Post Traumatic Stress Theory: Research and Application

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This threat is all the more serious considering the fact that PTSD symptoms seldom disappear completely; recovery from PTSD is a lengthy, ongoing, gradual and costly process, which is often hampered by continuing reaction to memories. Treatment usually aims at reducing reactions and to diminishing the acuity of the reactions. Treatments also seek to increase the subject's ability to manage trauma-related emotions and to greater confidence in coping abilities. This work discusses our current understanding about PTSD. It explores current developments in stress research and discusses its applications and implication to the complex psychobiological prognosis of PTSD.

The work concludes by presenting a view into the future of PTSD treatment from the perspective of evidence-based medicine, which many regard as the break-open research of the next decades—systematic and critical research on research to establish and determine what is the best available evidence for treatment for the patients. Indeed, this will be particularly true in the case of subjects with PTSD, if the austere predictions of a sharp rise in prevalence consequential to most recent terrorist and war events worldwide that involve US soldiers and civilians prove true.

There are different psychiatric rating instruments and scales that can be used to assess adult PTSD. Some are part of comprehensive diagnostic manuals or instruments: Some are designed as either self-reports or as clinician-administered instruments specifically assessing adult PTSD: The underlying phenomena of PTSD are probably centrally mediated. Case in point is a study targeting women with early childhood abuse-related PTSD that found correlates of the emotional Stroop Subjects with and without PTSD were compared.

Both groups underwent PET scanning while performing in the color and emotional Stroop tasks and control condition. The control condition involved naming the color of rows of XXs red, blue, green and yellow. The active color condition involved naming the color of color words again with the same four colors , while the semantic context of the word was incongruous with the color. The active emotional condition involved naming the color again the same four colors of emotionally charged words rape, bruise, weapon, and stench.

These words have been shown to produce emotional arousal The study examined the effectiveness of the Stroop task as a probe of anterior cingulate function in PTSD, because of the role of the anterior cingulate and medial prefrontal cortex in stress response and emotional regulation. After comparing it with the color Stroop, the emotional Stroop displayed significantly decreased blood flow among the PTSD subjects in the anterior cingulate.

However, the emotional Stroop produced a relatively lower level blood flow response of anterior cingulate among PTSD abused women. These observations may indicate that PTSD anterior cingulate dysfunction is specific to the neural circuitry of the processing of emotional stimuli. Taken together, these findings indicate that PTSD may have a neural component, which could significantly alter psychoneuroendocrine-immune regulation, as discussed below. Certain scales have been developed that specifically target military personnel. The prevalence of PTSD diagnosis varies depending on the assessment method.

Such differences in rates, depending on the assessment instrument may hold significance. Symptoms may differ in both intensity and kind among older and younger prisoners of war. In the paradoxical side, it is possible for an individual to be diagnosed with PTSD while reporting minimal stress levels; in fact, subjective stress can be seen as a confounding factor that can have an influence on diagnosis Such chronic and stable PTSD may not be clinically relevant and may not require focused intervention.

They recommend to measure symptom intensity with such instruments as the CAPS Such an approach could decrease PTSD-positive diagnoses among subjects with low levels of distress Allostasis refers to the psychobiological regulatory process that brings about stability through change of state consequential to stress. Psycho-emotional stress can be defined as a perceived lack, or loss of fit of one's perceived abilities and the demands of one's inner world or the surrounding environment i.

Traumatic events that trigger PTSD are perfect examples of such onerous demands that lead to the conscious or unconscious perception on the part of the subject of not being able to cope The perception of stress is often associated with psychological manifestations of anxiety, irritability and anger, sad and depressed moods, tension and fatigue, and with certain bodily manifestations, including perspiration, blushing or blanching of the face, increased heart beat or decreased blood pressure, and intestinal cramps and discomfort.

These signs mirror the spectrum of psychobiological symptoms in PTSD. These manifestations are generally associated with the nature of the stress, its duration, chronicity and severity. A group of symptoms, now referred to as the sickness behavior, is also noted that is associated with clinically relevant changes in the balance between the psychoneuroendocrine and the immune systems 35 — By the early s, Walter Cannon — proposed that organisms engage in a dynamic process of adjustment of the physiological balance of the internal milieu in response to changing environmental conditions.

Stress alters the regulation of both the sympathetic and the parasympathetic branches of the autonomic nervous system, with consequential alterations in hypothalamic control of the endocrine response controlled by the pituitary gland. Autonomic activation and the elevation of hormones, including those produced by the hypothalamic-pituitary-adrenal axis, play a pivotal role in regulating cell-mediated immune surveillance mechanisms, including the production of cytokines that control inflammatory and healing events 35 , In brief, the perception of stress leads to a significant load upon physiological regulation, including circadian regulation, sleep and psychoneuroendocrine-immune interaction.

In brief, stress is profound alterations in the cross-regulation and interaction of the hormonal-immune regulatory axis. The experience of stress, as well as that of traumatic events and the anxiety-laden recollections thereof, produce a primary endocrine response, which involves the release of glucocorticoids GCs. GCs regulate cellular immune activity in vivo systemically and locally.

They block the production of pro-inflammatory cytokines e. IL-2 at the molecular level in vitro and in vivo , but may have little effects upon TH2 cytokines e. The net effect of challenging immune cells with GC is to impair immune T cell activation and proliferation, while maintaining antibody production. The secretion of GC by the adrenal cortex is under the control of the anterior pituitary adrenocorticotropin hormone ACTH.

Immune challenges release pro-inflammatory cytokines e. Stressful stimuli also lead to the significant activation of the sympathetic nervous system and a rise in the levels of pro-inflammatory cytokines i. It follows that the consequences of stress are not uniform. The psychopathological and the physiopathological impacts of stress may be significantly greater in certain people, compared with those of others. The impact of stress is dynamic and multifaceted and the same person may exhibit a variety of manifestations of the psychoneuroendocrine-immune stress response with varying degrees of severity at different times.

The outcome of stress can be multivalent Allostatic regulation now signifies the recovery and the maintenance of internal balance and viability amidst changing circumstances consequential to stress. It encompasses a range of behavioral and physiological functions that direct the adaptive function of regulating homeostatic systems in response to challenges 37 — The cumulative load of the allostatic process is the allostatic load. The pathological side effects of failed adaptation are the allostatic overload.

Allostasis pertains to the psychobiological regulatory system with variable set points. These set points are characterized by individual differences. They are associated with anticipatory behavioral and physiological responses and are vulnerable to physiological overload and breakdown of regulatory capacities 39 , Type 1 allostatic load utilizes, as it were, stress responses as a means of self-preservation by developing and establishing temporary or permanent adaptation skills. The organism aims at surviving the perturbation in the best condition possible and at normalizing the normal life cycle.

In Type 2 allostatic load, the stressful challenge is excessive, sustained or continued and drives allostasis chronically. An escape response cannot be found. Type I versus type II allostatic responses curiously reiterate Myers' observations that his patients seem to abandon themselves to the emotion and the fear that assailed them, rather than engage in the effort to counter and to overcome the challenge, which normal subjects typically undertook.

Future research in PTSD from the perspective of allostasis may reveal a learned helplessness component, which could become key in the development and evaluation of treatment interventions Fig. Allostatic regulation describes the recovery and the maintenance of internal balance and viability amidst changing circumstances consequential to stress.

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It encompasses the Type 1 allostatic load that reflects the utilization by the organism of the range of behavioral and physiological functions that direct the adaptive function of regulating homeostatic systems in response to challenges i. Type 1 allostatic responses translate the organism aims at surviving the perturbation in the best condition possible and at normalizing the normal life cycle.

By contrast, the Type 2 allostatic responses reflect a load to the organism that is excessive, sustained, or continued, and drives allostasis chronically and that precludes effective escape from the stress. It is clear that stress research and PTSD research are intertwined. Psychobiological manifestations in PTSD and in complex PTSD disorder of extreme stress evidently pertain to the same domain of mind—body interactions, which are elucidated in psychoneuroimmunology research. The stress response, more than likely, underlies the psychobiological sequelae of PTSD.

The relevance of the field of current research on allostasis to PTSD is all the more evident when one considers that subjects position themselves along a spectrum of allostatic regulation, somewhere between allostasis i. In brief, the recent advances in our understanding of the adaptation of the organism to stressful challenges, the allostatic process, present a new and a rich paradigm for research in the psychobiology of PTSD. Future research must investigate whether or not the dichotomy of Type I and Type II allostatic responses will provide an effective theoretical model for the development of novel and improved modes of intervention to treat PTSD.

The treatment of PTSD is complex, both in terms of available treatments and the myriad of trauma possibilities that cause it. This should be followed by treatments with various degrees of demonstrated efficacy Historically, it was in the early eighties when research on the treatment efficacy for PTSD began, with multitude of case studies dealing with different kinds of PTSD having been produced since then.

Overall, both cognitive behavioral approaches and selective serotonin reuptake inhibitor regimes have been proved to be effective to deal with different kinds of PTSD. At the same time, there is also evidence that other treatment modalities, such as psychodynamic psychotherapy, hypnotherapy, eye movement desensitization and reprocessing can be effective as well; albeit their evidence is derived from less numerous and less well-controlled studies i.

PTSD intervention is complicated further by the fact that co-morbidities e. Particularly in situations where co-morbidity exists, a combined approached should be considered. Of interest due to the perilous state of the world i. According to experts, combat veterans with PTSD may be less responsive to treatment that other victims of other traumatic exposures 41 , Following is a list of possible reasons:.

Combat-caused PTSD is often associated with other psychiatric disorders, including depression, anxiety, mood disorders and substance abuse disorders It is usually believed that the most effective treatment results are obtained when both PTSD and the other disorder s are treated together rather than one after the other. It is becoming increasingly critical to ascertain this position because the prevalence of PTSD and disorder of complex stress is bound to rise sharply in the next decade consequential to the present multinational state of alert and anxiety following ongoing tragic, wanton and widespread terrorism and particularly with respect to combat-related PTSD in present times.

Some have more proven efficacy than others. Some of these approaches may be appropriate to address the initial stages of trauma. Psychological debriefing is an intervention given shortly after the occurrence of a traumatic event. The goal is to prevent the subsequent development of negative psychological effects. In fact, psychological debriefing approaches to PTSD can be described as semi-structured interventions aimed at reducing initial psychological stress.

Strategies include emotional processing via catharsis, normalization and preparation for future contingencies Gulf War veterans who underwent psychological debriefing showed no significant differences in their scores of two scales measuring PTSD when compared with the control group In general, there is little evidence of psychological debriefing approaches effectively acting to prevent psychopathology, although participants seem to be open to it, which may indicate its usefulness as a rapport builder or as a screening tool.

In general however, there is a lack of rigorously conducted research in this area. To this day there is paucity in the data to orient the treatment of combat-related PTSD for veterans The International Consensus Group on Depression and Anxiety supports that exposure psychotherapy is the most appropriate approach for this disorder 41 , although this approach does not show a significant influence on PTSD's negative symptomatology, such as avoidance, impaired relationships or anger control In terms of proven efficacy, cognitive behavior therapy and eye movement desensitization and reprocessing are effective approaches to deal with PTSD 50 — 54 , while other psychotherapeutic approaches e.

Cognitive-behavioral psychotherapy encompasses a myriad of approaches i. Vietnam veterans receiving exposure therapy displayed improvement as evidenced in terms of reducing intrusive combat memories 55 , physiological responding, anxiety 56 , depression and feelings of alienation, while also promoting increased vigor and skills confidence Exposure therapy, combined with a standard treatment also showed effectiveness with other Vietnam veterans in terms of subject self-report symptoms related to the traumatic experiences, sleep and subjective anxiety responding to trauma stimuli In fact, typically, there is a combination of psychotherapy and medication treatments to treat chronic PTSD In general, the different co-morbidities associated with PTSD play a role in the kinds of pharmacotherapeutic treatments used for its treatment.

Antidepressants and other medications commonly used are tricyclic antidepressants, monoamine oxidase inhibitors, selective serotonin reuptake inhibitors, antianxiety and adrenergic agents and mood stabilizers Sertraline has been found effective to reduce PTSD symptomatology 61 , Sertraline and fluoxetine have produced clinical improvements among PTSD patients in randomized clinical trials Paroxetine, another selective serotonin reuptake inhibitor like sertraline, is also habitually used to treat chronic PTSD Mirtazapine was another successful agent when used in the treatment of PTSD afflicted Korean veterans In addition, Olanzapine and fluphenazine have been successfully used with combat-induced PTSD subjects from the Balkans.

Both medicines were successful in ameliorating both PTSD and psychotic symptomatology Rigorous, well-controlled methods are necessary for conducting studies on the efficacy of PTSD treatments. Well-controlled studies are characterized by the following characteristics:. Future clinical research in PTSD requires the stringent, rigorous and systematic approach provided by evidence-based medicine. Evidence-based research in medicine goes beyond the routine narrative literature review. It systematically evaluates the strength of the available evidence and generates a consensus statement of the best available evidence in the form of a systematic review of the available research Fig.

What are the interventions being looked at, e. Are the interventions being compared or are predictions being drawn, i. What is the outcome of interest, e.


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The second step involves methodology, including the sampling of the research literature, and the tools for the critical analysis of the reports. The fourth step is concerned with the analysis of the data gathered in the evidence-based research process. This commonly entails meta-analytical and meta-regression techniques, as well as individual patient data analysis e.

Depending upon the tools utilized to evaluate the scientific literature, scores about the completeness and quality of research methodology, design and statistical handling of the findings are generated SESTA, systematic evaluation of the statistical analysis. These values are analyzed by acceptable sampling statistical protocols to establish whether or not the sample of research reports studied by means of the evidence-based process was statistically acceptable to produce reliable inferences.

The last step is a cumulative synthesis, which summarizes the process and the findings. The process is applied to the performance of systematic reviews, which are all-encompassing of the available literature. Best case studies in evidence-based research entail a random performance of the process of evidence-based research with a random sample of the available literature. The future of clinical and translational research in PTSD lies in the systematic evaluation of the research evidence in treatment intervention for the patients.

The collected evidence is then evaluated for research quality along certain standards [e. Timmer scale, Jadad scale and Wong scale The data from separate reports are pooled, when appropriate, for meta-analysis, meta-regression and individual patient data analyses. The data are analyzed from the perspective of Bayesian modeling in order to interpret data from research in the context of external evidence and judgments In the context of the treatment of patients with PTSD and co-morbidities, it is important and timely to generate a systematic review of the clinical research evidence for joint and simultaneous treatment of PTSD and the co-morbidities versus a staggered approach.

The summative evaluation of the outcome of such a systematic review will generate a consensus statement that will establish whether or not the problem was framed in a clinically relevant manner e. The statement must discuss the validity of the process of integration e. Was the search comprehensive and explicitly described? Was the validity of the individual studies adequately assessed?

Were the process of study selection, searching, assessing validity and data abstraction reliable? The statement also produces evidence about the rigor of the process by which information was integrated e. Are the summary findings representative of the largest and most rigorously performed studies? The quality, presentation and relevance of the findings must be discussed e.

Are the key elements of each study clearly displayed? Is the magnitude of the findings statistically significant? Are the findings homogeneous or heterogeneous? Are sensitivity analyses presented and discussed? Do the findings suggest an overall net benefit for patients with PTSD? This concerted, systematic and scientific-process driven mode of evaluating current treatment interventions for subjects with PTSD is timely and urgent to insure that the medical establishment will be prepared to handle the fast-approaching wave of PTSD cases in the next decade.

This method-driven approach for the evaluation of clinical data has merit that its product, the consensus statement, must also generate a cost-effectiveness analysis i. The relevant findings in this cost-effectiveness analysis are usually expressed as the incremental cost-effectiveness between joint and simultaneous treatment of PTSD and its co-morbidities versus a staggered approach.

Such barriers to data sharing have in effect excluded VA investigators from the large consortia that are necessary for genomic research. Addressing such barriers would help ensure progress in PTSD genomics research. Ideally the occurrence of PTSD should be prevented. Unlike other psychiatric disorders, PTSD results from a known event, and this allows for immediate intervention and possibly even the prevention of pathological symptoms.

It remains unclear why some people are resilient to trauma whereas others develop PTSD. Clarifying the reasons for this difference might improve strategies for enhancing resilience and preventing the development of PTSD. Logistically, this research is challenging to conduct in humans, as it requires recruiting people into studies immediately after a traumatic event and following them longitudinally.

Establishing best practices for recruiting people into studies immediately after trauma and improving basic research techniques for early behavioral or neural interventions could result in new methods to prevent PTSD symptoms.

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The committee identified some research projects that explore methods for increasing resilience and reducing adverse effects after exposure, such as investigations of early interventions for example, intervening in the emergency room or as soon as the event occurs , of early behavioral and pharmacological interventions and different delivery systems for example, telephone or Web-based delivery , and of different populations at risk.

An early-intervention study found that a course of three sessions of modified prolonged exposure PE therapy in an emergency department was associ ated with significantly less depression and PTSD at 1-month and 3-month follow-up than in those who received assessment alone, and the early intervention appeared to mitigate a genetic risk of PTSD Rothbaum et al. Some research is being done on prevention, but it does not appear to be sufficient. DoD is implementing prevention and resilience training programs, but most of them have yet to be evaluated IOM, The committee did not identify any service-specific research that assessed whether existing programs successfully minimize PTSD after trauma or prevent the reemergence of symptoms and other sequelae.

Advances in basic science and PTSD genetics could help to identify social, psychological, or biological markers that might indicate vulnerability to PTSD either before or after trauma exposure. Such research could help to identify modifiable risk factors that might be targets for prevention interventions and people who are at high risk for PTSD and might benefit from enhanced training or early interventions after trauma exposure.

Equally important but less studied is the question of whether psychological, social, or environmental variables may increase or decrease the likelihood of PTSD. Prevention research is examining risk and protective factors for the development of PTSD symptoms. In addition, the application of results to other populations—such as service members, veterans, or women—is questionable. This challenge could provide an opportunity for NIH, VA, and DoD to collaborate to support research that may help to actively build consensus around a specific prevention program, biomarker, or other scientific advancement.

A notable gap is the absence of research that pools analyses or meta-analyses of extant studies. The committee reviewed many research projects that might lead to advances in screening for PTSD and comorbidities see Appendix E. A few studies were identified that screen for PTSD in high-risk populations, such as those with chronic pain, burns, mild TBI, accidental injury, and functional somatoform syndromes. The type of screening to be conducted depends on the question of interest, for example, whether the intention is to compare those who have PTSD with those who are healthy or to distinguish those who have PTSD from those who have a related diagnosis, such as mild TBI.

Research is needed to move beyond the traditional questionnaire-based screening methods to neurobiological and behavioral screening for PTSD. There is also a need for randomized controlled trials that prospectively assess whether large-scale screening results in greater benefits to the population than more traditional approaches.

Much PTSD research has been directed toward improving the diagnostic precision of structured interviews or self-ratings. Those techniques not only assist in diagnosis but are valuable tools for promoting measurement-based care. Efforts that go beyond structured interviews and rating scales have been under way for many years and include the study of physiological measures, neuroimaging, genetic markers, and neurotransmitters; the goal is to enhance diagnostic processes by incorporating neurobiological measures.

The committee identified a research gap in the area of diagnosis—one potentially useful approach that is not being studied is the use of advanced statistical procedures, such as random forest classification and functional magnetic resonance imaging, to develop a neurobiologically based approach to diagnosis PTSD and to evaluate it against standard that is, clinically based diagnostic predictors. However, although such treatments as PE, cognitive processing therapy CPT , eye movement desensitization and reprocessing EMDR , selective serotonin reuptake inhibitors, and other pharmacotherapies are more effective than placebo or other controls in civilians, they do not work in all people with PTSD.

Some patients show only a partial response, others show no response, and some relapse after an initially promising response. There are a limited number of studies that have investigated PTSD treatments in service member and veteran populations. Other treatment challenges include the delayed onset of therapeutic action and adverse effects. Better and safer treatments are needed, not just modifications of current ones. Research targets for treatment see Appendix E include several that are innovative and promising.

Some of the most promising research is the use of new technologies to improve the effectiveness and accessibility of treatment. The combination of various clinical approaches to address the complexity of PTSD issues for example, concurrent treatment for PTSD and comorbidities or treatments that combine psychotherapies, pharmacotherapies, and complementary and alternative therapies needs to be studied further in military and veteran populations.

Overarching research considerations for PTSD treatment are discussed below. Both preclinical pharmacotherapies for example, pilot studies and pharmacotherapies are being investigated in military and civilian populations see Appendix E.

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New pharmacotherapies, such as endocannabinoids, are promising and important for research. The committee found research gaps in the study of preclinical pharmacotherapies, such as the use of oxytocin, to identify molecular markers of reconsolidation and of hippocampal adult neurogenesis as related to pattern separation and pattern completion. A broad array of new and established pharmaceuticals are being studied; some are being given as monotherapy and some to augment other therapies.

Some are believed to work through different neurotransmitter pathways and should add valuable information to the knowledge base on PTSD pharmacotherapy. Particularly promising are the clinical investigation of low doses of anesthetic drugs, such as ketamine, and the increasing evidence base on prazosin. This study is the first major placebo-controlled trial of pharmacotherapy in active-duty service members who had been exposed to combat. On the basis of an extensive review of current studies and a brief review of research published since its phase 1 report IOM, , the committee identified several gaps in PTSD-treatment research.

First, studies of drug effects on brain structure and chemistry, such as effects of escitalopram on BDNF, are valuable, and more studies of this type are needed. Third, pharmacotherapy for PTSD comorbid with bipolar disorder, attention deficit disorder, and mild TBI is not well studied but should be. Fourth, polypharmacy is a continuing concern; it may result in improvement in PTSD symptoms, but it can also result in more side effects and be a factor in noncompliance to treatment.

Research that compares the efficacy of new psychotherapies with that of established evidence-based treatments is essential for a high-performing system of PTSD management. It is important to continue to develop and evaluate new psychotherapy options because there is currently no evidence-based treatment that is effective for everyone who has PTSD and no treatment that is so appealing, engaging, and pragmatically deliverable to patients that it breaks down all barriers to care.

Once efficacy is established, primary treatments can be studied in combination with other treatments to determine the added value of combination treatments or how treatment-protocol modifications can improve benefits. Rather than research gaps, there appears to be considerable diversity in the approaches being tested, including both trauma-focused and non-trauma-focused approaches. Examples are controlled studies to assess the value of adding components to evidence-based treatments. Various new treatments are being tested in randomized controlled trials, such as acceptance and commitment therapy, adaptive disclosure therapy, behavioral activation therapy, interpersonal psychotherapy, trauma-management therapy, and relatively new and untested cognitive training approaches to enhance modulation of emotion.

That may constitute a research gap inasmuch as psychotherapy approaches may be more effective when combined to address both cognitive control of emotional regulation and extinction-based cognitive and behavioral concerns. Overall, current psychotherapy research reflects a diverse mixture of efforts. Some experimental methods for studying PTSD treatments involve computer-delivered approaches, which are discussed later in this chapter.

The combined use of pharmacotherapy and psychotherapy is an important approach in the management of PTSD. A combined approach might result in greater therapeutic gains in two ways. In the first, a single dose of a drug is administered immediately before or after a psychotherapy session either to hasten the onset of therapeutic action or to produce greater therapeutic gains than psychotherapy alone. In the second, a drug is administered chronically with psychotherapy, and the combined treatment may result in a greater gain than either treatment alone.

In this model, use of the drug might precede the introduction of psychotherapy, be started simultaneously, or be added after the start of psychotherapy. The antidepressant drug sertraline and the anticonvulsant drug zonisamide see Appendix E are being studied as enhancements of psychotherapy. Several trials of medication-enhanced psychotherapy have been reported recently. For example, Oehen et al. The use of single-dose DCS in combination with PE therapy has also been studied; mixed results have been reported. De Kleine et al.

Neurostimulatory treatments for depression and obsessive compulsive disorder have shown benefit in some people who are resistant to first-line treatments.


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Food and Drug Administration has approved devices for the use of repetitive transcranial magnetic stimulation rTMS in treatment-resistant depression. The committee identified several current studies that are funded by DoD, VA, and others to investigate rTMS, cranial electrotherapy stimulation, stellate ganglion block, trigeminal nerve stimulation, and bright-light therapy see Appendix E. Those and other stimulatory and somatic interventions are promising treatments for PTSD and clearly warrant further study. In the last several years, research projects have assessed the effectiveness of couple therapy for PTSD Fredman et al.

In a small randomized controlled trial of cognitive-behavioral conjoint therapy for PTSD, Monson et al. As part of its statement of task, the committee was asked to look at complementary and alternative therapies for PTSD, particularly animal-assisted therapy. Surveys have demonstrated that the use of complementary and alternative therapies is substantial in the U. The more frequently studied complementary and alternative therapies are meditation, acupuncture, yoga, and biofeedback.

Less studied therapies include animal-assisted therapy, mantram repetition, and music therapy. The former studies are being conducted in a variety of PTSD populations, including veterans, and they are being evaluated in combination with treatment as usual. Their value as stand-alone treatments for PTSD is unknown. The committee identified different types of meditation—including mindfulness-based, loving-kindness, self-compassion, and transcendental meditation—that are being studied for PTSD.

Most such studies were being conducted as randomized controlled trials with either an active or an inactive control see Appendix E. The committee found that there were as many mindfulness projects in the NIH RePORT database as there were projects for treating for PTSD with a combination of pharmacotherapy and psychotherapy approaches—an indication that research on mindfulness is growing.

There is a lack of well-controlled studies on animal-assisted therapy and on acupuncture for PTSD; more research is needed on both. The study of psychobiotics for example, gut microbiota is a new field of medicine that is relevant to stress and related psychological disorders.

Some researchers have suggested that preclinical and clinical studies of psychobiotics could inform treatment for stress-related conditions Burnet and Cowen, ; Dinan et al. A high-performing PTSD management system should expedite the translation of positive research findings into practice. Optimally, the translation would take advantage of proven methods for the delivery of clinical services in a way that breaks down barriers to care.

The best evidence-based treatments will have little value without a model for promoting their effective and widespread delivery. The committee identified a research gap with regard to the use of mobile communication devices and their applications. However, considering the relatively recent availability and adoption of mobile devices and applications, it is perhaps understandable that they are the subject of little research. The committee identified several studies that focused on treatment modality—that is, whether a treatment is given in a group setting, a couple setting, or an individual setting.

Varied treatment modalities are being tested, either by delivering treatment in groups or in conjoint therapy or by adjusting the pace at which treatment is administered for example, moving from one session per week to two sessions per week. More research is needed to determine the characteristics of patients who can benefit from treatment delivered in a group or from combinations of individual and group or conjoint treatment. More research is needed to determine the role of the family in different treatment settings and the benefits of family involvement.

Research is also needed to determine whether providing more choices of treatment modalities for service members and veterans helps to reduce barriers to care. And research is necessary to understand whether a patient who has initial involvement in a group setting with a non-evidence-based treatment such as yoga or psychoeducation is more likely to engage in an evidence-based treatment later.

The committee identified current research that is aimed at assessing the potentially different needs of men and women who have PTSD and alcohol or substance use disorders, or who have experienced military sexual trauma. Some studies are focused on making PTSD treatment more accessible to members of minority groups, on adapting manualized PE for Hispanic patients, and on developing culturally relevant treatment for American Indians. As noted in Chapter 2 , people who have PTSD are often diagnosed with one or more comorbidities, including other anxiety disorders, depression, and alcohol and substance use disorders Brown and Wolfe, ; IOM, ; Jacobsen et al.

To better understand the pathophysiology of PTSD, some studies have focused solely on it as the primary diagnosis and often excluded patients from studies if they present with comorbidities. Excluding certain patients may be important for studying the psychopathology of PTSD itself, but research examining the interactions between the pathophysiology of PTSD and other psychiatric conditions is as important as research that explores the psychological and neural processes underlying the interaction of drug addiction or TBI with the development and treatment of PTSD.

Some literature published since the phase 1 report shows an improvement in PTSD symptoms and a reduction in comorbid alcohol use when the disorders are treated together. There is an emphasis on promoting adherence to treatment and maintenance of long-term treatment gains by using motivational interviewing and relapse-prevention strategies. There is little redundancy in the research being conducted in this area. The committee noted one study designed to generate comorbidity clusters to predict outcomes.

Other treatment approaches included physiological response-tailored exposure therapy, imagery rehearsal with or without CBT, and group CBT. The diversity of the study targets and clinical approaches suggests that DoD and VA recognize the importance and challenge of treating for PTSD and comorbid conditions. Most research on barriers is related to individual, provider, and institutional obstacles to the delivery of high-quality, evidence-based PTSD care.

It includes barriers to awareness, accessibility, availability, and acceptability; the role of leaders in reducing stigma; adherence to evidence-based treatments, and the dissemination of the outcomes. Two studies are looking at military culture, operational tempo, and institutional processes that impede research for example, variations in institutional review board functioning and recruitment challenges. Two studies are identifying barriers to the delivery of such new treatments as acupuncture.

There is no research on overcoming barriers to translation of basic research to treatment and clinical practice. The research portfolio is top-heavy with studies on OEF and OIF cohorts, including several studies of National Guard and reserve cohorts, but the committee identified very few studies that included Vietnam-era veterans. Longitudinal studies can advance the understanding of how aging affects PTSD and comorbidities and can help to elucidate whether some interventions are beneficial in altering the course of the disorder.

Thus, long-term follow-up of large DoD and VA cohorts might shed light on the effectiveness of prevention programs, early screening, and a variety of treatment interventions for PTSD. See Appendixes D and E for examples of long-term studies. Intimate partner violence is an often overlooked research topic with regard to PTSD, but it can have substantial impact on families. There is a continuing need to conduct research that identifies effective ways to assess intimate partner violence and to determine what factors encourage potential or actual perpetrators or their partners to seek access to mental health care.

Several recent research efforts are designed to validate intimate-partner violence treatment interventions Taft et al. The committee identified promising innovative studies that focused on racial and ethnic factors associated with PTSD and intimate partner violence; the intersections of TBI, intimate partner violence, and PTSD; and the effects of PTSD and intimate partner violence on children in military and veteran families. Continuing research is needed to develop and validate couple, family, and group interventions that address intimate partner violence in military and veteran families.

Provider training is important for diagnosing and for disseminating and implementing evidence-based treatments. The committee divided research on training into training providers to improve the diagnosis of and treatment for PTSD and administering training grants for career development see Appendix E. The committee considered efforts to train providers to be particularly important. One innovative study is under way on the use of virtual patients for training providers. Another study is attempting to develop and evaluate a Web-based CBT training system that expands on existing content and incorporates live online training.

Considering the need for well-trained providers of evidence-based treatments and the ubiquitous penetration of high-bandwidth Internet connectivity, the absence of more studies on online clinical training appears to be a gap in research and practice. If current or recently completed studies on developing Web-based or new training curricula or tools are effective, they could be used to reach a larger audience.

Translating research into practice can be thought of in different ways, depending on the context. For example, a laboratory scientist may be interested in how the basic science of cell lines or animals can be translated to humans. A researcher conducting a clinical trial may be interested in how the results in a controlled experimental setting are translated to the general population in a real-world setting.

A health care administrator may be interested in taking a body of evidence and translating it to clinical practice guidelines. To distinguish between types and contexts of translation, investigators sometimes think of translation as a continuum of activities see Table All research does not have to go through each stage of translation, nor does the translation have to be linear; some research may move directly from an early stage to direct application.

The committee recognizes the importance of conducting basic research that translates from animal models to healthy humans and to clinical and trauma-exposed populations. Basic research on physiological and biological mechanisms potentially relevant to PTSD has used primarily animal models Almli et al. These models are vitally important to understanding many of the neurobiological principles governing learning, memory, trauma, and stress. However, this research has limited usefulness if its applicability to and modification by the complex cognitive, social, and emotional factors typical of human experiences cannot be explored.

Animal models also cannot capture the impacts of social factors, including such emotions as shame and guilt; social structures; cultural attitudes; or the complex cognitive abilities in people that may change the expression and persistence of PTSD symptoms. Basic research that explores the psychological and biological mechanisms of learning, memory, trauma, and stress in people should be expanded to include psychological and neurobiological mechanisms in healthy people and in trauma-exposed military populations.

Unless a broad range of researchers can access relevant populations to conduct studies on how trauma exposure and PTSD influence the brain or behavior, the applicability of basic research to treatments for PTSD will continue to be limited. New research models—for example, pragmatic trials, practical clinical trials, and hybrid effectiveness—implementation trials—may be useful for addressing the common translational gap between randomized controlled trials and clinical practice Curran et al. Translational research can provide feedback from population-based studies of new interventions that lead to their modification and eventual implementation as evidence-based interventions for a variety of populations Glasgow et al.

NIH has made an effort to streamline the translation of mental health research to the clinic. The NIMH Research Domain Criteria Project is defining functional dimensions, such as fear circuitry or working memory, that will be studied in multiple dimensions, including genes, neural circuits, and behavior. In addition, NIH is revising its clinical trials process to make NIH-funded research more efficient, to encourage data sharing and publication, and to have a greater impact on the burden of illness. Emphasis is being placed on target validation and experimental therapeutic studies instead of traditional efficacy trials in an effort to identify new targets for treatment and to improve knowledge of the disease process NIMH, b.

The committee commends NIH for these efforts, and it encourages DoD and VA to use best practices learned from NIH to improve the efficiency and transparency of their own mental health research and to continue to use such collaborative mechanisms as the National Research Action Plan. The last decade has seen a dramatic increase in the use of innovative digital technologies, such as mobile devices, high-speed network access, smart televisions, social media, hyperrealistic computer and video games, and new interaction and behavioral sensing devices. The power of these technologies to automate processes and create engaging user experiences has led to health care applications that leverage off-the-shelf technology and push the boundaries of new technological development.

An increased focus has been placed on the use of technology to enhance the management of and treatment for PTSD and comorbid health conditions. DoD and VA have driven advances in mental health care technology by supporting research to improve the delivery of evidence-based treatments for mental health conditions and to reduce barriers to care by investigating ways to improve the awareness of, availability of, access to, appeal of, acceptance of, and adherence to evidence-based treatments and services IOM, Technology-based advances in mental health care include telehealth, informational and self-help websites, mobile smartphone applications, virtual reality and online virtual worlds, intelligent health care agents, and interactive clinical training systems.

One of the more widely studied applications of technology in mental health is the use of telehealth sometimes referred to as teletherapy or telemental health to expand the accessibility of and adherence to evidence-based treatments. Telehealth refers to an approach that uses technology typically videoconferencing for the delivery of clinical care by a provider who is geographically distant from the patient Schopp et al. The number of published reports on telehealth outcomes has grown exponentially since , and the number of trials continues to grow Backhaus et al.

The research needs to be assessed to determine whether telehealth approaches for both screening and treatment offer a preferable and cost-effective approach to PTSD care Jones et al. DoD and VA have supported the development of online self-help and informational websites. These efforts are intended to break down barriers to care by building user awareness of PTSD and treatment options, promoting accessibility to care with self-help content, encouraging acceptance of seeking treatment with persuasive information, and enhancing adherence by providing self-help treatment options or between-session support.

Receiving PTSD-relevant content privately via the Internet may encourage those who are initially reluctant to seek help to reach out eventually to a mental health care professional. Another new form of online deliverable treatment is the use of computerized training programs to build the cognitive skills that may help to modulate emotions. Often termed cognitive remediation therapy, this approach is a standardized intervention that involves performing cognitive exercises to improve attention, processing speed, executive function, and memory through practice by using various software packages.

The committee identified six projects that evaluate cognitive remediation therapy programs as an alternative intervention for PTSD in combat veterans. One study compared a commercial program called CogPack with playing Tetris. Two projects evaluated similar computer-based systems to retrain negative attentional bias in people who have a diagnosis of PTSD and to address comorbid mild TBI. All the cognitive remediation therapy projects test the hypothesis that this form of care will promote home-based practice by using cognitive training programs that are available online.

Other DoD and VA websites intended for service members, veterans, and their families present less structured treatment activities and are generally information-rich, reviewed, and regularly updated, and present a wide array of PTSD resources, including some self-assessment materials and information on where to access treatment. T2 also hosts the Moving Forward site http: DoD supports the wider-ranging Military OneSource site http: Two novel online approaches leverage interactions with virtual human characters to engage users with PTSD-related content.

Another virtual human site is the DoD-funded SimCoach www. Considering the expense and effort of creating those websites, there is a lack of knowledge about how they are used and what outcomes they produce. As the general population increasingly views the Internet as an acceptable and natural option for shopping, education, health care information, and social interaction and bonding, the committee believes that research will continue to focus on whether and how evidence-based mental health treatment can be delivered to service members and veterans via online tools and websites.

Research needs to evaluate which treatments can be delivered to which patients who have which health conditions to maximize safe access to evidence-based treatment for service members, veterans, and their significant others. DoD and VA have supported research to create and evaluate virtual-reality exposure therapy applications. Avoidance of trauma reminders is symptomatic of PTSD and some patients are unable or unwilling to visualize traumatic events and memories effectively Difede and Hoffman, To address the avoidance issue, virtual reality delivery of PE is one way to immerse users in personalized simulations of trauma-relevant environments in which the emotional intensity of the scenes can be controlled by a clinician.

Thus, virtual-reality exposure therapy offers a way to circumvent a natural avoidance tendency by directly delivering multisensory and context-relevant cues that aid in the confrontation and processing of traumatic memories.

Post-traumatic stress theory: Research and application

Favorable outcomes have been reported in several PTSD populations treated with virtual reality therapy Difede and Hoffman, ; Difede et al. Those studies are assessing virtual reality alone or in combination with other enhancing treatments, such as imaginal PE, DCS, and trauma management therapy Beidel et al. In addition to providing more and better options for PTSD treatment, virtual-reality exposure therapy may be useful for overcoming barriers to care by improving treatment appeal, acceptability, and adherence.

Young service members, many of whom have grown up with digital gaming technology, may be attracted to and comfortable with participation in virtual reality therapy Reger et al. In spite of DoD and VA efforts to foster adoption of PE as a first-line treatment, its dissemination has been a challenge, in part owing to clinician hesitancy to adopt and use it Becker et al.

Virtual reality can also be used to help meet this challenge through the use of virtual reality systems that allow a mental health care provider to create customized simulated scenarios to support patient trauma narratives more easily with a computer control interface.

DoD is supporting research on training social workers to work with military families using conversational interactions with life-size, voice-interactive, high-fidelity virtual military patients and is developing a toolkit for clinical educators so that they can create virtual patients for training others. Other virtual reality projects seek to train primary care providers to screen, treat, and refer patients who have PTSD using a series of challenging menu-driven, role-play conversations with virtual patients Albright et al. However, the attraction and adoption of virtual-reality exposure therapy still requires controlled research to determine how and to what extent this approach may break down barriers to PTSD care and enhance treatment dissemination.

It also requires research to determine best practices for training providers to use and to implement the technology in DoD and VA settings. Mobile devices, including mobile telephones, tablets, computers, e-readers, and wearable body sensors that can record various physiological measurements, can be used to wirelessly deliver health care services. Mobile applications can potentially be used to motivate and inform people and to monitor and track health measures and activities.

Many of the applications such as fitness applications and calorie counters focus on providing information to the end user, and others provide information to clinicians via a network connection. The availability of mobile health care applications has grown at a dramatic pace, in large part owing to the massive adoption of smartphone and tablet technology and the ubiquitous access to network connections.

All the applications attempt to extend the reach of currently used practices—such as self-monitoring, self-assessment, biofeedback, CBT tactics, and relaxation strategies—via mobile devices. T2 has worked with VA to develop, test, and conduct research on the PE Coach, a smartphone application.

Those programs require evaluation as they are further developed and disseminated. VA is also investing substantial effort in its Mobile Health program to evolve its mobile application portfolio. It is piloting the use of iPads that have a suite of 10 applications to 1, seriously injured veterans Miller, There are practical challenges to studying the use of the technologies in DoD and VA with regard to development, dissemination, sustainability, and privacy protection, but current research efforts fit in well with the DoD and VA visions for using mobile health technologies to expand care options for service members and veterans.

The creation of engaging and effective mobile health technologies will require an interdisciplinary effort by clinicians, device manufacturers, application developers, communication service providers, and patient and consumer end users, who appreciate the need to integrate portable computing devices, cloud infrastructures, network capabilities, data analytics, and human factors. Virtual patient systems offer a novel technological approach to address the training needs of health care providers, and these systems take many forms Talbot et al. Basic applications can be as simple as providing trainees with static patient images and accompanying text-based case summaries and tests.

Simple computer animations can also be used, with interactions driven by trainee menu choices. More recently, virtual human conversational agents have been created that can credibly fill the role of standardized patients by simulating diverse varieties of clinical presentations. These agents can be available for anytime—anywhere training via computer. As mentioned in the section on training, DoD and VA are funding a few studies to assess the use of virtual reality for training see also Appendix E.

Such prototype systems, designed for interacting with highly realistic and natural-language-capable virtual patients, do not yet have an evidence base for their effectiveness for training. However, if found to be effective, virtual patient technology could have a considerable impact by supplementing existing in-person training approaches. Over the last few decades, the departments have spent hundreds of millions of dollars on PTSD research. Those research priorities reflect the mental health needs of the service member and veteran populations that each department serves and are reflected in the types and numbers of studies that are funded see Table The committee identified areas of research that are critical to improving PTSD management for service members and veterans—basic research, use of technology, PTSD treatment, and overcoming system-level barriers.

Much work is being accomplished in basic research, but the scientific community still lacks an understanding of the biological mechanisms that lead to PTSD, factors that may prevent or promote its development, and biomarkers that could improve PTSD prevention, diagnosis, and treatment. PTSD researchers are trying to identify more and better treatments, such as psychotherapies, pharmacotherapies, combinations of therapies, and complementary and alternative therapies. Identifying treatments for PTSD and any comorbidities is particularly important, considering the high prevalence of mental health disorders, such as depression and substance use disorder, and physical ailments, such as TBI and chronic pain, in many service members and veterans who have PTSD.

Such comorbidities as cardiovascular disease, are likely to increase as the veteran population ages. The use of technology to improve the management and treatment of PTSD has potential to improve treatment options, clinical practice, and real-time contact with service members and veterans.

Technology is also expanding the use of system-wide approaches to better capture and monitor patient treatments and outcomes in a systematic and continuous manner, but questions remain as to whether such technological enhancements will achieve improved treatment delivery and outcomes.

Given the current and growing number of service members and veterans who have PTSD symptoms and the availability of effective treatments for PTSD, a topic of research that is often overlooked but would be beneficial in the short term is methods to overcome barriers that prevent the widespread use of effective treatments in DoD and VA health care systems. This may include research on health services, effective models for PTSD management, the establishment of evidence-based practice competencies, provider training, and the effective implementation and dissemination of evidence-based care.

The committee encourages research on all those subjects and new efforts to be undertaken. This funding supports research, equipment typically Year 1 investment , salaries for nonclinical primary investigators, and VA administrative overhead Gleason, It does not support research administration at VA medical centers, clinician primary investigator salaries which are supported by medical care appropriation , animal facility support, research supported by non—Office of Research funding, or research system infrastructure Gleason, Turn recording back on.

National Center for Biotechnology Information , U. The following databases provided most of the research information: The committee recognizes that this database is not static and that new projects may have been funded since June Although it does not include all clinical trials conducted in the United States, it does contain the majority of federally and privately funded studies conducted under investigational new drug applications. Studies were eliminated if they were completed or expected to be completed before , or were withdrawn.

Genomics The factors that lead to individual differences in the development of PTSD are both experiential and genetic Admon et al. Screening The committee reviewed many research projects that might lead to advances in screening for PTSD and comorbidities see Appendix E. Diagnosis Much PTSD research has been directed toward improving the diagnostic precision of structured interviews or self-ratings.

Pharmacotherapies Both preclinical pharmacotherapies for example, pilot studies and pharmacotherapies are being investigated in military and civilian populations see Appendix E. Psychotherapies Research that compares the efficacy of new psychotherapies with that of established evidence-based treatments is essential for a high-performing system of PTSD management. Combining Psychotherapy and Pharmacotherapy The combined use of pharmacotherapy and psychotherapy is an important approach in the management of PTSD.

Somatic Treatments Neurostimulatory treatments for depression and obsessive compulsive disorder have shown benefit in some people who are resistant to first-line treatments. Complementary and Alternative Therapies As part of its statement of task, the committee was asked to look at complementary and alternative therapies for PTSD, particularly animal-assisted therapy. Models of Care Delivery A high-performing PTSD management system should expedite the translation of positive research findings into practice.

Modality of Treatment Intervention The committee identified several studies that focused on treatment modality—that is, whether a treatment is given in a group setting, a couple setting, or an individual setting. Concurrent Treatment of Comorbidities As noted in Chapter 2 , people who have PTSD are often diagnosed with one or more comorbidities, including other anxiety disorders, depression, and alcohol and substance use disorders Brown and Wolfe, ; IOM, ; Jacobsen et al.

Barriers Most research on barriers is related to individual, provider, and institutional obstacles to the delivery of high-quality, evidence-based PTSD care. Intimate Partner Violence Intimate partner violence is an often overlooked research topic with regard to PTSD, but it can have substantial impact on families.

Training Provider training is important for diagnosing and for disseminating and implementing evidence-based treatments. Telehealth One of the more widely studied applications of technology in mental health is the use of telehealth sometimes referred to as teletherapy or telemental health to expand the accessibility of and adherence to evidence-based treatments. Virtual Reality DoD and VA have supported research to create and evaluate virtual-reality exposure therapy applications.

Mobile Applications Mobile devices, including mobile telephones, tablets, computers, e-readers, and wearable body sensors that can record various physiological measurements, can be used to wirelessly deliver health care services. A causal model of post-traumatic stress disorder: Disentangling predisposed from acquired neural abnormalities.

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