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.

Measuring dissociation across adolescence and adulthood: developing the short-form Cernis Felt Sense of Anomaly scale (CEFSA-14).

BACKGROUND: Dissociation may be important across many mental health disorders, but has been variously conceptualised and measured. We introduced a conceptualisation of a common type of dissociative experience, 'felt sense of anomaly' (FSA), and developed a corresponding measure, the Cernis Felt Sense of Anomaly (CEFSA) scale. AIMS: We aimed to develop a short-form version of the CEFSA that is valid for adolescent and adult respondents. METHOD: Data were collected from 1031 adult NHS patients with psychosis and 932 adult and 1233 adolescent non-clinical online survey respondents. Local structural equation modelling (LSEM) was used to establish measurement invariance of items across the age range. Ant colony optimisation (ACO) was used to produce a 14-item short-form measure. Finally, the expected test score function derived from item response theory modelling guided the establishment of interpretive scoring ranges. RESULTS: LSEM indicated 25 items of the original 35-item CEFSA were age invariant. They were also invariant across gender and clinical status. ACO of these items produced a 14-item short-form (CEFSA-14) with excellent psychometric properties (CFI=0.992; TLI=0.987; RMSEA=0.034; SRMR=0.017; Cronbach's alpha=0.92). Score ranges were established based on the expected test scores at approximately 0.7, 1.25 and 2.0 theta (equivalent to standard deviations above the mean). Scores of 29 and above may indicate elevated levels of FSA-dissociation. CONCLUSIONS: The CEFSA-14 is a psychometrically valid measure of FSA-dissociation for adolescents and adults. It can be used with clinical and non-clinical respondents. It could be used by clinicians as an initial tool to explore dissociation with their clients.

Coping strategies as a causal mediator of the effect of loss-related memory characteristics and negative loss-related appraisals on symptoms of PGD, PTSD and depression.

BACKGROUND: Psychological models of posttraumatic stress disorder (PTSD) and prolonged grief disorder (PGD) make predictions about the role of unhelpful coping strategies in maintaining difficulties by blocking self-correction of negative appraisals and memory integration following stressful life events like bereavement. However, few studies have tested these predictions directly. METHOD: We used counterfactually based causal mediation to assess whether unhelpful coping strategies mediated the relationship between (1) loss-related memory characteristics and/or (2) negative grief-related appraisals and symptoms of PGD, PTSD and depression using a three-wave longitudinal sample (N = 275). Appraisals and memory characteristics were measured at time point 1, unhelpful coping strategies at T2, and symptom variables at T3. Additionally, multiple mediation analyses within a structural equation modelling (SEM) framework assessed which types of coping strategies differentially mediated symptoms of PGD, PTSD and depression. RESULTS: Coping strategies mediated the relationship between negative appraisals and memory characteristics and symptoms of PGD, PTSD and depression after adjusting for demographics and loss characteristics. Sensitivity analyses suggested that these results were most robust for PGD, followed by PTSD and then depression. Multiple mediation analyses suggested that all four subscales (avoidance, proximity seeking, loss rumination and injustice rumination) individually mediated the effect of memory characteristics and appraisals on PGD. CONCLUSIONS: These results suggest that core predictions of the cognitive model for PTSD and the cognitive behavioural model of PGD are useful in predicting symptoms of post-loss mental health problems in the first 12-18 months after loss. Targeting unhelpful coping strategies is likely to reduce symptoms of PGD, PTSD and depression.

More than doubling the clinical benefit of each hour of therapist time: a randomised controlled trial of internet cognitive therapy for social anxiety disorder.

BACKGROUND: Cognitive therapy for social anxiety disorder (CT-SAD) is recommended by NICE (2013) as a first-line intervention. Take up in routine services is limited by the need for up to 14 ninety-min face-to-face sessions, some of which are out of the office. An internet-based version of the treatment (iCT-SAD) with remote therapist support may achieve similar outcomes with less therapist time. METHODS: 102 patients with social anxiety disorder were randomised to iCT-SAD, CT-SAD, or waitlist (WAIT) control, each for 14 weeks. WAIT patients were randomised to the treatments after wait. Assessments were at pre-treatment/wait, midtreatment/wait, posttreatment/wait, and follow-ups 3 & 12 months after treatment. The pre-registered (ISRCTN 95 458 747) primary outcome was the social anxiety disorder composite, which combines 6 independent assessor and patient self-report scales of social anxiety. Secondary outcomes included disability, general anxiety, depression and a behaviour test. RESULTS: CT-SAD and iCT-SAD were both superior to WAIT on all measures. iCT-SAD did not differ from CT-SAD on the primary outcome at post-treatment or follow-up. Total therapist time in iCT-SAD was 6.45 h. CT-SAD required 15.8 h for the same reduction in social anxiety. Mediation analysis indicated that change in process variables specified in cognitive models accounted for 60% of the improvements associated with either treatment. Unlike the primary outcome, there was a significant but small difference in favour of CT-SAD on the behaviour test. CONCLUSIONS: When compared to conventional face-to-face therapy, iCT-SAD can more than double the amount of symptom change associated with each therapist hour.

Early intervention in post-traumatic stress disorder without exposure to trauma memories using internet-delivered cognitive therapy: A pilot case series.

OBJECTIVES: Trauma-focussed psychological interventions are the treatments of choice for post-traumatic stress disorder (PTSD). As many clinical services receive high demand for PTSD interventions, strategies to improve treatment efficiency are needed. Some people seek help in the early phase post-trauma, including as soon as the first few months. It is unclear whether all components of trauma-focussed CBT are needed in this initial stage. Providing brief intervention in this early phase without work on trauma memories may be feasible and effective. This service evaluation study describes a case series of five participants experiencing PTSD following recent traumas. METHODS: Participants completed a shortened 6-week form of Internet-delivered Cognitive Therapy for PTSD (iCT-PTSD), which used fewer treatment modules and focussed primarily on psychoeducation about PTSD, and two key treatment components, 'reclaiming your life' and trigger discrimination. Unlike the full course of iCT-PTSD, this format did not include working directly with trauma memories. RESULTS: The intervention was associated with large reductions in symptoms of PTSD, depression and anxiety at the 6-week timepoint, which were maintained at 3-month follow-up. Scores on the composite PTSD measure showed an average reduction of 91% between baseline and end of follow-up. One client required an extension to the weekly phase of treatment and received further treatment modules. All were discharged after follow-up and did not require further treatment. CONCLUSIONS: The findings provide preliminary evidence that this briefer format of iCT-PTSD was of benefit for those seeking support following recent traumas. Further examination in a larger controlled study is required.

Effective psychological therapy for PTSD changes the dynamics of specific large-scale brain networks.

In posttraumatic stress disorder (PTSD), re-experiencing of the trauma is a hallmark symptom proposed to emerge from a de-contextualised trauma memory. Cognitive therapy for PTSD (CT-PTSD) addresses this de-contextualisation through different strategies. At the brain level, recent research suggests that the dynamics of specific large-scale brain networks play an essential role in both the healthy response to a threatening situation and the development of PTSD. However, very little is known about how these dynamics are altered in the disorder and rebalanced after treatment and successful recovery. Using a data-driven approach and fMRI, we detected recurring large-scale brain functional states with high temporal precision in a population of healthy trauma-exposed and PTSD participants before and after successful CT-PTSD. We estimated the total amount of time that each participant spent on each of the states while being exposed to trauma-related and neutral pictures. We found that PTSD participants spent less time on two default mode subnetworks involved in different forms of self-referential processing in contrast to PTSD participants after CT-PTSD (mtDMN+ and dmDMN+ ) and healthy trauma-exposed controls (only mtDMN+ ). Furthermore, re-experiencing severity was related to decreased time spent on the default mode subnetwork involved in contextualised retrieval of autobiographical memories, and increased time spent on the salience and visual networks. Overall, our results support the hypothesis that PTSD involves an imbalance in the dynamics of specific large-scale brain network states involved in self-referential processes and threat detection, and suggest that successful CT-PTSD might rebalance this dynamic aspect of brain function.

Knowledge and awareness about and use of iodised salt among students in Germany and Greece.

BACKGROUND: Iodine is an essential trace element, which is important for human metabolism, growth and mental development. Iodine deficiency may still occur in Europe and the use of iodised salt is an effective measure to enhance iodine intake. Knowledge and awareness about the importance of iodine in nutrition and health can have a positive impact on the use of iodised salt. Therefore, the aim of this study was to assess the knowledge about and use of iodised salt among university students in two European countries. METHOD: Data from two countries (Germany and Greece) were extracted from a multi-centre cross-sectional survey, conducted among non-nutrition science/non-medical students from October 2018 to April 2019. RESULTS: Among the 359 participants in Germany (35% females, median age: 22 years) and the 403 participants in Greece (51% females, median age: 21 years), 41% and 37%, respectively, reported use of iodised salt at home. Users and non-users did not differ by age, gender and Body Mass Index or general interest in nutrition in both cohorts. However, those who had a better knowledge about iodine and (iodised) salt or had previously attended nutrition classes were more likely to report iodised salt usage. CONCLUSION: The results suggest that strengthening the imparting of nutritional information and additional education of young adults are needed and may improve knowledge about and usage of iodised salt.

Catastrophic cognitions about coronavirus: the Oxford psychological investigation of coronavirus questionnaire [TOPIC-Q].

BACKGROUND: Cognitive therapies are developed on the principle that specific cognitive appraisals are key determinants in the development and maintenance of mental health disorders. It is likely that particular appraisals of the coronavirus pandemic will have explanatory power for subsequent mental health outcomes in the general public. To enable testing of this hypothesis we developed a questionnaire assessing coronavirus-related cognitions. METHODS: 12 285 participants completed online a 46-item pool of cognitions about coronavirus and six measures of different mental health problems. The sample was randomly split into derivation and validation samples. Exploratory factor analyses determined the factor structure, selection of items, and model fit in the derivation sample. Confirmatory factor analysis (CFA) then tested this model in the validation sample. Associations of the questionnaire with mental health outcomes were examined. RESULTS: The 26-item, seven-factor, Oxford Psychological Investigation of Coronavirus Questionnaire [TOPIC-Q] was developed. CFA demonstrated a good model fit (χ2 = 2108.43, df = 278, p < 0.001, comparative fit index (CFI) = 0.950, Tucker-Lewis index (TLI) = 0.942, root mean square error of approximation (RMSEA) = 0.033, standardized root mean square residual (SRMR) = 0.038). The factors were: cognitions about (1) safety and vulnerability, (2) negative long-term impact, (3) having the virus, (4) spreading the virus, (5) social judgment, (6) negative self, and (7) being targeted. The questionnaire explained significant variance in depression (45.8%), social anxiety (37.3%), agoraphobia (23.2%), paranoia (27.3%), post-traumatic stress disorder (57.1%), and panic disorder (31.4%). Cognitions about negative long-term impact had the greatest explanatory power across disorders. CONCLUSIONS: TOPIC-Q provides a method to assess appraisals of the pandemic, which is likely to prove helpful both in longitudinal studies assessing mental health outcomes and in delivery of psychological therapy.

Assessing panic disorder-specific competencies: evaluation of the Cognitive Therapy Competence Scale for panic disorder.

BACKGROUND: Evidence-based treatment for panic disorder consists of disorder-specific cognitive behavioural therapy (CBT) protocols. However, most measures of CBT competence are generic and there is a clear need for disorder-specific assessment measures. AIMS: To fill this gap, we evaluated the psychometric properties of the Cognitive Therapy Competence Scale (CTCP) for panic disorder. METHOD: CBT trainees (n = 60) submitted audio recordings of CBT for panic disorder that were scored on a generic competence measure, the Cognitive Therapy Scale - Revised (CTS-R), and the CTCP by markers with experience in CBT practice and evaluation. Trainees also provided pre- to post-treatment clinical outcomes on disorder-specific patient report measures for cases corresponding to their therapy recordings. RESULTS: The CTCP exhibited strong internal consistency (α = .79-.91) and inter-rater reliability (ICC = .70-.88). The measure demonstrated convergent validity with the CTS-R (r = .40-.54), although investigation into competence classification indicated that the CTCP may be more sensitive at detecting competence for panic disorder-specific CBT skills. Notably, the CTCP demonstrated the first indication of a relationship between therapist competence and clinical outcome for panic disorder (r = .29-.35); no relationship was found for the CTS-R. CONCLUSIONS: These findings provide initial support for the reliability and validity of the CTCP for assessing therapist competence in CBT for panic disorder and support the use of anxiety disorder-specific competence measures. Further investigation into the psychometric properties of the measure in other therapist cohorts and its relationship with clinical outcomes is recommended.

Cognitive paths from trauma to posttraumatic stress disorder: a prospective study of Ehlers and Clark's model in survivors of assaults or road traffic collisions.

BACKGROUND: Individual differences in cognitive responses to trauma may represent modifiable risk factors that could allow early identification, targeted early treatment and possibly prevention of chronic posttraumatic stress disorder (PTSD). Ehlers and Clark's cognitive model of PTSD suggests that negative appraisals, disjointed trauma memories, and unhelpful coping strategies maintain PTSD. These are thought to be influenced by cognitive processing during trauma. The aim of this study was to test this model prospectively with path analyses. METHODS: Participants (N = 828) were recruited from an emergency department following injury in a violent assault or road traffic collision and 700 participated in the 6-month assessments. Cognitive processing was assessed shortly after the event, negative appraisals, disjointed memories, and unhelpful coping strategies at 1 month, persistent PTSD symptom severity at 6 months, and early PTSD symptom severity at 2 weeks. RESULTS: Cognitive variables, with trauma type and gender, explained 52% of the variance in PTSD symptom severity at 6 months. Including early symptom severity in the model did not explain more variance (53%). Early PTSD symptom severity, with trauma type and gender, only predicted 40%. Negative appraisals and disjointed memories predicted persistent symptom severity both directly and indirectly via unhelpful strategies. Peritraumatic processing predicted persistent symptom severity mainly indirectly. The effects of trauma type and gender were fully mediated by the cognitive factors. CONCLUSIONS: The results are consistent with theoretically derived predictions and support cognitive factors as indicators of risk for chronic PTSD and as a target for the treatment and prevention of PTSD.

The Dunn Worry Questionnaire and the Paranoia Worries Questionnaire: new assessments of worry.

BACKGROUND: The cognitive process of worry, which keeps negative thoughts in mind and elaborates the content, contributes to the occurrence of many mental health disorders. Our principal aim was to develop a straightforward measure of general problematic worry suitable for research and clinical treatment. Our secondary aim was to develop a measure of problematic worry specifically concerning paranoid fears. METHODS: An item pool concerning worry in the past month was evaluated in 250 non-clinical individuals and 50 patients with psychosis in a worry treatment trial. Exploratory factor analysis and item response theory (IRT) informed the selection of scale items. IRT analyses were repeated with the scales administered to 273 non-clinical individuals, 79 patients with psychosis and 93 patients with social anxiety disorder. Other clinical measures were administered to assess concurrent validity. Test-retest reliability was assessed with 75 participants. Sensitivity to change was assessed with 43 patients with psychosis. RESULTS: A 10-item general worry scale (Dunn Worry Questionnaire; DWQ) and a five-item paranoia worry scale (Paranoia Worries Questionnaire; PWQ) were developed. All items were highly discriminative (DWQ a = 1.98-5.03; PWQ a = 4.10-10.7), indicating small increases in latent worry lead to a high probability of item endorsement. The DWQ was highly informative across a wide range of the worry distribution, whilst the PWQ had greatest precision at clinical levels of paranoia worry. The scales demonstrated excellent internal reliability, test-retest reliability, concurrent validity and sensitivity to change. CONCLUSIONS: The new measures of general problematic worry and worry about paranoid fears have excellent psychometric properties.

Cognitive appraisals of dissociation in psychosis: a new brief measure.

BACKGROUND: Catastrophic cognitive appraisals, similar to those in anxiety disorders, are implicated in depersonalisation, a form of dissociation. No scales exist to measure appraisals of dissociative experiences. Dissociation is common in psychosis. Misinterpretations of dissociative experiences may maintain psychotic symptoms. Therefore, assessing appraisals in this context may be valuable. AIMS: The primary aim was to develop a measure of key appraisals of dissociation in psychosis. Secondary aims were to test the relationship between appraisals and psychotic experiences (paranoia and hallucinations), and determine whether appraisals explain additional variance in psychotic symptoms above dissociative symptoms. METHOD: Fifty items were generated from transcripts of interviews with patients. The measure was developed and psychometrically validated via factor analysis of data from 9902 general population participants and 1026 patients with psychosis. Convergent validity, test-re-test reliability, and internal reliability were assessed. Regression analyses tested relationships with psychotic symptoms. RESULTS: A 13-item single-factor measure was developed. Factor analysis indicated good model fit [χ2(65) = 247.173, comparative fit index (CFI) = 0.960, root mean square error of approximation (RMSEA) = 0.052]. The scale had good convergent validity with a rumination (non-clinical: r = 0.71; clinical: r = 0.73) and dissociation measure (r = 0.81; r = 0.80), high internal consistency (α = 0.93; α = 0.93), and excellent 1-week test-re-test reliability [intraclass correlation (ICC) = 0.90]. It explained variance in psychotic symptoms (paranoia: 36.4%; hallucinations: 35.0%), including additional variance compared with dissociation alone (paranoia: 5.3%; hallucinations: 2.3%). CONCLUSIONS: The Cognitive Appraisals of Dissociation in Psychosis (CAD-P) measure is a psychometrically robust scale identifying appraisals of dissociative experiences in psychosis and is associated with the presence of psychotic experiences. It is likely to prove useful for clinical assessment and research.

A longitudinal investigation of the role of parental responses in predicting children's post-traumatic distress.

BACKGROUND: While parental post-trauma support is considered theoretically important for child adjustment, empirical evidence concerning the specific aspects of parental responding that influence child post-traumatic distress, or the processes via which any such impacts occur, is extremely limited. We conducted a longitudinal examination of whether parental post-trauma appraisals, trauma-specific support style and general parenting style predicted child post-traumatic stress symptom severity (PTSS) following trauma; and whether such influences operated via the child's own appraisals and coping style. METHOD: We recruited 132 parent-child pairs following children's experience of acute trauma. We examined whether parental responses assessed at 1-month post-trauma, predicted child PTSS at 6-month follow-up. Parental trauma-specific appraisals and responses, and general parenting style, were assessed via both self-report and direct observations. Child-report questionnaires were used to assess PTSS and potential mediators. RESULTS: Initial parent negative appraisals and encouragement of avoidant coping were associated with higher child-reported PTSS at 6-month follow-up. Predictive effects were maintained even when controlling for initial child symptom levels. Observational assessments broadly supported conclusions from self-report. There was evidence that parental influences may operate, in part, by influencing the child's own appraisals and coping responses. In contrast, there was no evidence for an influence of more "adaptive" support or general parenting style on child PTSS. CONCLUSIONS: Findings provide important insight into how elements of social support may influence child post-trauma outcomes.

Pragmatic RAndomised controlled trial of a trauma-focused guided self-help Programme versus InDividual trauma-focused cognitive Behavioural therapy for post-traumatic stress disorder (RAPID): trial protocol.

BACKGROUND: There is good evidence that trauma-focused therapies for Post-Traumatic Stress Disorder are effective. However, they are not always feasible to deliver due a shortage of trained therapists and demands on the patient. An online trauma-focused Guided Self-Help (GSH) programme which could overcome these barriers has shown promise in a pilot study. This study will be the first to evaluate GSH against standard face-to-face therapy to assess its suitability for use in the NHS. METHODS: The study is a large-scale multi-centre pragmatic randomised controlled non-inferiority trial, with assessors masked to treatment allocation. One hundred and ninety-two participants will be randomly allocated to receive either face-to-face trauma-focused cognitive behaviour therapy (TFCBT) or trauma-focused online guided self-help (GSH). The primary outcome will be the severity of symptoms of PTSD over the previous week as measured by the Clinician Administered PTSD Scale for DSM5 (CAPS-5) at 16 weeks post-randomisation. Secondary outcome measures include PTSD symptoms over the previous month as measured by the CAPS-5 at 52 weeks plus the Impact of Event Scale - revised (IES-R), Work and Social Adjustment Scale (WSAS), Patient Health Questionnaire-9 (PHQ-9), General Anxiety Disorder-7 (GAD-7), Alcohol Use Disorders Test (AUDIT-O), Multidimensional Scale for Perceived Social Support (MSPSS), short Post-Traumatic Cognitions Inventory (PTCI), Insomnia Severity Index (ISI) and General Self Efficacy Scale (GSES) measured at 16 and 52 weeks post-randomisation. Changes in health-related quality of life will be measured by the EQ-5D and the level of healthcare resource utilisation for health economic analysis will be determined by an amended version of the Client Socio-Demographic and Service Receipt Inventory European Version. The Client Satisfaction Questionnaire (CSQ) will be collected at 16 weeks post-randomisation to evaluate treatment satisfaction. DISCUSSION: This study will be the first to compare online GSH with usual face-to-face therapy for PTSD. The strengths are that it will test a rigorously developed intervention in a real world setting to inform NHS commissioning. The potential challenges of delivering such a pragmatic study may include participant recruitment, retention and adherence, therapist retention, and fidelity of intervention delivery. TRIAL REGISTRATION: ISRCTN13697710 registered on 20/12/2016.

The Preliminary Development and Validation of a Trauma-Related Safety-Seeking Behavior Measure for Youth: The Child Safety Behavior Scale (CSBS).

Safety-seeking behaviors (SSBs) may be employed after exposure to a traumatic event in an effort to prevent a feared outcome. Cognitive models of posttraumatic stress disorder propose SSBs contribute to maintaining this disorder by preventing disconfirmation of maladaptive beliefs and preserving a sense of current threat. Recent research has found that SSBs impact children's posttraumatic stress symptoms (PTSS) and recovery. In this paper, we sought to develop and validate a novel 22-item Child Safety Behavior Scale (CSBS) in a school-based sample of 391 pupils (age 12-15 years) who completed a battery of questionnaires as well as 68 youths (age 8-17 years) who were recently exposed to a trauma. Of the sample, 93.1% (N = 426) completed the new questionnaire. The sample was split (n = 213), and we utilized principal components analysis alongside parallel analysis, which revealed that 13 items loaded well onto a two-factor structure. This structure was superior to a one-factor model and overall demonstrated a moderately good model of fit across indices, based upon a confirmatory factory analysis with the other half of the sample. The CSBS showed excellent internal consistency, r = .90; good test-retest reliability, r = .64; and good discriminant validity and specificity. In a multiple linear regression, SSBs, negative appraisals, and number of trauma types each accounted for unique variance in a model of PTSS. This study provides initial support for the use of the CSBS in trauma-exposed youth as a valuable tool for further research, clinical assessment, and targeted intervention.

Cognitive therapy as an early treatment for post-traumatic stress disorder in children and adolescents: a randomized controlled trial addressing preliminary efficacy and mechanisms of action.

BACKGROUND: Few efficacious early treatments for post-traumatic stress disorder (PTSD) in children and adolescents exist. Previous trials have intervened within the first month post-trauma and focused on secondary prevention of later post-traumatic stress; however, considerable natural recovery may still occur up to 6-months post-trauma. No trials have addressed the early treatment of established PTSD (i.e. 2- to 6-months post-trauma). METHODS: Twenty-nine youth (8-17 years) with PTSD (according to age-appropriate DSM-IV or ICD-10 diagnostic criteria) after a single-event trauma in the previous 2-6 months were randomly allocated to Cognitive Therapy for PTSD (CT-PTSD; n = 14) or waiting list (WL; n = 15) for 10 weeks. RESULTS: Significantly more participants were free of PTSD after CT-PTSD (71%) than WL (27%) at posttreatment (intent-to-treat, 95% CI for difference .04-.71). CT-PTSD yielded greater improvement on child-report questionnaire measures of PTSD, depression and anxiety; clinician-rated functioning; and parent-reported outcomes. Recovery after CT-PTSD was maintained at 6- and 12-month posttreatment. Beneficial effects of CT-PTSD were mediated through changes in appraisals and safety-seeking behaviours, as predicted by cognitive models of PTSD. CT-PTSD was considered acceptable on the basis of low dropout and high treatment credibility and therapist alliance ratings. CONCLUSIONS: This trial provides preliminary support for the efficacy and acceptability of CT-PTSD as an early treatment for PTSD in youth. Moreover, the trial did not support the extension of 'watchful waiting' into the 2- to 6-month post-trauma window, as significant improvements in the WL arm (particularly in terms of functioning and depression) were not observed. Replication in larger samples is needed, but attention to recruitment issues will be required.

Seeing Is Believing: Using Video Feedback in Cognitive Therapy for Social Anxiety Disorder.

Distorted negative self-images and impressions appear to play a key role in maintaining Social Anxiety Disorder (SAD). In previous research, McManus et al. (2009) found that video feedback can help people undergoing cognitive therapy for SAD (CT-SAD) to develop a more realistic impression of how they appear to others, and this was associated with significant improvement in their social anxiety. In this paper we first present new data from 47 patients that confirms the value of video feedback. Ninety-eighty percent of the patients indicated that they came across more favorably than they had predicted after viewing a video of their social interactions. Significant reductions in social anxiety were observed during the following week and these reductions were larger than those observed after control periods. Comparison with our earlier data (McManus et al., 2009) suggests we may have improved the effectiveness of video feedback by refining and developing our procedures over time. The second part of the paper outlines our current strategies for maximizing the impact of video feedback. The strategies have evolved in order to help patients with SAD overcome a range of processing biases that could otherwise make it difficult for them to spot discrepancies between their negative self-imagery and the way they appear on video.

[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.

The latent structure of Acute Stress Disorder symptoms in trauma-exposed children and adolescents.

BACKGROUND: The revision of Acute Stress Disorder (ASD) in the DSM-5 (DSM-5, 2013) proposes a cluster-free model of ASD symptoms in both adults and youth. Published evaluations of competing models of ASD clustering in youth have rarely been examined. METHODS: We used Confirmatory Factor Analysis (combined with multigroup invariance tests) to explore the latent structure of ASD symptoms in a trauma-exposed sample of children and young people (N = 594). The DSM-5 structure was compared with the previous DSM-IV conceptualization (4-factor), and two alternative models proposed in the literature (3-factor; 5-factor). Model fit was examined using goodness-of-fit indices. We also established DSM-5 ASD prevalence rates relative to DSM-IV ASD, and the ability of these models to classify children impaired by their symptoms. RESULTS: Based on both the Bayesian Information Criterion, the interfactor correlations and invariance testing, the 3-factor model best accounted for the profile of ASD symptoms. DSM-5 ASD led to slightly higher prevalence rates than DSM-IV ASD and performed similarly to DSM-IV with respect to categorising children impaired by their symptoms. Modifying the DSM-5 ASD algorithm to a 3+ or 4+ symptom requirement was the strongest predictor of impairment. CONCLUSIONS: These findings suggest that a uni-factorial general-distress model is not the optimal model of capturing the latent structure of ASD symptom profiles in youth and that modifying the current DSM-5 9+ symptom algorithm could potentially lead to a more developmentally sensitive conceptualization.

SLEEP AND TREATMENT OUTCOME IN POSTTRAUMATIC STRESS DISORDER: RESULTS FROM AN EFFECTIVENESS STUDY.

BACKGROUND: Most patients with posttraumatic stress disorder (PTSD) suffer from sleep problems. Concerns have been raised about possible detrimental effects of sleep problems on the efficacy of psychological treatments for PTSD. In this study, we investigated the relation of session-to-session changes in PTSD symptoms and sleep, and tested whether sleep problems predicted poorer short- and long-term treatment outcome. METHODS: Self-reported sleep quality, sleep duration, and PTSD symptoms were assessed weekly in a consecutive sample of 246 patients who received cognitive therapy for PTSD (CT-PTSD; Ehlers & Clark, 2000), and at follow-up (mean = 247 days posttreatment). Additionally, moderating effects of medication use and comorbid depression were assessed. RESULTS: Sleep and PTSD symptoms improved in parallel. The relation was moderated by depression: Sleep problems at the start of therapy did not predict improvement in PTSD symptoms during treatment for patients without comorbid depression. Patients with comorbid depression, however, showed less rapid decreases in PTSD symptoms, but comparable overall outcome, if their sleep quality was poor. Residual sleep problems at the end of treatment did not predict PTSD symptoms at follow-up once residual PTSD symptoms were taken into account. CONCLUSIONS: CT-PTSD leads to simultaneous improvement in sleep and PTSD symptoms. Sleep problems may reduce the speed of recovery in PTSD patients with comorbid depression. For these patients, additional treatment sessions are indicated to achieve comparable outcomes, and additional interventions targeting sleep may be beneficial. For those without comorbid depression, self-reported sleep problems did not interfere with response to trauma-focused psychological treatment.