Formation of DNA Adducts by 1-Methoxy-3-indolylmethylalcohol, a Breakdown Product of a Glucosinolate, in the Mouse: Impact of the SULT1A1 Status-Wild-Type, Knockout or Humanised.

We previously found that feeding rats with broccoli or cauliflower leads to the formation of characteristic DNA adducts in the liver, intestine and various other tissues. We identified the critical substances in the plants as 1-methoxy-3-indolylmethyl (1-MIM) glucosinolate and its degradation product 1-MIM-OH. DNA adduct formation and the mutagenicity of 1-MIM-OH in cell models were drastically enhanced when human sulfotransferase (SULT) 1A1 was expressed. The aim of this study was to clarify the role of SULT1A1 in DNA adduct formation by 1-MIM-OH in mouse tissues in vivo. Furthermore, we compared the endogenous mouse Sult1a1 and transgenic human SULT1A1 in the activation of 1-MIM-OH using genetically modified mouse strains. We orally treated male wild-type (wt) and Sult1a1-knockout (ko) mice, as well as corresponding lines carrying the human SULT1A1-SULT1A2 gene cluster (tg and ko-tg), with 1-MIM-OH. N2-(1-MIM)-dG and N6-(1-MIM)-dA adducts in DNA were analysed using isotope-dilution UPLC-MS/MS. In the liver, caecum and colon adducts were abundant in mice expressing mouse and/or human SULT1A1, but were drastically reduced in ko mice (1.2-10.6% of wt). In the kidney and small intestine, adduct levels were high in mice carrying human SULT1A1-SULT1A2 genes, but low in wt and ko mice (1.8-6.3% of tg-ko). In bone marrow, adduct levels were very low, independently of the SULT1A1 status. In the stomach, they were high in all four lines. Thus, adduct formation was primarily controlled by SULT1A1 in five out of seven tissues studied, with a strong impact of differences in the tissue distribution of mouse and human SULT1A1. The behaviour of 1-MIM-OH in these models (levels and tissue distribution of DNA adducts; impact of SULTs) was similar to that of methyleugenol, classified as "probably carcinogenic to humans". Thus, there is a need to test 1-MIM-OH for carcinogenicity in animal models and to study its adduct formation in humans consuming brassicaceous foodstuff.

Examining the levels of psychological support available to patients with haematological cancer in England: a mixed methods study.

OBJECTIVES: The psychological impact of a haematological malignancy is well documented. However, few studies have assessed the provision of psychological support to people with these diagnoses. This study explores the extent and nature of psychological support for people diagnosed with haematological cancer to inform future service provision. DESIGN: This study consisted of an online survey with healthcare professionals (phase 1) and qualitative interviews with patients (phase 2) and key health professionals (phase 3). A descriptive analysis of survey data and thematic analysis of interviews were conducted. PARTICIPANTS: Two hundred health professionals practising in England completed the survey. Twenty-five interviews were conducted with people diagnosed with haematological cancer in the past 3 years, and 10 with key health professionals, including haematologists, cancer nurse specialists and psychologists were conducted. PRIMARY OUTCOME MEASURES: Level of psychological assessment undertaken with people with haematological cancer, and level and nature of psychological support provided. RESULTS: Less than half (47.3%) of survey respondents strongly agreed/agreed that their patients were well supported in terms of their psychological well-being and approximately half (49.4%) reported providing routine assessment of psychological needs of patients, most commonly at the time of diagnosis or relapse. Patients described their need for psychological support, their experiences of support from health professionals and their experiences of support from psychological therapy services. There was considerable variation in the support patients described receiving. Barriers to providing psychological support reported by health professionals included time, skills, resources and patient barriers. Most doctors (85%) and 40% of nurse respondents reported receiving no training for assessing and managing psychological needs. CONCLUSIONS: Psychological well-being should be routinely assessed, and person-centred support should be offered regularly throughout the haematological cancer journey. Greater provision of healthcare professional training in this area and better integration of psychological support services into the patient care pathway are required.

A qualitative analysis of loss-related memories after cancer loss: a comparison of bereaved people with and without prolonged grief disorder.

Objective: The study aimed to explore the content and features of loss-related memories in a sample of individuals bereaved by cancer with and without a probable diagnosis of prolonged grief disorder/persistent complex bereavement disorder (PGD/PCBD). Methods: Semi-structured interviews with 28 bereaved adults (PGD/PCBD = 12, NoPGD/PCBD = 16) were analysed using thematic analysis. Results: Three superordinate themes were identified: (1) intrusive imagery, (2) qualities of memory, and (3) triggers. Results showed that individuals suffering from probable PGD/PCBD reported a predominance of negative and upsetting memories, happy memories triggering pain and more negative intrusive imagery than those without PGD/PCBD. Conclusions: Bereavement by cancer can result in troubling intrusive memories that overshadow positive memories. Sufferers of PGD/PCBD are more likely to experience loss-related memories as negative and upsetting. Clinical approaches that utilise memory processing may be of particular relevance in this group.

Objetivo: El estudio tuvo como objetivo explorar el contenido y las características de los recuerdos relacionados con la pérdida en una muestra de personas viviendo un duelo por cáncer con y sin un diagnóstico probable de trastorno de duelo prolongado/trastorno de duelo complejo persistente (PGD/PCBD).Métodos: Se analizaron entrevistas semiestructuradas con 28 adultos dolientes (PGD/PCBD = 12, NoPGD/PCBD = 16) mediante análisis temático.Resultados: Se identificaron tres temas supraordinados: (1) imágenes intrusivas, (2) cualidades de la memoria y (3) gatillantes. Los resultados mostraron que las personas que padecen un probable PGD/PCBD informaron un predominio de recuerdos negativos y molestos, recuerdos felices que desencadenan dolour y más imágenes intrusivas negativas que aquellos sin PGD/PCBD.Conclusiones: El duelo por cáncer puede provocar recuerdos intrusivos problemáticos que eclipsan los recuerdos positivos. Las víctimas de PGD/PCBD tienen más probabilidades de experimentar los recuerdos relacionados con la pérdida como negativos y molestos. Los enfoques clínicos que utilizan el procesamiento de memoria pueden ser de particular relevancia en este grupo.

Preventing PTSD, depression and associated health problems in student paramedics: protocol for PREVENT-PTSD, a randomised controlled trial of supported online cognitive training for resilience versus alternative online training and standard practice.

INTRODUCTION: Emergency workers dedicate their lives to promoting public health and safety, yet suffer higher rates of post-traumatic stress disorder (PTSD) and major depression (MD) compared with the general population. They also suffer an associated increased risk for physical health problems, which may be linked to specific immunological and endocrine markers or changes in relevant markers. Poor physical and mental health is costly to organisations, the National Health Service and society. Existing interventions aimed at reducing risk of mental ill health in this population are not very successful. More effective preventative interventions are urgently needed. We first conducted a large-scale prospective study of newly recruited student paramedics, identifying two cognitive factors (rumination and resilience appraisals) that predicted episodes of PTSD and MD over a 2-year period. We then developed internet-delivered cognitive training for resilience (iCT-R), a supported online intervention, to modify cognitive predictors. This protocol is for a randomised controlled trial to evaluate the efficacy of the resilience intervention. METHODS AND ANALYSIS: 570 student paramedics will be recruited from participating universities. They will be randomly allocated to iCT-R or to supported online training of an alternative, widely available intervention or to training-as-usual. Follow-up will occur after the intervention/standard practice period and at 6, 12 and 24 months. Primary outcomes include rates of PTSD and MD and subsydnromal PTSD and MD, measured by the Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders, fifth edition, the Patient-Health Questionnaire-9 and the Post-traumatic Stress Disorder Checklist for Diagnostic and Statistical Manual of Mental Disorders, fifth edition. Secondary outcomes include measures of resilience, rumination, anxiety, psychological distress, well-being, salivary cortisol, plasma levels of C-reactive protein, smoking and alcohol use, weight gain, sleep problems, health-related quality of life, health resource utilisation and productivity. ETHICS AND DISSEMINATION: The Medical Sciences Inter-Divisional Research Ethics Committee at the University of Oxford granted approval, reference: R44116/RE001. The results will be published in a peer-reviewed journal. Access to raw data and participant information will be available only to members of the research team. TRIAL REGISTRATION NUMBER: ISRCTN16493616; Pre-results.

Folic acid modulates cancer-associated micro RNAs and inflammatory mediators in neoplastic and non-neoplastic colonic cells in a different way.

SCOPE: Scientific evidence suggests that folic acid (FA) supplementation protects the healthy colonic mucosa from neoplastic transformation but may promote the progression of precancerous lesions. The underlying molecular mechanisms are not fully understood. Therefore, we explored, if high physiological FA doses provoke changes in (i) promoter-specific DNA methylation (ii) expression of cancer-associated micro RNAs (miRNAs) and (iii) inflammatory mediators in human neoplastic and non-neoplastic colonic cell lines. METHODS AND RESULTS: The malignant and the non-malignant colonic cell lines HT29 and HCEC were adapted to different near-physiological FA concentrations. Using DNA methylation and pathway specific PCR arrays, high-physiological FA concentrations revealed no relevant impact on promoter methylation but a number of differences between the cell lines in the expression of miRNAs and inflammatory mediators. In the HCEC cell line pro-inflammatory genes were repressed and the miRNA expression remained nearly unaffected. In contrast, in the HT29 cell line tumour-suppressive miRNAs were predominantly down-regulated and the expression of genes involved in chemotaxis and immunity were modulated. CONCLUSION: The different effects of high-physiological FA concentrations in malignant and non-malignant colonic cell lines regarding cancer-associated miRNAs and inflammatory mediators may contribute to the different effects of FA supplementation on colonic carcinogenesis.

[A two-faced vitamin : Folic acid - prevention or promotion of colon cancer?] / Ein Vitamin mit zwei Gesichtern : Folsäure ­ Prävention oder Promotion von Dickdarmkrebs?

In the late 1930s, it was discovered that liver and yeast extracts can be used to correct certain cases of megaloblastic anemia in pregnancy. The factor responsible for this was isolated from spinach leaves in the 1940s, and referred to as folate, a term derived from the Latin word folium for leaf. Folate is considered an essential nutrient for human beings. Folic acid, the synthetic form of the vitamin, is used in dietary supplements, medicines and fortified foods. Since the 1980s, it has been recommended that women who plan to become pregnant and pregnant women during the first trimester of pregnancy take folic acid supplements. This recommendation was based on studies that revealed that periconceptional folic acid supplementation can reduce the risk for neural tube defects (NTDs). Many countries later implemented folic acid fortification programs. The resulting population-wide increase of folic acid intakes led to significant reductions in NTD rates. However, a temporarily increased colorectal cancer incidence has been reported to coincide with the fortification programs in the USA and Canada. On the basis of currently available data from experimental and human studies it can be concluded that the association between folate/folic acid and cancer is rather complex: Folate intake in the range of the dietary reference intake (DRI) is associated with a reduced risk for cancer in healthy populations, whereas high intakes of folic acid might result in an increased risk for cancer incidence or progression in persons with precancerous lesions and under certain conditions. Since no adverse effects have been observed in association with the intake of dietary folate, research activities that aim at investigating cause and effect relationships focus on folic acid.

Differences in metabolism of the marine biotoxin okadaic acid by human and rat cytochrome P450 monooxygenases.

The ingestion of seafood contaminated with the marine biotoxin okadaic acid (OA) can lead to diarrhetic shellfish poisoning with symptoms like nausea, vomiting and abdominal cramps. Both rat and the human hepatic cytochrome P450 monooxygenases (CYP) metabolize OA. However, liver cell toxicity of metabolized OA is mainly unclear. The aim of our study was to detect the cellular effects in HepG2 cells exposed to OA in the presence of recombinant CYP enzymes of both rat and human for the investigation of species differences. The results should be set in correlation with a CYP-specific metabolite pattern. Comparative metabolite profiles of OA after incubation in rat and human recombinant CYP enzymes were established by using LC-MS/MS technique. Results demonstrated that metabolism of OA to oxygenated metabolites correlates with detoxification which was mainly catalyzed by human CYP3A4 and CYP3A5. Detoxification by rat Cyp3a1 was lower compared to human CYP3A enzymes and activation of OA by Cyp3a2 was observed, coincident with minor overall conversion capacity of OA. By contrast human and rat CYP1A2 seem to activate OA into cytotoxic intermediates. In conclusion, different mechanisms of OA metabolism may occur in the liver. At low OA doses, the human liver is likely well protected against cytotoxic OA, but for high shellfish consumers a potential risk cannot be excluded.

The glucosinolate metabolite 1-methoxy-3-indolylmethyl alcohol induces a gene expression profile in mouse liver similar to the expression signature caused by known genotoxic hepatocarcinogens.

SCOPE: Breakdown products of certain glucosinolates induce detoxifying enzymes and demonstrate preventive activities against chemically induced tumourigenesis in animal models. However, other breakdown products are genotoxic. 1-Methoxy-3-indolylmethyl alcohol (1-MIM-OH) is mutagenic in bacterial and mammalian cells upon activation by sulphotransferases and forms DNA adducts in mouse tissues. This effect is enhanced in mice transgenic for human sulphotransferases 1A1/2 (FVB/N-hSULT1A1/2). Therefore, we explored gene expression changes induced by 1-MIM-OH in mouse liver. METHODS AND RESULTS: FVB/N-hSULT1A1/2 mice were orally treated with 1-MIM-OH for 21 or 90 days, leading to high levels of hepatic 1-MIM-DNA adducts. Genome-wide expression analyses demonstrated no influence on detoxifying enzymes, but up-regulation of many mediators of the tumour suppressor p53 and down-regulation of Fhit and other long genes. While this p53 response might indicate protection, it was unable to prevent the accumulation of DNA adducts. However, various epidemiological studies reported inverse associations between the intake of cruciferous vegetables and cancer. This association may be due to the presence of other glucosinolates with tumour-preventing influences possibly outweighing adverse effects of some metabolites. CONCLUSION: 1-MIM-OH is a genotoxic substance inducing a gene expression profile similar to the expression signature caused by known genotoxic hepatocarcinogens.

Active elimination of the marine biotoxin okadaic acid by P-glycoprotein through an in vitro gastrointestinal barrier.

The consumption of okadaic acid (OA) contaminated shellfish can induce acute toxic symptoms in humans such as diarrhea, nausea, vomiting and abdominal pain; carcinogenic and embryotoxic effects have also been described. Toxicokinetic studies with mice have shown that high cytotoxic doses of OA can pass the gastrointestinal barrier presumably by paracellular passage. However, in vitro studies using human intestinal Caco-2 cell monolayers to represent the intestinal barrier have shown that at low-dose exposure OA is transported against a concentration gradient suggesting an active efflux mechanism. Since P-glycoprotein (P-gp) transports a wide variety of substrates, we investigated its possible influence on the observed elimination of OA. We used two different cellular transwell models: (i) Caco-2 cell monolayer endogenously expressing human P-gp and simulating the intestinal barrier and (ii) MDCK-II cell monolayer stably over-expressing P-gp. Our study demonstrates clearly that OA at non-cytotoxic concentrations passes the monolayer barrier only to a low degree, and that it is actively eliminated by P-gp over the apical membrane. Therefore, our in vitro data indicate that humans appear to have efficient defense mechanisms to protect themselves against low-dose contaminated shellfish by exhibiting a low bioavailability as a result of active elimination of OA by P-gp.

Polycyclic aromatic hydrocarbons stimulate human CYP3A4 promoter activity via PXR.

Metabolic activation of polycyclic aromatic hydrocarbons (PAH) is mediated mainly by cytochrome P450 monooxygenases (CYP) CYP1A1, 1A2 and 1B1. Several PAH are known to induce these CYP via aryl hydrocarbon receptor (AhR) signaling. Recently, it was shown that the PAH benzo[a]pyrene (BaP) can induce CYP3A4 as well. The induction was suggested to be mediated by the pregnane X receptor (PXR) rather than AhR. Metabolism by CYP3A4 is only known for dihydrodiol metabolites of PAH but not for their parent compounds. In the present study, a CYP3A4 reporter gene assay, requiring the overexpression of PXR, was used to investigate whether the PAH parent compounds BaP, benzo[c]phenanthrene (BcP) and dibenzo[a,l]pyrene (DBalP) as well as their corresponding phase I metabolites, the respective dihydrodiols and diol epoxides, can induce CYP3A4 promoter activity. BaP, BcP and their dihydrodiols were found to significantly activate the CYP3A4 promoter. Moreover, activation of PXR by all four compounds was detected by using a PXR transactivation assay, supporting that PXR mediates CYP3A4 induction by PAH. Taken together, these results show that both PAH parent compounds as well as their phase I metabolites induce CYP3A4 promoter via the transcription factor PXR.

Trans fatty acids affect cellular viability of human intestinal Caco-2 cells and activate peroxisome proliferator-activated receptors.

Trans fatty acids (TFA) are hypothesized to have an impact not only on coronary heart diseases but also on the development of colon cancer. To analyze if TFA exhibit cellular and molecular effects which could be involved in colon tumor progression, cells of the human colorectal adenocarcinoma-derived cell line Caco-2 were treated with various TFA isomers differing in the number and position of trans double bonds. The TFA tested in this study did not increase cellular proliferation but displayed growth-inhibitory effects at concentrations higher than 500 µM. In case of the TFA isomer C18:3 t9, t11, t13, an IC50 value of 23 µM was estimated for cytotoxicity indicating a high cytotoxic potential of this compound. In addition to the cytotoxicity studies, the TFA isomers were tested for their ability to activate peroxisome proliferator-activated receptors (PPAR) by taking advantage of a PPAR-dependent reporter gene assay. In contrast to PPARγ that was not activated by the TFA isomers tested in this study, the substances were shown to moderately activate PPARα, and strong activation was observed for PPARδ. The putative impact of TFA on colon cancer development with respect to PPARδ activation is being discussed.

Deep sequencing of MYC DNA-binding sites in Burkitt lymphoma.

BACKGROUND: MYC is a key transcription factor involved in central cellular processes such as regulation of the cell cycle, histone acetylation and ribosomal biogenesis. It is overexpressed in the majority of human tumors including aggressive B-cell lymphoma. Especially Burkitt lymphoma (BL) is a highlight example for MYC overexpression due to a chromosomal translocation involving the c-MYC gene. However, no genome-wide analysis of MYC-binding sites by chromatin immunoprecipitation (ChIP) followed by next generation sequencing (ChIP-Seq) has been conducted in BL so far. METHODOLOGY/PRINCIPAL FINDINGS: ChIP-Seq was performed on 5 BL cell lines with a MYC-specific antibody giving rise to 7,054 MYC-binding sites after bioinformatics analysis of a total of approx. 19 million sequence reads. In line with previous findings, binding sites accumulate in gene sets known to be involved in the cell cycle, ribosomal biogenesis, histone acetyltransferase and methyltransferase complexes demonstrating a regulatory role of MYC in these processes. Unexpectedly, MYC-binding sites also accumulate in many B-cell relevant genes. To assess the functional consequences of MYC binding, the ChIP-Seq data were supplemented with siRNA- mediated knock-downs of MYC in BL cell lines followed by gene expression profiling. Interestingly, amongst others, genes involved in the B-cell function were up-regulated in response to MYC silencing. CONCLUSION/SIGNIFICANCE: The 7,054 MYC-binding sites identified by our ChIP-Seq approach greatly extend the knowledge regarding MYC binding in BL and shed further light on the enormous complexity of the MYC regulatory network. Especially our observations that (i) many B-cell relevant genes are targeted by MYC and (ii) that MYC down-regulation leads to an up-regulation of B-cell genes highlight an interesting aspect of BL biology.

Classical Hodgkin's lymphoma shows epigenetic features of abortive plasma cell differentiation.

BACKGROUND: Epigenetic changes are involved in the extinction of the B-cell gene expression program of classical Hodgkin's lymphoma. However, little is known regarding epigenetic similarities between cells of classical Hodgkin's lymphoma and plasma cell myeloma, both of which share extinction of the gene expression program of mature B cells. DESIGN AND METHODS: Global histone H3 acetylation patterns were determined in cell lines derived from classical Hodgkin's lymphoma, plasma cell myeloma and B-cell lymphoma by chromatin immunoprecipitation and subsequent hybridization onto promoter tiling arrays. H3K27 trimethylation was analyzed by chromatin immunoprecipitation and real-time DNA polymerase chain reaction for selected genes. Epigenetic modifications were compared to gene expression data. RESULTS: Characteristic B-cell genes were hypoacetylated in classical Hodgkin's lymphoma and plasma cell myeloma cell lines as demonstrated by comparison of their histone H3 acetylation patterns to those of B-cell lines. However, the number of genes jointly hyperacetylated and expressed in classical Hodgkin' lymphoma and plasma cell myeloma cell lines, such as IRF4/MUM1 and RYBP, is limited. Moreover, H3K27 trimethylation for selected characteristic B-cell genes revealed that this additional epigenetic silencing is much more prevalent in classical Hodgkin's lymphoma than in plasma cell myeloma. CONCLUSIONS: Our epigenetic data support the view that classical Hodgkin's lymphoma is characterized by abortive plasma cell differentiation with a down-regulation of characteristic B-cell genes but without activation of most genes typical of plasma cells.

Analysis of the passage of the marine biotoxin okadaic acid through an in vitro human gut barrier.

The marine biotoxin okadaic acid (OA), produced by dinoflagellates, can accumulate in various bivalve molluscs. In humans, oral consumption of shellfish contaminated with OA induces acute toxic effects like diarrhea, nausea, vomiting and abdominal pain. However, tumorigenic and embryotoxic effects of OA have been also described. Current toxicokinetic studies with mice were performed with high cytotoxic oral doses leading presumably to a paracellular passage of OA through the gastrointestinal barrier. There are no studies available analyzing the absorption at low concentrations, which represent a realistic dietary exposure, making a reliable risk assessment difficult. Therefore, we performed a low-dose study using the human intestinal Caco-2 cell model to simulate the intestinal barrier. Low level exposure of 20-200 nM OA to the cell monolayer allows an only limited passage from the "luminal" to the "blood side". Furthermore, we could detect a significant efflux of OA, which led to the suggestion that active transport mechanisms are involved in the elimination process of OA. In conclusion, our results indicate that besides the well known defense mechanisms of humans against this marine biotoxin--vomiting and diarrhea--further detoxification mechanisms are available to limit the absorption of toxic OA.

Clinically significant avoidance of public transport following the London bombings: travel phobia or subthreshold posttraumatic stress disorder?

Following the London bombings of 7 July 2005 a "screen and treat" program was set up with the aim of providing rapid treatment for psychological responses in individuals directly affected. The present study found that 45% of the 596 respondents to the screening program reported phobic fear of public transport in a screening questionnaire. The screening program identified 255 bombing survivors who needed treatment for a psychological disorder. Of these, 20 (8%) suffered from clinically significant travel phobia. However, many of these individuals also reported symptoms of posttraumatic stress disorder [PTSD]. Comparisons between the travel phobia group and a sex-matched group of bombing survivors with PTSD showed that the travel phobic group reported fewer re-experiencing and arousal symptoms on the Trauma Screening Questionnaire (Brewin et al., 2002). The only PTSD symptoms that differentiated the groups were anger problems and feeling upset by reminders of the bombings. There was no difference between the groups in the reported severity of trauma or in presence of daily transport difficulties. Implications of these results for future trauma response are discussed.

An investigation of whether patients with post-traumatic stress disorder overestimate the probability and cost of future negative events.

This study compared estimations of the probability and cost of negative events occurring made by patients with post-traumatic stress disorder (PTSD) (n=43), patients with other anxiety disorders (n=29) and non-patients' (n=35). Prior to treatment PTSD patients overestimated the probability and cost of all types of traumatic events occurring relative to non-patients, and overestimated the probability and cost of the specific type of traumatic event that they had been traumatized by relative to the anxious controls as well as non-patients. These judgment biases were specific to traumatic events and did not generalise to all negative events. PTSD patients' estimations of the probability and cost of traumatic events were significantly reduced following treatment, and were no longer significantly different from those of non-patients. Results suggest that patients with PTSD show specific judgment biases in the estimation of probability and cost, which can be successfully modified by cognitive therapy.

Promoting mental health following the London bombings: a screen and treat approach.

Following the 2005 London bombings, a novel public health program was instituted to address the mental health needs of survivors. In this article, the authors describe the rationale for the program, characteristics of individuals assessed within the program, and preliminary outcome data. In addition to validated screening instruments and routine service usage data, standardized questionnaire outcome measures were collected. Seventy-one percent of individuals screened positive for a mental disorder. Of those receiving a more detailed clinical assessment, PTSD was the predominant diagnosis. Preliminary outcome data on 82 patients revealed large effect sizes for treatment comparable to those previously obtained in randomized controlled trials. The program succeeded in its aim of generating many more referrals of affected individuals than came through normal referral channels.

Screening for posttraumatic stress disorder: what combination of symptoms predicts best?

Several symptom screening instruments have been developed to identify trauma survivors at risk for chronic posttraumatic stress disorder, but few of these have been thoroughly evaluated to date. In this study, a range of symptom combination scoring rules derived from the literature were applied to the Posttraumatic Diagnostic Scale and evaluated in 4 different samples of trauma survivors (total N = 522) regarding their power to identify people with posttraumatic stress disorder. Results were replicated in a fifth sample (N = 253). Most scoring rules showed lower diagnostic efficiencies than in the original reports. The most stable results were obtained for cutoffs on the Posttraumatic Diagnostic Scale total scale and a new subset of 8 items. The results underscore the need to cross-validate findings before using screening instruments for clinical applications.