches, back pain, and neuropathic pain follows, including treatment recommendations such as pharmacological, psychotherapeutic, and complementary approaches, given the high rates of these pain complaints for Veterans in PTSD clinical programs. Integrated care is presented as a viable solution and approach that challenges clinicians and researchers to develop innovative, scientifically based therapeutics and treatments to enhance the recovery and quality of life for Veterans with PTSD and chronic pain.
Exploring the Convergence of Posttraumatic Stress Disorder and Mild Traumatic Brain Injury
. Am J Psychiatry 2009 Jul; 166(7):768–776
The authors examine the relationship of the two signature injuries experienced by military personnel serving in Afghanistan and Iraq: posttraumatic stress disorder (PTSD) and mild traumatic brain injury (mild TBI). Studies show that a substantial minority of those serving develop persistent emotional sequelae (such as PTSD and other psychological health problems) and/or somatic or cognitive sequelae (postconcussive symptoms) of traumatic exposure. Remarkably, the mechanism (emotional versus biomechanical) and locus (head versus other regions) of injury are weak determinants of whether an individual develops PTSD, persistent postconcussive symptoms, or both. Preexisting or traumatically acquired cognitive dysfunction can increase the risk for these syndromes, probably by reducing cognitive reserve. Structural and functional neuroimaging studies can be interpreted to explain part of the shared symptomatic and functional variance in these syndromes, but this literature is far from consistent and serves mainly to raise new, challenging questions about mutual pathophysiology. The frequent confluence of PTSD and persistent postconcussive symptoms in military personnel strains the bounds of these constructs. New studies are needed to improve our understanding of how emotional and biomechanical stressors can yield these adverse outcomes and how such outcomes can be prevented and treated.
A Multidimensional Meta-Analysis of Psychotherapy for PTSD
. Am J Psychiatry 2005; 162(2):214–227.
Objective: The authors present a multidimensional meta-analysis of studies published between 1980 and 2003 on psychotherapy for PTSD. Method: Data on variables not previously meta-analyzed such as inclusion and exclusion criteria and rates, recovery and improvement rates, and follow-up data were examined. Results: Results suggest that psychotherapy for PTSD leads to a large initial improvement from baseline. More than half of patients who complete treatment with various forms of cognitive behavior therapy or eye movement desensitization and reprocessing improve. Reporting of metrics other than effect size provides a somewhat more nuanced account of outcome and generalizability. Conclusions: The majority of patients treated with psychotherapy for PTSD in randomized trials recover or improve, rendering these approaches some of the most effective psychosocial treatments devised to date. Several caveats, however, are important in applying these findings to patients treated in the community. Exclusion criteria and failure to address polysymptomatic presentations render generalizability to the population of PTSD patients indeterminate. The majority of patients posttreatment continue to have substantial residual symptoms, and follow-up data beyond very brief intervals have been largely absent. Future research intended to generalize to patients in practice should avoid exclusion criteria other than those a sensible clinician would impose in practice (e.g. schizophrenia), should avoid wait-list and other relatively inert control conditions, and should follow patients through at least 2 years.
