Psychiatry and NHS

Depressive and anxiety symptoms are common in childhood-onset systemic lupus erythematosus (cSLE), yet their etiology and course remain unclear. We investigated the frequency of depressive and anxiety symptoms longitudinally in youth with cSLE, and associated socio-demographic and disease factors.

Medication safety incidents have been identified as an important target to improve patient safety in mental healthcare. Despite this, the causes of preventable medication safety incidents affecting patients with mental illness have historically been poorly understood, with research now addressing this knowledge gap through a healthcare professional lens. However, patients and carers can also provide complimentary insight into safety issues, and as key stakeholders in healthcare, it is vital to consider their needs when designing effective interventions.

Pain is the prominent feature of sickle cell disease (SCD) and negatively affects quality of life. Delivery of pain management programmes (PMPs) has been suggested in clinical guidelines for pain management in SCD; however, further evidence of the feasibility and effectiveness of PMPs in this population is needed. This study explored the feasibility of delivering a sickle cell pain management programme (SCPMP) for adults within a haemoglobinopathies service.

Despite global concerns of an opioid epidemic, there is no systematic literature review on how frequently these drugs are used in nursing home (NH) populations, including those living with dementia. This systematic review aims to describe the prevalence and incidence of opioid use in NHs. A secondary objective is to describe the use of these drugs in a subset of NH residents, namely among persons living with dementia. A systematic literature review was carried out using MEDLINE and Scopus (PROSPERO registration number CRD42021254210). Screening of title and abstract was carried out by 2 persons independently for studies published between January 1, 2011 and May 19, 2021. The main outcomes were annual prevalence, period prevalence, and duration of opioid use. From a total of 178 identified studies, 29 were considered eligible for inclusion. The annual prevalence of any opioid use among all NH residents without any selection criteria ranged from 6.3% to 50% with a median annual prevalence of 22.9% (Q25-Q75: 19.5%-30.2%), based on 17 studies. Five studies measured the annual prevalence in NH residents living with dementia, finding that this ranged from 10% to 39.6%. More evidence is needed quantifying opioid use in NH, especially among persons living with dementia. Given that opioid use in NH is still a problem, implementation of a pain management protocol in NH or nationally would help improve clinical outcomes.

Homelessness is associated with adverse health and social outcomes. People experiencing homelessness have been found to have a high risk of violent crime victimisation as well as high prevalence of psychiatric disorders. It is poorly understood whether experiencing homelessness is associated with additional risks of violent offending and whether psychiatric disorders contribute to these risks. We examined the association between homelessness, psychiatric disorders, and first violence offence leading to conviction.

Air pollution (AP) significantly jeopardises health, with the Royal College of Physicians accepting the adverse effects of AP are not being sufficiently communicated to patients by healthcare professionals (HCP). To explore HCPs' understanding and attitudes toward AP and its health impacts, we conducted a service evaluation survey in a group of hospital doctors. A questionnaire comprising 20 questions about AP and its health associations was completed by 133 hospital doctors working at University Hospital Southampton NHS Foundation Trust, UK. While 65% ( = 86) of respondents strongly agreed that AP is relevant to health, 79% ( 105) felt insufficiently trained on AP and its health associations. The survey shows that HCPs' knowledge of AP and its connection to poor health is a major barrier in discussions with patients. Further research is needed to understand whether these views are nationally shared among HCPs and to explore the most effective strategies for enhancing AP awareness.

Metabolic syndrome (MetS) is common following first-episode psychosis (FEP), contributing to substantial morbidity and mortality. The Psychosis Metabolic Risk Calculator (PsyMetRiC), a risk prediction algorithm for MetS following a FEP diagnosis, was developed in the United Kingdom and has been validated in other European populations. However, the predictive accuracy of PsyMetRiC in Chinese populations is unknown.

Fibromyalgia (FM) is a chronic pain disorder characterised by widespread pain, fatigue and cognitive symptoms. Acceptance and commitment therapy (ACT) aims to improve psychological flexibility and has been found to be beneficial in treating chronic pain; however, there are few studies evaluating its efficacy in treating FM.

We examined behavior (Child Behavior Checklist) and family functioning (Family Impact Questionnaire) in 65 children with congenital cytomegalovirus. Behavioral problems were present in 30.8%. Parents of children with moderate/severe outcomes reported strain on all areas of family functioning. Behavioral problems were associated with negative impact on parental feelings and marital/partnership relationship. Our findings inform planning support services.

Previous research has suggested that the core features of autism spectrum disorders (ASD) may contribute to offending behaviours and increased vulnerability within the Criminal Justice System. To date, there is a paucity of evidence assessing the effectiveness of interventions for offending behaviour in adults with ASD but without co-occurring intellectual disability (ID) across a broad range of forensic settings. The lack of robust evidence is concerning, as limited effectiveness may contribute to an increased likelihood of prolonged incarceration, particularly in the most restrictive settings. A PRISMA systematic review was conducted with a narrative synthesis to: (a) evaluate the evidence of the effectiveness of interventions aimed at reducing recidivism, (b) assess whether the core features of ASD impact the effectiveness of these interventions, and (c) identify additional factors that may affect the effectiveness of interventions within this population. Seven studies involving ten male participants were identified. The findings suggest that interventions for offending behaviours in adults with ASD without intellectual disability (ID) are largely inadequate, and that core ASD features need to be considered. Additionally, a complex interplay of risk factors potentially impacting intervention effectiveness was suggested. Limitations include heterogeneity across intervention types, measures of effectiveness, and what constitutes effectiveness. Despite the limited number of studies and data quality, the review aligns with a growing body of literature highlighting vulnerability and a need for evidence-based interventions for people with ASD. The review also discusses the broader implications of ineffective interventions.

We comprehensively summarized the cohort evidence to date on adult-onset hearing loss as risk factor for incident cognitive impairment and dementia, and examined the evidence for dose-response, risk for various dementia subtypes, and other moderators. Previous meta-analyses were less comprehensive.

Repetitive transcranial magnetic stimulation (rTMS) has demonstrated benefits in adults with psychiatric disorders, but its clinical utility in children and young people (CYP) is unclear. This PRISMA systematic review used published and ongoing studies to examine the effects of rTMS on disorder-specific symptoms, mood and neurocognition in CYP with psychiatric disorders. We searched Medline via PubMed, Embase, PsychINFO via OVID, and Clinicaltrials.gov up to July 2023. Eligible studies involved multiple-session (i.e., treatment) rTMS in CYP (≤ 25 years-old) with psychiatric disorders. Two independent raters assessed the eligibility of studies and extracted data using a custom-built form. Out of 78 eligible studies (participant N = 1389), the majority (k = 54; 69%) reported an improvement in at least one outcome measure of disorder-specific core symptoms. Some studies (k = 21) examined rTMS effects on mood or neurocognition,: findings were largely positive. Overall, rTMS was well-tolerated with minimal side-effects. Of 17 ongoing or recently completed studies, many are sham-controlled RCTs with better blinding techniques and a larger estimated participant enrolment. Findings provide encouraging evidence for rTMS-related improvements in disorder-specific symptoms in CYP with different psychiatric disorders. However, in terms of both mood (for conditions other than depression) and neurocognitive outcomes, evidence is limited. Importantly, rTMS is well-tolerated and safe. Ongoing studies appear to be of improved methodological quality; however, future studies should broaden outcome measures to more comprehensively assess the effects of rTMS and develop guidance on dosage (i.e., treatment regimens).

Lithium is an effective mood stabiliser, but its mechanism of action is incompletely defined. Even at very low doses, lithium may have neuroprotective effects, but it is not clear if these relate to brain lithium concentration in vivo. We have developed magnetic resonance imaging (Li-MRI) methods to detect lithium in the brain following supplementation at a very low dose.

Personality traits have been associated with eating disorders (EDs) and comorbidities. However, it is unclear which personality profiles are premorbid risk rather than diagnostic markers.

Accessible patient information sources are vital in educating patients about the benefits and risks of spinal surgery, which is crucial for obtaining informed consent. We aim to assess the effectiveness of a natural language processing (NLP) pipeline in recognizing surgical procedures from clinic letters and linking this with educational resources.

Omega-3 fatty acids have been implicated in the aetiology of depressive disorders, though trials supplementing omega-3 to prevent major depressive disorder (MDD) have so far been unsuccessful. Whether this association is causal remains unclear. We used two sample Mendelian randomization (MR) to investigate causality. Genetic variants associated with circulating omega-3 and omega-6 fatty acids in UK Biobank (UKBB, n = 115,078) were selected as exposures. The Psychiatric Genomics Consortium (PGC) genome-wide association studies (GWAS) of MDD (n = 430,775; cases = 116,209; controls = 314,566) and recurrent depression (rMDD, n = 80,933; cases = 17,451; controls = 62,482), were used as outcomes. Multivariable MR (MVMR) models were used to account for biologically correlated lipids, such as high- and low-density cholesterol and triglycerides, and to explore the relative importance of longer-chain omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) using data from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE, n = 8866). Genetic colocalization analyses were used to explore the presence of a shared underlying causal variant between traits. Genetically predicted total omega-3 fatty acids reduced the odds of MDD (OR 0.96 per standard deviation (SD, i.e. 0.22 mmol/l) (95% CIs 0.93-0.98, p = 0.003)). The largest point estimates were observed for eicosapentaenoic acid (EPA), a long-chain omega-3 fatty acid (OR 0.92; 95% CI 0.88-0.96; p = 0.0002). The effect of omega-3 fatty acids was robust to MVMR models accounting for biologically correlated lipids. 'Leave-one-out' analyses highlighted the FADS gene cluster as a key driver of the effect. Colocalization analyses suggested a shared causal variant using the primary outcome sample, but genomic confounding could not be fully excluded. This study supports a role for omega-3 fatty acids, particularly EPA, in the aetiology of depression, although pleiotropic mechanisms cannot be ruled out. The findings support guidelines highlighting the importance of EPA dose and ratio for MDD and question whether targeted interventions may be superior to universal prevention trials, as modest effect sizes will limit statistical power.

Post-COVID-19 condition in children is a still largely unknown syndrome with a diverse pattern of symptoms, which can have a major impact on daily life. Currently, there are no evidence-based proven treatments, and the focus is on symptom management and recovery of daily functioning. A multidisciplinary, tailored approach is recommended, with attention to energy management and activity building, where the main goal should be a return to baseline levels of cognitive, physical and social activity.

Previous research indicates an association of body dysmorphic disorder (BDD) with suicidal thoughts and behaviours, but has largely relied on small cohorts drawn from specialist clinics.

Comprehensive understanding of the neural circuits involving the ventral tegmental area is essential for elucidating the anatomo-functional mechanisms governing human behaviour as well as the therapeutic and adverse effects of deep brain stimulation for neuropsychiatric diseases. While the ventral tegmental area has been successfully targeted with deep brain stimulation for different neuropsychiatric diseases, the axonal connectivity of the region has not been fully understood. Here using fiber micro-dissections in human cadaveric hemispheres, population-based high-definition fiber tractography, and previously reported deep brain stimulation hotspots, we find that the ventral tegmental area participates in an intricate network involving the serotonergic pontine nuclei, basal ganglia, limbic system, basal forebrain, and prefrontal cortex, which is implicated in the treatment of obsessive-compulsive disorder, major depressive disorder, Alzheimer's disease, cluster headaches, and aggressive behaviors.

People living in less urban areas in the UK may have reduced access to mental healthcare compared with people in urban areas. Although this was not reported in the 2000 Adult Psychiatric Morbidity Survey (APMS) data, subsequent changes to mental health provision and economic recession may have impacted care inequalities. We re-examined this, hypothesising that those living in less urban areas of England received less antidepressant medication and psychological interventions, compared with those living in urban areas, after adjusting for covariates including common mental disorders (CMDs) and socioeconomic status.

Lamotrigine is an effective mood stabiliser, largely used for the management and prevention of depression in bipolar disorder. The neuropsychological mechanisms by which lamotrigine acts to relieve symptoms as well as its neural effects on emotional processing remain unclear. The primary objective of this current study was to investigate the impact of an acute dose of lamotrigine on the neural response to a well-characterised fMRI task probing implicit emotional processing relevant to negative bias. 31 healthy participants were administered either a single dose of lamotrigine (300 mg, n = 14) or placebo (n = 17) in a randomized, double-blind design. Inside the 3 T MRI scanner, participants completed a covert emotional faces gender discrimination task. Brain activations showing significant group differences were identified using voxel-wise general linear model (GLM) nonparametric permutation testing, with threshold free cluster enhancement (TFCE) and a family wise error (FWE)-corrected cluster significance threshold of p < 0.05. Participants receiving lamotrigine were more accurate at identifying the gender of fearful (but not happy or angry) faces. A network of regions associated with emotional processing, including amygdala, insula, and the anterior cingulate cortex (ACC), was significantly less activated in the lamotrigine group compared to the placebo group across emotional facial expressions. A single dose of lamotrigine reduced activation in limbic areas in response to faces with both positive and negative expressions, suggesting a valence-independent effect. However, at a behavioural level lamotrigine appeared to reduce the distracting effect of fear on face discrimination. Such effects may be relevant to the mood stabilisation effects of lamotrigine.

Schizophrenia is a leading cause of global disease burden. Current drug treatments are associated with significant side-effects and have limited efficacy for many patients; highlighting the need to develop new approaches that target other aspects of the neurobiology of schizophrenia. Preclinical, in vivo imaging, post-mortem, genetic and pharmacological studies have highlighted the key role of cortical GABA-glutamatergic microcircuits and their projections to subcortical dopaminergic circuits in the pathoetiology of negative, cognitive and psychotic symptoms. Antipsychotics primarily act downstream of the dopaminergic component of this circuit. However, multiple drugs are currently in development that could target other elements of this circuit to treat schizophrenia. These include drugs for GABA or glutamatergic targets, including glycine transporters, d-amino acid oxidase, sodium channels or potassium channels. Other drugs in development are likely to primarily act on pathways that regulate the dopaminergic system such as muscarinic or trace amine receptors or serotonin 2A receptors, whilst phosphodiesterase 10 A inhibitors are being developed to modulate the downstream consequences of dopaminergic dysfunction. Our review considers where new drugs may act on this circuit and their latest clinical trial evidence in terms of indication, efficacy and side-effects. Limitations of the circuit model, including whether there are neurobiologically distinct subgroups of patients, and future directions are also considered. Several drugs based on the mechanisms reviewed have promising clinical data, with the muscarinic agonist KarXT most advanced. If they are approved for clinical use, they have the potential to revolutionise understanding of the pathophysiology and treatment of schizophrenia.

Does neurodegenerative disease underlie the increased rate of dementia observed in older people with schizophrenia? Several studies have reported a higher prevalence of dementia in people with schizophrenia compared with the general population. This may reflect a higher risk of developing neurodegenerative diseases such as vascular dementia or Alzheimer's disease (AD). Alternatively, this may reflect non-pathological, age-related cognitive decline in a population with low cognitive reserve.

Telepsychiatry is an effective tool to support and provide mental health services to prison inmates. In Greece, telepsychiatry was formally applied in two correctional facilities in 2018. The objective of this study was to compare inmates' perceptions and satisfaction with telepsychiatry versus face-to-face consultation. The sample consisted of 100 male inmates with a multicultural background and prior experience with both methods of services provision. The data were obtained through a Demographic Data Questionnaire, a Participant Satisfaction Questionnaire to assess satisfaction with face-to-face psychiatric services, and another Participant Satisfaction Questionnaire to assess satisfaction with telepsychiatric services. The results have shown a higher level of satisfaction with telepsychiatry compared to face-to-face care. Statistically significant improvements (all p-values <0.001) were noted in: waiting times, support for relapse prevention, follow up, quality of mental health care, quality of care in the management of psychiatric problems and related medication, behaviour of psychiatrists, duration of the assessment, sense of comfort, and confidentiality. Telepsychiatry has proved to be an acceptable way of approaching and supporting inmates in Greece, with most of the participants expressing high acceptance, satisfaction, and preference rates. Implications for additional research and further development of telepsychiatry are discussed.

This study evaluates longitudinal associations between glycaemic control, measured by mean and within-patient variability of glycated haemaglobin (HbA1c) levels, and major depressive disorder (MDD) in individuals with type 2 diabetes (T2D), focusing on the timings of these diagnoses.

Palmoplantar pustulosis (PPP) is an inflammatory skin disorder that mostly affects smokers and manifests with painful pustular eruptions on the palms and soles. While the disease can present with concurrent plaque psoriasis, TNF and IL-17/IL-23 inhibitors show limited efficacy. There is therefore a pressing need to uncover PPP disease drivers and therapeutic targets.

Dopaminergic receptor antagonism is a crucial component of all licensed treatments for psychosis, and dopamine dysfunction has been central to pathophysiological models of psychotic symptoms. Some clinical trials, however, indicate that drugs that act through muscarinic receptor agonism can also be effective in treating psychosis, potentially implicating muscarinic abnormalities in the pathophysiology of psychosis. Here, we discuss understanding of the central muscarinic system, and we examine preclinical, behavioural, post-mortem, and neuroimaging evidence for its involvement in psychosis. We then consider how altered muscarinic signalling could contribute to the genesis and maintenance of psychotic symptoms, and we review the clinical evidence for muscarinic agents as treatments. Finally, we discuss future research that could clarify the relationship between the muscarinic system and psychotic symptoms.

The prevalence of pediatric constipation ranges from 0.7 to 29.6% across different countries. Functional constipation accounts for 95% of pediatric constipation, and the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. We aimed to compare the efficacy and acceptability of different probiotic supplements for pediatric functional constipation. The current frequentist model-based network meta-analysis (NMA) included RCTs of probiotic supplements for functional constipation in children. The primary outcome was changes in bowel movement or stool frequency; acceptability outcome was all-cause discontinuation. Nine RCTs were included (N = 710; mean age = 5.5 years; 49.4% girls). Most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives (standardized mean difference (SMD) = 1.87, 95% confidence interval (95% CI) = 0.85 to 2.90) were associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments (SMD = 1.37, 95% CI: 0.32 to 2.43). All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.  Conclusion: The results of our NMA support the application of an advanced combination of probiotics and laxatives for pediatric functional constipation if there is no concurrent contraindication.  Registration: PROSPERO (CRD42022298724). What is Known: • Despite of the high prevalence of pediatric constipation, which ranges from 0.7% to 29.6%, the efficacy of pharmacotherapy is limited, with a success rate of 60%. Several randomized controlled trials (RCTs) have shown the benefits of probiotic supplements in treating this condition. However, the reported strains of probiotics varied among the RCTs. The widely heterogeneous strains of probiotics let the traditional meta-analysis, which pooled all different strains into one group, be nonsense and insignificant. What is New: • By conducting a comprehensive network meta-analysis, we aimed to compare the efficacy and acceptability of different strains of probiotic supplements for pediatric functional constipation. Network meta-analysis of nine randomized controlled trials revealed that the most probiotic products, used either alone or combined with laxatives, were associated with significantly better improvement in bowel movement or stool frequency than placebo/control. Protexin plus laxatives was associated with the greatest improvement in bowel movement or stool frequency among all the investigated probiotic products. For the single probiotic interventions, only Lactobacillus casei rhamnosus Lcr35 was associated with significant efficacy compared to placebo/control treatments. All the investigated probiotic products had fecal incontinence and patient drop-out rates similar to those of placebo/control treatments.

This is the final of four papers updating standards for the care of people with CF. That this paper "Planning a longer life" was considered necessary, highlights how much CF care has progressed over the past decade. Several factors underpin this progress, notably increased numbers of people with CF with access to CFTR modulator therapy. As the landscape for CF changes, so do the hopes and aspirations of people with CF and their families. This paper reflects the need to consider people with CF not as a "problem" to be solved, but as a success, a potential and a voice to be heard. People with CF and the wider CF community have driven this approach, reflecting many of the topics in this paper. This exercise involved wide stakeholder engagement. People with CF are keen to contribute to research priorities and be involved in all stages of research. People with CF want healthcare professionals to respect them as individuals and consider the impact of our actions on the world around us. Navigating life presents challenges to all, but for people with CF these challenges are heightened and complex. In this paper we highlight the concerns and life moments that impact people with CF, and events that the CF team should aim to support, including the challenges around having a family. People with CF and their care teams must embrace the updated standards outlined in these four papers to enjoy the full potential for a healthier life.

Despite major advances in linking single genetic variants to single causal genes, the significance of genetic variation on transcript-level regulation of expression, transcript-specific functions, and relevance to human disease has been poorly investigated. Strawberry notch homolog 2 (SBNO2) is a candidate gene in a susceptibility locus with different variants associated with Crohn's disease and bone mineral density. The SBNO2 locus is also differentially methylated in Crohn's disease but the functional mechanisms are unknown. Here we show that the isoforms of SBNO2 are differentially regulated by lipopolysaccharide and IL-10. We identify Crohn's disease associated isoform quantitative trait loci that negatively regulate the expression of the noncanonical isoform 2 corresponding with the methylation signals at the isoform 2 promoter in IBD and CD. The two isoforms of SBNO2 drive differential gene networks with isoform 2 dominantly impacting antimicrobial activity in macrophages. Our data highlight the role of isoform quantitative trait loci to understand disease susceptibility and resolve underlying mechanisms of disease.

Recent findings suggest the incidence of first-episode psychotic disorders (FEP) varies according to setting-level deprivation and cannabis use, but these factors have not been investigated together. We hypothesized deprivation would be more strongly associated with variation in FEP incidence than the prevalence of daily or high-potency cannabis use between settings.

Climate change not only directly impacts older people's longevity but also healthy ageing, which is the process of maintaining physical and mental capacities while optimising functional abilities. The urgency to address both population ageing and climate change necessitates a rethink and assessment of the impact of climate change on older people. This includes identifying what can be done to anticipate, mitigate and adapt to climate change and engage older persons.

There have been increasing efforts to develop prediction models supporting personalised detection, prediction, or treatment of ADHD. We overviewed the current status of prediction science in ADHD by: (1) systematically reviewing and appraising available prediction models; (2) quantitatively assessing factors impacting the performance of published models. We did a PRISMA/CHARMS/TRIPOD-compliant systematic review (PROSPERO: CRD42023387502), searching, until 20/12/2023, studies reporting internally and/or externally validated diagnostic/prognostic/treatment-response prediction models in ADHD. Using meta-regressions, we explored the impact of factors affecting the area under the curve (AUC) of the models. We assessed the study risk of bias with the Prediction Model Risk of Bias Assessment Tool (PROBAST). From 7764 identified records, 100 prediction models were included (88% diagnostic, 5% prognostic, and 7% treatment-response). Of these, 96% and 7% were internally and externally validated, respectively. None was implemented in clinical practice. Only 8% of the models were deemed at low risk of bias; 67% were considered at high risk of bias. Clinical, neuroimaging, and cognitive predictors were used in 35%, 31%, and 27% of the studies, respectively. The performance of ADHD prediction models was increased in those models including, compared to those models not including, clinical predictors (β = 6.54, p = 0.007). Type of validation, age range, type of model, number of predictors, study quality, and other type of predictors did not alter the AUC. Several prediction models have been developed to support the diagnosis of ADHD. However, efforts to predict outcomes or treatment response have been limited, and none of the available models is ready for implementation into clinical practice. The use of clinical predictors, which may be combined with other type of predictors, seems to improve the performance of the models. A new generation of research should address these gaps by conducting high quality, replicable, and externally validated models, followed by implementation research.

Cognitive control (CC) involves a top-down mechanism to flexibly respond to complex stimuli and is impaired in schizophrenia.

It is well evidenced that healthcare professionals working in paediatric critical care experience high levels of burn-out, compassion fatigue and moral distress. This worsened during the COVID-19 pandemic. This work examines the nature of challenges to workplace well-being and explores what well-being means to staff. This evidence will inform the development of staff interventions to improve and maintain staff well-being.

Eating disorders (EDs) are serious, often chronic, conditions associated with pronounced morbidity, mortality, and dysfunction increasingly affecting young people worldwide. Illness progression, stages and recovery trajectories of EDs are still poorly characterised. The STORY study dynamically and longitudinally assesses young people with different EDs (restricting; bingeing/bulimic presentations) and illness durations (earlier; later stages) compared to healthy controls. Remote measurement technology (RMT) with active and passive sensing is used to advance understanding of the heterogeneity of earlier and more progressed clinical presentations and predictors of recovery or relapse.

Early life environmental stressors play an important role in the development of multiple chronic disorders. Previous studies that used environmental risk scores (ERS) to assess the cumulative impact of environmental exposures on health are limited by the diversity of exposures included, especially for early life determinants. We used machine learning methods to build early life exposome risk scores for three health outcomes using environmental, molecular, and clinical data.

Growing evidence associates air pollution exposure with various psychiatric disorders. However, the importance of early-life (eg, prenatal) air pollution exposure to mental health during youth is poorly understood, and few longitudinal studies have investigated the association of noise pollution with youth mental health.

While some people with mild cognitive impairment (MCI) progress to dementia, many others show no progression. The aim of this study was to identify factors associated with risk of dementia development in this population.

We validated the CREST model, a 5 variable score for stratifying risk of circulatory etiology death (CED) following out of hospital cardiac arrest (OHCA), and compared its discrimination with the SCAI shock classification.

In our previous paper on the Future of Cognitive Remediation published more than 10 years ago, we envisaged an imminent and wide implementation of cognitive remediation therapies into mental health services. This optimism was misplaced. Despite evidence of the benefits, costs, and savings of this intervention, access is still sparse. The therapy has made its way into some treatment guidance, but these documents weight the same evidence very differently, causing confusion, and do not consider barriers to implementation. This paper revisits our previous agenda and describes how some challenges were overcome but some remain. The scientific community, with its commitment to Open Science, has produced promising sets of empirical data to explore the mechanisms of treatment action. This same community needs to understand the specific and nonspecific effects of cognitive remediation if we are to provide a formulation-based approach that can be widely implemented. In the last 10 years we have learned that cognitive remediation is not "brain training" but is a holistic therapy that involves an active therapist providing motivation support, and who helps to mitigate the impact of cognitive difficulties through metacognition to develop awareness of cognitive approaches to problems. We conclude that, of course, more research is needed but, in addition and perhaps more importantly at this stage, we need more public and health professionals' understanding of the benefits of this therapy to inform and include this approach as part of treatment regimens.

A two-stage process, wherein self-report screening precedes the structured interview, is suggested for identifying individuals at clinical high-risk for psychosis (CHR-P) in community samples. Aim of this study was to screen a community youth sample from India for CHR-P using the two-stage method. Specific objectives were to assess concordant validity of the self-report measure and predictive validity of the two-stage method.

Workplace violence and aggression toward healthcare staff has a significant impact on the individual, causing self-blame, isolation and burnout. Timely and appropriate support can mitigate harm, but there is little research into how this should be delivered. We conducted multi-speciality peer groups for London doctors in postgraduate training (DPT), held over a 6-week period. Pre- and post-group burnout questionnaires and semi-structured interviews were used to evaluate peer support. Thematic analysis and descriptive statistical methods were used to describe the data.

Some brain-gut behavioral treatments (BGBTs) are beneficial for global symptoms in irritable bowel syndrome (IBS). US management guidelines suggest their use in patients with persistent abdominal pain but their specific effect on this symptom has not been assessed systematically.

Freud proposed that excessive self-blame-related motivations such as self-punishing tendencies play a key role in depression. Most of the supporting evidence, however, is based on cross-sectional studies and questionnaire measures.

Antiseizure medications (ASMs) during the first trimester of pregnancy have been associated with an increased risk of miscarriage.

Anti-CGRP monoclonal antibodies (anti-CGRP MAbs) are approved and available treatments for migraine prevention. Patients do not respond alike and many countries have reimbursement policies, which hinder treatments to those who might respond. This study aimed to investigate clinical factors associated with good and excellent response to anti-CGRP MAbs at 6 months.

While healthcare policy has fostered implementation strategies to improve inclusion and access of under-served groups to clinical care, systemic and structural elements still disproportionately prevent service users from accessing research opportunities embedded within clinical settings. This contributes to the widening of health inequalities, as the absence of representativeness prevents the applicability and effectiveness of evidence-based interventions in under-served clinical populations. The present study aims to identify the individual (micro), organisational (meso) and structural (macro) barriers to clinical research access in patients with comorbid alcohol use disorder and alcohol-related liver disease.

Abnormal self-experiences are a common feature of major depression despite their absence from current diagnostic manuals. Current diagnostic criteria leave us with an impoverished conception of depressive disorders, and they fail to exploit the diverse experiential alterations that might be useful for understanding and diagnosing patients, and last but not least for explaining the aetiology of these disorders. Although some phenomenological descriptions of abnormal self-experiences in major depression are available, further research is needed to validate these through detailed clinical interviews.

Adolescents exposed to adversity show higher levels of depression and anxiety, with the strongest links seen in socially/societally disadvantaged individuals (e.g., females, low socioeconomic status [SES]), as well as neurodivergent individuals. The intersection of these characteristics may be important for the differential distribution of adversity and mental health problems, though limited findings pertain to the extent to which intersectional effects moderate this association.

When making choices, individuals differ from one another, as well as from normativity, in how they weigh different types of information. One explanation for this relates to idiosyncratic preferences in what information individuals represent when evaluating choice options. Here, we test this explanation with a simple risky-decision making task, combined with magnetoencephalography (MEG). We examine the relationship between individual differences in behavioral markers of information weighting and neural representation of stimuli pertinent to incorporating that information. We find that the extent to which individuals (N = 19) behaviorally weight probability versus reward information is related to how preferentially they neurally represent stimuli most informative for making probability and reward comparisons. These results are further validated in an additional behavioral experiment (N = 88) that measures stimulus representation as the latency of perceptual detection following priming. Overall, the results suggest that differences in the information individuals consider during choice relate to their risk-taking tendencies.

Intravenous thrombolysis (IVT) and/or endovascular therapy (EVT) are currently considered best practices in acute stroke patients. Data regarding the efficacy and safety of reperfusion therapies in patients with atrial fibrillation (AF) are conflicting as regards haemorrhagic transformation, mortality, and functional outcome. This study sought to investigate for any differences, in terms of safety and effectiveness, between AF patients with acute ischaemic stroke (AIS) treated and untreated with reperfusion therapies.

Neurofilament heavy-chain gene (NEFH) variants are associated with multiple neurodegenerative diseases, however, their relationship with ALS has not been robustly explored. Still, NEFH is commonly included in genetic screening panels worldwide. We therefore aimed to determine if NEFH variants modify ALS risk.

Around 700,000 family caregivers provide unpaid care for 900,000 people living with dementia in the United Kingdom. Few family caregivers receive support for their own psychological needs and funding for community respite services has declined. These trends are seen across Europe as demographic and budgetary pressures have intensified due to public spending cuts arising from the 2008 financial crisis and the COVID-19 pandemic. The World Health Organization has prioritized the need to expand the provision of support for caregivers and families of people with dementia by 2025. Web-based interventions have the potential for development as they require modest investment and can be accessed by family caregivers at home. Further cost benefits can be realized by adapting existing interventions with demonstrated effectiveness for new contexts. This paper reports initial findings from the CareCoach study, which is adapting Partner in Balance (PiB), a web-based coaching intervention developed in the Netherlands, for family caregivers in the United Kingdom.

Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021.

Modern internet pornography allows users to harness sexual novelty in numerous ways, which can be used to overcome desensitisation through increasing volume of use (quantitative tolerance), progressing to more stimulating genres (qualitative escalation), skipping between stimuli (tab-jumping), delaying orgasm ('edging'), and engaging in pornographic binges. However, existing research has not yet evaluated how these potentially reciprocal consumption patterns relate to problematic pornography use (PPU). To this end, we recruited two independent samples of male pornography users (N = 1,356, M = 36.86, SD = 11.26; N = 944, M = 38.69, SD = 12.26) and examined the relationships between these behavioural dimensions and self-reported difficulties in controlling one's pornography use. Data were analysed through the network analysis approach (using Gaussian graphical models). As hypothesised, i) quantitative tolerance was centrally placed within the overall network, and ii) acted as a statistical bridge node between other patterns of pornography use (e.g., pornographic binges), and all measured facets of PPU. Our results are consistent with other emerging literature suggesting that tolerance, pornographic binges, tab-jumping, and edging behaviours as relevant features ofPPU, and that upscaling overall usage may connect broader patterns of use with problematic engagement. Clinical and theoretical implications, as well as future research directions, are discussed.

Stigma is common in people experiencing chronic pain and there are indications that it may adversely affect pain outcomes. However, to date, there is no systematic review exploring the impact of stigma on chronic pain-related outcomes. This systematic review and meta-analysis aimed to examine the association between stigma and key chronic pain outcomes and differences in stigma between pain conditions. Seven databases were searched for studies reporting a measure of association between stigma and at least one pain outcome in adults with chronic pain. Studies were screened by 2 independent researchers. Nineteen studies met eligibility criteria and data were extracted, quality-assessed, and narratively synthesised and meta-analysed where possible. Meta-analyses of bivariate cross-sectional correlations demonstrated significant positive correlations between stigma and pain intensity, disability, and depression, with small to moderate effects. Data from 2 prospective studies and those only reporting multivariate analyses that were not included in meta-analyses further supported these findings. There was some evidence that individuals who experience pain conditions with less clear pathophysiology may report greater stigma, although more research is needed. The review highlights that there is a growing number of studies on stigma in the pain field showing an adverse association between stigma and chronic pain outcomes.

Patent foramen ovale (PFO) is frequently identified in young patients with cryptogenic ischaemic stroke. Potential stroke mechanisms include paradoxical embolism from a venous clot which traverses the PFO, in situ clot formation within the PFO, and atrial arrhythmias due to electrical signalling disruption. The purpose of this guideline is to provide recommendations for diagnosing, treating, and long-term managing patients with ischaemic stroke and PFO. Conversely, Transient Ischaemic Attack (TIA) was not considered an index event in this context because only one RCT involved TIA patients. However, this subgroup analysis showed no significant differences between TIA and stroke outcomes. The working group identified questions and outcomes, graded evidence, and developed recommendations following the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach and the European Stroke Organisation (ESO) standard operating procedure for guideline development. This document underwent peer-review by independent experts and members of the ESO Guideline Board and Executive Committee. The working group acknowledges the current evidentiary gap in delineating an unequivocal diagnostic algorithm for the detection of PFO. Although transoesophageal echocardiography is conventionally held as the most accurate diagnostic tool for PFO identification, its status as the 'gold standard' remains unsubstantiated by rigorously validated evidence. We found high-quality evidence to recommend PFO closure plus antiplatelet therapy in selected patients aged 18-60 years in whom no other evident cause of stroke is found but a PFO (i.e. PFO-associated stroke). The PASCAL classification system can be used to select such candidates for PFO closure. Patients with both a large right-to-left shunt and an atrial septal aneurysm benefit most from PFO closure. There is insufficient evidence to make an evidence-based recommendation on PFO closure in patients older than 60 and younger than 18 years. We found low quality evidence to suggest against PFO closure in patients with unlikely PFO-related stroke according to the PASCAL classification, except in specific scenarios (Expert Consensus). We suggest against long-term anticoagulation in patients with PFO-associated stroke unless anticoagulation is indicated for other medical reasons. Regarding the long-term AF monitoring after PFO closure, the working group concluded that there remains significant uncertainty regarding the risks and benefits associated with the use of long-term cardiac monitoring, such as implantable loop recorders. This document provides additional guidance, in the form of evidence-based recommendations or expert consensus statements, on diagnostic methods for PFO detection, and medical management after PFO closure.

Depression and anxiety are increasingly prevalent in adolescents. The Brief Educational Workshops in Secondary Schools Trial investigated the effectiveness of a brief accessible stress workshop programme for 16-18-year-olds. We aimed to investigate the clinical effectiveness and cost-effectiveness of the DISCOVER cognitive behavioural therapy (CBT) workshop on symptoms of depression in 16-18-year-olds at 6 months compared with treatment-as-usual.

Seclusion is a restrictive practice that many healthcare services are trying to reduce. Previous studies have sought to identify predictors of seclusion initiation, but few have investigated factors associated with adverse outcomes after seclusion termination.

(STEPS) is a digital application (app) designed to help parents manage behaviour of their children who are referred to mental health services and are waiting for an assessment or treatment. STEPS is currently being evaluated in the Online Parent Training for the Initial Management of Attention-Deficit/Hyperactivity Disorder randomised controlled trial. Alongside the examination of STEPS' clinical and cost-effectiveness, we are conducting a process evaluation to better understand the contextual factors that may influence study outcomes. The purpose of this protocol is to describe the aims, objectives and methodology of the process evaluation prior to it taking place to add to the fidelity and rigour of the trial process and outcomes. Our goal is to adapt STEPS to optimise its benefits in future applications.

Plasma biomarkers of Alzheimer's disease (AD) pathology, neurodegeneration, and neuroinflammation are ideally suited for secondary prevention programs in self-sufficient persons at-risk of dementia. Plasma biomarkers have been shown to be highly correlated with traditional imaging biomarkers. However, their comparative predictive value versus traditional AD biomarkers is still unclear in cognitively unimpaired (CU) subjects and with mild cognitive impairment (MCI).

Gambling disorder affects 0.5-2.4% of the population and shows strong associations with lifetime alcohol use disorder. Very little is known regarding whether lifetime alcohol use disorder can impact the clinical presentation or outcome trajectory of gambling disorder.

To compare effects and side effects of 6 weeks of individually dose-titrated methylphenidate or placebo on fatigue in palliative care patients with advanced cancer.

Amygdala and dorsal anterior cingulate cortex responses to facial emotions have shown promise in predicting treatment response in medication-free major depressive disorder (MDD). Here, we examined their role in the pathophysiology of clinical outcomes in more chronic, difficult-to-treat forms of MDD.

During the COVID-19 pandemic, mental health problems increased as access to mental health services reduced. Recovery colleges are recovery-focused adult education initiatives delivered by people with professional and lived mental health expertise. Designed to be collaborative and inclusive, they were uniquely positioned to support people experiencing mental health problems during the pandemic. There is limited research exploring the lasting impacts of the pandemic on recovery college operation and delivery to students.

Although the presence of psychotic symptoms has been widely recognized in Borderline Personality Disorder (BPD), no study previously investigated cognitive Basic Symptoms (BS) and their clinical implications in patients with BPD.

It is increasingly recognised that traditional models of mental health (MH) care, with a service transition at age 18 years, may not reflect best practice. The literature supports a move towards youth and young adult focused models of MH care, for young people up to the age of 25, which specifically cater to the unique psychosocial and developmental needs of this population. This service evaluation aimed to explore the facilitators and barriers to the implementation of youth models of MH care across England (UK).

Evaluations of interventions targeting the population level are an essential component of the policy development cycle. Pre-post designs are widespread in suicide prevention research but have several significant limitations. To inform future evaluations, our aim is to explore the three most frequently used approaches for assessing the association between population-level interventions or exposures and suicide - the pre-post design, the difference-in-difference design, and Poisson regression approaches. The pre-post design and the difference-in-difference design will only produce unbiased estimates of an association if there are no underlying time trends in the data and there is no additional confounding from other sources. Poisson regression approaches with covariates for time can control for underlying time trends as well as the effects of other confounding factors. Our recommendation is that the default position should be to model the effects of population-level interventions or exposures using regression methods that account for time effects. The other designs should be seen as fall-back positions when insufficient data are available to use methods that control for time effects.

New National Institute for Health and Care Excellence (NICE) guidance endorses the prescription of statins in larger population groups for the prevention of cardiovascular and cerebrovascular morbidity and mortality, especially in people with severe mental illness. However, the evidence base for their safety and risk/benefit balance in depression is not established.

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis represents one of the most consistent pathophysiological findings in depressive disorders. Cortisol signaling is affected by proteins that mediate its cellular responses or alters its availability to mineralocorticoid and glucocorticoid receptors. In our study, we evaluated candidate genes that may influence the risk for depression and suicide due to its involvement in cortisol signaling. The aim of the study was to assess whether the genotypes of these genes are associated with the risk for depression, severity of depressive symptoms, suicidal ideation, and suicide attempts. And whether there is interaction between genes and early-life stress. In this study, 100 healthy controls and 140 individuals with depression were included. The subjects were clinically assessed using the 21-item GRID-Hamilton questionnaires (GRID-HAMD-21), Beck Scale for Suicidal Ideation (BSI), and the Childhood Trauma Questionnaire (CTQ). A robust multifactorial dimensionality reduction analysis was used to characterize the interactions between the genes HSD11B1, NR3C1, NR3C2, and MDR1 and early-life stress. It was found a significant association of the heterozygous genotype of the MDR1 gene rs1128503 polymorphism with reduced risk of at least one suicide attempt (OR: 0.08, p = 0.003*) and a reduction in the number of suicide attempts (β = -0.79, p = 0.006*). Furthermore, it was found that the MDR1 rs1228503 and NR3C2 rs2070951 genes interact with early-life stress resulting in a strong association with depression (p = 0.001). Our findings suggest that polymorphisms in the MDR1 and NR3C2 genes and their interaction with childhood trauma may be important biomarkers for depression and suicidal behaviors.

Complex posttraumatic stress disorder (CPTSD) is characterized in the by affect dysregulation, negative self-concept, and relationship impairments, symptoms also presented in borderline personality disorder (BPD). Some research shows CPTSD as a distinct disorder, others as a subgroup or a replacement for BPD. No review currently amalgamates the findings on whether CPTSD presents too similarly to BPD to be a standalone disorder. This article systematically reviewed similarities and differences in symptom presentations of the two disorders. Six databases were searched (PsycINFO, EMBASE, PubMed, Web of Science, PsycEXTRA, and Open Access Theses and Dissertations) and identified papers were summarized narratively. The majority of studies found distinct profiles for CPTSD and BPD. One study found no differences between the constructs; however, this used a population without severe trauma. CPTSD and BPD can present comorbidly, these individuals will have likely experienced earlier and more frequent interpersonal trauma and display greater functional impairment. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

More than 200 clinical trials have been performed worldwide in ALS so far, but no agents with substantial efficacy on disease progression have been found.

Alzheimer's disease (AD) is characterized by the accumulation of amyloid-β (Aβ) plaques, neurofibrillary tau tangles, and neurodegeneration in the brain parenchyma. Here, we aimed to (i) assess differences in blood and imaging biomarkers used to evaluate neurodegeneration among cognitively unimpaired APOE ε4 homozygotes, heterozygotes, and non-carriers with varying risk for sporadic AD, and (ii) to determine how different cerebral pathologies (i.e., Aβ deposition, medial temporal atrophy, and cerebrovascular pathology) contribute to blood biomarker concentrations in this sample.

Autistic children and young people (CYP) experience mental health difficulties but face many barriers to accessing and benefiting from mental health care. There is a need to explore strategies in mental health care for autistic CYP to guide clinical practice and future research and support their mental health needs. Our aim was to identify strategies used to improve mental health care for autistic CYP and examine evidence on their acceptability, feasibility, and effectiveness. A systematic review and meta-analysis were carried out. All study designs reporting acceptability/feasibility outcomes and empirical quantitative studies reporting effectiveness outcomes for strategies tested within mental health care were eligible. We conducted a narrative synthesis and separate meta-analyses by informant (self, parent, and clinician). Fifty-seven papers were included, with most investigating cognitive behavioral therapy (CBT)-based interventions for anxiety and several exploring service-level strategies, such as autism screening tools, clinician training, and adaptations regarding organization of services. Most papers described caregiver involvement in therapy and reported adaptations to communication and intervention content; a few reported environmental adjustments. In the meta-analyses, parent- and clinician-reported outcomes, but not self-reported outcomes, showed with moderate certainty that CBT for anxiety was an effective treatment compared to any comparison condition in reducing anxiety symptoms in autistic individuals. The certainty of evidence for effectiveness, synthesized narratively, ranged from low to moderate. Evidence for feasibility and acceptability tended to be positive. Many identified strategies are simple, reasonable adjustments that can be implemented in services to enhance mental health care for autistic individuals. Notable research gaps persist, however.

This comprehensive narrative review endeavors to dissect the intricate web of neuropsychiatric disorders that significantly impact cognition, emotion regulation, behavior, and mental health. With a keen focus on Alzheimer's disease (AD), anxiety disorders, epilepsy, schizophrenia, and autism spectrum disorder (ASD), this article delves into their underlying mechanisms, clinical presentations, diagnostic challenges, and therapeutic interventions. Highlighting the considerable disability and societal costs that these conditions impose, it reflects on the over six million individuals grappling with Alzheimer's, the 19 million American adults living with anxiety disorders, the three million with epilepsy, and the global reach of schizophrenia affecting approximately 20 million people. Furthermore, it examines the emerging landscape of ASD, noting the escalating diagnosis rates and the pressing need for innovative treatments and equitable healthcare access. Through a detailed exploration of current research, technological innovations, and the promise of personalized medicine, this review aims to illuminate the complexities of these conditions, advocate for early intervention strategies, and call for a unified approach to tackling the multifaceted challenges they present. The ultimate goal is to inform and inspire healthcare professionals, researchers, and policymakers to foster advancements that improve outcomes and quality of life for individuals affected by these profound neuropsychiatric disorders, steering towards a future where these conditions are no longer insurmountable.

In this narrative, comprehensive, and updated review of the literature, we summarize evidence about the effectiveness of interventions aimed at reducing emotion dysregulation and improving emotion regulation in children, adolescents, and adults. After introducing emotion dysregulation and emotion regulation from a theoretical standpoint, we discuss the factors commonly associated with emotion regulation, including neurobiological and neuropsychological mechanisms, and the role of childhood adverse experiences and psycho-social factors in the onset of emotion dysregulation. We then present evidence about pharmacological and non-pharmacological interventions aiming at improving emotion dysregulation and promoting emotion regulation across the lifespan. Although our review was not intended as a traditional systematic review, and the search was only restricted to systematic reviews and meta-analyses, we highlighted important implications and provided recommendations for clinical practice and future research in this field.

Speculum lubrication may help to reduce the pain experienced during Pap-smear collection and hence increase uptake of cervical cancer screening and repeat testing, but there are fears of its interference with cytological results.

Low social participation is a potentially modifiable risk factor for cognitive deterioration in the general population and related to lower quality of life (QoL). We aimed to find out whether social participation is linked to cognitive deterioration and QoL for people with borderline intellectual functioning and mild intellectual disability.

Young women who are not in education, employment, or training (NEET) experience poorer health and social outcomes compared to non-NEET young women and to NEET young men, especially in deprived areas with intersecting inequalities. The evidence on effective public health approaches is scarce. Interventions that target hope, which NEET young women notably lack, offer a promising theory-driven and intuitive means to prevent mental health problems and improve social outcomes. Hope can be defined as a goal-focused mindset comprising self-agency (motivation and self-belief) and pathways (identifying routes to achieving goals). Hope is implicated in a variety of evidence-based psychosocial interventions for young people, but is not directly targeted by existing prevention programmes for NEET populations. The current study used a phased qualitative research design and participatory methods to model a hope-focused intervention for NEET young women. Phase 1 investigated population needs and intervention parameters through semi-structured interviews with 28 key informants living or working in disadvantaged coastal communities in South-East England. The sample comprised eight NEET young women, four family members, and 16 practitioners from relevant support organisations. Phase 2 refined intervention parameters and outcomes through co-design sessions with four NEET young women, followed by a theory of change workshop with 10 practitioners. The resulting intervention model is articulated as a mentor-supported, in-person psychosocial intervention that builds hope by enhancing positive sense of self and time spent in meaningful activities, before explicitly teaching the skills needed to identify, set, and pursue personally meaningful goals.

Psychotherapists need effective tools to monitor changes in the patient's affective perception of the therapist and the therapeutic relationship during sessions to tailor therapeutic interventions and improve treatment outcomes. This study aims to evaluate the factor structure, reliability, and validity of the (SPARQ), a concise self-report measure designed for practical application in real-world psychotherapy settings.

Spontaneous haemoperitoneum in pregnancy is a rare but potentially life-threatening condition that requires prompt recognition and management to avert a catastrophic outcome for the mother and baby. The main aim of this review is to summarise the current knowledge on this topic, including its incidence and clinical presentation, highlight the diagnostic challenges, and suggest management strategies. To achieve our objective, we examine the existing literature to provide insights into this complex clinical presentation to enhance our understanding and, in so doing, contribute to the existing body of knowledge on the subject of spontaneous haemoperitoneum in pregnancy.

Schizophrenia is a severe mental illness that usually begins in late adolescence or early adulthood. Current pharmacological treatments, while acceptably effective for many patients, are rarely clinically tailored or individualized. The lack of sufficient etiopathological knowledge of the disease, together with overall comparable effect sizes for efficacy between available antipsychotics and the absence of clinically actionable biomarkers, has hindered the advance of individualized medicine in the treatment of schizophrenia. Nevertheless, some degree of stratification based on clinical markers could guide treatment choices and help clinicians move toward individualized psychiatry. To this end, a panel of experts met to formally discuss the current approach to individualized treatment in schizophrenia and to define how treatment individualization could help improve clinical outcomes.

Functional neurological disorder (FND) is a common cause of referral to neurology services. FND has been shown to lead to significant healthcare resource use and is associated with significant disability, comorbidity and distress. This leads to substantial direct, indirect and intangible costs to the patient and society.

Despite the development of many successful pharmaceutical interventions, a significant subset of patients experience treatment-resistant depression (TRD). Ketamine and its derivatives constitute a novel therapeutic approach to treat TRD; however, standard tools, such as the Montgomery-Åsberg Depression Rating Scale (MADRS) are still being used to measure symptoms and track changes.

The Social media, Smartphone use and Self-Harm (3S-YP) study is a prospective observational cohort study to investigate the mechanisms underpinning associations between social media and smartphone use and self-harm in a clinical youth sample. We present here a comprehensive description of the cohort from baseline data and an overview of data available from baseline and follow-up assessments.

PRECISE-DYAD is an observational cohort study of mother-child dyads running in urban and rural communities in The Gambia and Kenya. The cohort is being followed for two years and includes uncomplicated pregnancies and those that suffered pregnancy hypertension, fetal growth restriction, preterm birth, and/or stillbirth.

Changes in the brain's physiology in Alzheimer's disease are thought to occur early in the disease's trajectory. In this study our aim was to investigate the brain's neurochemical profile in a midlife cohort in relation to risk factors for future dementia using single voxel proton magnetic resonance spectroscopy. Participants in the multi-site PREVENT-Dementia study (age range 40-59 year old) underwent 3T magnetic resonance spectroscopy with the spectroscopy voxel placed in the posterior cingulate/precuneus region. Using LCModel, we quantified the absolute concentrations of myo-inositol, total N-acetylaspartate, total creatine, choline, glutathione and glutamate-glutamine for 406 participants (mean age 51.1; 65.3% female). Underlying partial volume effects were accounted for by applying a correction for the presence of cerebrospinal fluid in the magnetic resonance spectroscopy voxel. We investigated how metabolite concentrations related to apolipoprotein ɛ4 genotype, dementia family history, a risk score (Cardiovascular Risk Factors, Aging and Incidence of Dementia -CAIDE) for future dementia including non-modifiable and potentially-modifiable factors and dietary patterns (adherence to Mediterranean diet). Dementia family history was associated with decreased total N-acetylaspartate and no differences were found between apolipoprotein ɛ4 carriers and non-carriers. A higher Cardiovascular Risk Factors, Aging, and Incidence of Dementia score related to higher myo-inositol, choline, total creatine and glutamate-glutamine, an effect which was mainly driven by older age and a higher body mass index. Greater adherence to the Mediterranean diet was associated with lower choline, myo-inositol and total creatine; these effects did not survive correction for multiple comparisons. The observed associations suggest that at midlife the brain demonstrates subtle neurochemical changes in relation to both inherited and potentially modifiable risk factors for future dementia.