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The UK Biobank contains data with varying degrees of reliability and completeness for assessing depression. A third of participants completed a Mental Health Questionnaire (MHQ) containing the gold-standard Composite International Diagnostic Interview (CIDI) criteria for assessing mental health disorders.
To investigate whether multiple observations of depression from sources other than the MHQ can enhance the validity of major depressive disorder (MDD).
In participants who did not complete the MHQ, we calculated the number of other depression measures endorsed, for example from hospital episode statistics and interview data. We compared cases defined this way with CIDI-defined cases for several estimates: the variance explained by polygenic risk scores (PRS), area under the curve attributable to PRS, single nucleotide polymorphisms (SNPs)-based heritability and genetic correlations with summary statistics from the Psychiatric Genomics Consortium MDD genome-wide association study.
The strength of the genetic contribution increased with the number of measures endorsed. For example, SNP-based heritability increased from 7% in participants who endorsed only one measure of depression, to 21% in those who endorsed four or five measures of depression. The strength of the genetic contribution to cases defined by at least two measures approximated that for CIDI-defined cases. Most genetic correlations between UK Biobank and the Psychiatric Genomics Consortium MDD study exceeded 0.7, but there was variability between pairwise comparisons.
Multiple measures of depression can serve as a reliable approximation for case status where the CIDI measure is not available, indicating sample size can be optimised using the entire suite of UK Biobank data.
Major depression (MD) is often characterised as a categorical disorder; however, observational studies comparing sub-threshold and clinical depression suggest MD is continuous. Many of these studies do not explore the full continuum and are yet to consider genetics as a risk factor. This study sought to understand if polygenic risk for MD could provide insight into the continuous nature of depression.
Factor analysis on symptom-level data from the UK Biobank (N = 148 957) was used to derive continuous depression phenotypes which were tested for association with polygenic risk scores (PRS) for a categorical definition of MD (N = 119 692).
Confirmatory factor analysis showed a five-factor hierarchical model, incorporating 15 of the original 18 items taken from the PHQ-9, GAD-7 and subjective well-being questionnaires, produced good fit to the observed covariance matrix (CFI = 0.992, TLI = 0.99, RMSEA = 0.038, SRMR = 0.031). MD PRS associated with each factor score (standardised β range: 0.057–0.064) and the association remained when the sample was stratified into case- and control-only subsets. The case-only subset had an increased association compared to controls for all factors, shown via a significant interaction between lifetime MD diagnosis and MD PRS (p value range: 2.23 × 10−3–3.94 × 10−7).
An association between MD PRS and a continuous phenotype of depressive symptoms in case- and control-only subsets provides support against a purely categorical phenotype; indicating further insights into MD can be obtained when this within-group variation is considered. The stronger association within cases suggests this variation may be of particular importance.
Between 2009 and 2013, the Fly on the Wall (FLY) leaked 58% of recommendation revisions with a median delay of 27 minutes relative to the IBES announcement time. We show that FLY improves price discovery, but leaked recommendations hamper brokers’ ability to offer price improvement on trades routed through them. Three major brokers sued FLY; using key court dates, we show significant wealth and real effects to the brokerage industry. Overall, the speed with which analyst recommendations are disseminated has led to more rapid price discovery at the expense of a decline in the scope of the sell-side research industry.
Recent years have seen an exponential increase in the variety of healthcare data captured across numerous sources. However, mechanisms to leverage these data sources to support scientific investigation have remained limited. In 2013 the Pediatric Heart Network (PHN), funded by the National Heart, Lung, and Blood Institute, developed the Integrated CARdiac Data and Outcomes (iCARD) Collaborative with the goals of leveraging available data sources to aid in efficiently planning and conducting PHN studies; supporting integration of PHN data with other sources to foster novel research otherwise not possible; and mentoring young investigators in these areas. This review describes lessons learned through the development of iCARD, initial efforts and scientific output, challenges, and future directions. This information can aid in the use and optimisation of data integration methodologies across other research networks and organisations.
The 11th revision to the WHO International Classification of Diseases (ICD-11) identified complex post-traumatic stress disorder (CPTSD) as a new condition. There is a pressing need to identify effective CPTSD interventions.
We conducted a systematic review and meta-analysis of randomised controlled trials (RCTs) of psychological interventions for post-traumatic stress disorder (PTSD), where participants were likely to have clinically significant baseline levels of one or more CPTSD symptom clusters (affect dysregulation, negative self-concept and/or disturbed relationships). We searched MEDLINE, PsycINFO, EMBASE and PILOTS databases (January 2018), and examined study and outcome quality.
Fifty-one RCTs met inclusion criteria. Cognitive behavioural therapy (CBT), exposure alone (EA) and eye movement desensitisation and reprocessing (EMDR) were superior to usual care for PTSD symptoms, with effects ranging from g = −0.90 (CBT; k = 27, 95% CI −1.11 to −0.68; moderate quality) to g = −1.26 (EMDR; k = 4, 95% CI −2.01 to −0.51; low quality). CBT and EA each had moderate–large or large effects on negative self-concept, but only one trial of EMDR provided useable data. CBT, EA and EMDR each had moderate or moderate–large effects on disturbed relationships. Few RCTs reported affect dysregulation data. The benefits of all interventions were smaller when compared with non-specific interventions (e.g. befriending). Multivariate meta-regression suggested childhood-onset trauma was associated with a poorer outcome.
The development of effective interventions for CPTSD can build upon the success of PTSD interventions. Further research should assess the benefits of flexibility in intervention selection, sequencing and delivery, based on clinical need and patient preferences.
Background: Scrupulosity is a common yet understudied presentation of obsessive compulsive disorder (OCD) that is characterized by obsessions and compulsions focused on religion. Despite the clinical relevance of scrupulosity to some presentations of OCD, little is known about the association between scrupulosity and symptom severity across religious groups. Aims: The present study examined the relationship between (a) religious affiliation and OCD symptoms, (b) religious affiliation and scrupulosity, and (c) scrupulosity and OCD symptoms across religious affiliations. Method: One-way ANOVAs, Pearson correlations and regression-based moderation analyses were conducted to evaluate these relationships in 180 treatment-seeking adults with OCD who completed measures of scrupulosity and OCD symptom severity. Results: Scrupulosity, but not OCD symptoms in general, differed across religious affiliations. Individuals who identified as Catholic reported the highest level of scrupulosity relative to individuals who identified as Protestant, Jewish or having no religion. Scrupulosity was associated with OCD symptom severity globally and across symptom dimensions, and the magnitude of these relationships differed by religious affiliation. Conclusions: Findings are discussed in terms of the dimensionality of scrupulosity, need for further assessment instruments, implications for assessment and intervention, and the consideration of religious identity in treatment.
Optimising short- and long-term outcomes for children and patients with CHD depends on continued scientific discovery and translation to clinical improvements in a coordinated effort by multiple stakeholders. Several challenges remain for clinicians, researchers, administrators, patients, and families seeking continuous scientific and clinical advancements in the field. We describe a new integrated research and improvement network – Cardiac Networks United – that seeks to build upon the experience and success achieved to-date to create a new infrastructure for research and quality improvement that will serve the needs of the paediatric and congenital heart community in the future. Existing gaps in data integration and barriers to improvement are described, along with the mission and vision, organisational structure, and early objectives of Cardiac Networks United. Finally, representatives of key stakeholder groups – heart centre executives, research leaders, learning health system experts, and parent advocates – offer their perspectives on the need for this new collaborative effort.
Background: Two ‘sibling’ disorders have been proposed for the fourthcoming 11th version of the International Classification of Diseases (ICD-11): post-traumatic stress disorder (PTSD) and complex PTSD (CPTSD). Examining psychological factors that may be associated with CPTSD, such as self-compassion, is an important first step in its treatment that can inform consideration of which problems are most salient and what interventions are most relevant. Aims: We set out to investigate the association between self-compassion and the two factors of CPTSD: the PTSD factor (re-experiencing, avoidance, sense of threat) and the Disturbances in Self-Organization (DSO) factor (affect dysregulation, negative self-concept and disturbances in relationships). We hypothesized that self-compassion subscales would be negatively associated with both PTSD and DSO symptom clusters. Method: A predominantly female, clinical sample (n = 106) completed self-report scales to measure traumatic life events, ICD-11 CPTSD and self-compassion. Results: Significant negative associations were found between the CPTSD DSO clusters of symptoms and self-compassion subscales, but not for the PTSD ones. Specifically it was also found that self-judgement and common humanity significantly predicted hypoactive affect dysregulation whereas self-judgement and isolation significantly predicted negative self-concept. Conclusions: Our results indicate that self-compassion may be a useful treatment target for ICD-11 CPTSD, particularly for symptoms of negative self-concept and affect dysregulation. Future research is required to investigate the efficacy and acceptability of interventions that have implicit foundations on compassion.
Background: Almost all patients admitted at acute crisis to a psychiatric ward experience clinically significant symptoms of insomnia. Ward environments pose challenges to both sleep and the delivery of therapy. Despite this, there is no description of how to adapt cognitive behavioural therapy (CBT) for insomnia to overcome these challenges. Aims: (i) To describe the key insomnia presentations observed in the Oxford Ward Sleep Solution (OWLS) trial and (ii) outline key adaptations aimed to increase accessibility and hence effectiveness of CBT for insomnia for a ward setting. Methods: Trial therapists collaboratively agreed the key insomnia presentations and therapy adaptations based on their individual reflective logs used during the trial. Results: Three key insomnia presentations are outlined. These are used to illustrate the application of 10 CBT for insomnia therapy adaptations. These include use of sleep monitoring watches to engage patients in treatment, stabilizing circadian rhythms, reducing the impact of night-time observations and managing discharge as a sleep challenge. Conclusions: Whilst inpatient wards bring challenges for sleep and therapy delivery, creative adaptations can increase the accessibility of evidence based CBT for insomnia techniques. This therapy has proven popular with patients.
When patients are admitted onto psychiatric wards, sleep problems are highly prevalent. We carried out the first trial testing a psychological sleep treatment at acute admission (Oxford Ward sLeep Solution, OWLS).
This assessor-blind parallel-group pilot trial randomised patients to receive sleep treatment at acute crisis [STAC, plus standard care (SC)], or SC alone (1 : 1). STAC included cognitive–behavioural therapy (CBT) for insomnia, sleep monitoring and light/dark exposure for circadian entrainment, delivered over 2 weeks. Assessments took place at 0, 2, 4 and 12 weeks. Feasibility outcomes assessed recruitment, retention of participants and uptake of the therapy. Primary efficacy outcomes were the Insomnia Severity Index and Warwick–Edinburgh Mental Wellbeing Scale at week 2. Analyses were intention-to-treat, estimating treatment effect with 95% confidence intervals.
Between October 2015 and July 2016, 40 participants were recruited (from 43 assessed eligible). All participants offered STAC completed treatment (mean sessions received = 8.6, s.d. = 1.5). All participants completed the primary end point. Compared with SC, STAC led to large effect size (ES) reductions in insomnia at week 2 (adjusted mean difference −4.6, 95% CI −7.7 to −1.4, ES −0.9), a small improvement in psychological wellbeing (adjusted mean difference 3.7, 95% CI −2.8 to 10.1, ES 0.3) and patients were discharged 8.5 days earlier. One patient in the STAC group had an adverse event, unrelated to participation.
In this challenging environment for research, the trial was feasible. Therapy uptake was high. STAC may be a highly effective treatment for sleep disturbance on wards with potential wider benefits on wellbeing and admission length.
Background: Our view is that sleep disturbance may be a contributory causal factor in the development and maintenance of psychotic experiences. A recent series of randomized controlled intervention studies has shown that cognitive-behavioural approaches can improve sleep in people with psychotic experiences. However, the effects of psychological intervention for improving sleep have not been evaluated in young people at ultra-high risk of psychosis. Improving sleep might prevent later transition to a mental health disorder. Aims: To assess the feasibility and acceptability of an intervention targeting sleep disturbance in young people at ultra-high risk of psychosis. Method: Patients were sought from NHS mental health services. Twelve young people at ultra-high risk of psychosis with sleep problems were offered an eight-session adapted CBT intervention for sleep problems. The core treatment techniques were stimulus control, circadian realignment, and regulating day-time activity. Participants were assessed before and after treatment and at a one month follow-up. Results: All eligible patients referred to the study agreed to take part. Eleven patients completed the intervention, and one patient withdrew after two sessions. Of those who completed treatment, the attendance rate was 89% and an average of 7.6 sessions (SD = 0.5) were attended. There were large effect size improvements in sleep. Post-treatment, six patients fell below the recommended cut-off for clinical insomnia. There were also improvements in negative affect and psychotic experiences. Conclusion: This uncontrolled feasibility study indicates that treating sleep problems in young people at ultra-high of psychosis is feasible, acceptable, and may be associated with clinical benefits.
Persecutory delusions may be unfounded threat beliefs maintained by
safety-seeking behaviours that prevent disconfirmatory evidence being
successfully processed. Use of virtual reality could facilitate new
To test the hypothesis that enabling patients to test the threat
predictions of persecutory delusions in virtual reality social
environments with the dropping of safety-seeking behaviours (virtual
reality cognitive therapy) would lead to greater delusion reduction than
exposure alone (virtual reality exposure).
Conviction in delusions and distress in a real-world situation were
assessed in 30 patients with persecutory delusions. Patients were then
randomised to virtual reality cognitive therapy or virtual reality
exposure, both with 30 min in graded virtual reality social environments.
Delusion conviction and real-world distress were then reassessed.
In comparison with exposure, virtual reality cognitive therapy led to
large reductions in delusional conviction (reduction 22.0%,
P = 0.024, Cohen's d = 1.3) and
real-world distress (reduction 19.6%, P = 0.020, Cohen's
d = 0.8).
Cognitive therapy using virtual reality could prove highly effective in
Background: Many patients do not respond adequately to current pharmacological or psychological treatments for psychosis. Persistent persecutory delusions are common in clinical services, and cause considerable patient distress and impairment. Our aim has been to build a new translational personalized treatment, with the potential for wide use, that leads to high rates of recovery in persistent persecutory delusions. We have been developing, and evaluating individually, brief modular interventions, each targeting a key causal factor identified from our cognitive model. These modules are now combined in “The Feeling Safe Programme”. Aims: To test the feasibility of a new translational modular treatment for persistent persecutory delusions and provide initial efficacy data. Method: 12 patients with persistent persecutory delusions in the context of non-affective psychosis were offered the 6-month Feeling Safe Programme. After assessment, patients chose from a personalized menu of treatment options. Four weekly baseline assessments were carried out, followed by monthly assessments. Recovery in the delusion was defined as conviction falling below 50% (greater doubt than certainty). Results: 11 patients completed the intervention. One patient withdrew before the first monthly assessment due to physical health problems. An average of 20 sessions (SD = 4.4) were received. Posttreatment, 7 out of 11 (64%) patients had recovery in their persistent delusions. Satisfaction ratings were high. Conclusions: The Feeling Safe Programme is feasible to use and was associated with large clinical benefits. To our knowledge this is the first treatment report focused on delusion recovery. The treatment will be tested in a randomized controlled trial.
Cigarette smoking is an independent risk factor for heart disease and is linked to sudden cardiac death. In this study, we examined the effects of cigarette smoke (CS) on the volume overload stressed heart. Our hypothesis was that CS exacerbates volume overload (VO)–induced cardiac dysfunction by accelerating ventricular remodeling. VO stress was surgically induced in male Sprague-Dawley rats by abdominal aortocaval fistula (ACF). Rats, with and without ACF, were exposed to either room air or CS (6 cigarettes/day) for 6 weeks. Temporal echocardiogram measurements indicated that CS significantly increased VO-induced left ventricular dilatation, prevented compensatory wall thickening, and depressed fractional shortening. Morphological analysis of ventricular collagen revealed that CS blunted compensatory collagen expression (45% decrease versus ACF alone). CS exacerbated the VO-induced increase of MMP-9 and TIMP-1 expression in the heart. CS also blocked the compensatory increases of HIF-1α, VEGF, and TGF-β in the VO-stressed heart. These data indicate that CS worsens VO remodeling by disrupting compensatory mechanisms, thereby promoting eccentric dilation and dysfunction.