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A prospective study of risk factors and new prediction model for inpatient aggression in a Turkish forensic psychiatric cohort with psychotic illness
Background: Aggression among psychiatric inpatients causes harm and disrupts care. While often linked to modifiable risk factors, their role remains unclear, and many prediction tools overlook them. This study aimed to assess the relationship between risk factors and inpatient aggression among forensic patients with psychotic disorders in Turkiye and to develop a population-specific prediction model. Methods: Eight static and ten dynamic risk factors were assessed. Dynamic factors were collected fortnightly, with the outcome defined as any physical or verbal aggression between assessment rounds. Multilevel logistic regression analyses assessed the association between dynamic risk factors and outcomes. A new population-specific prediction model was developed by refitting the previously developed elsewhere (FOxWeb). Models incorporating fixed effects were used to assess predictive performance. Results: Over four months, 102 forensic psychiatric inpatients underwent 811 dynamic risk assessments, with 603 aggressive incidents recorded. Forty-two patients were involved in at least one incident. Many dynamic factors were significantly associated with outcomes in both univariable and multivariable analyses. The total dynamic score was a significant predictor, improving the discrimination of the fixed-effects model (AUC = 0.84, 95 % CI: 0.81–0.87) compared to the model using static factors alone (AUC=0.73, 95 % CI: 0.69–0.77). Conclusion: Combining dynamic and static factors in the prediction model showed strong performance for assessing aggression risk. Refitting existing prediction models to specific populations may offer enhanced performance, but this requires external validation in independent samples as development models may be overfitted. Highly quality predicative models could enhance interventions, optimize resource use, and improve clinical decision-making.
Neurotransmitter modulation of human facial emotion recognition
Human facial emotion recognition (FER) is an evolutionarily preserved process that influences affiliative behaviours, approach/avoidance and fight-or-flight responses in the face of detecting threat cues, thus enhancing adaptation and survival in social groups. Here, we provide a narrative literature review on how human FER is modulated by neurotransmitters and pharmacological agents, classifying the documented effects by central neurotransmitter systems. Synthesising the findings from studies involving functional neuroimaging and FER tasks, we highlight several emerging themes; for example, noradrenaline promotes an overall positive bias in FER, while serotonin, dopamine and gamma-aminobutyric acid modulate emotions relating to self-preservation. Finally, other neurotransmitters including the cholinergic and glutamatergic systems are responsible for rather non-specific pro-cognitive effects in FER. With the ongoing accumulation of evidence further characterising the individual contributions of each neurotransmitter system, we argue that a sensible next step would be the integration of experimental neuropharmacology with computational models to infer further insights into the temporal dynamics of different neurotransmitter systems modulating FER.
THE OXFORD CHARACTER PROJECT*
The Oxford Character Project (OCP) is an interdisciplinary research and education project at the University of Oxford. Established in 2014, its work joins theoretical and empirical research in virtue ethics, character development and leadership education with the design and delivery of character and leadership development programmes. Its aim is to advance character-based leadership and leadership education through strategic partnerships in the United Kingdom and around the world. This chapter presents the work of the OCP, focusing on: (1) the OCP’s approach to character education, (2) the connection between character and leadership that is manifested in several educational programmes, (3) the OCP’s research on character, culture and leadership in UK business and (4) the OCP’s research on global leadership.
Knowledge, Attitudes, and Experiences of Self-Harm and Suicide in Low- and Middle-Income Countries.
Background: Over three-quarters of suicides occur in low- and middle-income countries (LMICs) and a better understanding of this behavior within these settings is crucial. Aim: To investigate stakeholders' knowledge, attitudes, and experiences of self-harm and suicide in LMICs. Method: A systematic search was conducted using British Nursing Index, Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Embase, MEDLINE, PsycINFO, and Social Sciences electronic databases from inception to March 2022, combined with hand-searching reference lists. The search was updated using the PubMed Similar Articles function in February 2024. Analysis followed a modified narrative synthesis approach. Results: One hundred and fifty-four articles met the inclusion criteria, of which 60 included relevant quantitative data. Attitudes toward suicide were often contradictory although, overall, were negative and suicide literacy was poor. Healthcare staff reported lacking training in this area. Willingness to seek help was linked to suicide literacy and attitudes toward suicide. Limitations: Heterogeneity of included studies. Conclusion: Tackling stigma and improving awareness of suicide and self-harm in LMICs are needed to facilitate suicide prevention. Training should include people with lived experience of suicide and self-harm. The complex and contradictory influences of age, gender, religious, and cultural beliefs and lived experience must be considered.
‘Not Angels but Humans’ An Exploratory Qualitative Study of Female Nurses With Lived Experience of Self-Harm and Suicidal Behaviours
Aims: To explore the experiences of qualified nurses who have lived experience of self-harm (with or without suicidal intent) during nursing training or practice. Specifically, to examine characteristics and contributing factors and ideas for tailored suicide prevention interventions. Design: Exploratory qualitative study. Methods: Individual semi-structured interviews were conducted with eight qualified female nurses who had self-harmed during nursing training or practice. Participants were recruited from three NHS hospital Trusts. Data were collected between June and September 2023 and analysed using reflexive thematic analysis. Results: Four themes were generated: (1) ‘I don't think work triggered it, but I don't think it helped’: characteristics and contributors to self-harm, (2) ‘You're a nurse now you can't talk about that’: nursing culture and barriers to workplace support seeking, (3) ‘Are you a nurse or are you a lived experience practitioner – can you be both?’: navigating a dual identity as a nurse with lived experience and (4) ‘We need the permission that it's ok to put us first’: workplace support and suggestions for suicide prevention. Conclusion: Participants described their experiences of self-harm, including citing a range of contributory factors, with occupational issues being particularly salient. Cultural expectations and stigma prevented help-seeking and unique challenges regarding being both a clinician and an individual who has self-harmed were described. Reflections and perspectives on workplace and independent mental health support for nurses were shared. Implications for the Profession: Potential avenues for suicide prevention interventions tailored for the nursing profession may include challenging nursing culture and promoting help-seeking, peer support opportunities and implementation of education surrounding mental health and well-being in nursing curricula. Reporting Method: Reporting complied with the COREQ. Patient or Public Contribution: The topic guide and participant information sheet were developed in consultation with a group of qualified and student nurses with lived experience of suicidal thoughts and behaviours.
Cognitive behavioural therapy for sleep problems in psychosis: systematic review of effectiveness and acceptability.
BACKGROUND: Sleep problems are common among people with psychosis. Research suggests poor sleep is causally related to psychosis, anxiety and depression. AIMS: This review investigates the effectiveness and acceptability of cognitive-behavioural therapy (CBT) in targeting sleep problems in people with and at risk of psychosis. METHOD: Four databases were searched in line with PRISMA guidelines. Eligible studies either evaluated (a) CBT targeting sleep problems in people with or at risk of psychosis, or (b) subjective experiences of this treatment. Articles not published in peer-review journals were excluded. Treatment effectiveness was investigated for sleep, psychosis and other clinical outcomes. Acceptability was evaluated using qualitative data, drop-out rates, adverse events and relevant questionnaires. Adaptations to standard treatment protocols were described. Research quality was appraised using Cochrane Risk of Bias tools for randomised and non-randomised trials, and a checklist was developed for qualitative papers. RESULTS: Of the 975 records identified, 14 were eligible. The most common CBT target was insomnia. Treatment protocols were typically adapted by omitting sleep restriction. Large effect sizes were reported for sleep outcomes; however, effects for other clinical outcomes were less clear. Qualitative data and acceptability outcomes suggest that treatment was received positively by participants. CONCLUSIONS: CBT is an effective and acceptable treatment for sleep problems in people with and at risk of psychosis. However, our conclusions are limited by few good-quality studies and small samples. Further gold-standard research is required to inform evidence-based guidelines.
Paranoia and unusual sensory experiences in Parkinson's disease.
OBJECTIVES: There has been limited exploration into the nature and development of psychotic experiences (PEs) in Parkinson's disease (PD). We aimed to comprehensively assess the frequency, severity, and associated distress of paranoia and unusual sensory experiences (USEs) in PD, and to assess what variables are significantly associated with these experiences, focussing on psychological processes central to understanding PEs in non-PD groups. METHOD: A questionnaire battery was completed by 369 individuals with PD with a mean age of 66 years and mean time since diagnosis of 5 years. Recruitment was via Parkinson's UK, social media, and local community groups. For a subset of measures, comparisons were made to age-matched controls using pre-existing data. RESULTS: 182 (49%) participants reported USEs, including almost half of those not taking dopaminergic medication. For 83 (23%), the experience was distressing. Paranoia across the sample was significantly lower than in age-matched controls. However, specific paranoid concerns around abandonment (16%) and spousal betrayal (10%) were reported by some. Depression, anxiety, loneliness, and stigma and desire for support with PEs were high across the sample. Almost all psychological variables were significantly associated with PEs in structural equation models. CONCLUSION: PEs in PD are common, even in those not taking dopaminergic medication. For a small subset, these experiences are distressing and not resolved by existing treatment. Cognitive-affective variables like depression and anxiety could play a maintaining role in PEs in PD thus providing easy avenues for trialling intervention.
Safety outcomes following COVID-19 vaccination and infection in 5.1 million children in England.
The risk-benefit profile of COVID-19 vaccination in children remains uncertain. A self-controlled case-series study was conducted using linked data of 5.1 million children in England to compare risks of hospitalisation from vaccine safety outcomes after COVID-19 vaccination and infection. In 5-11-year-olds, we found no increased risks of adverse events 1-42 days following vaccination with BNT162b2, mRNA-1273 or ChAdOX1. In 12-17-year-olds, we estimated 3 (95%CI 0-5) and 5 (95%CI 3-6) additional cases of myocarditis per million following a first and second dose with BNT162b2, respectively. An additional 12 (95%CI 0-23) hospitalisations with epilepsy and 4 (95%CI 0-6) with demyelinating disease (in females only, mainly optic neuritis) were estimated per million following a second dose with BNT162b2. SARS-CoV-2 infection was associated with increased risks of hospitalisation from seven outcomes including multisystem inflammatory syndrome and myocarditis, but these risks were largely absent in those vaccinated prior to infection. We report a favourable safety profile of COVID-19 vaccination in under-18s.
Magnetic Resonance Imaging Characteristics of LGI1-Antibody and CASPR2-Antibody Encephalitis.
IMPORTANCE: Rapid and accurate diagnosis of autoimmune encephalitis encourages prompt initiation of immunotherapy toward improved patient outcomes. However, clinical features alone may not sufficiently narrow the differential diagnosis, and awaiting autoantibody results can delay immunotherapy. OBJECTIVE: To identify simple magnetic resonance imaging (MRI) characteristics that accurately distinguish 2 common forms of autoimmune encephalitis, LGI1- and CASPR2-antibody encephalitis (LGI1/CASPR2-Ab-E), from 2 major differential diagnoses, viral encephalitis (VE) and Creutzfeldt-Jakob disease (CJD). DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study involved a retrospective, blinded analysis of the first available brain MRIs (taken 2000-2022) from 192 patients at Oxford University Hospitals in the UK and Mayo Clinic in the US. These patients had LGI1/CASPR2-Ab-E, VE, or CJD as evaluated by 2 neuroradiologists (discovery cohort; n = 87); findings were validated in an independent cohort by 3 neurologists (n = 105). Groups were statistically compared with contingency tables. Data were analyzed in 2023. MAIN OUTCOMES AND MEASURES: MRI findings including T2 or fluid-attenuated inversion recovery (FLAIR) hyperintensities, swelling or volume loss, presence of gadolinium contrast enhancement, and diffusion-weighted imaging changes. Correlations with clinical features. RESULTS: Among 192 participants with MRIs reviewed, 71 were female (37%) and 121 were male (63%); the median age was 66 years (range, 19-92 years). By comparison with VE and CJD, in LGI1/CASPR2-Ab-E, T2 and/or FLAIR hyperintensities were less likely to extend outside the temporal lobe (3/42 patients [7%] vs 17/18 patients [94%] with VE; P
The immunobiology of herpes simplex virus encephalitis and post-viral autoimmunity.
Herpes simplex virus encephalitis (HSE) is the leading cause of non-epidemic encephalitis in the developed world and, despite antiviral therapy, mortality and morbidity is high. The emergence of post-HSE autoimmune encephalitis reveals a new immunological paradigm in autoantibody-mediated disease. A reductionist evaluation of the immunobiological mechanisms in HSE is crucial to dissect the origins of post-viral autoimmunity and supply rational approaches to the selection of immunotherapeutics. Herein, we review the latest evidence behind the phenotypic progression and underlying immunobiology of HSE including the cytokine/chemokine environment, the role of pathogen-recognition receptors, T- and B-cell immunity and relevant inborn errors of immunity. Second, we provide a contemporary review of published patients with post-HSE autoimmune encephalitis from a combined cohort of 110 patients. Third, we integrate novel mechanisms of autoimmunization in deep cervical lymph nodes to explore hypotheses around post-HSE autoimmune encephalitis and challenge these against mechanisms of molecular mimicry and others. Finally, we explore translational concepts where neuroglial surface autoantibodies have been observed with other neuroinfectious diseases and those that generate brain damage including traumatic brain injury, ischaemic stroke and neurodegenerative disease. Overall, the clinical and immunological landscape of HSE is an important and evolving field, from which precision immunotherapeutics could soon emerge.
Stem-cell derived neurosphere assay highlights the effects of viral infection on human cortical development.
Aberrant cortical development is a key feature of neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. Both genetic and environmental risk factors are thought to contribute to defects in cortical development; however, model systems that can capture the dynamic process of human cortical development are not well established. To address this challenge, we combined recent progress in induced pluripotent stem cell differentiation with advanced live cell imaging techniques to establish a novel three-dimensional neurosphere assay, amenable to genetic and environmental modifications, to investigate key aspects of human cortical development in real-time. For the first time, we demonstrate the ability to visualise and quantify radial glial extension and neural migration through live cell imaging. To show proof-of-concept, we used our neurosphere assay to study the effect of a simulated viral infection, a well-established environmental risk factor in neurodevelopmental disorders, on cortical development. This was achieved by exposing neurospheres to the viral mimic, polyinosinic:polycytidylic acid. The results showed significant reductions in radial glia growth and neural migration in three independent differentiations. Further, fixed imaging highlighted reductions in the HOPX-expressing outer radial glia scaffolding and a consequent decrease in the migration of CTIP2-expressing cortical cells. Overall, our results provide new insight into how infections may exert deleterious effects on the developing human cortex.
Maternal immune activation induces methylation changes in schizophrenia genes.
Susceptibility to schizophrenia is mediated by genetic and environmental risk factors. Infection driven maternal immune activation (MIA) during pregnancy is a key environmental risk factor. However, little is known about how MIA during pregnancy could contribute to adult-onset schizophrenia. In this study, we investigated if maternal immune activation induces changes in methylation of genes linked to schizophrenia. We found that differentially expressed genes in schizophrenia brain were significantly enriched among MIA induced differentially methylated genes in the foetal brain in a cell-type-specific manner. Upregulated genes in layer V pyramidal neurons were enriched among hypomethylated genes at gestational day 9 (fold change = 1.57, FDR = 0.049) and gestational day 17 (fold change = 1.97, FDR = 0.0006). A linear regression analysis, which showed a decrease in gene expression with an increase in methylation in gestational day 17, supported findings from our enrichment analysis. Collectively, our results highlight a connection between MIA driven methylation changes during gestation and schizophrenia gene expression signatures in the adult brain. These findings carry important implications for early preventative strategies in schizophrenia.
The role of latitude and infections in the month-of-birth effect linked to schizophrenia.
There is an intriguing association between winter births and subsequent increased risk of schizophrenia. However, little is known about the environmental risk factors that contribute this month-of-birth effect. The aims of this study were to carry out a systematic review and meta-analysis of studies investigating the month-of-birth effect in schizophrenia and to explore possible factors such as latitude, daylight and infections that could explain this epidemiological observation. Medline, Embase and the Cochrane Library were searched for articles published up to December 23, 2021. Study selection, data extraction and analysis were undertaken according to Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. Generic inverse-variance with random effects models were used to determine the risk ratios (RR) and 95% confidence intervals (CI) for each month-of-birth. Associations between variables latitude and daylight were investigated using linear regression and Kendall's rank correlation coefficients were calculated assess the relationship between monthly infections rates schizophrenia births. Ten studies were included in the meta-analysis encompassing 262,188 schizophrenia patients. We identified significantly higher number of schizophrenia births in December [1.04 (95%CI 1.00-1.08)], January [1.06 (95%CI 1.03-1.1)] and February [1.03 (95%CI 1.00-1.05)]. We did not find any association between latitude and the magnitude of the month-of-birth effect. On the other hand, we found a significant negative correlation between monthly severe enterovirus cases and schizophrenia births (tau -0.57, p = 0.0099) using data from Taiwan. This highlights a role for enterovirus infections in mediating the month-of-birth effect in schizophrenia and these results carry implications for disease prevention strategies.