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Objective: Previous studies of veterans have linked posttraumatic stress disorder (PTSD) after combat-related trauma to increased reports of health problems. It is unclear whether this association between PTSD and increased health problems generalizes to civilians who are exposed to a broader array of traumatic events. We also do not know whether trauma exposure is associated with increased health problems in individuals who do not develop PTSD. Using a non-treatment-seeking civilian sample, we examined whether lifetime PTSD or trauma exposure by itself was associated with current health problems.Methods: Using a cross-sectional design and self-report measures, we evaluated urban Canadian bus drivers (n = 342) on trauma exposure, lifetime PTSD, and current health problems. Based on their responses, we divided our sample into individuals who had never experienced trauma (n = 91), trauma-exposed individuals who had never developed PTSD (n = 218), and persons who developed PTSD at some point after trauma (n = 33). We compared these groups on health problems, treatment service use, and health assessment measures.Results: The PTSD group reported increased health complaints, more frequent use of health treatments, and poorer health self-ratings compared with the exposed non-PTSD and nonexposed groups. Trauma-exposed drivers without PTSD did not differ from unexposed drivers on any health measure. Controlling for sex and trauma frequency did not alter our findings.Conclusions: Trauma exposure that leads to PTSD is associated with increased health problems, while trauma exposure alone is not. Our results extend previous findings to a broader civilian context and clarify associations between trauma exposure and health. [ABSTRACT FROM AUTHOR]

The Multiple Stressor Debriefing (MSD) model was used to debrief 112 American Red Cross workers individually or in groups after their participation in the 1994 Los Angeles earthquake relief effort. Two composite case examples are presented that illustrate individual and group debriefings using the MSD model. A questionnaire which evaluated workers' experience of debriefing, was completed by 95 workers. Results indicated that workers evaluated the debriefings in which they participated positively. In addition, as participant to facilitator ratio increases, workers shared less of their feelings and reactions about the disaster relief operation. These findings, as well as more specific issues about debriefing, are discussed. [ABSTRACT FROM AUTHOR]

Study Objectives: Trauma nightmares are a core feature of PTSD, with potentially devastating implications for mental health outcomes. Treatments remain unsatisfactory and nightmares are poorly understood, both biologically and phenomenologically; measurement methods are limited. The aims of the current analyses were to (1) characterize distressing dreams in trauma survivors, (2) examine the relationships of dream features to next-day symptoms and to suicidal ideation, and (3) validate sleep diary mobile app items for the measurement of clinically relevant dream characteristics., Methods: Adult male and female veterans and nonveterans with a history of PTSD criterion trauma and at least 1 nightmare weekly were enrolled. Participants completed 3 weeks of sleep diary, including bedtime and morning surveys and weekly assessments. They also completed a Clinician-Administered PTSD Scale (CAPS)-5 PTSD assessment. Multivariable mixed models with repeated measures and standard regression were utilized to examine relationships between dream features and next-day symptoms and suicidal ideation., Results: Dream features and dream distress independently predict clinically relevant outcomes; no single feature was sufficient for predicting all outcomes of interest. In particular, the replicative quality of trauma nightmares stood out in terms of associations with next-day symptoms, CAPS severity, and suicidal ideation. Subjective dream duration, extent of postdream arousal, and subjective distress severity also independently predicted daytime symptoms., Conclusions: Results underscore the importance of examining dream characteristics to understand nightmare effects and associations with suicidal ideation. These findings also underscore the utility of mobile app technology for obtaining informative data with high temporal resolution in an appealing and user-friendly manner., (Published by Oxford University Press on behalf of Sleep Research Society 2025.)

In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo. We also show that phenotype-specific therapeutic vulnerabilities and modes of treatment-induced phenotype reprogramming can be captured in phenotypic heterogeneity maps. Our methodology and analyses of tumour-cell heterogeneity in PDAC may guide the development of phenotype-targeted treatment strategies., Competing Interests: Competing interests: M.L. was a contractor for the Chan Zuckerberg Initiative and received speaker fees from Pfizer and Janssen Pharmaceuticals. F.J.T. consults for Immunai Inc., Singularity Bio B.V., CytoReason Ltd, Cellarity and Omniscope, and has ownership interest in Dermagnostix GmbH and Cellarity. The other authors declare no competing interests., (© 2024. The Author(s).)

Background and Aims: Histomorphology is a powerful and cost-efficient tool for evaluating inflammatory and neoplastic conditions. Inflammatory bowel disease (IBD) is a widespread condition with globally rising incidences, and a lot of research is done to better understand the pathogenesis of IBD and to identify potential therapeutic approaches. However, standardized and reproducible scores for the histomorphological evaluation of murine IBD models are lacking. Therefore, we aimed to develop an easy-to-use and reproducible score for standardized assessment of colitis and associated cancer models., Methods: In this study, samples from three different colitis models with and without associated cancer formation were analyzed to develop a universal, robust, and reproducible score for the grading of murine colitis models using the following three parameters: 1. Extent of leucocyte infiltration, 2. Tissue damage, 3. Architectural disruption of the mucosa., Results: A scoring system was established for different kinds of colitis models (genetically induced enterocolitis, genetically induced metabolic injury, and chemically induced colitis-associated cancer) and all stages of the disease, from mild inflammatory changes to severe inflammation with neoplastic changes as the extreme extent of IBD. The scoring scheme is easy to use, can easily be learned, and proves to have a high interrater reliability., Conclusions: We propose a robust histological scoring system for the assessment of murine colitis and colitis-associated cancer models, giving more researchers access to conclusive and reliable histological assessment., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest related to this work., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cellular plasticity is a hallmark of pancreatic ductal adenocarcinoma (PDAC) starting from the conversion of normal cells into precancerous lesions, to the progression of carcinoma subtypes associated with aggressiveness and therapeutic response. We discovered that normal acinar cell differentiation, maintained by the transcription factor PDX1, suppresses a broad gastric cell identity that is maintained in metaplasia, neoplasia, and the classical subtype of PDAC in a mouse and human. We identified the receptor tyrosine kinase ROR2 as marker of a gastric metaplasia-like identity in pancreas neoplasms. Ablation of Ror2 in a mouse model of pancreatic tumorigenesis promoted a switch to a gastric pit cell identity that largely persisted through progression to the classical subtype of PDAC. In both human and mouse pancreatic cancer, ROR2 activity continued to antagonize the gastric pit cell identity, strongly promoting an epithelial to mesenchymal transition, conferring resistance to KRAS inhibition, and vulnerability to AKT inhibition. Significance: We discovered the receptor tyrosine kinase ROR2 as an important regulator of cellular identity in pancreatic precancerous lesions and pancreatic cancer. ROR2 drives an aggressive PDAC phenotype and confers resistance to KRAS inhibitors, suggesting that targeting ROR2 will enhance sensitivity to this new generation of targeted therapies. See related commentary by Marasco and Misale, p. 2018., (©2024 The Authors; Published by the American Association for Cancer Research.)

Tumors weakly infiltrated by T lymphocytes poorly respond to immunotherapy. We aimed to unveil malignancy-associated programs regulating T cell entrance, arrest, and activation in the tumor environment. Differential expression of cell adhesion and tissue architecture programs, particularly the presence of the membrane tetraspanin claudin (CLDN)18 as a signature gene, demarcated immune-infiltrated from immune-depleted mouse pancreatic tumors. In human pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer, CLDN18 expression positively correlated with more differentiated histology and favorable prognosis. CLDN18 on the cell surface promoted accrual of cytotoxic T lymphocytes (CTLs), facilitating direct CTL contacts with tumor cells by driving the mobilization of the adhesion protein ALCAM to the lipid rafts of the tumor cell membrane through actin. This process favored the formation of robust immunological synapses (ISs) between CTLs and CLDN18-positive cancer cells, resulting in increased T cell activation. Our data reveal an immune role for CLDN18 in orchestrating T cell infiltration and shaping the tumor immune contexture., Competing Interests: Declaration of interests V.B. reports past personal fees from Codiak BioSciences and IO Biotech ApS outside of the submitted work. U.S. and Ö.T. are co-founders and respectively Chief Executive Officer and Chief Medical Officer of BioNTech AG, Mainz Germany and shareholders in the privately owned BioNTech AG as mentioned in the affiliation. F.D.S., M.E., and V.B. hold proprietary rights on the patent application no. PCT/EP2023/058504: “Methods for predicting and improving the therapeutic efficacy of cancer treatments and methods for cancer prognosis.”, (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The missing requirement for resection for the majority of hepatic hemangiomas (HH) and tissue scarcity for rare diseases such as hepatic epithelioid hemangioendotheliomas (HEHE) complicate the characterization of the spatial immunovascular niche of these benign and malignant vascular neoplastic diseases., Methods: Two tissue cohorts containing 98 HHs and 13 HEHEs were used to study entity-specific and disease stage-specific endothelial cell (EC) phenotype and immune cell abundance. Using semiquantitative assessment, annotation-based cell classifiers, digital cell detection on whole slides, and tissue microarrays, we quantified 23 immunologic and vascular niche-associated markers and correlated this with clinicopathologic data., Results: Both HH and HEHE ECs were characterized by a CD31high, CD34high, FVIII-related antigenhigh expression phenotype with entity-specific expression differences of sinusoidal EC markers Stabilin1, Stabilin2, CD32, and Lymphatic Vessel Endothelial Hyaluronan Receptor 1 (LYVE-1). Cell detection identified an HH margin-prevailing immunologic response dominated by Myeloperoxidase+ (MPO+) macrophages, CD3+ and CD8+ T cell subsets, and B cells (CD20+, CD79A+). In HEHE, increased CD68+ and CD20+ cell demarcation of lesion margins was observed, while CD3+ and CD8+ T cells were equally detectable both marginally and intralesionally. Stage-specific pairwise correlation analysis of HH and HEHE revealed disease entity-specific immunologic infiltration patterns as seen by high CD117+ cell numbers in HH, while HEHE samples showed increased CD3+ T cell infiltration., Conclusions: ECs in HH and HEHE share a continuous EC expression phenotype, while the expression of sinusoidal EC markers is more highly retained in HEHE. These phenotypic differences are associated with a unique and disease-specific immunovascular landscape., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)

pH alterations are a hallmark of many pathologies including cancer and kidney disease. Here, we introduce [1,5- 13 C 2 ]Z-OMPD as a hyperpolarized extracellular pH and perfusion sensor for MRI which allows to generate a multiparametric fingerprint of renal disease status and to detect local tumor acidification. Exceptional long T 1 of two minutes at 1 T, high pH sensitivity of up to 1.9 ppm per pH unit and suitability of using the C 1 -label as internal frequency reference enables pH imaging in vivo of three pH compartments in healthy rat kidneys. Spectrally selective targeting of both 13 C-resonances enables simultaneous imaging of perfusion and filtration in 3D and pH in 2D within one minute to quantify renal blood flow, glomerular filtration rates and renal pH in healthy and hydronephrotic kidneys with superior sensitivity compared to clinical routine methods. Imaging multiple biomarkers within a single session renders [1,5- 13 C 2 ]Z-OMPD a promising new hyperpolarized agent for oncology and nephrology., (© 2023. Springer Nature Limited.)

Objective: Veterans with posttraumatic stress disorder (PTSD) initiate and complete cognitive processing therapy (CPT) and prolonged exposure (PE) at low rates within Veterans Health Administration (VHA) despite substantial dissemination and training. This study investigated how trauma-informed, skills-based treatment ("stabilization") administered before CPT and PE was related to initiation and completion of trauma-focused evidence-based psychotherapies (TF-EBPs)., Method: Data were extracted from the VHA electronic medical record to identify veterans who initiated outpatient treatment in the PTSD Clinical Team (PCT) at a Veterans Affairs Health Care System. Treatment initiation was defined as three or more PCT visits with no prior PCT care for at least 18 months ( N = 341). Before initiation of TF-EBP, veterans received either no stabilization or received individual and/or group stabilization., Results: Twenty-eight percent of veterans without stabilization ( n = 115) initiated TF-EBP, compared with 34% of veterans who completed individual-only stabilization ( n = 82), and 10% of veterans who completed group-only stabilization ( n = 29, p = .050). Compared with those with no stabilization, individual stabilization was associated with significantly higher TF-EBP completion (93% vs. 50%, p < .001). CPT completion was also significantly higher for veterans who received individual-only stabilization (90% vs. 43%, p = .001). Results for PE followed the same relationship, but did not reach significance (100% vs. 67%, p = .090)., Conclusions: Findings suggest that individual stabilization may improve delivery of TF-EBPs in VHA settings by increasing TF-EBP completion without reducing initiation, while pretreatment with group-only stabilization may reduce initiation of TF-EBPs. Results inform how models of care can improve TF-EBP retention and completion among veterans with PTSD. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Importance: Sleep disturbance is common among patients with neurodegenerative diseases. Examining the subcortical neuronal correlates of sleep disturbances is important to understanding the early-stage sleep neurodegenerative phenomena., Objectives: To examine the correlation between the number of important subcortical wake-promoting neurons and clinical sleep phenotypes in patients with Alzheimer disease (AD) or progressive supranuclear palsy (PSP)., Design, Setting, and Participants: This longitudinal cohort study enrolled 33 patients with AD, 20 patients with PSP, and 32 healthy individuals from the Memory and Aging Center of the University of California, San Francisco, between August 22, 2008, and December 31, 2020. Participants received electroencephalographic and polysomnographic sleep assessments. Postmortem neuronal analyses of brainstem hypothalamic wake-promoting neurons were performed and were included in the clinicopathological correlation analysis. No eligible participants were excluded from the study., Exposures: Electroencephalographic and polysomnographic assessment of sleep and postmortem immunohistological stereological analysis of 3 wake-promoting nuclei (noradrenergic locus coeruleus [LC], orexinergic lateral hypothalamic area [LHA], and histaminergic tuberomammillary nucleus [TMN])., Main Outcomes and Measures: Nocturnal sleep variables, including total sleep time, sleep maintenance, rapid eye movement (REM) latency, and time spent in REM sleep and stages 1, 2, and 3 of non-REM (NREM1, NREM2, and NREM3, respectively) sleep, and wake after sleep onset. Neurotransmitter, tau, and total neuronal counts of LC, LHA, and TMN., Results: Among 19 patients included in the clinicopathological correlation analysis, the mean (SD) age at death was 70.53 (7.75) years; 10 patients (52.6%) were female; and all patients were White. After adjusting for primary diagnosis, age, sex, and time between sleep analyses and death, greater numbers of LHA and TMN neurons were correlated with decreased homeostatic sleep drive, as observed by less total sleep time (LHA: r = -0.63; P = .009; TMN: r = -0.62; P = .008), lower sleep maintenance (LHA: r = -0.85; P < .001; TMN: r = -0.78; P < .001), and greater percentage of wake after sleep onset (LHA: r = 0.85; P < .001; TMN: r = 0.78; P < .001). In addition, greater numbers of LHA and TMN neurons were correlated with less NREM2 sleep (LHA: r = -0.76; P < .001; TMN: r = -0.73; P < .001). A greater number of TMN neurons was also correlated with less REM sleep (r = -0.61; P = .01). A greater number of LC neurons was mainly correlated with less total sleep time (r = -0.68; P = .008) and greater REM latency (r = 0.71; P = .006). The AD-predominant group had significantly greater sleep drive, including higher total sleep time (mean [SD], 0.49 [1.18] vs -1.09 [1.37]; P = .03), higher sleep maintenance (mean [SD], 0.18 [1.22] vs -1.53 [1.78]; P = .02), and lower percentage of wake after sleep onset during sleep period time (mean [SD], -0.18 [1.20] vs 1.49 [1.72]; P = .02) than the PSP-predominant group based on unbiased k-means clustering and principal component analyses., Conclusions and Relevance: In this cohort study, subcortical wake-promoting neurons were significantly correlated with sleep phenotypes in patients with AD and PSP, suggesting that the loss of wake-promoting neurons among patients with neurodegenerative conditions may disturb the control of sleep-wake homeostasis. These findings suggest that the subcortical system is a primary mechanism associated with sleep disturbances in the early stages of neurodegenerative diseases.

Canine digital melanoma, in contrast to canine oral melanoma, is still largely unexplored at the molecular genetic level. The aim of this study was to detect mutant genes in digital melanoma. Paraffin-embedded samples from 86 canine digital melanomas were examined for the BRAF V595E variant by digital droplet PCR (ddPCR), and for exon 11 mutations in c-kit. Furthermore, exons 2 and 3 of KRAS and NRAS were analysed by Sanger sequencing. Copy number variations (CNV) of KITLG in genomic DNA were analysed from nine dogs. The BRAF V595E variant was absent and in c-kit , a single nucleotide polymorphism was found in 16/70 tumours (23%). The number of copies of KITLG varied between 4 and 6. KRAS exon 2 codons 12 and 13 were mutated in 22/86 (25.6%) of the melanomas examined. Other mutually exclusive RAS mutations were found within the hotspot loci, i.e., KRAS exon 3 codon 61: 2/55 (3.6%); NRAS exon 2 codons 12 and 13: 2/83 (2.4%); and NRAS exon 3 codon 61: 9/86 (10.5%). However, no correlation could be established between histological malignancy criteria, survival times and the presence of RAS mutations. In summary, canine digital melanoma differs from molecular genetic data of canine oral melanoma and human melanoma, especially regarding the proportion of RAS mutations.

While the BDNF Val66Met polymorphism has been linked to various trauma and anxiety - related psychiatric disorders, limited focus has been on the neural structures that might modulate its relationship with objective measures of threat sensitivity. Therefore, we assessed whether there was an interaction of Val66Met polymorphism with brain area volumes previously associated with anxiety and PTSD, such as the ventromedial prefrontal cortex (vmPFC), insular cortex (IC), and dorsal and ventral anterior cingulate cortices (dACC and vACC), in predicting fear-potentiated psychophysiological response in a clinical sample of Veterans. 110 participants engaged in a fear-potentiated acoustic startle paradigm and provided genetic and imaging data. Fear conditions included no, ambiguous, and high threat conditions (shock). Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate (HR). PTSD status, trauma history, and demographics were also assessed. There was an interaction of Met allele carrier status with vmPFC, IC, dACC, and vACC volumes for predicting SCR (p < 0.001 for all regions). However, only vmPFC and IC significantly moderated the relationship between Val66Met and psychophysiological response (SCR). The Val66met polymorphism may increase susceptibility to PTSD and anxiety disorders via an interaction with reduced vmPFC and IC volume. Future research should examine whether these relationships might be associated with a differential course of illness longitudinally or response to treatments., (Copyright © 2021. Published by Elsevier Ltd.)

Study Objectives: Our objective was to examine the ability of a consumer-grade wearable device (Basis B1) with accelerometer and heart rate technology to assess sleep patterns compared with polysomnography (PSG) and research-grade actigraphy in healthy adults., Methods: Eighteen adults underwent consecutive nights of sleep monitoring using Basis B1, actigraphy, and PSG; 40 nights were used in analyses. Discrepancies in gross sleep parameters and epoch-by-epoch agreements in sleep/wake classification were assessed., Results: Basis B1 accuracy was 54.20 ± 8.20%, sensitivity was 98.90 ± 2.70%, and specificity was 8.10 ± 15.00%. Accuracy, sensitivity, and specificity for distinguishing between the different sleep stages were 60-72%, 48-62%, and 57-86%, respectively. Pearson correlations demonstrated strong associations between Basis B1 and PSG estimates of sleep onset latency and total sleep time; moderate associations for sleep efficiency, duration of light sleep, and duration of rapid eye movement sleep; and a weak association for duration of deep sleep. Basis B1 significantly overestimates total sleep time, sleep efficiency, and duration of light sleep and significantly underestimates wake after sleep onset and duration of deep sleep., Conclusions: Basis B1 demonstrated utility for estimates of gross sleep parameters and performed similarly to actigraphy for estimates of total sleep time. Basis B1 specificity was poor, and Basis B1 is not useful for the assessment of wake. Basis B1 accuracy for sleep stages was better than chance but is not a suitable replacement for PSG assessment. Despite low cost, ease of use, and attractiveness for patients, consumer devices are not yet accurate or reliable enough to guide treatment decision making in clinical settings., (© 2020 American Academy of Sleep Medicine.)

Truth-telling to cancer patients challenges health care providers in China. Providers confront a series of cultural, ethical, and legal dilemmas in terms of patients' right to know and autonomy. Underlying reasons for truth-telling dilemmas include traditional culture, the role of family, and ambiguity about patients' right to know in accordance with Chinese laws and regulations. These factors complicate ethical judgment by requiring interaction with traditional Chinese culture and laws before health care providers deliver bad news to patients with a range of conditions, including cancer. In this article ethical questions are raised, and strategies concerning breaking bad news are suggested for Chinese health care providers., Competing Interests: None.

Background: Few longitudinal studies have investigated the potentially dynamic relationship between Posttraumatic Stress Disorder (PTSD) and physical functioning, and the number of follow-up timepoints have been limited. We evaluated whether PTSD symptoms predicted future physical functioning and vice versa using five assessments over four years., Methods: Data was used from a longitudinal cohort of 695 participants recruited from Veteran Affairs medical outpatient clinics who experienced a traumatic event. PTSD symptom severity was assessed annually with the PTSD Checklist (PCL). Physical functioning was measured with the 10-item subscale of the SF-36. An autoregressive cross-lagged panel model was used to determine the temporal associations between PTSD and physical functioning, adjusting for age, sex, ethnicity, education and employment. Comorbidities and health behaviors were added to assess their roles in the relationship., Results: Greater PTSD symptom severity predicted worse physical functioning the following year (average β = -0.10, P <0.001), where a 10-point increase in PCL score predicted a 0.3-point decline in physical function score over one year. Similarly, better physical functioning also predicted reduced PTSD severity the following year, but to a smaller magnitude (average β = -0.04, P = .003). The pattern of effects was similar after controlling for comorbidities and health behaviors., Limitations: Both primary variables relied on self-report, and generalizability may be limited by the mostly male Veteran sample., Conclusions: Our results support a bidirectional, but unequal, relationship between PTSD and physical functioning over time. They also highlight the importance of long-term control of PTSD symptoms in preventing functional decline., (Copyright © 2019. Published by Elsevier B.V.)

Objective: To explore the role of the novel cardiac output response to stress (CORS), test in the current diagnostic pathway for heart failure and the opportunities and challenges to potential implementation in primary care., Design: Qualitative study using semistructured in-depth interviews which were audio recorded and transcribed verbatim. Data from the interviews were analysed thematically using an inductive approach., Setting: Newcastle upon Tyne, UK., Participants: Fourteen healthcare professionals (six males, eight females) from primary (general practitioners (GPs), nurses, healthcare assistant, practice managers) and secondary care (consultant cardiologists)., Results: Four themes relating to opportunities and challenges surrounding the implementation of the new diagnostic technology were identified. These reflected that the adoption of CORS test would be an advantage to primary care but the test had barriers to implementation which include: establishment of clinical utility, suitability for immobile patients and cost implication to GP practices., Conclusion: The development of a simple non-invasive clinical test to accelerate the diagnosis of heart failure in primary care maybe helpful to reduce unnecessary referrals to secondary care. The CORS test has the potential to serve this purpose; however, factors such as cost effectiveness, diagnostic accuracy and seamless implementation in primary care have to be fully explored., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Introduction: While the BDNF Val66Met polymorphism has been linked to various psychological disorders, limited focus has been on its relationship to posttraumatic stress disorder (PTSD) and early traumas such as child abuse. Therefore, we assessed whether Val66Met was associated with fear potentiated psychophysiological response and HPA axis dysfunction and whether PTSD status or child abuse history moderated these outcomes in a sample of Veterans., Methods: 226 and 173 participants engaged in a fear potentiated acoustic startle paradigm and a dexamethasone suppression test (DST) respectively. Fear conditions included no, ambiguous, and high threat conditions. Psychophysiological response measures included electromyogram (EMG), skin conductance response (SCR), and heart rate. The Clinician Administered PTSD Scale (CAPS) and the Trauma History Questionnaire (THQ) were used to assess PTSD status and child abuse history respectively., Results: Met allele carriers exhibited greater SCR magnitudes in the no and ambiguous threat conditions (p < 0.01 and p < 0.05 respectively). Met carriers with PTSD exhibited greater physiological response magnitudes in the ambiguous (SCR, p < 0.001) and high threat conditions (SCR and heart rate, both p ≤ 0.005). Met carrier survivors of child abuse exhibited blunted heart rate magnitudes in the high threat condition (p < 0.01). Met allele carries with PTSD also exhibited greater percent cortisol suppression (p < 0.005)., Limitations: Limitations included small sample size and the cross-sectional nature of the data., Conclusions: The Val66met may impact PTSD susceptibility differentially via enhanced threat sensitivity and HPA axis dysregulation. Child abuse may moderate Val66Met's impact on threat reactivity. Future research should explore how neuronal mechanisms might mediate this risk., (Published by Elsevier B.V.)

Posttraumatic stress symptoms are associated with poorer social and occupational functioning and quality of life. However, general assessments of functioning do not determine the extent to which these difficulties are directly related to PTSD symptoms. This study examines the psychometric properties of a self-report measure, the 27-item Posttraumatic Stress Related Functioning Inventory (PRFI), which was developed to provide a self-report tool for clinicians and researchers to better understand the perceived impact of PTSD symptoms on functioning. The psychometric properties of the PRFI were examined utilizing data collected within a larger study examining quality of life and functioning in 251 veterans who had served in OEF/OIF/OND and endorsed the presence of subsyndromal or greater levels of PTSD symptoms at screening. One-year test-retest reliability of the measure was examined in a subset of the baseline sample who received a second administration of the PRFI (n = 109). Higher levels of PTSD symptoms were associated with poorer functioning in all domains. The PRFI demonstrated convergent validity with a measure of PTSD symptoms and was less correlated with measures of alcohol and drug use, good internal consistency and test-retest reliability from baseline to one-year follow-up. The PRFI provides self-report information regarding several domains of functioning. This initial examination of psychometric properties of the scale indicated that it may be useful for efficiently eliciting information about the ways in which PTSD symptoms in veterans impact everyday functioning., (Published by Elsevier Ltd.)

Background: The course of posttraumatic stress disorder (PTSD) is frequently and severely complicated by co-occurring alcohol use disorder (AUD), yet there are few reports of pharmacologic treatments for these comorbid conditions. The objective of this pilot study was to obtain a preliminary assessment of the efficacy and safety of topiramate in reducing alcohol use and PTSD symptoms in veterans with both disorders., Methods: This was a prospective 12-week, randomized, double-blind, placebo-controlled pilot trial of flexible-dose topiramate up to 300 mg/d in 30 veterans with PTSD and AUD. The primary outcome measure was frequency of drinking. Secondary outcomes consisted of other measures of alcohol use and PTSD symptom severity., Results: Within-group analyses showed that topiramate treatment was associated with significant reductions in frequency and amount of alcohol use and alcohol craving from baseline through week 12. Between-group analyses showed that topiramate reduced frequency of alcohol use and alcohol craving significantly more than placebo and tended to reduce drinking amount. Topiramate treatment was also associated with decreased PTSD symptom severity and tended to reduce hyperarousal symptoms compared with placebo. Topiramate transiently impaired learning and memory, with significant recovery by the end of treatment., Conclusions: These preliminary results indicate that in veterans with co-occurring PTSD and AUD, topiramate may be effective in reducing alcohol consumption, alcohol craving, and PTSD symptom severity-particularly hyperarousal symptoms. Topiramate was associated with transient cognitive impairment but was otherwise well tolerated., (Copyright © 2014 by the Research Society on Alcoholism.)

Study Objectives: To test if posttraumatic stress disorder (PTSD) is associated with low brain gamma-aminobutyric acid (GABA) levels and if reduced GABA is mediated by poor sleep quality., Design: Laboratory study using in vivo proton magnetic resonance spectroscopy (1H MRS) and behavioral testing., Setting: VA Medical Center Research Service, Psychiatry and Radiology., Patients or Participants: Twenty-seven patients with PTSD (PTSD+) and 18 trauma-exposed controls without PTSD (PTSD-), recruited from United States Army reservists, Army National Guard, and mental health clinics., Interventions: None., Measurements and Results: 1H MRS at 4 Tesla yielded spectra from three cortical brain regions. In parieto-occipital and temporal cortices, PTSD+ had lower GABA concentrations than PTSD-. As expected, PTSD+ had higher depressive and anxiety symptom scores and a higher Insomnia Severity Index (ISI) score. Higher ISI correlated with lower GABA and higher glutamate levels in parieto-occipital cortex and tended to correlate with lower GABA in the anterior cingulate. The relationship between parieto-occipital GABA and PTSD diagnosis was fully mediated through insomnia severity. Lower N-acetylaspartate and glutamate concentrations in the anterior cingulate cortex correlated with higher arousal scores, whereas depressive and anxiety symptoms did generally not influence metabolite concentrations., Conclusions: Low brain gamma-aminobutyric acid (GABA) concentration in posttraumatic stress disorder (PTSD) is consistent with most findings in panic and social anxiety disorders. Low GABA associated with poor sleep quality is consistent with the hyperarousal theory of both primary insomnia and PTSD. Our data demonstrate that poor sleep quality mediates low parieto-occipital GABA in PTSD. The findings have implications for PTSD treatment approaches.

Exposure to traumatic psychological stress increases risk for disease events and mortality in patients with cardiovascular disease (CVD). While the biological mechanisms of these effects are not known, inflammation may play a key role as it is both elevated by psychological stress and involved in the development and progression of CVD. In a prospective study of patients with stable CVD (n=979), we examined if higher lifetime trauma exposure was associated with elevated levels of inflammation at baseline and at five-year follow-up, and with greater increases in inflammation over time. Inflammation was indexed by a composite score incorporating the inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP) and resistin. In follow-up analyses, we adjusted for sociodemographic factors, psychiatric disorders and health behaviors that were significantly associated with trauma exposure. Higher trauma exposure was associated with elevated inflammation at baseline (β=.09, p=.01) and at five-year follow-up (β=.09, p=.03). While levels of inflammation increased from baseline to follow-up in the sample, there was no significant association between trauma exposure and rate of change in inflammation. Findings were robust to adjustments for sociodemographic factors and psychiatric disorders, but health behaviors appeared to contribute to the association between trauma and inflammation at follow-up. This is the first large-scale demonstration of an association between lifetime trauma exposure and inflammation. High lifetime exposure to traumatic stress may contribute to an accelerated rate of CVD progression through elevated inflammation., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The hypothalamic-pituitary-adrenal axis is a major stress response system hypothesized to be involved in the pathogenesis of posttraumatic stress disorder (PTSD). However, few studies have prospectively examined the relationships among pre-exposure hypothalamic-pituitary-adrenal activity, acute stress reactions and PTSD., Methods: Two hundred ninety-six police recruits were assessed during academy training before critical incident exposure and provided salivary cortisol at first awakening and after 30 minutes. A measure of cortisol awakening response (CAR) was computed as the change in cortisol level from the first to the second collection. At 12, 24, and 36 months following the start of active police service, officers were assessed for peritraumatic distress, peritraumatic dissociation, acute stress disorder (ASD) symptoms, and PTSD symptoms to their self-identified worst duty-related critical incident. Mixed models for repeated measures were used to analyze the effects of CAR on the outcome variables pooled across the three follow-up assessments., Results: After controlling for time of awakening, first awakening cortisol levels, and cumulative critical incident stress exposure, CAR during academy training was associated with greater peritraumatic dissociation, β = .14, z = 3.49, p < .0001, and greater ASD symptoms during police service assessed at 12, 24, and 36 months, β = .09, Z = 2.03, p < .05, but not with peritraumatic distress, β = .03, z = .81, p = .42, or PTSD symptoms, β = -.004, z = -.09, p = .93., Conclusions: These findings suggest that greater cortisol response to awakening is a pre-exposure risk factor for peritraumatic dissociation and ASD symptoms during police service., (Published by Elsevier Inc.)