Article

Posttraumatic Stress Disorder

June 2015
CONTINUUM Lifelong Learning in Neurology 21(3 Behavioral Neurology and Neuropsychiatry):789-805

DOI:10.1212/01.CON.0000466667.20403.b1

Source
PubMed

Authors:

Baylor College of Medicine

The objectives of this article are to update the reader on the current definition and diagnostic assessment of posttraumatic stress disorder (PTSD) and to describe its clinical characteristics, discuss its epidemiology and pathophysiologic aspects, as well as to summarize the current therapeutic options for PTSD. The new nomenclature of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) includes 20 PTSD symptoms clustered into four symptomatic domains: intrusive symptoms, active avoidance, disturbed emotional states, and alterations of arousal and reactivity. Diagnostic structured interviews and severity scales have been updated in order to address this recent revision. It is also recognized that the neural circuits whose disruption might explain the genesis of PTSD symptoms, although overlapping, may be different between these four domains, a fact that may inform new biologically based phenotypes with prognostic and therapeutic implications.During the past years, there has been active research into the different factors influencing vulnerability and resilience to stress, including the effect of genetic and epigenetic variations. The neural circuits involved in the processing of threatening stimuli have been studied in patients with PTSD through paradigms inspired in animal research. These studies suggest that patients with PTSD have difficulty discriminating danger from safety cues and have problems suppressing fear in the presence of safety cues. Functional MRI (fMRI) studies suggest that the increased amygdala activation observed in these patients results from abnormal modulatory input from the ventromedial prefrontal cortex. Structural brain abnormalities, on the other hand, have been more consistently identified in the hippocampus.Prolonged exposure therapy and cognitive reprocessing are the interventions that have the more extensive validation of their psychotherapeutic efficacy. Medications are modestly more effective than placebo to treat PTSD symptoms, and selective serotonin reuptake inhibitors (SSRIs) are considered a safe initial choice. Use of combined strategies including pharmacologic modulation of fear processing is an area of active research. PTSD is a frequent psychopathologic condition with a lifetime prevalence that is close to 10%. In the past few years, there have been significant advances in the definition of the disorder, in elucidating the neurobiology of vulnerability and resilience, and in developing new treatment alternatives.

Revisiting the Role of the Amygdala in Posttraumatic Stress Disorder

Chapter

Full-text available

Jul 2017

Hypothalamus volume mediates the association between adverse childhood experience and PTSD development after adulthood trauma

Article

Full-text available

Aug 2023

The hypothalamus is critical for regulation of the hypothalamic-pituitary-adrenal (HPA) axis and response to stress. Adverse childhood experience (ACE) can affect brain structure, which may contribute to development of posttraumatic stress disorder (PTSD) after subsequent adult trauma. It is unclear, however, if ACE history is particularly associated with aspects of hypothalamic structure which contribute to development of PTSD. To address this issue, the present study longitudinally assessed hypothalamic volumes and their associations with ACE and early post-trauma stress symptoms in subjects who did or did not develop PTSD during 12 months after adult trauma. 109 subjects (18–60 years, F/M = 75/34) completed the PTSD Checklist (PCL) questionnaire for post-trauma stress symptoms, the Childhood Trauma Questionnaire (CTQ) for ACE assessment, and an initial MRI brain scan for hypothalamic volume measurement, within 2 weeks after adult trauma. At post-trauma 12 months, subjects underwent a subsequent PTSD diagnosis interview using the Clinician-Administered PTSD Scale (CAPS), and a follow-up MRI scan. Left and right hypothalamus volumes at 2 weeks after adult trauma negatively correlated with CTQ scores. Right hypothalamus volume at this early time mediated an association between ACE and PTSD symptoms 12 months later. Right hypothalamus volumes also remained persistently smaller from 2 weeks to 12 months after trauma in survivors who developed PTSD. These results suggest that smaller right hypothalamus volume may be related to ACE history in ways that contribute to PTSD development after trauma in adulthood.

Post-traumatic stress disorder: a psychiatric disorder requiring urgent attention

Article

Full-text available

Aug 2022

Post-traumatic stress disorder (PTSD) is a severe and heterogenous psychiatric disorder that was first defined as a mental disorder in 1980. Currently, the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5) and the International Classification of Diseases 11th Edition (ICD-11) offer the most widely accepted diagnostic guidelines for PTSD. In both diagnostic categories, experiencing a traumatic event (TE) is the necessary criterion for diagnosing PTSD. The TEs described in the DSM-5 include actual or threatened death, serious injury, sexual violence, and other extreme stressors, either directly or indirectly. More than 70% of adults worldwide are exposed to a TE at least once in their lifetime, and approximately 10% of individuals develop PTSD after experiencing a TE. The important features of PTSD are intrusion or re-experiencing fear memories, pervasive sense of threat, active avoidance, hyperarousal symptoms, and negative alterations of cognition and mood. Individuals with PTSD have high comorbidities with other psychiatric diseases, including major depressive disorder, generalized anxiety disorder, and substance use disorder. Multiple lines of evidence suggest that the pathophysiology of PTSD is complex, involving abnormal neural circuits, molecular mechanisms, and genetic mechanisms. A combination of both psychotherapy and pharmacotherapy is used to treat PTSD, but has limited efficacy in patients with refractory PTSD. Because of the high prevalence, heavy burden, and limited treatments, PTSD is a psychiatric disorder that requires urgent attention. In this review, we summarize and discuss the diagnosis, prevalence, TEs, pathophysiology, and treatments of PTSD and draw attention to its prevention.

Detection of Microstructural Medial Prefrontal Cortex Changes Using Magnetic Resonance Imaging Texture Analysis in a Post-Traumatic Stress Disorder Rat Model

Article

Full-text available

Apr 2022

Background Radiomics is characterized by high-throughput extraction of texture features from medical images and the mining of information that can potentially be used to define neuroimaging markers in many neurological or psychiatric diseases. However, there have been few studies concerning MRI radiomics in post-traumatic stress disorder (PTSD). The study's aims were to appraise changes in microstructure of the medial prefrontal cortex (mPFC) in a PTSD animal model, specifically single-prolonged stress (SPS) rats, by using MRI texture analysis. The feasibility of using a radiomics approach to classify PTSD rats was examined.Methods Morris water maze and elevated plus maze were used to assess behavioral changes in the rats. Two hundred and sixty two texture features were extracted from each region of interest in T2-weighted images. Stepwise discriminant analysis (SDA) and LASSO regression were used to perform feature selection and radiomics signature building to identify mPFC radiomics signatures consisting of optimal features, respectively. Receiver operating characteristic curve plots were used to evaluate the classification performance. Immunofluorescence techniques were used to examine the expression of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) in the mPFC. Nuclear pycnosis was detected using 4′,6-diamidino-2-phenylindole (DAPI) staining.ResultsBehavioral results indicated decreased learning and spatial memory performance and increased anxiety-like behavior after SPS stimulation. SDA analysis showed that the general non-cross-validated and cross-validated discrimination accuracies were 86.5% and 80.4%. After LASSO dimensionality reduction, 10 classification models were established. For classifying PTSD rats between the control and each SPS group, these models achieved AUCs of 0.944, 0.950, 0.959, and 0.936. Among four SPS groups, the AUCs were 0.927, 0.943, 0.967, 0.916, 0.932, and 0.893, respectively. The number of GFAP-positive cells and intensity of GFAP-IR within the mPFC increased 1 day after SPS treatment, and then decreased. The intensity of NeuN-IR and number of NeuN-positive cells significantly decreased from 1 to 14 days after SPS stimulation. The brightness levels of DAPI-stained nuclei increased in SPS groups.Conclusion Non-invasive MRI radiomics features present an efficient and sensitive way to detect microstructural changes in the mPFC after SPS stimulation, and they could potentially serve as a novel neuroimaging marker in PTSD diagnosis.

Translocator protein 18 kDa: a potential therapeutic biomarker for post traumatic stress disorder

Article

Full-text available

Jun 2020
METAB BRAIN DIS

Post traumatic stress disorder (PTSD) is widely regarded as a stress-related and trauma disorder. The symptoms of PTSD are characterized as a spectrum of vulnerabilities after the exposure to an extremely traumatic stressor. Considering as one of complex mental disorders, little progress has been made toward its diagnostic biomarkers, despite the involvement of PTSD has been studied. Many studies into the underlying neurobiology of PTSD implicated the dysfunction of neurosteroids biosynthesis and neuorinflammatory processes. Translocator protein 18 kDa (TSPO) has been considered as one of the promising therapeutic biomarkers for neurological stress disorders (like PTSD, depression, anxiety, et al) without the benzodiazepine-like side effects. This protein participates in the formation of neurosteroids and modulation of neuroinflammation. The review outlines current knowledge involving the role of TSPO in the neuropathology of PTSD and the anti-PTSD-like effects of TSPO ligands.

Associations between changes in resilient coping and posttraumatic stress disorder symptoms

Article

Feb 2020

The pervasive, damaging nature of posttraumatic stress disorder (PTSD) presents enormous clinical challenges. Understanding the relationship between patients’ perceptions of PTSD symptoms and resilient coping strategies may prompt investigation of clinical interventions that improve adaptive, resilient coping skills. In this study, we examined whether changes in resilient coping were related to changes over time in the PTSD symptoms of intrusion and avoidance. A secondary analysis was conducted using longitudinal data from the community‐based Washington State Twin Registry. Participants completed the four‐item Brief Resilient Coping Scale (BRCS) and the Avoidance and Intrusion subscales of the Impact of Events Scale (IES) at two points in time that were at least 2 years apart. To limit analyses to participants reporting PTSD symptoms at baseline, an initial value of at least 1.0 on either Avoidance (n = 1,337) or Intrusion (n = 1,206) was required for inclusion in the sample. Using linear regression, we assessed associations of change in BRCS with a change in IES scores, controlling for the respective initial scores on each measure. Controlling for initial BRCS and IES‐Intrusion values, we observed a small, statistically significant association between change in BRCS and change in IES‐Intrusion scores (b* = −0.07; p = .003). There was no statistically significant association between change in BRCS and change in IES‐Avoidance (b* < 0.01; p = .869). In this large, longitudinal sample, increases in resilient coping were related to decreases in intrusive thoughts over time. Because coping patterns can be taught, these results warrant further investigations into adaptive coping patterns associated with diminishing PTSD symptoms.

Environmental contaminants, endocrine disruption, and transgender: Can “born that way” in some cases be toxicologically real?

Article

Full-text available

Sep 2023
HUM EXP TOXICOL

Steven David Holladay

Gender is viewed by many as strictly binary based on a collection of body traits typical of a female or male phenotype, presence of a genotype that includes at least one copy of a Y chromosome, or ability to produce either egg or sperm cells. A growing non-binary view is that these descriptors, while compelling, may nonetheless fail to accurately capture an individual’s true gender. The position of the American Psychological Association (APA) agrees with this view and is that transgender people are a defendable and real part of the human population. The considerable diversity of transgender expression then argues against any unitary or simple explanations, however, prenatal hormone levels, genetic influences, and early and later life experiences have been suggested as playing roles in development of transgender identities. The present review considers existing and emerging toxicologic data that may also support an environmental chemical contribution to some transgender identities, and suggest the possibility of a growing nonbinary brain gender continuum in the human population.

Association of age of adverse childhood experiences with thalamic volumes and post-traumatic stress disorder in adulthood

Article

Full-text available

May 2023

Background Adverse childhood experiences (ACEs) have been linked to brain development and mental disorders, however, the impact of the age of occurrence of ACEs on thalamic volume and post-traumatic stress disorder (PTSD) after adult trauma remains unclear. This study assessed associations between ACEs at different ages to thalamic volumes and PTSD development following acute adult trauma. Methods Seventy-nine adult trauma survivors were recruited immediately after trauma. Within 2 weeks of the traumatic event, participants completed the PTSD Checklist (PCL) to assess PTSD symptoms, the Childhood Trauma Questionnaire (CTQ) and Childhood Age Range Stress Scale (CARSS) to evaluate ACEs and perceived stress level at preschool (<6 years old) and school (6–13 years old) ages, and structural magnetic resonance imaging (sMRI) to measure thalamic volumes. Participants were divided into three groups: those who experienced no childhood trauma or stress (non-ACEs), those who experienced childhood trauma and stress onset at preschool ages (Presch-ACEs), and those who experienced childhood trauma and stress onset at school ages (Sch-ACEs). At 3 months, participants underwent PTSD symptom evaluation using the Clinician Administered PTSD Scale (CAPS). Results Adult trauma survivors in the Presch-ACEs group had higher CTQ and CAPS scores. In addition, survivors in the Presch-ACEs group had smaller thalamic volume compared to survivors in the non-ACEs and Sch-ACEs groups. Furthermore, smaller thalamic volume moderated a positive association between post-trauma 2-week PCL and subsequent 3-month CAPS scores. Discussion Earlier occurrence of ACEs was associated with smaller thalamic volume, which appears to moderate a positive association between early posttraumatic stress symptom severity and PTSD development after adult trauma. This raises the possibility that early occurrence of ACEs may impact thalamic structure, specifically a reduction in thalamic volume, and that smaller thalamic volume may contribute to susceptibility to PTSD development after adult trauma.

Pseudopheochromocytoma -an epidemic of the modern world? Case series and review of literature

Article

Full-text available

Apr 2023

Background: Pseudopheochromocytoma is a condition that occurs more frequently than other diseases presenting with similar symptoms such as: paroxysmal hypertension, diaphoresis, pallor, palpitations. However, due to the lack of specific guidelines and awareness among physicians, it is widely underdiagnosed. Conventional antihypertensive treatment is ineffective in controlling symptoms which leads to decreased quality of life in patients affected by this disorder. Case presentation: In our paper, we present three female patients with paroxysmal hypertension who were admitted to the Department of Endocrinology for an investigation of suspected pheochromocytoma. The biochemical findings and imaging carried out at the hospital ruled out the diagnosis of an adrenal tumor in all three of the patients. Given the proposed criteria the clinical features of the patients were suggestive of pseudopheochromocytoma. In all three cases, the anxiolytic or SSRI treatment was applied with satisfactory symptom control. Conclusions: After ruling out pheochromocytoma in patients presenting with paroxysmal hypertension, physicians should consider a diagnosis of pseudopheochromocytoma. Management of the disorder should include anxiolytic, antidepressant, a-adrenoceptor blockers, and b-adrenoceptor blockers treatment, with close cooperation between hypertension specialist and psychiatrist or psychologist. Early proper diagnosis can reduce emotional distress related to an extensive diagnostic process as well as the overall cost of healthcare in patients with pseudopheochromocytoma. Key words: pseudopheochromocytoma; paroxysmal hypertension; pheochromocytoma; hypertension; panic attacks

Machine Learning Models Based on Hippocampal T2-Weighted-Fluid-Attenuated Inversion Recovery Radiomics for Diagnosis of Posttraumatic Stress Disorder

Preprint

Full-text available

Jan 2023

Background Radiomics is characterized by high-throughput extraction of texture features from medical images for deep mining and analysis to establish meaningful associations between image texture data and specific diseases. Radiomics has demonstrated significant advantages and potential in the diagnosis and evaluation of numerous neurological and psychiatric diseases. However, few studies on its use in the diagnosis of posttraumatic stress disorder (PTSD) have been reported. This study investigated the feasibility of machine learning models based on hippocampal T2-weighted-fluid-attenuated inversion recovery (T2-FLAIR) radiomics for the diagnosis of PTSD. Methods We performed a retrospective analysis of the demographic, clinical, and magnetic resonance imaging data of 94 patients with a history of road traffic accident. Regions of interest were manually selected at the bilateral hippocampus on the slices showing the largest respective sizes of the hippocampus. Additionally, the 524 texture features on T2-FLAIR images were extracted. Least absolute shrinkage and selection operator regression was used to screen for the optimal texture features. Thereafter, logistic regression (LR), support vector machine (SVM), and random forest (RF) machine learning models were constructed using the R language for PTSD diagnosis. Receiver operating characteristic curves were used to evaluate the diagnostic performance of each machine learning model. Results No statistically significant differences in demographic and clinical characteristics were observed between PTSD and non-PTSD cases after road traffic accident (P > 0.05). However, statistically significant differences in the simplified coping style questionnaire positive/-negative coping scores and PTSD Checklist-Civilian Version scores existed between PTSD and non-PTSD cases at 3 months after road traffic accident (P < 0.01). The performance of three machine learning models in distinguishing PTSD cases from non-PTSD cases was good. In the training and test groups, the area under curves (AUCs) of the LR were 0.829 (95% confidence interval [CI]: 0.717–0.911) and 0.779 (95% CI: 0.584–0.913), with sensitivities and specificities of 74.19% and 77.13%, 76.92% and 80.00%, respectively. The AUCs of the SVM were 0.899 (95% CI: 0.801–0.960) and 0.810 (95% CI: 0.618–0.933), with sensitivities and specificities of 96.77% and 74.29%, 61.54% and 86.67%, respectively. The AUCs of the RF were 0.865 (95% CI: 0.758–0.936) and 0.728 (95% CI: 0.537–0.878), with sensitivities and specificities of 87.10% and 77.14%, 92.31% and 53.33%, respectively. Conclusions Machine learning models based on hippocampal T2-FLAIR radiomics have good diagnostic performance for PTSD and can be used as novel neuroimaging biomarkers for the clinical diagnosis of PTSD.

Does Blast Mild Traumatic Brain Injury Have an Impact on PTSD Severity? A Systematic Review and Meta-Analysis

Article

Full-text available

Jan 2023

Blast mild traumatic brain injury (mTBI) is a unique injury in the military population and post-traumatic stress disorder (PTSD) is shown to be linked with it. The main purpose of the systematic review was to understand the impact of blast mTBI on PTSD symptom severity. We systematically searched Pubmed, Web of Science, Embase (Ovid), APAPsycINFO (Ovid) and Medline (R) and In-Process, In-Data-Review and Other Non-Indexed Citations (Ovid). Data extraction and quality assessment was completed using the AXIS tool. Statistical analysis was undertaken to determine differences between blast mTBI and the control group (no blast and no TBI in military personnel) and a meta-analysis using the random effects model was used to calculate between-study heterogeneity and variance through I2 and Tau2, respectively. Additionally, the likelihood of PTSD, analysed using the average PTSD Checklist (PCL) score, was also determined based. Statistically higher PCL scores were found in the blast mTBI group compared to control groups, but high heterogeneity was found between the studies (p < 0.001, I2 = 84%, Tau2 = 0.44). Furthermore, all studies reported that blast mTBI had probable PTSD, but this was not the case for the control group. Blast mTBI appears to impact on PTSD symptom severity and the likelihood of developing PTSD, which healthcare professionals need to be aware of. The high heterogeneity present in the studies means that caution must be exercised when interpreting the data from this study. However, future studies require more well-defined, high-quality studies to answer the question of how blast mTBI affects PTSD symptom severity.

Effectiveness of virtual reality exposure treatment for posttraumatic stress disorder due to motor vehicle or industrial accidents

Article

Full-text available

Apr 2022

Virtual reality exposure treatment (VRET) for post-traumatic stress disorder (PTSD) is an emerging treatment. The purpose of this study was to examine the effectiveness and safety of VRET in patients with PTSD due to motor vehicle or industrial accidents. Twenty-six patients with PTSD (19 motor vehicle accidents and 7 industrial accidents) and eighteen subjects without PTSD were enrolled in five VRET sessions that were conducted using a head-mounted display. The VRET was based on systematic desensitization and included psychoeducation and training for breathing and relaxation techniques. The effectiveness of VRET was evaluated using the Posttraumatic Stress Disorder Checklist-Civilian version (PCL-C), Impact of Event Scale-Revised (IES-R), Clinical Global Impression-Severity scale (CGI-S), and Sheehan Disability Scale (SDS). Safety was assessed using the Simulator Sickness Questionnaire and Presence Questionnaire. After controlling for age, sex, marital status, job, economic status, and body mass index, we found that the CGI-S (F = 12.76, p = 0.001), PCL-C (F = 11.87, p = 0.002), IES-R (total score; F-8.31, p = 0.007), and SDS-A (F = 7.53, p = 0.010) scores in the VRET group were lower than those in the control group. Responses to the Simulator Sickness and Presence questionnaires did not differ significantly between the VRET and control groups (p > 0.05). In conclusion, for patients with PTSD due to motor vehicle accidents, VRET is a safe and potentially effective treatment method. Future randomized controlled studies are needed to provide stronger evidence for the effectiveness of VRET in patients with PTSD.

COVID-19 and post-traumatic stress disorder in nurses: a descriptive cross-sectional study in a Covid Hospital

Article

Full-text available

May 2021
MED LAV

Background: In March 2020, the World Health Organisation (WHO) declared the novel coronavirus (COVID-19) outbreak a global pandemic. Healthcare professionals directly involved in diagnosing, treating and caring for patients with COVID-19 are at risk of developing post-traumatic stress disorder (PTSD). Objective: This study investigated the prevalence of PTSD among nurses working in a COVID hospital and evaluated associated factors. Methods: A descriptive cross-sectional study was conducted at Crema Hospital and the Impact of Event Scale - Revised (IES-R) was administered. Data collection took place from July to September 2020, during which 275 questionnaires were distributed. Results: Of the total sample, 39.88% received a provisional PTSD diagnosis deserving of further analysis. Nurses stated that they were predominantly overwhelmed by intrusive thoughts (M = 1.55). Working in the emergency department during the COVID-19 pandemic (OR=2.40; p=0.02), irregular work shifts (OR=5.41; p=0.01) and coming from a mental health ward (OR=3.80; p=0.02) increased the risk of receiving a provisional PTSD diagnosis. Our findings showed significantly higher IES-R scores among women than among men (p = 0.01). The activities that caused the most distress were related to technical skills required for managing ventilation and intubation devices. Conclusions: The results of the study highlighted the presence of considerable psychological distress in the sample. There is an urgent need to monitor the short- and long-term consequences of the COVID-19 pandemic and implement early intervention measures.

The effect of motor interference therapy in traumatic memories: A pilot study

Article

Full-text available

Dec 2020

Introduction Traumatic memories of events such as a life‐threatening incident, serious injury, or sexual violence are a core symptom of stress‐related disorders; they might be susceptible to positive modification with interference tasks (reconsolidation‐based interventions). Our objective was to test the effect of performing a motor interference task (finger tapping in response to audio cues) on patients who suffer from traumatic memories. Methods We designed an uncontrolled pilot prospective clinical trial. Ten participants listened to an audio track that instructed them to tap their fingers in response to specific audio cues while trying to recall the traumatic event. Each patient underwent an assessment including the Spanish version of the PTSD Symptom Severity Scale‐Revised (EGS‐R), the visual analogue scale (EQ‐VAS) from EuroQol 5D (EQ‐5D), and a simple visual analogue scale (VAS) before the intervention, immediately after, and a week after the treatment. Results All measures exhibited a statistically significant improvement 1 week after the study. On the PTSD scale, 1 week later, 30% of the patients did not score high enough for such diagnosis. The VAS measured immediately following the intervention (4.4, SD = 2.22) also improved (p < .001), and 30% of the patients scored zero. One week after the intervention, the VAS improved more than 50% Conclusion The rapid 1‐week improvement on the PSTD scale and the VAS after a 30 min intervention support the idea of further research using a double‐blind, controlled design powered to demonstrate the efficacy of motor interference, an easy‐to‐apply therapeutic tool, in the treatment of traumatic memories.

The Efficacy of Virtual Reality Exposure Therapy for PTSD Symptoms: A Systematic Review and Meta-analysis

Article

Jul 2019
J AFFECT DISORDERS

Background: Virtual reality exposure therapy (VRET) for PTSD is an emerging treatment of remarkable promise, but its efficacy and safety are still unclear. Our aim was to investigate the efficacy of VRET for individuals with PTSD, and to identify the potential moderating variables associated with interventions. Methods: Literature search was conducted via PubMed, Embase, Web of Science, Cochrane Library, PsycInfo, Science Direct, and EBSCO. We identified 18 studies on PTSD including 13 randomized controlled trials (RCTs; 654 participants) and 5 single-group trials (60 participants). Results: The main effects analysis showed a moderate effect size (g = 0.327, 95% CI: 0.105-0.550, p<0.01) for VRET compared to control conditions on PTSD symptoms. Subgroup analysis revealed that the effects of VRET were larger when compared to inactive groups (g = 0.567) than active control groups (g = 0.017). This finding was in agreement with depressive symptoms. A dose-response relationship existed with more VRET sessions showing larger effects. There was a long-range effect of VRET on PTSD symptoms indicating a sustained decrease in PTSD symptoms at 3-month follow-up (g = 0.697) and 6-month follow-up (g = 0.848). The single-group trials analysis revealed that the VRET intervention had a significant effect on PTSD. Limitations: Many of the combat-related PTSD subjects resulted in uncertainty regarding meta-analytical estimates and subsequent conclusions. Conclusions: These findings demonstrated that VRET could produce significant PTSD symptoms reduction and supported its application in treating PTSD.

Genomics of posttraumatic stress disorder in veterans: Methods and rationale for Veterans Affairs Cooperative Study #575B

Article

Full-text available

Feb 2019
INT J METH PSYCH RES

Objectives Heritability in the risk for developing posttraumatic stress disorder (PTSD) has been established, but most genome‐wide association studies (GWASs) of PTSD involve relatively small sample sizes and limited identification of associated genetic loci. This report describes the methodology of a Veterans Affairs (VA) Cooperative Studies Program GWAS of PTSD among combat‐exposed U.S. veterans. Methods Probable cases (with PTSD) and probable controls (without PTSD) were identified from among veterans enrolled in the VA Million Veteran Program (MVP) with an algorithm developed using questionnaire responses and electronic health record information. This algorithm, based on a statistical model, relied on medical chart reviews as a reference standard and was refined using telephone interviews. Subsequently, to evaluate the impact of probabilistic phenotyping on statistical power, the threshold probability for case–control selection was varied in simulations. Results As of September 2018, >695,000 veterans have enrolled in MVP. For current analyses, genotyping data were available for >353,000 participants, including >83,000 combat‐exposed veterans. A threshold probability of 0.7 for case and control designation yielded an interim >16,000 cases and >33,000 controls. Conclusions A formal methodological approach was used to identify cases and controls for subsequent GWAS analyses to identify genetic risk loci for PTSD.

La mémoire hippocampo-dépendante : altérations dans un modèle de vieillissement accéléré et régulation par le système nociceptinergique chez la souris

Thesis

Dec 2017

Khaoula Rekik

La mémoire est définie comme une activité biologique et psychique qui permet d'emmagasiner, de conserver et restituer des informations. La formation de la mémoire à long terme a lieu en plusieurs étapes : acquisition, consolidation. Une fois consolidée, la mémoire peut être réactivée puis reconsolidée. C'est un processus dynamique qui au cours de la vie d'un individu peut subir des altérations physiologiques (vieillissement) ou pathologiques (maladies neurodégénératives, syndrome de stress post traumatique (PTSD)). Dans un premier temps nous avons caractérisé du point de vue comportemental les souris Werner (WRN), un modèle de vieillissement accéléré. Nos résultats ont montré que les souris WRN de différents âges (3, 5 et 8 mois) ne présentaient aucun problème moteur ni d'anxiété, deux paramètres altérés chez des souris âgées de 21 mois. Ces souris ne montrent pas non plus de déficit de mémoire non hippocampo-dépendante mais par contre présentent des déficits de mémoire hippocampo-dépendante. En termes d'intégrité fonctionnelle de l'hippocampe, les souris Werner sont capables de stocker l'information après un apprentissage mais à partir de 8 mois, elles présentent un déficit de flexibilité comportementale dans les tests de mémoire spatiale et contextuelle, un défaut caractéristique des animaux agés. Nos résultats montrent qu'au niveau comportemental, les souris WRN sont un bon modèle pour étudier le vieillissement car elles présentent dès 8 mois des déficits comparables à des souris normales âgées sans effets confondants liés à des troubles de la locomotion ou de l'anxiété. Dans un second temps nous avons évalué l'effet d'un système neuropeptidergique, le système nociceptine (peptide N/OFQ, récepteur NOP), sur la mémoire à long terme. Nous avons tout d'abord montré que différents agonistes du récepteur NOP inhibaient spécifiquement la reconsolidation de la mémoire aversive de type contextuelle dans le test du conditionnement de peur. Cet effet inhibiteur a également été observé dans un test hippocampo-dépendant non aversif, le test de localisation d'objet. Puisque l'activation des récepteurs NOP produit un effet amnésiant on peut émettre l'hypothèse que leur inhibition par des antagonistes pourrait favoriser l'apprentissage et la mémoire. Nos premiers résultats montrent en effet que l'injection d'un antagoniste NOP améliore les performances dans le test de localisation d'objet chez des souris Tg2576, modèles d'une forme familiale de la maladie d'Alzheimer. L'ensemble de ces résultats valident l'intérêt du système nociceptinergique en tant que cible thérapeutique pour atténuer les formes pathologiques de mémoire aversive comme dans le cas du PTSD ou au contraire améliorer les performances mnésiques chez les patients Alzheimer.

Embitterment in War Veterans with Posttraumatic Stress Disorder

Article

Full-text available

Nov 2018

Olivera Batic-Mujanovic

Orexins and Stress

Article

Jun 2018

The neuropeptides orexins are important in regulating the neurobiological systems that respond to stressful stimuli. Furthermore, orexins are known to play a role many of the phenotypes associated with stress-related mental illness such as changes in cognition, sleep-wake states, and appetite. Interestingly, orexins are altered in stress-related psychiatric disorders such as Major Depressive Disorder and Anxiety Disorders. Thus, orexins may be a potential target for treatment of these disorders. In this review, we will focus on what is known about the role of orexins in acute and repeated stress, in stress-induced phenotypes relevant to psychiatric illness in preclinical models, and in stress-related psychiatric illness in humans. We will also briefly discuss how orexins may contribute to sex differences in the stress response and subsequent phenotypes relevant to mental health, as many stress-related psychiatric disorders are twice as prevalent in women.

Embitterment in War Veterans with Posttraumatic Stress Disorder

Article

Full-text available

Apr 2018
Med Arh

Aim The aim of this study was to analyze frequency of embitterment in war veterans with Posttraumatic stress disorder (PTSD). Patients and Methods It was analyzed 174 subjects (from Health Center Zivinice/ Mental Health Center) through a survey conducted in the period from March 2015 to June 2016, of witch 87 war veterans with PTSD and control subjects 87 war veterans without PTSD. The primary outcome measure was the Post-Traumatic Embitterment Disorder Self-Rating Scale (PTED Scale) who contains 19 items designed to assess features of embitterment reactions to negative life events. Secondary efficacy measures included the Clinician-Administered PTSD Scale - V (CAPS), the PTSD CheckList (PCL), the Combat Exposure Scale (CES), the Hamilton Depression Rating Scale (HAM-D), the Hamilton Anxiety Rating Scale (HAM-A) and the World Health Organization Quality of Life Scale (WHOQOL-Bref). All subjects were male. The average age of patients in the group war veterans with PTSD was 52·78 ± 5·99. In the control group average age was 51·42 ± 5·98. Statistical data were analyzed in SPSS statistical program. Results Comparing the results, t tests revealed significant difference between group veterans with PTSD and control group (t=–21·216, p<0·0001). War veterans group with PTSD (X= 51·41 SD= 8·91), war veterans without PTSD (X=14·39, SD=13·61). Conclusion Embitterment is frequent in war veterans with PTSD.

Multimodale Charakterisierung von Patienten mit Vertebralarteriendissektion, funktionelles Outcome und Lebensqualität sowie Korrelation zu psychischen, kognitiven und neurologischen Merkmalen - eine explorative Untersuchung

Article

Jan 2016

Rainer Joachim Strege

Background and Purpose: Cervical artery dissections may cause cerebral ischemia and impair quality of life despite of good functional outcome. The aim of this study was the multimodal analysis of such patients. Methods: In a prospective exploratory study consecutive patients with vertebral artery dissection, patients with cerebral ischemia without dissection and stroke mimics were examined for psychological, cognitive and neurological factors, functional outcome and quality of life. Results: About 40% of patients with vertebral artery dissection showed reduced quality of life despite of good mid-term functional outcome. Subgroup analysis yielded significantly higher screening scores for posttraumatic stress symptoms predictive for quality of life. This finding could be interpreted as maladaptive psychological reaction. Conclusion: Posttraumatic stress symptoms are significantly important for the quality of life after vertebral artery dissection. The screening tools used in this study may enable the early detection of psychological, neurological and cognitive impairments, therapeutic interventions and a better quality of life.

The Association Between Genetic Variants in the Dopaminergic System and Posttraumatic Stress Disorder: A Meta-Analysis

Article

Full-text available

Mar 2016
MEDICINE

Posttraumatic stress disorder (PTSD) is a complex mental disorder and can severely interfere with the normal life of the affected people. Previous studies have examined the association of PTSD with genetic variants in multiple dopaminergic genes with inconsistent results. To perform a systematic literature search and conduct meta-analysis to examine whether genetic variants in the dopaminergic system is associated with PTSD. PubMed, Cochrane Library, Embase, Google Scholar, and HuGE. The studies included subjects who had been screened for the presence of PTSD; the studies provided data for genetic variants of genes involved in the dopaminergic system; the outcomes of interest included diagnosis status of PTSD; and the studies were case–control studies. Odds ratio was used as a measure of association. We used random-effects model in all the meta-analyses. Between-study heterogeneity was assessed using I², and publication bias was evaluated using Egger test. Findings from meta-analyses were confirmed using random-effects meta-analyses under the framework of generalized linear model (GLM). A total of 19 studies met the eligibility criteria and were included in our analyses. We found that rs1800497 in DRD2 was significantly associated with PTSD (OR = 1.96, 95% CI: 1.15–3.33; P = 0.014). The 3′-UTR variable number tandem repeat (VNTR) in SLC6A3 also showed significant association with PTSD (OR = 1.62, 95% CI: 1.12–2.35; P = 0.010), but there was no association of rs4680 in COMT with PTSD (P = 0.595). Sample size is limited for some studies; type and severity of traumatic events varied across studies; we could not control for potential confounding factors, such as age at traumatic events and gender; and we could not examine gene–environment interaction due to lack of data. We found that rs1800497 in DRD2 and the VNTR in SLC6A3 showed significant association with PTSD. Future studies controlling for confounding factors, with large sample sizes and more homogeneous traumatic exposure, are needed to validate the findings from this study.

Use of Noninvasive Parameters to Evaluate Swiss Webster Mice During Trypanosoma cruzi Experimental Acute Infection

Article

Full-text available

Jan 2016
J Parasitol

Until now, there has been neither an agreed-upon experimental model nor descriptors of the clinical symptoms that occur over the course of acute murine infection. The aim of this work is to use non-invasive methods to evaluate clinical signs in Swiss Webster mice that were experimentally infected with the Y strain of Trypanosoma cruzi during acute phase (Inf group). Infected mice showed evident clinical changes beginning in the second week of infection (wpi): (i) animals in hunched postures, closed eyes, lowered ears, peeling skin, increased piloerection, prostration and social isolation; (ii) significant decrease in the body weight (Inf: 26.2Â±2.6 g vs. non-infected group (NI) 34.2Â±2.5 g), chow (1.5Â±0.3 vs. 6.3Â±0.5 mg) and water (2.4Â±0.5 vs. 5.8Â±0.7 ml) intake; (iii) significant decrease of the spontaneous activity as locomotor parameters: distance (0.64Â±0.06 vs. 1.8Â±0.13 m), the velocity (1.9Â±0.3 vs. 6.7Â±1.5 cm/s) and exploratory behaviour by the frequency (1.0Â±0.5 vs.5.7Â±1.0 events) and the duration (1.4Â±0.3 vs. 5.1Â±0.5 s in central arena region); (iv) significant increase in the PR (41.7Â±8.7 vs. 27.6Â±1.9 ms) and QT intervals (39.7Â±2.0 vs. 27.5Â±4.0 ms), and a decreased cardiac frequency (505Â±52.8 vs. 774Â±17.8 ms), showing a marked sinus bradycardia and an AV block. At 3 and 4 wpi, the surviving animals showed a tendency of recovery in body weight, food intake, locomotor activity and exploratory interest. Through the use of non-invasive parameters, we were able to monitor the severity of the infection in individuals prior to death. Our perspective is the application of non-invasive methods to describe clinical signs over the course of acute infection complementing the preclinical evaluation of new agents, alone or in combination with benznidazole.

Use of haloperidol and risperidone in highly aggressive Swiss Webster mice by applying the model of spontaneous aggression (MSA)

Article

Full-text available

Dec 2015

The pros and cons of computer-mediated therapy in the treatment of posttraumatic stress disorder and trauma induced mental health problems

Article

Full-text available

Oct 2010
J COGN BEHAV PSYCHOT

Dramatic increases in the number of individuals affected by mental disorders lead to the reconsideration of the basic principles according to which health-care has this far been delivered. Cost-effective, easily accessible and effective prevention and intervention programs are needed to remedy the actual trend in mental health problems. A viable solution resides in the possibilities offered by computerized programs. The present paper intends to briefly present the advantages and disadvantages of Computer Mediated Therapy in the case of posttraumatic stress disorder and other trauma-induced mental health problems, simultaneously offering alternatives to remedy possible shortcomings.

A Terapia Cognitivo-Comportamental Aplicada à Perturbação Pós-Stresse Traumático - Cognitive-Behavioral Therapy Applied to Post-Traumatic Stress Disorder

Research

Full-text available

May 2015

Este artigo dá sequência ao que é requerido como trabalho de grupo para a unidade curricular designada por Psicologia Clínica e da Saúde: caraterização de uma psicopatologia escolhida pelo grupo (que foi a PPST); descrição das possíveis intervenções para essa psicopatologia e caraterização da mais eficaz (que é a TCC); descrição da aplicação da TCC à PPST e estudos sobre a sua eficácia (onde se incluem duas meta-análises); descrição de um caso clínico (de uma ex-combatente) e reflexão crítica, onde foi salientada a importância de a TCC considerar a vertente positiva da PPST bem como a de considerar os conhecimentos mais recentes da epigenética (sobre a transmissão transgeracional de memórias traumáticas) no sentido de se efetuar um trabalho etiológico mais completo e transgeracionalmente preventivo. --- --- --- --- --- --- --- --- --- --- --- --- --- --- This paper follows up the requirements for the group work of this curricular unit called Clinical and Health Psychology: characterization of a psychopathology chosen by the group (which was PTSD); description of possible interventions for that psychopathology and characterization of the most effective (which is CBT); description of the application of CBT to PTSD and studies on its effectiveness (which includes two meta-analyzes); description of a clinical case (of a war veteran) and critical reflection, which stressed the importance of CBT consider the positive side of PTSD as well as the consideration of the latest knowledge of epigenetics (on the transgenerational transmission of traumatic memories) in order to accomplish a more complete etiological work and transgenerationally preventive.

Sex difference affects fear extinction but not lithium efficacy in rats following fear-conditioning with respect to the hippocampal level of BDNF

Article

Nov 2023
PHARMACOL BIOCHEM BE

Current Understanding of Biomarkers in Post Traumatic Stress Disorder and Mild Traumatic Brain Injury: A Systematic Review and Implications for Research and Treatment

Chapter

Full-text available

Feb 2022

For nearly 100 years, it was erroneously believed that the loss of consciousness and/or the altered mental status associated with a mild traumatic brain injury (mTBI) offered protection from the development of posttraumatic stress disorder (PTSD). However, it is now accepted that it is possible for PTSD to result from mTBI, and that the co-occurrence of these two conditions creates a more difficult condition to treat and worsens prognosis. In addition, it is known that the symptomology associated with PTSD and mTBI have a great deal of overlap, complicating diagnoses. The objective of this chapter is to review the current state of biomarkers aimed at diagnosing comorbid mTBI and PTSD that are useful on a single-patient basis and are not reliant on self-report or arduous interviews. Further, implications for future research and treatment are discussed.

Adverse childhood experiences associate with early post-trauma thalamus and thalamic nuclei volumes and PTSD development in adulthood

Article

Nov 2021
PSYCHIAT RES-NEUROIM

Adverse childhood experiences (ACEs) potentially contribute to posttraumatic stress disorder (PTSD) after adult trauma exposure, but underlying brain changes remain unclear. The present study tested relationships between ACEs, whole thalamus and thalamic nuclei volumes, and post-trauma stress symptoms (PTSS) after adult trauma. Trauma survivors (n=101) completed the Childhood Trauma Questionnaire (CTQ), the PTSD checklist-special stressor version 5 (PCL), and a structural magnetic resonance imaging (sMRI) scan within post-trauma 2 weeks. At post-trauma 3 months, survivors completed a second PCL survey and a PTSD diagnosis interview using the Clinician-Administered PTSD Scale (CAPS). CTQ scores significantly positively correlated with PCL scores at post-trauma 2 weeks and 3 months (respective p's < 0.01 and < 0.001). CTQ scores significantly negatively correlated with whole thalamus and 7 thalamic nuclei volumes at post-trauma 2 weeks in the PTSD (N=50), but not the non-PTSD (N=51) group. Whole thalamus and 22 nuclei volumes significantly negatively correlated with PCL scores at post-trauma 3 months in the PTSD, but not the non-PTSD group. These results suggest ACEs negatively influence early post-trauma thalamic volumes which, in turn, are negatively associated with PTSS in survivors who develop PTSD.

Using deep learning to classify pediatric posttraumatic stress disorder at the individual level

Article

Full-text available

Oct 2021
BMC PSYCHIATRY

Background Children exposed to natural disasters are vulnerable to developing posttraumatic stress disorder (PTSD). Previous studies using resting-state functional neuroimaging have revealed alterations in graph-based brain topological network metrics in pediatric PTSD patients relative to healthy controls (HC). Here we aimed to apply deep learning (DL) models to neuroimaging markers of classification which may be of assistance in diagnosis of pediatric PTSD. Methods We studied 33 pediatric PTSD and 53 matched HC. Functional connectivity between 90 brain regions from the automated anatomical labeling atlas was established using partial correlation coefficients, and the whole-brain functional connectome was constructed by applying a threshold to the resultant 90 * 90 partial correlation matrix. Graph theory analysis was used to examine the topological properties of the functional connectome. A DL algorithm then used this measure to classify pediatric PTSD vs HC. Results Graphic topological measures using DL provide a potentially clinically useful classifier for differentiating pediatric PTSD and HC (overall accuracy 71.2%). Frontoparietal areas (central executive network), cingulate cortex, and amygdala contributed the most to the DL model’s performance. Conclusions Graphic topological measures based on fMRI data could contribute to imaging models of clinical utility in distinguishing pediatric PTSD from HC. DL model may be a useful tool in the identification of brain mechanisms PTSD participants.

fMRI neurofeedback for disorders of emotion regulation

Chapter

Jan 2021

This chapter reviews existing work on fMRI neurofeedback in disorders of emotion regulation such as depression, posttraumatic stress disorder, borderline personality disorder, and anxiety disorders. We present a framework of what to target (disturbed or compensatory functions) as well as how to target (what interface to use and whether to up or downregulate). Considering what to target we suggest the following distinction: (a) targeting disturbed processes which aims to restore neural functions that are aberrant compared to the level of that seen in healthy controls, and (b) targeting compensatory functions which are aimed at leveraging what patients are already using to perform some task/function. With regard to targeting disturbed processes: in major depressive disorder this includes increasing amygdala responses to positive stimuli and decreasing salience network responses to negative stimuli. In posttraumatic stress disorder and borderline personality disorder this includes decreasing limbic brain activity including that of the amygdala. With regard to targeting compensatory processes: in major depressive disorder this involves increasing responses to positive stimuli in prefrontal regions in order to compensate for the lack of limbic and salience network activation. These approaches require identifying neural substrates that may compensate for disturbed functions. In addition to an overview of results in these populations using these approaches, we also discuss major issues in clinical application of neurofeedback for emotion regulation including what and how to target and how to measure training outcome.

Prevalence and risk factors for post‐traumatic stress disorder in Japanese relatives of out‐of‐hospital cardiac arrest patients after receiving a pamphlet concerning the grieving process

Article

Full-text available

Jul 2020

Aim To investigate the prospective frequency of post‐traumatic stress disorder (PTSD) among relatives of sudden death patients following provision of a pamphlet explaining the stages of the complicated grief process and self‐regulating techniques. Methods From May 2017 to February 2018, we prospectively and consecutively provided a pamphlet to relatives of out‐of‐hospital sudden cardiac arrest victims who failed to obtain spontaneous circulation. We investigated the psychiatric status of the bereaved relatives using the Impact of Event Scale – Revised (IES‐R). An IES‐R score over 24 was defined as PTSD. Results Fifty‐four relatives of the 54 dead patients (victims) provided permission of entry to this research. All subjects and victims were Japanese. Among them, 24 subjects had an IES‐R score of 0 and 5 (9.3%) had PTSD approximately 1 month after their bereavement. There were no relatives who received spontaneous psychiatric treatment. The IES‐R scores for non‐medical cardiac arrest, death inquests, and parent variables were significantly higher compared with medical cardiac arrest, no inquest, and no parent, respectively. The IES‐R scores in those who were a child of the victim were significantly lower than in those who were not. Conclusion The present study showed that the frequency of PTSD was 9.3% at 1 month following bereavement among Japanese relatives of sudden death victims after an intervention. This frequency was minimal compared with previous reports.

Pseudopheochromocytoma

Article

Sep 2019
ENDOCRIN METAB CLIN

Pseudopheochromocytoma manifests as severe, symptomatic paroxysmal hypertension without significant elevation in catecholamine and metanephrine levels and lack of evidence of tumor in the adrenal gland. The clinical manifestations are similar but not identical to those in excess circulating catecholamines. The underlying symptomatic mechanism includes augmented cardiovascular responsiveness to catecholamines alongside heightened sympathetic nervous stimulation. The psychological characteristics are probably attributed to the component of repressed emotions related to a past traumatic episode or repressive coping style. Successful management can be achieved by strong collaboration between a hypertension specialist and a psychiatrist or psychologist with expertise in cognitive-behavioral panic management.

The contribution of orexins to sex differences in the stress response

Article

Aug 2018
BRAIN RES

Women are twice as likely as men to suffer from stress-related psychiatric disorders, such as post-traumatic stress disorder (PTSD) and Major Depressive Disorder (MDD), however, the biological basis of these sex differences is not fully understood. Interestingly, orexins are known to be dysregulated in these disorders. This review first discusses the important role of orexins regulating the response to stress. Next, we review the evidence for sex differences in the orexin system, in which the majority of both preclinical and clinical studies have reported higher orexin system expression in females. Finally, we discuss the functional consequences of these sex differences in orexin expression. Most importantly, the preclinical literature reveals that higher orexin system activity in females contributes to exaggerated neuroendocrine and behavioral responses to stress. In sum, the available data suggests that orexins may be important in the etiology of stress-related psychiatric disorders that present differently in men and women. Thus, targeting orexins could potentially ameliorate many phenotypes of stress-related illness in a sex-specific way.

Burnout and posttraumatic stress in paediatric critical care personnel: Prediction from resilience and coping styles

Article

Mar 2018
Aust Crit Care

Introduction: Our aims were (1) to explore the prevalence of burnout syndrome (BOS) and posttraumatic stress disorder (PTSD) in a sample of Spanish staff working in the paediatric intensive care unit (PICU) and compare these rates with a sample of general paediatric staff and (2) to explore how resilience, coping strategies, and professional and demographic variables influence BOS and PTSD. Materials and methods: This is a multicentre, cross-sectional study. Data were collected in the PICU and in other paediatric wards of nine hospitals. Participants consisted of 298 PICU staff members (57 physicians, 177 nurses, and 64 nursing assistants) and 189 professionals working in non-critical paediatric units (53 physicians, 104 nurses, and 32 nursing assistants). They completed the Brief Resilience Scale, the Coping Strategies Questionnaire for healthcare providers, the Maslach Burnout Inventory, and the Trauma Screening Questionnaire. Results: Fifty-six percent of PICU working staff reported burnout in at least one dimension (36.20% scored over the cut-off for emotional exhaustion, 27.20% for depersonalisation, and 20.10% for low personal accomplishment), and 20.1% reported PTSD. There were no differences in burnout and PTSD scores between PICU and non-PICU staff members, either among physicians, nurses, or nursing assistants. Higher burnout and PTSD rates emerged after the death of a child and/or conflicts with patients/families or colleagues. Around 30% of the variance in BOS and PTSD is predicted by a frequent usage of the emotion-focused coping style and an infrequent usage of the problem-focused coping style. Discussion and conclusions: Interventions to prevent and treat distress among paediatric staff members are needed and should be focused on: (i) promoting active emotional processing of traumatic events and encouraging positive thinking; (ii) developing a sense of detached concern; (iii) improving the ability to solve interpersonal conflicts, and (iv) providing adequate training in end-of-life care.

Brain Structural Abnormalities in Posttraumatic Stress Disorder and Relations with Sleeping Problems

Chapter

Jan 2018

Increasing number of neuroimaging studies examine brain structure in posttraumatic stress disorder (PTSD) patients. Limited studies begin to examine the relationship of brain structure and sleep problems in PTSD patients. The current review summarizes the existing findings on structural brain differences between the PTSD patients and control subjects without PTSD, with emphasis on studies related to sleep problems in PTSD patients. The findings of structural differences in hippocampus, prefrontal cortex, anterior cingulate cortex, insular cortex, and corpus callosum of PTSD patients have been reported in multiple studies, but changes in other brain regions are yet to be reliably replicated. Limited studies on pediatric PTSD suggest different picture of structural abnormalities as compared to adult patients. The longitudinal studies suggest that structural properties of prefrontal cortex in trauma-exposed individuals dynamically change over time, and these dynamic brain changes may associate with progression of PTSD symptoms. Finally, limited studies suggest that structural changes in hippocampus and prefrontal brain regions may be associated with the severity of sleep problems in trauma-exposed individuals, but further investigation on this issue is clearly needed.

Stellate Ganglion Block in the Treatment of Post-traumatic Stress Disorder: A Review of Historical and Recent Literature

Article

Oct 2016

Concerns over the rising prevalence of post-traumatic stress disorder (PTSD), particularly among military service members returning from combat, and over barriers that hinder individuals from seeking out or adhering to standard therapies have contributed to interest in alternative therapies for the disorder. A novel alternative therapy for PTSD—stellate ganglion block (SGB)—may be considered lacking in formal evidence of efficacy despite having shown considerable promise. This review of the recent and historical literature related to SGB finds evidence of substantial beneficial psychiatric effects and substantiates that this fast-acting, somatic treatment may provide positive results for patients with PTSD and may reduce barriers to therapy, particularly among military populations.

Posttraumatic Stress Disorder-Related Hospitalizations in the United States (2002-2011): Rates, Co-Occurring Illnesses, Suicidal Ideation/Self-Harm, and Hospital Charges

Article

Nov 2015
J NERV MENT DIS

The purpose of the present study was to evaluate posttraumatic stress disorder (PTSD)-related hospitalizations in the United States (2002-2011). Over this period, there were an estimated 1,477,944 hospitalizations (915,591 women) with either a primary (reason for hospitalization) or secondary PTSD diagnosis. Population-based hospitalization rates rose from 2002 to 2011; women in the age range of 20 to 44 years had the highest rates and the steepest rise. Most of the hospitalizations for men and women younger than 45 years had been assigned a primary diagnosis of mental illness (including PTSD). Mood and substance use disorders were among the most commonly co-occurring psychiatric diagnoses with PTSD. Suicidal ideation/suicide attempts declined with increasing age. The strongest predictor of this criterion was mood disorder, and its importance as a predictor increased as people aged. Total inflation-adjusted charges for all PTSD-related hospitalizations were $34.9 billion, with 36% being for hospitalizations where a mental illness (including PTSD) was the primary diagnosis.

Avaliação Psicológica: Entrevista Clínica - Psychological Assessment: Clinical Interview

Research

Full-text available

Jun 2015

Sandra Ramos and Jorge A. Ramos

Este artigo dá sequência ao que é requerido como trabalho de grupo para a unidade curricular designada por Avaliação Psicológica: efetuar um relatório psicológico intermédio. Para o efeito efetuámos uma entrevista semiestruturada (a uma pessoa encaminhada pelo seu médico com a hipótese de possui PPST) cujo guião foi elaborado tendo por base o DSM-5 e o PTGI. Efetuámos depois uma análise de conteúdo de onde extraímos conclusões preliminares e fizemos recomendações: uma segunda avaliação com a administração da CAPS-5, da LEC-5 e do PTGI e uma terceira avaliação onde: sendo confirmado o diagnóstico de PPST, se aplique a ESE, a VIA-IS e se analise a TTT; sendo infirmada a hipótese de a entrevistada possuir PPST, se aplique a SMGAD-A, a ESE e a VIA-IS. Finalizamos com possibilidades sobre potenciais intervenções psicoterapêuticas, caso se confirme o diagnóstico de PPST. ------------------------------------------------------------------------ This paper follows up the requirements for the group work of this curricular unit called Psychological Assessment: make an intermediate psychological report. For this purpose we made a semi-structured interview (with a person who was directed by her doctor with the hypothesis that she has PTSD) whose script has been prepared based on DSM-5 and PTGI. Then we made a content analysis from where we obtained preliminary findings and made recommendations: a second evaluation with the administration of CAPS-5, LEC-5 and PTGI and a third evaluation where: being confirmed the diagnosis of PTSD, apply the ESE, the VIA-IS and analyze the TTT; being ruled out the possibility that the interviewed have PTSD, apply the SMGAD-A, the ESE and the VIA-IS. We finish with possibilities about potential psychotherapeutic interventions, if the diagnosis of PTSD is confirmed.

Clinician administered PTSD scale

Article

Full-text available

Jan 1990
BEHAV THER

A Randomized, Double-Blind Evaluation of D-Cycloserine or Alprazolam Combined With Virtual Reality Exposure Therapy for Posttraumatic Stress Disorder in Iraq and Afghanistan War Veterans

Article

Full-text available

Apr 2014
AM J PSYCHIAT

Objective: The authors examined the effectiveness of virtual reality exposure augmented with D-cycloserine or alprazolam, compared with placebo, in reducing posttraumatic stress disorder (PTSD) due to military trauma. Method: After an introductory session, five sessions of virtual reality exposure were augmented with D-cycloserine (50 mg) or alprazolam (0.25 mg) in a double-blind, placebo-controlled randomized clinical trial for 156 Iraq and Afghanistan war veterans with PTSD. Results: PTSD symptoms significantly improved from pre- to posttreatment across all conditions and were maintained at 3, 6, and 12 months. There were no overall differences in symptoms between D-cycloserine and placebo at any time. Alprazolam and placebo differed significantly on the Clinician-Administered PTSD Scale score at posttreatment and PTSD diagnosis at 3 months posttreatment; the alprazolam group showed a higher rate of PTSD (82.8%) than the placebo group (47.8%). Between-session extinction learning was a treatment-specific enhancer of outcome for the D-cycloserine group only. At posttreatment, the D-cycloserine group had the lowest cortisol reactivity and smallest startle response during virtual reality scenes. Conclusions: A six-session virtual reality treatment was associated with reduction in PTSD diagnoses and symptoms in Iraq and Afghanistan veterans, although there was no control condition for the virtual reality exposure. There was no advantage of D-cycloserine for PTSD symptoms in primary analyses. In secondary analyses, alprazolam impaired recovery and D-cycloserine enhanced virtual reality outcome in patients who demonstrated within-session learning. D-cycloserine augmentation reduced cortisol and startle reactivity more than did alprazolam or placebo, findings that are consistent with those in the animal literature.

Epigenetic modulation of glucocorticoid receptors in posttraumatic stress disorder

Article

Full-text available

Mar 2014

Some individuals suffering from posttraumatic stress disorder (PTSD) exhibit lower basal salivary cortisol and higher glucocorticoid receptor (GR) sensitivity. Recent studies suggest that epigenetic mechanisms regulate the activity of cortisol and GR. As a means to combine and cross-validate those findings, we compared cortisol, GR expression and promoter methylation levels in peripheral T lymphocytes of healthy controls versus individuals endorsing a diagnosis of lifetime PTSD. Thirty subjects with lifetime (current or remitted) PTSD and 16 subjects never exposed to trauma were recruited. Salivary cortisol was collected at six time points over the course of a single weekday and analyzed utilizing a time-resolved fluorescence immunoassay. GR expression (GRtotal, 1B, 1C, 1F and 1H) was measured by quantitative RT-PCR. DNA methylation levels in human glucocorticoid receptor (hGR) 1B and 1C variant's promoter were quantified by epityper in T lymphocytes isolated by magnetic-assisted cell sorting. Individuals with lifetime PTSD have lower morning cortisol release, higher mRNA expression of hGRtotal, 1B, and 1C and lower overall methylation levels in hGR 1B and 1C promoters. Cortisol levels were inversely correlated with hGR 1B mRNA expression. Moreover, overall and CpG site-specific methylation levels were inversely correlated with hGRtotal and 1B mRNA expression. There was no difference between current and remitted PTSD across cortisol, GR expression mRNA and DNA methylation data. Traumatic events induce DNA methylation alterations in distinct promoters of hGR with transcriptional modifications that associate with hypoactive hypothalamus-pituitary-adrenal axis in individuals with PTSD. Our results also point toward an important role of hGR 1B variant in PTSD.

Prolonged Exposure vs Supportive Counseling for Sexual Abuse-Related PTSD in Adolescent Girls A Randomized Clinical Trial

Article

Full-text available

Dec 2013
J Am Med Assoc

Importance: Evidence-based treatments for posttraumatic stress disorder (PTSD) have not been established for adolescents despite high prevalence of PTSD in this population. Objective: To examine the effects of counselor-delivered prolonged exposure therapy compared with supportive counseling for adolescents with PTSD. Design, setting, and participants: A single-blind, randomized clinical trial of 61 adolescent girls with PTSD using a permuted block design. Counselors previously naive to prolonged exposure therapy provided the treatments in a community mental health clinic. Data collection lasted from February 2006 through March 2012. Interventions: Participants received fourteen 60- to 90-minute sessions of prolonged exposure therapy (n = 31) or supportive counseling (n = 30). Main outcomes and measures: All outcomes were assessed before treatment, at mid-treatment, and after treatment and at 3-, 6-, and 12-month follow-up. The primary outcome, PTSD symptom severity, was assessed by the Child PTSD Symptom Scale-Interview (range, 0-51; higher scores indicate greater severity). Secondary outcomes were presence or absence of PTSD diagnosis assessed by the DSM-IV Schedule for Affective Disorders and Schizophrenia for School-Age Children and functioning assessed by the Children's Global Assessment Scale (range, 1-100; higher scores indicate better functioning). Additional secondary measures, PTSD severity assessed by the Child PTSD Symptom Scale-Self-Report (range, 0-51; higher scores indicate greater severity) and depression severity assessed by the Children's Depression Inventory (range, 0-54; higher scores indicate greater severity), were also assessed weekly during treatment. Results: Data were analyzed as intent to treat. During treatment, participants receiving prolonged exposure demonstrated greater improvement on the PTSD symptom severity scale (difference between treatments in improvement, 7.5; 95% CI, 2.5-12.5; P < .001) and on all secondary outcomes (loss of PTSD diagnosis: difference, 29.3%, 95% CI, 20.2%-41.2%; P = .01; self-reported PTSD severity: difference, 6.2; 95% CI, 1.2-11.2; P = .02; depression: difference, 4.9; 95% CI, 1.6-8.2; P = .008; global functioning: difference, 10.1; 95% CI, 3.4-16.8; P = .008). These treatment differences were maintained through the 12-month follow-up: for interviewer-assessed PTSD (difference, 6.0; 95% CI, 1.6-10.4; P = .02), loss of PTSD diagnosis (difference, 31.1; 95% CI, 14.7-34.8; P = .01), self-reported PTSD (difference, 9.3; 95% CI, 1.2-16.5; P = .02), depression (difference, 7.2; 95% CI, 1.4-13.0; P = .02), and global functioning (difference, 11.2; 95% CI, 4.5-17.9; P = .01). Conclusion and relevance: Adolescents girls with sexual abuse-related PTSD experienced greater benefit from prolonged exposure therapy than from supportive counseling even when delivered by counselors who typically provide supportive counseling. Trial registration: clinicaltrials.gov Identifier: NCT00417300.

Epigenetics of Stress Adaptations in the Brain.

Article

Full-text available

Jul 2013

Recent findings in epigenetics shed new light on the regulation of gene expression in the central nervous system (CNS) during stress. The most frequently studied epigenetic mechanisms are DNA methylation, histone modifications and microRNA activity. These mechanisms stably determine cell phenotype but can also be responsible for dynamic molecular adaptations of the CNS to stressors. The limbic-hypothalamic-pituitary-adrenal axis (LHPA) is the primary circuit that initiates, regulates and terminates a stress response. The same brain areas that control stress also react to stress dynamically and with long-term consequences. One of the biological processes evoking potent adaptive changes in the CNS such as changes in behavior, gene activity or synaptic plasticity in the hippocampus is psychogenic stress. This review summarizes the current data regarding the epigenetic basis of molecular adaptations in the brain including genome-wide epigenetic changes of DNA methylation and particular genes involved in epigenetic responses that participate in the brain response to chronic psychogenic stressors. It is concluded that specific epigenetic mechanisms in the CNS are involved in the stress response.

The Role of Intelligence in Posttraumatic Stress Disorder: Does it Vary by Trauma Severity?

Article

Full-text available

Jun 2013
PLOS ONE

Only a small minority of trauma victims develops post-traumatic stress disorder (PTSD), suggesting that victims vary in their predispositions to the PTSD response to stressors. It is assumed that the role of predispositions in PTSD varies by trauma severity: when stressors are less severe, predispositions play a bigger role. In this study, we test whether the role of intelligence in PTSD varies by trauma severity. Specifically, does low intelligence plays a bigger part among victims of lower magnitude stressors than among victims of extreme stressors? Data come from a longitudinal study of randomly selected sample in Southeast Michigan (n = 713). IQ was measured at age 6. PTSD was measured at age 17, using the NIMH-DIS for DSM-IV. Stressors were classified as extreme if they involved assaultive violence (e.g. rape, sexual assault, threatened with a weapon); other stressors in the list (e.g. disaster, accidents) were classified as lower magnitude. Assaultive violence victims had experienced assaultive violence plus other event types or only assaultive violence. Victims of other stressors were participants who had never experienced assaultive violence. We compared the influence of age 6 IQ on PTSD among persons exposed to assaultive violence vs. other stressors, using multinomial logistic regression. Relative risk ratio (RRR) for PTSD associated with a one point drop in age 6 IQ among victims of assaultive violence was 1.04 (95% CI 1.01, 1.06); among victims of other stressors, it was 1.03 (95% CI 0.99, 1.06). A comparison of the two RRRs indicates no significant difference between the two estimates (p = 0.652). IQ does not play a bigger role in PTSD among victims of other stressors than it does among victims of assaultive violence. Lower IQ exerts an adverse PTSD effect on trauma victims, with no evidence of variability by the severity of trauma they have experienced.

Treatment Preference among Suicidal and Self-Injuring Women with Borderline Personality Disorder and PTSD

Article

Full-text available

Jul 2013
J CLIN PSYCHOL

Objectives: This study examined treatment preferences among suicidal and self-injuring women with borderline personality disorder (BPD) and PTSD. Method: Women (N = 42, M(age) = 34) with BPD, PTSD and recent intentional self-injury were evaluated upon entry into a psychotherapy outcome study. Results: The majority preferred a combined dialectical behavior therapy (DBT) and prolonged exposure (PE) treatment (73.8%), followed by DBT alone (26.2%), and PE alone (0%). Women who preferred the combined treatment were more likely to report a desire to obtain relief from PTSD and to receive specific DBT and PE treatment components as reasons underlying this preference. Few women (21.4%) reported concerns about PE, but those who did were more likely to prefer DBT alone. More severe PTSD re-experiencing symptoms, a childhood index trauma, and less reduction in positive affect after a trauma interview predicted a preference for the combined treatment. Conclusions: These results may help to inform treatment for these complex patients.

Neural Mechanisms of Impaired Fear Inhibition in Posttraumatic Stress Disorder

Article

Full-text available

Jul 2011

Posttraumatic stress disorder (PTSD) can develop in some individuals who are exposed to an event that causes extreme fear, horror, or helplessness (APA, 1994). PTSD is a complex and heterogeneous disorder, which is often co-morbid with depression, substance abuse, and anxiety disorders such as panic or social phobia. Given this complexity, progress in the field can be greatly enhanced by focusing on phenotypes that are more proximal to the neurobiology of the disorder. Such neurobiological intermediate phenotypes can provide investigative tools to increase our understanding of the roots of the disorder and develop better prevention or intervention programs. In the present paper, we argue that the inhibition of fear responses is an intermediate phenotype that is related to both the neurocircuitry associated with the disorder, and is linked to its clinical symptoms. An advantage of focusing on fear inhibition is that the neurobiology of fear has been well investigated in animal models providing the necessary groundwork in understanding alterations. Furthermore, because many paradigms can be tested across species, fear inhibition is an ideal translational tool. Here we review both the behavioral tests and measures of fear inhibition and the related neurocircuitry in neuroimaging studies with both healthy and clinical samples.

Prolonged exposure therapy for post-traumatic stress disorder: A review of evidence and dissemination

Article

Full-text available

Aug 2011

Post-traumatic stress disorder (PTSD) is a highly prevalent, often chronic and disabling psychiatric disorder that is associated with significant adverse health and life consequences. Fortunately, there is compelling evidence that cognitive-behavioral therapies, notably exposure therapies, are effective in reducing PTSD symptomology relative to waiting list and active control conditions. Prolonged exposure is a specific exposure therapy program that is considered a first-line evidence-based treatment for PTSD. Unfortunately, barriers to treatment dissemination prevent the majority of individuals with PTSD from receiving evidence-based treatment. Strategies to increase the availability of treatment and boost the efficiency of exposure therapy are now being examined.

A Novel Role of the WNT-Dishevelled-GSK3 Signaling Cascade in the Mouse Nucleus Accumbens in a Social Defeat Model of Depression

Article

Full-text available

Jun 2011
J NEUROSCI

Based on earlier gene expression and chromatin array data, we identified the protein, dishevelled (DVL)-2, as being regulated in the nucleus accumbens (NAc), a key brain reward region, in the mouse social defeat model of depression. Here, we validate these findings by showing that DVL2 mRNA and protein levels are downregulated in NAc of mice susceptible to social defeat stress, effects not seen in resilient mice. Other DVL isoforms, DVL1 and DVL3, show similar patterns of regulation. Downregulation of DVL was also demonstrated in the NAc of depressed humans examined postmortem. Interestingly, several members of the WNT (Wingless)-DVL signaling cascade, including phospho-GSK3β (glycogen synthase kinase-3β), also show significant downregulation in the NAc of susceptible, but not resilient, mice, demonstrating concerted regulation of this pathway in the NAc due to social defeat stress. By using viral-mediated gene transfer to overexpress a dominant-negative mutant of DVL in NAc, or by using a pharmacological inhibitor of DVL administered into this brain region, we show that blockade of DVL function renders mice more susceptible to social defeat stress and promotes depression-like behavior in other assays. Similar prodepression-like effects were induced upon overexpressing GSK3β in the NAc, while overexpressing a dominant-negative mutant of GSK3β promoted resilience to social defeat stress. These findings are consistent with the knowledge that downregulation of DVL and phospho-GSK3β reflects an increase in GSK3β activity. These studies reveal a novel role for the DVL-GSK3β signaling pathway, acting within the brain's reward circuitry, in regulating susceptibility to chronic stress.

Does Reconsolidation Occur in Humans?

Article

Full-text available

May 2011

Evidence for reconsolidation in non-human animals has accumulated rapidly in the last decade, providing compelling` demonstration for this phenomenon across species and memory paradigms. In vast contrast, scant evidence exists for human reconsolidation to date. A major reason for this discrepancy is the invasive nature of current techniques used to investigate reconsolidation, which are difficult to apply in humans. Pharmacological blockade of reconsolidation, for example, has been typically used in animals as a proof of concept. However, most compounds used in these studies are toxic for humans, and those compounds that are safe target related, but not direct mechanisms of reconsolidation. Thus, although human reconsolidation has been hypothesized, there is limited evidence it actually exists. The best evidence for human reconsolidation emerges from non-invasive techniques that "update" memory during reconsolidation rather than block it, a technique only rarely used in animal research. Here we discuss the current state of human reconsolidation and the challenges ahead. We review findings on reconsolidation of emotional associative, episodic, and procedural memories, using invasive and non-invasive techniques. We discuss the possible interpretation of these results, attempt to reconcile some inconsistencies, and suggest a conceptual framework for future research.

Tailoring therapeutic strategies for treating posttraumatic stress disorder symptom clusters

Article

Full-text available

Sep 2010

According to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, posttraumatic stress disorder (PTSD) is characterized by three major symptom clusters following an event that elicited fear, helplessness, or horror. This review will examine each symptom cluster of PTSD separately, giving case study examples of patients who exhibit a preponderance of a given symptom domain. We use a translational approach in describing the underlying neurobiology that is relevant to particular symptoms and treatment options, thus showing how clinical practice can benefit from current research. By focusing on symptom clusters, we provide a more specific view of individual patient's clinical presentations, in order to better address treatment needs. Finally, the review will also address potential genetic approaches to treatment as another form of individualized treatment.

ΔFosB in brain reward circuits mediates resilience to stress and antidepressant responses

Article

Full-text available

Jun 2010
NAT NEUROSCI

In contrast with the many studies of stress effects on the brain, relatively little is known about the molecular mechanisms of resilience, the ability of some individuals to escape the deleterious effects of stress. We found that the transcription factor DeltaFosB mediates an essential mechanism of resilience in mice. Induction of DeltaFosB in the nucleus accumbens, an important brain reward-associated region, in response to chronic social defeat stress was both necessary and sufficient for resilience. DeltaFosB induction was also required for the standard antidepressant fluoxetine to reverse behavioral pathology induced by social defeat. DeltaFosB produced these effects through induction of the GluR2 AMPA glutamate receptor subunit, which decreased the responsiveness of nucleus accumbens neurons to glutamate, and through other synaptic proteins. Together, these findings establish a previously unknown molecular pathway underlying both resilience and antidepressant action.

Magnetic Resonance Imaging of Hippocampal Subfields in Posttraumatic Stress Disorder

Article

Full-text available

Mar 2010

Most neuroimaging studies of posttraumatic stress disorder (PTSD) have focused on potential abnormalities in the whole hippocampus, but the subfields of this structure, which have distinctive histological characteristics and specialized functions, have not been investigated. Studies of individual subfields may clarify the role of the hippocampus in PTSD. To determine if PTSD is associated with structural alterations in specific subfields of the hippocampus. Case-control study. A total of 17 male veterans with combat trauma and PTSD (mean [SD] age, 41 [12] years) and 19 age-matched male veterans without PTSD who were recruited from the outpatient mental health clinic of the San Francisco Veterans Affairs Medical Center and by advertising in the community. High-resolution magnetic resonance imaging at 4 T. Volumes of hippocampal subfields. Posttraumatic stress disorder was associated with 11.4% (1.5%) (P = .02) smaller mean (SD) cornu ammonis 3 (CA3)/dentate gyrus subfield volumes, irrespective of age-related alterations, whereas other subfields were spared. Age was associated with reduced volume of the CA1 subfield (P = .03). Total hippocampal volume was also reduced in PTSD by a mean (SD) of 6.5% (0.6%) but, related to both PTSD (P = .05) and age (P = .01), was consistent with the measurements in the subfields. The findings indicate for the first time in humans that PTSD is associated with selective volume loss of the CA3/dentate gyrus subfields, consistent with animal studies, implying that chronic stress suppresses neurogenesis and dendritic branching in these structures.

A Genetic Variant BDNF Polymorphism Alters Extinction Learning in Both Mouse and Human

Article

Full-text available

Feb 2010
SCIENCE

Mouse models are useful for studying genes involved in behavior, but whether they are relevant to human behavior is unclear. Here, we identified parallel phenotypes in mice and humans resulting from a common single-nucleotide polymorphism in the brain-derived neurotrophic factor (BDNF) gene, which is involved in anxiety-related behavior. An inbred genetic knock-in mouse strain expressing the variant BDNF recapitulated the phenotypic effects of the human polymorphism. Both were impaired in extinguishing a conditioned fear response, which was paralleled by atypical frontoamygdala activity in humans. Thus, this variant BDNF allele may play a role in anxiety disorders showing impaired learning of cues that signal safety versus threat and in the efficacy of treatments that rely on extinction mechanisms, such as exposure therapy.

CRF receptor blockade prevents initiation and consolidation of stress effects on affect in the predator stress model of PTSD

Article

Full-text available

Sep 2009
INT J NEUROPSYCHOPH

Post traumatic stress disorder (PTSD) is a chronic anxiety disorder initiated by an intensely threatening, traumatic event. There is a great need for more efficacious pharmacotherapy and preventive treatments for PTSD. In animals, corticotropin-releasing factor (CRF) and the CRF1 receptor play a critical role in behavioural and neuroendocrine responses to stress. We tested the hypothesis that CRF1 activation is required for initiation and consolidation of long-term effects of trauma on anxiety-like behaviour in the predator exposure (predator stress) model of PTSD. Male C57BL6 mice were treated with the selective CRF1 antagonist CRA0450 (2, 20 mg/kg) 30 min before or just after predator stress. Long-term effects of stress on rodent anxiety were measured 7 d later using acoustic startle, elevated plus maze (EPM), light/dark box, and hole-board tests. Predator stress increased startle amplitude and delayed startle habituation, increased time in and decreased exits from the dark chamber in the light/dark box test, and decreased risk assessment in the EPM. CRF1 antagonism had limited effects on these behaviours in non-stressed controls, with the high dose decreasing risk assessment in the EPM. However, in stressed animals CRF1 antagonism blocked initiation and consolidation of stressor effects on startle, and returned risk assessment to baseline levels in predator-stressed mice. These findings implicate CRF1 activation in initiation and post-trauma consolidation of predator stress effects on anxiety-like behaviour, specifically on increased arousal as measured by exaggerated startle behaviours. These data support further research of CRF1 antagonists as potential prophylactic treatments for PTSD.

Protective Effect of CRHR1 Gene Variants on the Development of Adult Depression Following Childhood Maltreatment

Article

Full-text available

Oct 2009

A previous study reported a gene x environment interaction in which a haplotype in the corticotropin-releasing hormone receptor 1 gene (CRHR1) was associated with protection against adult depressive symptoms in individuals who were maltreated as children (as assessed by the Childhood Trauma Questionnaire [CTQ]). To replicate the interaction between childhood maltreatment and a TAT haplotype formed by rs7209436, rs110402, and rs242924 in CRHR1, predicting adult depression. Two prospective longitudinal cohort studies. England and New Zealand. Participants in the first sample were women in the E-Risk Study (N = 1116), followed up to age 40 years with 96% retention. Participants in the second sample were men and women in the Dunedin Study (N = 1037), followed up to age 32 years with 96% retention. Main Outcome Measure Research diagnoses of past-year and recurrent major depressive disorder. In the E-Risk Study, the TAT haplotype was associated with a significant protective effect. In this effect, women who reported childhood maltreatment on the CTQ were protected against depression. In the Dunedin Study, which used a different type of measure of maltreatment, this finding was not replicated. A haplotype in CRHR1 has been suggested to exert a protective effect against adult depression among research participants who reported maltreatment on the CTQ, a measure that elicits emotional memories. This suggests the hypothesis that CRHR1's protective effect may relate to its function in the consolidation of memories of emotionally arousing experiences.

The Lifetime Prevalence of Traumatic Events and Posttraumatic Stress Disorder in the Netherlands

Article

Full-text available

Aug 2009
J TRAUMA STRESS

Little information exists on the lifetime prevalence of traumatic events and posttraumatic stress disorder (PTSD) in the general population of the Netherlands. A national representative sample of 1087 adults aged 18 to 80 years was selected using random digit dialing and then surveyed by telephone using the Composite International Diagnostic Interview (CIDI) to determine the prevalence of trauma and DSM-IV PTSD. The lifetime prevalence of any potential trauma was 80.7%, and the lifetime prevalence of PTSD was 7.4%. Women and younger persons showed higher risk of PTSD. It was concluded that PTSD is a fairly common disorder and exposure to trauma is high throughout the population. Unexpectedly, prevalence rates resemble those found in the United States and are higher than in several other European countries.

The Neurocircuitry of Fear, Stress, and Anxiety Disorders

Article

Full-text available

Aug 2009
NEUROPSYCHOPHARMACOL

Anxiety disorders are a significant problem in the community, and recent neuroimaging research has focused on determining the brain circuits that underlie them. Research on the neurocircuitry of anxiety disorders has its roots in the study of fear circuits in animal models and the study of brain responses to emotional stimuli in healthy humans. We review this research, as well as neuroimaging studies of anxiety disorders. In general, these studies have reported relatively heightened amygdala activation in response to disorder-relevant stimuli in post-traumatic stress disorder, social phobia, and specific phobia. Activation in the insular cortex appears to be heightened in many of the anxiety disorders. Unlike other anxiety disorders, post-traumatic stress disorder is associated with diminished responsivity in the rostral anterior cingulate cortex and adjacent ventral medial prefrontal cortex. Additional research will be needed to (1) clarify the exact role of each component of the fear circuitry in the anxiety disorders, (2) determine whether functional abnormalities identified in the anxiety disorders represent acquired signs of the disorders or vulnerability factors that increase the risk of developing them, (3) link the findings of functional neuroimaging studies with those of neurochemistry studies, and (4) use functional neuroimaging to predict treatment response and assess treatment-related changes in brain function.

The Effects of Respiratory Sinus Arrhythmia Biofeedback on Heart Rate Variability and Posttraumatic Stress Disorder Symptoms: A Pilot Study

Article

Full-text available

May 2009
APPL PSYCHOPHYS BIOF

Recent studies have found a significant association between PTSD and low heart rate variability (HRV), a biomarker of autonomic dysregulation. Research indicates that respiratory sinus arrhythmia (RSA) biofeedback increases HRV while reducing related pathological symptoms. This controlled pilot study compared RSA biofeedback to progressive muscle relaxation (PMR) as adjunctive interventions for 38 persons with PTSD symptoms in a residential treatment facility for a substance use disorder. Both groups were assessed at pre-intervention and 4-week post-intervention. Group x time interactions revealed significantly greater reductions in depressive symptoms and increases in HRV indices for the RSA group. Both groups significantly reduced PTSD and insomnia symptoms and a statistical trend was observed for reduced substance craving for the RSA group. Increases in HRV were significantly associated with PTSD symptom reduction. Overall, these results provide preliminary support for the efficacy of RSA biofeedback in improving physiological and psychological health for individuals with PTSD.

Acceptance and Commitment Therapy: A Meta-Analytic Review

Article

Full-text available

Feb 2009
PSYCHOTHER PSYCHOSOM

There are now a substantial number of controlled trials investigating the efficacy of acceptance and commitment therapy (ACT). This meta-analysis combined multiple well-controlled studies to help clarify the overall impact of ACT relative to waiting lists, psychological placebos, treatment as usual, and established therapies. A comprehensive literature search produced 18 randomized controlled trials (n = 917) that were included in the final analyses. Effect size was computed with Hedges's g which can be interpreted with Cohen's convention of small (0.2), medium (0.5), and large (0.8) effects. There was a clear overall advantage of ACT compared to control conditions (effect size = 0.42). The average ACT-treated participant was more improved than 66% of the participants in the control conditions. Analyzed separately ACT was superior to waiting lists and psychological placebos (effect size = 0.68) and treatment as usual (effect size = 0.42). However, ACT was not significantly more effective than established treatments (effect size = 0.18, p = 0.13). Also, ACT was not superior to control conditions for the distress problems (anxiety/depression: effect size = 0.03, p = 0.84). The results reveal that ACT is more effective than control conditions for several problem domains, but there is no evidence yet that ACT is more effective than established treatments.

Posttraumatic Stress Disorder in the National Comorbidity Survey

Article

Full-text available

Jan 1996
ARCH GEN PSYCHIAT

Data were obtained on the general population epidemiology of DSM-III-R posttraumatic stress disorder (PTSD), including information on estimated life-time prevalence, the kinds of traumas most often associated with PTSD, sociodemographic correlates, the comorbidity of PTSD with other lifetime psychiatric disorders, and the duration of an index episode. Modified versions of the DSM-III-R PTSD module from the Diagnostic Interview Schedule and of the Composite International Diagnostic Interview were administered to a representative national sample of 5877 persons aged 15 to 54 years in the part II subsample of the National Comorbidity Survey. The estimated lifetime prevalence of PTSD is 7.8%. Prevalence is elevated among women and the previously married. The traumas most commonly associated with PTSD are combat exposure and witnessing among men and rape and sexual molestation among women. Posttraumatic stress disorder is strongly comorbid with other lifetime DSM-III-R disorders. Survival analysis shows that more than one third of people with an index episode of PTSD fail to recover even after many years. Posttraumatic stress disorder is more prevalent than previously believed, and is often persistent. Progress in estimating age-at-onset distributions, cohort effects, and the conditional probabilities of PTSD from different types of trauma will require future epidemiologic studies to assess PTSD for all lifetime traumas rather than for only a small number of retrospectively reported "most serious" traumas.

MRI-Based Measurement of Hippocampal Volume in Patients With Combat-Related Posttraumatic Stress Disorder

Article

Full-text available

Aug 1995

Studies in nonhuman primates suggest that high levels of cortisol associated with stress have neurotoxic effects on the hippocampus, a brain structure involved in memory. The authors previously showed that patients with combat-related posttraumatic stress disorder (PTSD) had deficits in short-term memory. The purpose of this study was to compare the hippocampal volume of patients with PTSD to that of subjects without psychiatric disorder. Magnetic resonance imaging was used to measure the volume of the hippocampus in 26 Vietnam combat veterans with PTSD and 22 comparison subjects selected to be similar to the patients in age, sex, race, years of education, socioeconomic status, body size, and years of alcohol abuse. The PTSD patients had a statistically significant 8% smaller right hippocampal volume relative to that of the comparison subjects, but there was no difference in the volume of other brain regions (caudate and temporal lobe). Deficits in short-term verbal memory as measured with the Wechsler Memory Scale were associated with smaller right hippocampal volume in the PTSD patients only. These findings are consistent with a smaller right hippocampal volume in PTSD that is associated with functional deficits in verbal memory.

Prevalence of civilian trauma and PTSD in a representative sample of women

Article

Full-text available

Dec 1993

Prevalence of crime and noncrime civilian traumatic events, lifetime posttraumatic stress disorder (PTSD), and PTSD in the past 6 months were assessed in a sample of U.S. adult women (N = 4,008). Random digit-dial telephone methods were used to identify study participants. Structured telephone interviews for assessment of specific crime or other traumatic event history and PTSD were conducted by trained female interviewers. Lifetime exposure to any type of traumatic event was 69%, whereas exposure to crimes that included sexual or aggravated assault or homicide of a close relative or friend occurred among 36%. Overall sample prevalence of PTSD was 12.3% lifetime and 4.6% within the past 6 months. The rate of PTSD was significantly higher among crime versus noncrime victims (25.8% vs. 9.4%). History of incidents that included direct threat to life or receipt of injury was a risk factor for PTSD. Findings are compared with data from other epidemiological studies. Results are discussed as they relate to PTSD etiology.

Magnetic Resonance Imaging-Based Measurement of Hippocampal Volume in Posttraumatic Stress Disorder Related to Childhood Physical and Sexual Abuse—A Preliminary Report

Article

Full-text available

Jan 1997
BIOL PSYCHIAT

We have previously reported smaller hippocampal volume and deficits in short-term memory in patients with combat-related posttraumatic stress disorder (PTSD) relative to comparison subjects. The purpose of this study was to compare hippocampal volume in adult survivors of childhood abuse to matched controls. Magnetic resonance imaging was used to measure volume of the hippocampus in adult survivors of childhood abuse (n = 17) and healthy subjects (n = 17) matched on a case-by-case basis for age, sex, race, handedness, years of education, body size, and years of alcohol abuse. All patients met criteria for PTSD secondary to childhood abuse. PTSD patients had a 12% smaller left hippocampal volume relative to the matched controls (p < .05), without smaller volumes of comparison regions (amygdala, caudate, and temporal lobe). The findings were significant after controlling for alcohol, age, and education, with multiple linear regression. These findings suggest that a decrease in left hippocampal volume is associated with abuse-related PTSD.

Treatment of post-traumatic stress disorder with venlafaxine extended release: a 6-month, randomized, controlled trial

Article

Oct 2006
ARCH GEN PSYCHIAT

Context No large-scale posttraumatic stress disorder drug trials have been conducted to evaluate treatment effects beyond 12 weeks outside of those with selective serotonin reuptake inhibitors. Objective To evaluate the efficacy of venlafaxine extended release (ER), a serotonin norepinephrine reuptake inhibitor, in posttraumatic stress disorder. Design 6-month, double-blind, placebo-controlled trial. Setting International study at 56 sites. Patients Adult outpatients (N = 329) with a primary diagnosis of posttraumatic stress disorder as defined in the DSM-IV, symptoms for 6 months or longer, and a 17-item Clinician-Administered Posttraumatic Stress Disorder Scale score of 60 or higher. Intervention Patients randomly assigned to receive flexible doses of venlafaxine ER (37.5-300 mg/d) or placebo for 24 weeks. Main Outcome Measures Primary measure was the change from baseline in the Clinician-Administered Posttraumatic Stress Disorder Scale score. Secondary measures included remission, defined as a Clinician-Administered Posttraumatic Stress Disorder Scale score of 20 or lower, and changes in symptom cluster scores, frequency of remission, and time to remission. Measures of stress vulnerability, resilience, depression, quality of life, functioning, and global illness severity were also taken. Results Mean changes from baseline in Clinician-Administered Posttraumatic Stress Disorder Scale total scores at end point were –51.7 for venlafaxine ER and –43.9 for placebo (P = .006). Improvement was significantly greater for the venlafaxine ER group than for the placebo group in cluster scores for reexperiencing (P = .008) and avoidance/numbing (P = .006), but not for hyperarousal. Remission rates were 50.9% for venlafaxine ER and 37.5% for placebo (P = .01). The venlafaxine ER group also showed significantly greater improvement at end point than the placebo group (P<.05) on all other reported outcome measures. The mean maximum daily dose of venlafaxine ER was 221.5 mg/d. Withdrawal rates were similar between groups with no significant difference in dropouts attributable to adverse events. Conclusion In this study, venlafaxine ER was effective and well tolerated in short-term and continuation treatment of patients with posttraumatic stress disorder.

Biology of Posttraumatic Stress Disorder

Article

May 2000

Rachel Yehuda

An understanding of the biological basis of posttraumatic stress disorder (PTSD) requires an examination of the underlying neurobiology of fear and the factors that might contribute to an unsuccessful termination of the fear response in some individuals. Several factors may lead to an inadequate termination of a stress response, and the failure to contain the biological alterations initiated by stress may have long-term adverse consequences. In particular, a prolonged continuation of biological responses following stress may lead to an inappropriate pairing of the traumatic memory with distress and may then initiate a cascade of secondary biological alterations. This article examines some of the biological alterations in PTSD and develops a framework for understanding the development progression of the neurobiology of this disorder. (J Clin Psychiatry 2000;61[suppl 7]:14–21)

Protective Effect of CRHR1 Gene Variants on the Development of Adult Depression Following Childhood Maltreatment Replication and Extension

Article

Sep 2009
ARCH GEN PSYCHIAT

Context: Aprevious study reported a gene X environment interaction in which a haplotype in the corticotropin-releasing hormone receptor 1 gene (CRHR1) was associated with protection against adult depressive symptoms in individuals who were maltreated as children (as assessed by the Childhood Trauma Questionnaire [CTQ]). Objective: To replicate the interaction between childhood maltreatment and a TAT haplotype formed by rs7209436, rs110402, and rs242924 in CRHR1, predicting adult depression. Design: Two prospective longitudinal cohort studies. Setting: England and New Zealand. Participants: Participants in the first sample were women in the E-Risk Study (N=1116), followed up to age 40 years with 96% retention. Participants in the second sample were men and women in the Dunedin Study (N=1037), followed up to age 32 years with 96% retention. Main Outcome Measure: Research diagnoses of past-year and recurrent major depressive disorder. Results: In the E-Risk Study, the TAT haplotype was associated with a significant protective effect. In this effect, women who reported childhood maltreatment on the CTQ were protected against depression. In the Dunedin Study, which used a different type of measure of maltreatment, this finding was not replicated. Conclusions: A haplotype in CRHR1 has been suggested to exert a protective effect against adult depression among research participants who reported maltreatment on the CTQ, a measure that elicits emotional memories. This suggests the hypothesis that CRHR1's protective effect may relate to its function in the consolidation of memories of emotionally arousing experiences.

National Institute of Mental Health Diagnostic Interview Schedule: Its history, characteristics and validity

Article

Apr 1981
ARCH GEN PSYCHIAT

A new interview schedule allows lay interviewers or clinicians to make psychiatric diagnoses according to DSM-III criteria, Feighner criteria, and Research Diagnostic Criteria. It is being used in a set of epidemiological studies sponsored by the National Institute of Mental Health Center for Epidemiological Studies. Its accuracy has been evaluated in a test-retest design comparing independent administrations by psychiatrists and lay interviewers to 216 subjects (inpatients, outpatients, ex-patients, and nonpatients).

Posttraumatic Stress Disorder in the National Comorbidity Survey

Article

Dec 1995
ARCH GEN PSYCHIAT

Ronald C. Kessler

Background: Data were obtained on the general population epidemiology of DSM-III-R posttraumatic stress disorder (PTSD), including information on estimated lifetime prevalence, the kinds of traumas most often associated with PTSD, sociodemographic correlates, the comorbidity of PTSD with other lifetime psychiatric disorders, and the duration of an index episode.Methods: Modified versions of the DSM-III-R PTSD module from the Diagnostic Interview Schedule and of the Composite International Diagnostic Interview were administered to a representative national sample of 5877 persons aged 15 to 54 years in the part II subsample of the National Comorbidity Survey.Results: The estimated lifetime prevalence of PTSD is 7.8%. Prevalence is elevated among women and the previously married. The traumas most commonly associated with PTSD are combat exposure and witnessing among men and rape and sexual molestation among women. Posttraumatic stress disorder is strongly comorbid with other lifetime DSM-III-R disorders. Survival analysis shows that more than one third of people with an index episode of PTSD fail to recover even after many years.Conclusions: Posttraumatic stress disorder is more prevalent than previously believed, and is often persistent. Progress in estimating age-at-onset distributions, cohort effects, and the conditional probabilities of PTSD from different types of trauma will require future epidemiologic studies to assess PTSD for all lifetime traumas rather than for only a small number of retrospectively reported "most serious" traumas.

The National Institute of Mental Health Diagnostic Interview Schedule for Children

Article

Apr 1981
ARCH GEN PSYCHIAT

Lee N. Robins

• A new interview schedule allows lay interviewers or clinicians to make psychiatric diagnoses according to DSM-III criteria, Feighner criteria, and Research Diagnostic Criteria. It is being used in a set of epidemiological studies sponsored by the National Institute of Mental Health Center for Epidemiological Studies. Its accuracy has been evaluated in a test-retest design comparing independent administrations by psychiatrists and lay interviewers to 216 subjects (inpatients, outpatients, ex-patients, and nonpatients).

Pharmacological interventions for preventing post-traumatic stress disorder (PTSD)

Article

Jul 2014
COCHRANE DB SYST REV

Background: Post-traumatic stress disorder (PTSD) is a debilitating disorder which, after a sufficient delay, may be diagnosed amongst individuals who respond with intense fear, helplessness or horror to traumatic events. There is some evidence that the use of pharmacological interventions immediately after exposure to trauma may reduce the risk of developing of PTSD. Objectives: To assess the effects of pharmacological interventions for the prevention of PTSD in adults following exposure to a traumatic event. Search methods: We searched the Cochrane Depression, Anxiety and Neurosis Controlled Trials Register (CCDANCTR-Studies and CCDANCTR-References) (to 14 February 2014). This register contains relevant reports of randomised controlled trials from the following bibliographic databases: CENTRAL (all years); EMBASE (1974 to date); MEDLINE (1950 to date) and PsycINFO (1967 to date). We identified unpublished trials by searching the National Institute of Health (NIH) Reporter, the metaRegister of Controlled Trials database (mRCT) and the WHO International Clinical Trials Registry Platform (to December 2013). We scanned the reference lists of articles for additional studies. We placed no constraints on language and setting. Selection criteria: We restricted studies to randomised controlled trials (RCTs) of pharmacological interventions compared with placebo for the prevention of PTSD in adults. Data collection and analysis: Two authors (TA and JI) independently assessed trials for eligibility and inclusion based on the review selection criteria. We independently extracted sample, methodological, outcome and 'Risk of bias' data, as well as the number of side effects, from each trial and entered these into a customised data extraction form. We contacted investigators for missing information. We calculated summary statistics for continuous and dichotomous variables (if provided). We did not undertake subgroup analyses due to the small number of included studies. Main results: We included nine short-term RCTs (duration 12 weeks or less) in the analysis (345 participants; age range 18 to 76 years). Participants were exposed to a variety of traumas, ranging from assault, traffic accidents and work accidents to cardiac surgery and septic shock. Seven studies were conducted at single centres. The seven RCTs included four hydrocortisone studies, three propranolol studies (of which one study had a third arm investigating gabapentin), and single trials of escitalopram and temazepam. Outcome assessment measures included the Clinician-Administered PTSD Scale (CAPS), the 36-Item Short-Form Health Survey (SF-36) and the Center for Epidemiological Studies - Depression Scale (CES-D).In four trials with 165 participants there was moderate quality evidence for the efficacy of hydrocortisone in preventing the onset of PTSD (risk ratio (RR) 0.17; 95% confidence interval (CI) 0.05 to 0.56; P value = 0.004), indicating that between seven and 13 patients would need to be treated with this agent in order to prevent the onset of PTSD in one patient. There was low quality evidence for preventing the onset of PTSD in three trials with 118 participants treated with propranolol (RR 0.62; 95% CI 0.24 to 1.59; P value = 0.32). Drop-outs due to treatment-emergent side effects, where reported, were low for all of the agents tested. Three of the four RCTs of hydrocortisone reported that medication was more effective than placebo in reducing PTSD symptoms after a median of 4.5 months after the event. None of the single trials of escitalopram, temazepam and gabapentin demonstrated evidence that medication was superior to placebo in preventing the onset of PTSD.Seven of the included RCTs were at a high risk of bias. Differential drop-outs between groups undermined the results of three studies, while one study failed to describe how the allocation of medication was concealed. Other forms of bias that might have influenced study results included possible confounding through group differences in concurrent medication and termination of the study based on treatment response. Authors' conclusions: There is moderate quality evidence for the efficacy of hydrocortisone for the prevention of PTSD development in adults. We found no evidence to support the efficacy of propranolol, escitalopram, temazepam and gabapentin in preventing PTSD onset. The findings, however, are based on a few small studies with multiple limitations. Further research is necessary in order to determine the efficacy of pharmacotherapy in preventing PTSD and to identify potential moderators of treatment effect.

Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder: A Randomized Clinical Trial

Article

Apr 2014

Importance: Few pharmacotherapies have demonstrated sufficient efficacy in the treatment of posttraumatic stress disorder (PTSD), a chronic and disabling condition. Objective: To test the efficacy and safety of a single intravenous subanesthetic dose of ketamine for the treatment of PTSD and associated depressive symptoms in patients with chronic PTSD. Design, setting, and participants: Proof-of-concept, randomized, double-blind, crossover trial comparing ketamine with an active placebo control, midazolam, conducted at a single site (Icahn School of Medicine at Mount Sinai, New York, New York). Forty-one patients with chronic PTSD related to a range of trauma exposures were recruited via advertisements. Interventions: Intravenous infusion of ketamine hydrochloride (0.5 mg/kg) and midazolam (0.045 mg/kg). Main outcomes and measures: The primary outcome measure was change in PTSD symptom severity, measured using the Impact of Event Scale-Revised. Secondary outcome measures included the Montgomery-Asberg Depression Rating Scale, the Clinical Global Impression-Severity and -Improvement scales, and adverse effect measures, including the Clinician-Administered Dissociative States Scale, the Brief Psychiatric Rating Scale, and the Young Mania Rating Scale. Results: Ketamine infusion was associated with significant and rapid reduction in PTSD symptom severity, compared with midazolam, when assessed 24 hours after infusion (mean difference in Impact of Event Scale-Revised score, 12.7 [95% CI, 2.5-22.8]; P = .02). Greater reduction of PTSD symptoms following treatment with ketamine was evident in both crossover and first-period analyses, and remained significant after adjusting for baseline and 24-hour depressive symptom severity. Ketamine was also associated with reduction in comorbid depressive symptoms and with improvement in overall clinical presentation. Ketamine was generally well tolerated without clinically significant persistent dissociative symptoms. Conclusions and relevance: This study provides the first evidence for rapid reduction in symptom severity following ketamine infusion in patients with chronic PTSD. If replicated, these findings may lead to novel approaches to the pharmacologic treatment of patients with this disabling condition. Trial registration: clinicaltrials.gov Identifier: NCT00749203.

Intranasal oxytocin as strategy for medication-enhanced psychotherapy of PTSD: Salience processing and fear inhibition processes

Article

Feb 2014
PSYCHONEUROENDOCRINO

The dimensional structure of posttraumatic stress symptomatology in 323,903 U.S. veterans

Article

Nov 2013

There is ongoing debate regarding the optimal dimensional structure of posttraumatic stress disorder symptomatology. A better understanding of this structure has significant implications, as it can provide more refined phenotypic measures for use in studies of the etiology and neurobiology of PTSD, as well as for use as endpoints in treatment studies of this disorder. In this study we analyzed the dimensional structure of PTSD symptomatology, as assessed using the PTSD Symptom Checklist-Military Version in 323,903 Veterans. Confirmatory factor analyses were used to compare two 4-factor models and a newly proposed 5-factor model to the 3-factor DSM-IV model of PTSD symptom dimensionality. To evaluate the external validity of the best-fitting model, we then conducted a structural equation model examining how the symptom dimensions of this model related to diagnoses of depression, anxiety, and substance use disorder. Results indicated that a newly proposed 5-factor 'dysphoric arousal' model comprised of separate re-experiencing, avoidance, numbing, dysphoric arousal, and anxious arousal symptom clusters provided a significantly better fit to the data compared to the DSM-IV and the two alternative four-factor models. External validity analyses revealed that numbing symptoms were most strongly related to diagnoses of depression and substance use disorder, and that dysphoric arousal symptoms were most strongly related to a diagnosis of anxiety disorder. Thus the dimensional structure of PTSD may be best represented by five symptom dimensions. The clinical implications of these results and implications for further refinement of extant PTSD assessment instruments are discussed.

Risk factors for post-deployment posttraumatic stress disorder in national guard/reserve service members

Article

Sep 2013

Identification of factors that increase risk for PTSD in military personnel following deployments is critical to early intervention and prevention. The study tested hypothesized main and moderating risk factors for PTSD in National Guard/Reserve members deployed to Iraq or Afghanistan. Members of the National Guard/Reserves (n=238) completed diagnostic interviews and measures of risk factors at a post-deployment assessment conducted an average of four and a half months following return from deployment. Hierarchical multivariate logistic regression analyses were used to test hypotheses. Higher levels of combat exposure, life and family concerns during deployment, and post-deployment social support independently predicted PTSD. Life/family concerns during deployment and perceived adequacy of training and preparation were significant moderators of the association between combat exposure and PTSD. Among those with higher levels of both combat exposure and life and family stress, 27% had PTSD in contrast to 3% of those with high exposure but lower levels of such stress during deployment. In addition to combat exposure, life and family stress during deployment is a particularly important predictor of PTSD. The findings highlight the importance of identifying and addressing such stress.

The Brain on Stress: Vulnerability and Plasticity of the Prefrontal Cortex over the Life Course

Article

Jul 2013

The prefrontal cortex (PFC) is involved in working memory and self-regulatory and goal-directed behaviors and displays remarkable structural and functional plasticity over the life course. Neural circuitry, molecular profiles, and neurochemistry can be changed by experiences, which influence behavior as well as neuroendocrine and autonomic function. Such effects have a particular impact during infancy and in adolescence. Behavioral stress affects both the structure and function of PFC, though such effects are not necessarily permanent, as young animals show remarkable neuronal resilience if the stress is discontinued. During aging, neurons within the PFC become less resilient to stress. There are also sex differences in the PFC response to stressors. While such stress and sex hormone-related alterations occur in regions mediating the highest levels of cognitive function and self-regulatory control, the fact that they are not necessarily permanent has implications for future behavior-based therapies that harness neural plasticity for recovery.

A Trial of Prazosin for Combat Trauma PTSD With Nightmares in Active-Duty Soldiers Returned From Iraq and Afghanistan

Article

Jul 2013
AM J PSYCHIAT

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 1.7 mg of prazosin (SD=0.5) and 2.0 mg 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.

Diagnostic and Statistical Manual of Mental Disorders: DSM-V

Book

Jan 1994

APA American Psychiatric Association

The development of a Clinican-Administered PTSD Scale

Article

Jan 1995

Several interviews are available for assessing PTSD. These interviews vary in merit when compared on stringent psychometric and utility standards. Of all the interviews, the Clinician-Administered PTSD Scale (CAPS-1) appears to satisfy these standards most uniformly. The CAPS-1 is a structured interview for assessing core and associated symptoms of PTSD. It assesses the frequency and intensity of each symptom using standard prompt questions and explicit, behaviorally-anchored rating scales. The CAPS-1 yields both continuous and dichotomous scores for current and lifetime PTSD symptoms. Intended for use by experienced clinicians, it also can be administered by appropriately trained paraprofessionals. Data from a large scale psychometric study of the CAPS-1 have provided impressive evidence of its reliability and validity as a PTSD interview.

Low Estradiol Levels: A Vulnerability Factor for the Development of Posttraumatic Stress Disorder

Article

Jul 2012

Diagnostic and Statistical Manual of Mental Disorders DSM-IV

Book

Jan 2000

A.P American Psychiatric Association

Fear Extinction as a Model for Translational Neuroscience: Ten Years of Progress

Article

Jan 2012
ANNU REV PSYCHOL

The psychology of extinction has been studied for decades. Approximately 10 years ago, however, there began a concerted effort to understand the neural circuits of extinction of fear conditioning, in both animals and humans. Progress during this period has been facilitated by a high degree of coordination between rodent and human researchers examining fear extinction. Here we review the major advances and highlight new approaches to understanding and exploiting fear extinction. Research in fear extinction could serve as a model for translational research in other areas of behavioral neuroscience.

Psychobiological allostasis: Resistance, resilience and vulnerability

Article

Nov 2011

The brain and body need to adapt constantly to changing social and physical environments. A key mechanism for this adaptation is the 'stress response', which is necessary and not negative in and of itself. The term 'stress', however, is ambiguous and has acquired negative connotations. We argue that the concept of allostasis can be used instead to describe the mechanisms employed to achieve stability of homeostatic systems through active intervention (adaptive plasticity). In the context of allostasis, resilience denotes the ability of an organism to respond to stressors in the environment by means of the appropriate engagement and efficient termination of allostatic responses. In this review, we discuss the neurobiological and organismal factors that modulate resilience, such as growth factors, chaperone molecules and circadian rhythms, and highlight its consequences for cognition and behavior.

The Serotonin Transporter and Emotionality: Risk, Resilience, and New Therapeutic Opportunities

Article

Mar 2011

Brain Structure Correlates of Individual Differences in the Acquisition and Inhibition of Conditioned Fear

Article

Aug 2011
CEREB CORTEX

Research employing aversive conditioning paradigms has elucidated the neurocircuitry involved in acquiring and diminishing fear responses. However, the factors underlying individual differences in fear acquisition and inhibition are not presently well understood. In this study, we explored whether the magnitude of individuals' acquired fear responses and the modulation of these responses via 2 fear reduction methods were correlated with structural differences in brain regions involved in affective processing. Physiological and structural magnetic resonance imaging data were obtained from experiments exploring extinction retention and intentional cognitive regulation. Our results identified 2 regions in which individual variation in brain structure correlated with subjects' fear-related arousal. Confirming previous results, increased thickness in ventromedial prefrontal cortex was correlated with the degree of extinction retention. Additionally, subjects with greater thickness in the posterior insula exhibited larger conditioned responses during acquisition. The data suggest a trend toward a negative correlation between amygdala volume and fear acquisition magnitude. There was no significant correlation between fear reduction via cognitive regulation and thickness in our prefrontal regions of interest. Acquisition and regulation measures were uncorrelated, suggesting that while certain individuals may have a propensity toward increased expression of conditioned fear, these responses can be diminished via both extinction and cognitive regulation.

Animal Models of Early Life Stress: Implications for Understanding Resilience

Article

Nov 2010
DEV PSYCHOBIOL

In the mid-1950s, Levine and his colleagues reported that brief intermittent exposure to early life stress diminished indications of subsequent emotionality in rats. Here we review ongoing studies of a similar process in squirrel monkeys. Results from these animal models suggest that brief intermittent exposure to stress promotes the development of arousal regulation and resilience. Implications for programs designed to enhance resilience in human development are discussed. 0 2010 Wiley Periodicals, Inc. Dev Psychobiol 52: 616-624, 2010.

Altered Processing of Contextual Information during Fear Extinction in PTSD: An fMRI Study

Article

Aug 2011
CNS NEUROSCI THER

Medial prefrontal cortical areas have been hypothesized to underlie altered contextual processing in posttraumatic stress disorder (PTSD). We investigated brain signaling of contextual information in this disorder. Eighteen PTSD subjects and 16 healthy trauma-exposed subjects underwent a two-day fear conditioning and extinction paradigm. On day 1, within visual context A, a conditioned stimulus (CS) was followed 60% of the time by an electric shock (conditioning). The conditioned response was then extinguished (extinction learning) in context B. On day 2, recall of the extinction memory was tested in context B. Skin conductance response (SCR) and functional magnetic resonance imaging (fMRI) data were collected during context presentations. There were no SCR group differences in any context presentation. Concerning fMRI data, during late conditioning, when context A signaled danger, PTSD subjects showed dorsal an

Posttraumatic Stress Disorder

Abstract

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