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The Palix Foundation has pledged £265,250 to support a cross-disciplinary project aimed at sharing scientific knowledge about early brain development and its effect on mental health and addiction. The project will be delivered by the Department of Psychiatry and the Department of Experimental Psychology, and will unite Oxford and the foundation's shared vision of improving outcomes for children, their families and future generations.
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THE BRAIN STORY © PALIX FOUNDATION / ALBERTA FAMILY WELLNESS INITIATIVE
Incidence and prevalence of asthma, chronic obstructive pulmonary disease and interstitial lung disease between 2004 and 2023: harmonised analyses of longitudinal cohorts across England, Wales, South-East Scotland and Northern Ireland
Background We describe the epidemiology of asthma, chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) from 2004 to 2023 in England, Wales, Scotland and Northern Ireland (NI) using a harmonised approach. Methods Data from the National Health Service England (NHSE), Clinical Practice Research Datalink Aurum in England, Secure Anonymised Information Linkage Databank in Wales, DataLoch in South-East Scotland and the Honest Broker Service in NI were used. A harmonised approach to COPD, asthma and ILD case definitions, study designs and study populations across the four nations was performed. Age-sex-standardised incidence rates and point prevalence were calculated between 2004 and 2023 depending on data availability. Logistic and negative binomial regression compared incidence and prevalence rates between the start and end of each study period. Linear extrapolation projected incidence rates between 2020 and 2023 to illustrate how observed and projected rates differed. Results Incidence rates were lower in 2019 versus 2005 for asthma (England: incidence rate ratio 0.89, 95% CI 0.88 to 0.90; Wales: 0.66, 0.65 to 0.68; Scotland: 0.67, 0.64 to 0.71; NI: 0.84, 0.81 to 0.86), COPD (England: 0.83, 0.82 to 0.85; Wales: 0.67, 0.65 to 0.69) and higher for ILD (England: 3.27, 3.05 to 3.50; Wales: 1.39, 1.27 to 1.53; Scotland: 1.63, 1.36 to 1.95; NI: 3.03, 2.47 to 3.72). In NHSE, the incidence of asthma was similar in June 2023 versus November 2019, but lower for COPD and higher for ILD. Prevalence of asthma in 2019 in England, Wales, Scotland and NI was 9.7%, 15.9%, 13.2% and 7.0%, respectively, for COPD 4.5%, 5.1%, 4.4% and 3.0%, and for ILD 0.4%, 0.5%, 0.6% and 0.3%. Projected incidence rates were 2.8, 3.4 and 1.8 times lower for asthma, COPD and ILD compared with observed rates at the height of the pandemic. Interpretation Asthma, COPD and ILD affect over 10 million people across the four nations, and a substantial number of diagnoses were missed during the pandemic.
Correction: Evaluating the generalisability of region-naïve machine learning algorithms for the identification of epilepsy in low-resource settings.
[This corrects the article DOI: 10.1371/journal.pdig.0000491.].
Future directions for brain health clinics.
Brain Health Services are second-generation memory clinics that aim to reduce the risk of progression to dementia in at-risk individuals. We describe the rationale for such a service, and comment on its novel implementation by Venkataraman and colleagues that integrates digital technologies and biomarker testing. We describe the advantages and possible limitations of such an approach, then investigate areas for further work - namely, the need to account for multiple pathologies in biomarker testing and to formulate standards for genetic counselling.
Clinical and cost-effectiveness of lithium versus quetiapine augmentation for treatment-resistant depression in adults: LQD a pragmatic randomised controlled trial.
BACKGROUND: Lithium and several atypical antipsychotics are the recommended first-line augmentation options for treatment-resistant depression; however, few studies have compared them directly, and none for longer than 8 weeks. Consequently, there is little evidence-based guidance for clinicians when choosing an augmentation option for patients with treatment-resistant depression. OBJECTIVES: This trial examined whether it is more clinically and cost-effective to prescribe lithium or quetiapine augmentation therapy for patients with treatment-resistant depression over 12 months. DESIGN: This was a parallel group, multicentre, pragmatic, open-label superiority trial comparing the clinical and cost-effectiveness of lithium versus quetiapine augmentation of antidepressant medication in treatment-resistant depression. Participants were randomised 1 : 1 at baseline to the decision to prescribe either lithium or quetiapine. SETTING: Six National Health Service trusts in England. PARTICIPANTS: Eligible participants were aged ≥ 18 years, met Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition criteria for major depressive disorder, scored ≥ 14 on the 17-item Hamilton Depression Rating Scale and whose depression had had an inadequate response to at least two therapeutic antidepressant treatment trials in the current episode, with a current antidepressant treatment at or above the therapeutic dose for ≥ 6 weeks. Patients with a history of psychosis or bipolar disorder were excluded. Patients were judged suitable for either treatment. INTERVENTIONS: After randomisation, pre-prescribing safety checks were undertaken as per standard care and trial clinicians decided whether to proceed with prescribing the allocated medication. Trial clinicians received recommendations for titration and dosing in line with current clinical guidelines; however, dosing regimens could be altered according to tolerability and response. Participants were followed up using weekly self-report questionnaires and 8-, 26- and 52-week research visits. MAIN OUTCOME MEASURES: The co-primary outcome measures were depressive symptom severity over 52 weeks, measured weekly using the self-rated Quick Inventory of Depressive Symptomatology, and time to all-cause treatment discontinuation of the trial medication. Economic analyses compared costs between the two treatment arms over 52 weeks, from a National Health Service and Personal Social Services perspective, and a societal perspective. RESULTS: Two hundred and twelve participants were randomised, 107 to quetiapine and 105 to lithium. The quetiapine arm showed a significantly greater reduction in depressive symptoms than the lithium arm over 52 weeks (quetiapine vs. lithium area under the differences curve = -68.36, 95% confidence interval: -129.95 to -6.76, p = 0.0296). Median days to discontinuation did not significantly differ between the two arms (quetiapine = 365.0, interquartile range = 57.0-365.0, lithium = 212.0, interquartile range = 21.0-365.0), p = 0.1196. Quetiapine was more cost effective than lithium. Thirty-two serious adverse events were recorded, only one of which was deemed possibly related to the intervention (lithium). LIMITATIONS: The trial was unblinded, therefore expectancies regarding the trial medications may have influenced the results. Further, there was substantial missing data for some of the secondary outcome measures. CONCLUSIONS: As well as being more cost-effective, quetiapine may be a more clinically effective augmentation option for treatment-resistant depression. FUTURE WORK: Examining predictors of treatment response, including clinical, sociodemographic and biological factors, will help establish whether there are additional factors to consider when choosing an augmentation treatment for treatment-resistant depression. TRIAL REGISTRATION: This trial is registered as ISRCTN16387615. FUNDING: This award was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme (NIHR award ref: 14/222/02) and is published in full in Health Technology Assessment; Vol. 29, No. 12. See the NIHR Funding and Awards website for further award information.
A Systematic Review of Guided, Parent-Led Digital Interventions for Preadolescent Children with Emotional and Behavioural Problems.
Emotional and behavioural problems (EBP) are prevalent amongst children, and guided, parent-led digital interventions offer one method of improving access to effective treatments. This systematic review (PROSPERO: CRD42023484098) aimed to examine the evidence base for, and characteristics of, these types of interventions through a narrative synthesis. Systematic searches were conducted using Medline, EMBASE, PsycINFO, Scopus and Web of Science in January 2024 and February 2025, supplemented with hand searching in March/April 2024 and February 2025. Studies were eligible if they reported outcomes related to preadolescent EBP from a guided, fully parent-led, fully digital intervention. Thirteen studies were eligible, including 2643 children and covering eight interventions (addressing anxiety problems, comorbid anxiety and depression, attention deficit hyperactivity disorder, conduct disorder and disruptive behaviour). Studies included randomised controlled trials and pre-post studies. The QualSyst checklist was used to assess study quality; all studies were rated as good quality. All studies showed statistically significant improvements in the child's symptoms or interference levels, with small to very large effect sizes immediately post-treatment, and at least medium effect sizes by follow-up, suggesting a promising evidence base. A wide range of intervention characteristics were identified, forming a basis for future intervention development for childhood EBP. However, there was a lack of consistency in how information was reported across studies (such as completion rates) and studies lacked information on parent demographics and key intervention details. Further high quality randomised controlled trials for a wider range of EBP are needed to continue building the evidence base.
Cadê o Kauê? Co-design and acceptability testing of a chat-story aimed at enhancing youth participation in the promotion of mental health in Brazil.
BACKGROUND: Adolescent mental health is vital for public health, yet many interventions fail to recognise adolescents as proactive community contributors. This paper discusses the co-design and acceptability testing of a chat-story intervention to enhance Brazilian adolescents' participation in the promotion of mental health in their peer communities. We specifically highlight the iterative process of co-creating this intervention with community stakeholders. METHODS: The co-design was led by researchers, a youth collaborative group, and health-tech experts. Part 1 included quantitative (n = 1,768) and qualitative (n = 46) studies with Brazilian adolescents aged 15-18 for priority-setting. Part 2 involved co-creation and technical production, with input from youth advisors (n = 24), school staff (n = 11), and policy experts (n = 3). In Part 3, the chat-story was user tested (n = 32). Parts 4 and 5 assessed acceptability through a qualitative study in schools (n = 138) and initial efficacy during an online campaign (n = 795). RESULTS: Participants aspired to support their peers' mental health in schools, both one-to-one and collectively, but felt unprepared. This informed the chat-story's goal of enhancing peer support and collective action skills. Themes identified during Part 1, such as prejudice and academic pressure, were woven into the narrative to raise awareness of the social determinants of mental health, drawing from real-life stories. In the final story, players search for their missing best friend at school, uncovering his anxiety struggles and practicing skills such as empathic listening and partnership building. A manual for teachers was collaboratively designed for use within school settings, supplementing direct-to-user online applications. Acceptability testing showed participants found the tool authentic and user-friendly. Online users perceived the tool as preparing and motivating them to offer peer support and engage in collective action. CONCLUSIONS: The immersive co-creation model, enriched by input from key stakeholders, yielded a relevant and well-received intervention for Brazilian adolescents. Co-designed creative tools like chat-stories hold promise as digital mental health tools, fostering awareness, critical reflection, and inspiring adolescents to drive positive social change.
Integrating TSPO-PET imaging with metabolomics for enhanced prognostic accuracy in multiple sclerosis.
BACKGROUND: Predicting disease progression in multiple sclerosis (MS) remains challenging. PET imaging with 18 kDa translocator protein (TSPO) radioligands can detect microglial and astrocyte activation beyond MRI-visible lesions, which has been shown to be highly predictive of disease progression. We previously demonstrated that nuclear magnetic resonance (NMR)-based metabolomics could accurately distinguish between relapsing-remitting (RRMS) and secondary progressive MS (SPMS). This study investigates whether combining TSPO imaging with metabolomics enhances predictive accuracy in a similar setting. METHODS: Blood samples were collected from 87 MS patients undergoing PET imaging with the TSPO-binding radioligand 11C-PK11195 in Finland. Patient disability was assessed using the expanded disability status scale (EDSS) at baseline and 1 year later. Serum metabolomics was performed to identify biomarkers associated with TSPO binding and disease progression. RESULTS: Greater TSPO availability in the normal-appearing white matter and perilesional regions correlated with higher EDSS. Serum metabolites glutamate (p=0.02), glutamine (p=0.006), and glucose (p=0.008), detected by NMR, effectively distinguished future progressors. These three metabolites alone predicted progression with the same accuracy as TSPO-PET imaging (AUC 0.78; p=0.0001), validated in an independent cohort. Combining serum metabolite data with PET imaging significantly improved predictive power, achieving an AUC of 0.98 (p<0.0001). CONCLUSION: Measuring three specific serum metabolites is as effective as TSPO imaging in predicting MS progression. However, integrating TSPO imaging with serum metabolite analysis substantially enhances predictive accuracy. Given the simplicity and affordability of NMR analysis, this approach could lead to more personalised, accessible treatment strategies and serve as a valuable tool for clinical trial stratification.
Grey-Matter Structure Markers of Alzheimer's Disease, Alzheimer's Conversion, Functioning and Cognition: A Meta-Analysis Across 11 Cohorts.
Alzheimer's disease (AD) brain markers are needed to select people with early-stage AD for clinical trials and as quantitative endpoint measures in trials. Using 10 clinical cohorts (N = 9140) and the community volunteer UK Biobank (N = 37,664) we performed region of interest (ROI) and vertex-wise analyses of grey-matter structure (thickness, surface area and volume). We identified 94 trait-ROI significant associations, and 307 distinct cluster of vertex-associations, which partly overlap the ROI associations. For AD versus controls, smaller hippocampus, amygdala and of the medial temporal lobe (fusiform and parahippocampal gyri) was confirmed and the vertex-wise results provided unprecedented localisation of some of the associated region. We replicated AD associated differences in several subcortical (putamen, accumbens) and cortical regions (inferior parietal, postcentral, middle temporal, transverse temporal, inferior temporal, paracentral, superior frontal). These grey-matter regions and their relative effect sizes can help refine our understanding of the brain regions that may drive or precede the widespread brain atrophy observed in AD. An AD grey-matter score evaluated in independent cohorts was significantly associated with cognition, MCI status, AD conversion (progression from cognitively normal or MCI to AD), genetic risk, and tau concentration in individuals with none or mild cognitive impairments (AUC in 0.54-0.70, p-value
Automated quality control of T1-weighted brain MRI scans for clinical research: methods comparison and design of a quality prediction classifier
T1-weighted (T1w) MRI is widely used in clinical neuroimaging for studying brain structure and its changes, including those related to neurodegenerative diseases, and as anatomical reference for analysing other modalities. Ensuring high-quality T1w scans is vital as image quality affects reliability of outcome measures. However, visual inspection can be subjective and time-consuming, especially with large datasets. The effectiveness of automated quality control (QC) tools for clinical cohorts remains uncertain. In this study, we used T1w scans from elderly participants within ageing and clinical populations to test the accuracy of existing QC tools with respect to visual QC and to establish a new quality prediction framework for clinical research use. Four datasets acquired from multiple scanners and sites were used (N = 2438, 11 sites, 39 scanner manufacturer models, 3 field strengths – 1.5T, 3T, 2.9T, patients and controls, average age 71 ± 8 years). All structural T1w scans were processed with two standard automated QC pipelines (MRIQC and CAT12). The agreement of the accept-reject ratings was compared between the automated pipelines and with visual QC. We then designed a quality prediction framework that combines the QC measures from the existing automated tools and is trained on clinical research datasets. We tested the classifier performance using cross-validation on data from all sites together, also examining the performance across diagnostic groups. We then tested the generalisability of our approach when leaving one site out and explored how well our approach generalises to data from a different scanner manufacturer and/or field strength from those used for training, as well as on an unseen new dataset of healthy young participants with movement related artefacts. Our results show significant agreement between automated QC tools and visual QC (Kappa=0.30 with MRIQC predictions; Kappa=0.28 with CAT12’s rating) when considering the entire dataset, but the agreement was highly variable across datasets. Our proposed robust undersampling boost (RUS) classifier achieved 87.7% balanced accuracy on the test data combined from different sites (with 86.6% and 88.3% balanced accuracy on scans from patients and controls respectively). This classifier was also found to be generalisable on different combinations of training and test datasets (average balanced accuracy of leave-one-site-out = 78.2%; exploratory models on field strengths and manufacturers = 77.7%; movement related artefact dataset when including 1% scans in the training = 88.5%). While existing QC tools may not be robustly applicable to datasets comprised of older adults, they produce quality metrics that can be leveraged to train a more robust quality control classifiers for ageing and clinical cohorts.
COVID-19 and substance use disorders: a review of international guidelines for frontline healthcare workers of addiction services.
BACKGROUND: People with substance use disorders may be at a greater risk of contracting COVID-19 infection and developing medical complications. Several institutional and governmental health agencies across the world developed ad hoc guidance for substance use disorder services and care of individuals misusing substances. We aimed to synthesise the best available recommendations on management and care of people with or at risk of substance use disorders during the COVID-19 pandemic from existing guidelines published in UK, USA, Australia, Canada, New Zealand, and Singapore. METHODS: We systematically searched existing guidelines and websites from 28 international institutions and governmental bodies in the context of the COVID-19 pandemic (May 4th 2021). We summarized the extracted data as answers to specific clinical questions. RESULTS: We organised the available recommendations from 19 sources in three sections. First, we focused on general advice and recommendations for people who misuse alcohol or drugs during the COVID-19 pandemic, the design of contingency plans, safeguarding issues for children and families of service users and advice to the public, patients, and carers. Then, we summarised specific guidelines for people who use illicit drugs and related services, such as opioid substitution treatment and needle and syringe programmes. Finally, we provided a synthesis on specific recommendations for services supporting people who misuse alcohol and key topics in the field, such as management of alcohol detoxification and safe transition between supervised and unsupervised consumption. CONCLUSIONS: Available guidance reflected different approaches, ranging from being extremely cautious in providing recommendations other than generic statements to proposing adaptation of previously available guidelines to confront the challenges of the COVID-19 pandemic. After the early phase, guidance focused on reduction of infection transmission and service delivery. Guidance did not provide advice on infection prevention via vaccination programmes and service access strategies tailored to individuals with substance use disorders.
Neural dynamics of reselecting visual and motor contents in working memory after external interference.
In everyday tasks, we must often shift our focus away from internal representations held in working memory to engage with perceptual events in the external world. Here, we investigated how our internal focus is reestablished following an interrupting task by tracking the reselection of visual representations and their associated action plans in working memory. Specifically, we ask whether reselection occurs for both visual and motor memory attributes and when this reselection occurs. We developed a visual-motor working-memory task in which participants were retrospectively cued to select one of two memory items before being interrupted by a perceptual discrimination task. To determine what information was reselected, the memory items had distinct visual and motor attributes. To determine when internal representations were reselected, the interrupting task was presented at one of three distinct time points following the retro-cue. We employed electroencephalography time-frequency analyses to track the initial selection and later reselection of visual and motor representations, as operationalized through modulations of posterior alpha (8-12 Hz) activity relative to the memorized item location (visual) and of central beta (13-30 Hz) activity relative to the required response hand (motor). Our results showed that internal visual and motor contents were concurrently reselected immediately after completing the interrupting task, rather than only when internal information was required for memory-guided behavior. Thus, following interruption, we swiftly resume our internal focus in working memory through the simultaneous reselection of memorized visual representations and their associated action plans, thereby restoring internal contents to a ready-to-use state.Significance statement A key challenge for working memory is to maintain past visual representations and their associated actions while engaging with the external environment. Our cognitive system must, therefore, often juggle multiple tasks within a common time frame. Despite the ubiquity of multi-task situations in everyday life, working memory has predominantly been studied devoid of additional perceptual, attentional, and response demands during the retention interval. Here, we investigate the neural dynamics of returning to internal contents following task-relevant interruptions. Particularly, we identify which attributes of internal representations are reselected and when this reselection occurs. Our findings demonstrate that both visual and motor contents are reselected immediately and in tandem after completion of an external, interrupting task.
A single dose of lamotrigine induces a positive memory bias in healthy volunteers.
BACKGROUND: Lamotrigine has been shown to be effective in the long-term treatment and relapse prevention of depression in bipolar disorder. However, the neuropsychological mechanisms underlying these effects are unclear. We investigated the effects of lamotrigine on a battery of emotional processing tasks in healthy volunteers, previously shown to be sensitive to antidepressant drug action in similar experimental designs. METHODS: Healthy volunteers (n = 36) were randomized in a double-blind design to receive a single dose of placebo or 300 mg lamotrigine. Mood and subjective effects were monitored throughout the study period, and emotional processing was assessed using the Oxford Emotional Test Battery (ETB) 3 hours post-administration. RESULTS: Participants receiving lamotrigine showed increased accurate recall of positive versus negative self-descriptors, compared to those in the placebo group. There were no other significant effects on emotional processing in the ETB, and lamotrigine did not affect ratings of mood or subjective experience. CONCLUSIONS: Lamotrigine did not induce widespread changes in emotional processing. However, there was increased positive bias in emotional memory, similar to the effects of antidepressants reported in previous studies. Further work is needed to assess whether similar effects are seen in the clinical treatment of patients with bipolar disorder and the extent to which this is associated with its clinical action in relapse prevention.
The impact of personality traits on the return of major depression: a case-control study.
BACKGROUND: Major depression is a common, chronic, recurrent, debilitating disorder. Despite effective treatments, remission rates remain low, and many of those who do experience remission then relapse. Some personality traits are potential risk factors for relapse, though they have, to date, received insufficient attention. There is growing attention to the role of emotional dysregulation in recurrent depression. We aimed to investigate the association between the return of major depression and emotional dysregulation, affective lability, and impulsivity personality traits. METHOD: A case-control design sampling adults over 18 years old with a history of depression and currently either experiencing a depressive episode (cases) or currently being free of a depressive episode (controls). Current depression was assessed using the Patient Health Questionnaire-9, and study participants were recruited online. Multi-staged logistic regression modelling was used to explore the association between personality traits and the return of depression, adjusting for important confounding factors. RESULTS: One hundred fifty two respondents (76 cases and 76 controls) were recruited. Emotional dysregulation was significantly associated with the return of depression (OR = 1.03, 95% CI [1.00-1.06], p = 0.04) even after adjustment for the confounding factors: marital status and childhood trauma. Childhood trauma (OR = 1.04, 95% CI [1.00-1.08], p = 0.03) and being widowed, divorced, or separated (OR = 13.95, 95% CI [1.16-166], p = 0.03) were also associated with the return of depression. Our analysis did not detect any association between affective lability and impulsivity and the return of depression. LIMITATIONS: Our study relied on self-report questionnaires, including measuring depression. We used cross-sectional data in the present study analysis. CONCLUSION: Our findings suggest emotional dysregulation and childhood trauma could work as risk factors and predate depression. This information can be used to develop targeted treatment plans and improve therapeutic outcomes.
Current and prospective roles of magnetic resonance imaging in mild traumatic brain injury
There is unmet clinical need for biomarkers to predict recovery or the development of long-term sequelae of mild traumatic brain injury, a highly prevalent condition causing a constellation of disabling symptoms. A substantial proportion of patients live with long-lasting sequelae affecting their quality of life and ability to work. At present, symptoms can be assessed through clinical tests; however, there are no imaging or laboratory tests fully reflective of pathophysiology routinely used by clinicians to characterize post-concussive symptoms. Magnetic resonance imaging has potential to link subtle pathophysiological alterations to clinical outcomes. Here, we review the state of the art of MRI research in adults with mild traumatic brain injury and provide recommendations to facilitate transition into clinical practice. Studies utilizing MRI can inform on pathophysiology of mild traumatic brain injury. They suggest presence of early cytotoxic and vasogenic oedema. They also show that mild traumatic brain injury results in cellular injury and microbleeds affecting the integrity of myelin and white matter tracts, all processes that appear to induce delayed vascular reactions and functional changes. Crucially, correlates between MRI parameters and post-concussive symptoms are emerging. Clinical sequences such as T1-weighted MRI, susceptibility-weighted MRI or fluid attenuation inversion recovery could be easily implementable in clinical practice, but are not sufficient, in isolation for prognostication. Diffusion sequences have shown promises and, although in need of analysis standardization, are a research priority. Lastly, arterial spin labelling is emerging as a high-utility research as it could become useful to assess delayed neurovascular response and possible long-term symptoms.