Accurate diagnosis of bipolar disorder (BPD) is difficult in clinical practice, with an average delay between symptom onset and diagnosis of about 7 years. A depressive episode often precedes the first manic episode, making it difficult to distinguish BPD from unipolar major depressive disorder (MDD).

We use genome-wide association analyses (GWAS) to identify differential genetic factors and to develop predictors based on polygenic risk scores (PRS) that may aid early differential diagnosis.

Based on individual genotypes from case–control cohorts of BPD and MDD shared through the Psychiatric Genomics Consortium, we compile case–case–control cohorts, applying a careful quality control procedure. In a resulting cohort of 51 149 individuals (15 532 BPD patients, 12 920 MDD patients and 22 697 controls), we perform a variety of GWAS and PRS analyses.

Although our GWAS is not well powered to identify genome-wide significant loci, we find significant chip heritability and demonstrate the ability of the resulting PRS to distinguish BPD from MDD, including BPD cases with depressive onset (BPD-D). We replicate our PRS findings in an independent Danish cohort (iPSYCH 2015, N = 25 966). We observe strong genetic correlation between our case–case GWAS and that of case–control BPD.

We find that MDD and BPD, including BPD-D are genetically distinct. Our findings support that controls, MDD and BPD patients primarily lie on a continuum of genetic risk. Future studies with larger and richer samples will likely yield a better understanding of these findings and enable the development of better genetic predictors distinguishing BPD and, importantly, BPD-D from MDD.

Following a health technology assessment, the Health Service Executive (HSE) supported reimbursement of dupilumab subject to a managed access protocol (MAP) being implemented. Reimbursement is restricted to a subgroup of the fully licensed indication, that is, moderate-to-severe refractory atopic dermatitis (AD) in adults and adolescents 12 years and older. This study provides an overview of the first year of the MAP.

All reimbursement applications submitted to the HSE Medicines Management Programme between 1 April 2021 and 31 March 2022 were reviewed. Key demographic and clinical characteristics of the approved population were analyzed. Reimbursement claims data within the specified period were extracted from the HSE Primary Care Reimbursement Services national pharmacy claims database. All data were compiled and analyzed using SPSS Statistics 27. Expenditure estimates were based on wholesale prices and were exclusive of value-added tax, fees, and confidential rebates.

During the study period, 382 applications were submitted, 96 percent (n=365) of which were approved. Among approved patients, the mean age was 35 years (range 12 to 79 years), the mean number of years between AD diagnosis and approval was 22.65 years (range 1 to 78 years), and 65 percent (n=238) were men. The mean Eczema Area and Severity Index score was 28.72 and the mean (Children’s) Dermatology Life Quality Index score was 19.72. Approved patients who had unsuccessfully tried other systemic immunosuppressants had trialed up to five different medicines (mean=1.6). Year one expenditure was EUR2.4million, with 70 percent of approved patients accessing treatment.

Most applications submitted through the MAP were approved. These patients met the predefined evidence-based eligibility criteria for treatment. Patient numbers were higher than estimated, suggesting that the MAP did not hinder access. Utilizing health technology management by way of a MAP has facilitated access to expensive medicines for patients with the greatest need, while controlling expenditure for the payer.

Clozapine is the antipsychotic medication with the greatest efficacy in treatment-resistant schizophrenia (TRS). Unfortunately, clozapine is ceased in approximately 0.2% to 8.5% of people due to concerns about clozapine-associated myocarditis (CAM). The opportunity for clozapine rechallenge is important for people with TRS and CAM, due to limited alternative treatments. However, there is a lack of consensus regarding the optimal process, monitoring, and dose titration to achieve successful clozapine rechallenge. The study aimed to review the process, monitoring, and dose titration within cases of clozapine rechallenge after CAM, to identify features associated with successful rechallenge.

A systematic review of clozapine rechallenge cases following CAM was conducted. PubMed, EMBASE, Cinahl, and PsycINFO were searched for cases. Reference lists of retrieved articles and field experts were consulted to identify additional studies.

Forty-five cases were identified that described clozapine rechallenge, 31 of which were successful. Successful rechallenge cases generally used a slower dose titration regime with more frequent monitoring than standard clozapine initiation protocols; however, this data was not always completely recorded within cases. Six cases referred to published rechallenge protocols to guide their rechallenge.

The process, monitoring, and dose titration of clozapine rechallenge are inconsistently reported in the literature. Despite this, 69% of case reports detailed a successful rechallenge post CAM; noting limitations associated with reliance on case data. Ensuring published clozapine rechallenge cases report standardised data, including titration speed and monitoring frequencies, is required to guide the development and validation of guidelines for clozapine rechallenge.

Disease-modifying therapies (DMTs) for Alzheimer’s disease (AD) are emerging following successful clinical trials of therapies targeting amyloid beta (Aβ) protofibrils or plaques. Determining patient eligibility and monitoring treatment efficacy and adverse events, such as Aβ-related imaging abnormalities, necessitates imaging with MRI and PET. The Canadian Consortium on Neurodegeneration in Aging (CCNA) Imaging Workgroup aimed to synthesize evidence and provide recommendations on implementing imaging protocols for AD DMTs in Canada.

The workgroup employed a Delphi process to develop these recommendations. Experts from radiology, neurology, biomedical engineering, nuclear medicine, MRI and medical physics were recruited. Surveys and meetings were conducted to achieve consensus on key issues, including protocol standardization, scanner strength, monitoring protocols based on risk profiles and optimal protocol lengths. Draft recommendations were refined through multiple iterations and expert discussions.

The recommendations emphasize standardized acquisition imaging protocols across manufacturers and scanner strengths to ensure consistency and reliability of clinical treatment decisions, tailored monitoring protocols based on DMTs’ safety and efficacy profiles, consistent monitoring regardless of perceived treatment efficacy and MRI screening on 1.5T or 3T scanners with adapted protocols. An optimal protocol length of 20–30 minutes was deemed feasible; specific sequences are suggested.

The guidelines aim to enhance imaging data quality and consistency, facilitating better clinical decision-making and improving patient outcomes. Further research is needed to refine these protocols and address evolving challenges with new DMTs. It is recognized that administrative, financial and logistical capacity to deliver additional MRI and positron emission tomography scans require careful planning.

This study examines how psychological aspects of vestibular disorders are currently addressed highlighting any national variation.

An online survey was completed by 101 UK healthcare professionals treating vestibular disorders. The survey covered service configurations, attitudes towards psychological aspects and current clinical practice.

Ninety-six per cent of respondents thought there was a psychological component to vestibular disorders. There was a discrepancy between perceived importance of addressing psychological aspects and low confidence to undertake this. Those with more experience felt more confident addressing psychological aspects. History taking and questionnaires containing one or two psychological items were the most common assessment approaches. Discussing symptoms and signposting were the most frequent management approaches. Qualitative responses highlighted the interdependence of psychological and vestibular disorders which require timely intervention. Barriers included limited referral pathways, resources and interdisciplinary expertise.

Although psychological distress is frequently identified, suitable psychological treatment is not routinely offered in the UK.

Estimate the impact of 20 % flat-rate and tiered sugary drink tax structures on the consumption of sugary drinks, sugar-sweetened beverages and 100 % juice by age, sex and socio-economic position.

We modelled the impact of price changes – for each tax structure – on the demand for sugary drinks by applying own- and cross-price elasticities to self-report sugary drink consumption measured using single-day 24-h dietary recalls from the cross-sectional, nationally representative 2015 Canadian Community Health Survey-Nutrition. For both 20 % flat-rate and tiered sugary drink tax scenarios, we used linear regression to estimate differences in mean energy intake and proportion of energy intake from sugary drinks by age, sex, education, food security and income.

Canada.

19 742 respondents aged 2 and over.

In the 20 % flat-rate scenario, we estimated mean energy intake and proportion of daily energy intake from sugary drinks on a given day would be reduced by 29 kcal/d (95 % UI: 18, 41) and 1·3 % (95 % UI: 0·8, 1·8), respectively. Similarly, in the tiered tax scenario, additional small, but meaningful reductions were estimated in mean energy intake (40 kcal/d, 95 % UI: 24, 55) and proportion of daily energy intake (1·8 %, 95 % UI: 1·1, 2·5). Both tax structures reduced, but did not eliminate, inequities in mean energy intake from sugary drinks despite larger consumption reductions in children/adolescents, males and individuals with lower education, food security and income.

Sugary drink taxation, including the additional benefit of taxing 100 % juice, could reduce overall and inequities in mean energy intake from sugary drinks in Canada.

Childhood obesity is a serious health epidemic affecting the world today. Children who are obese earlier in life are more likely to stay obese and have an increased risk of poorer health outcomes later in life, such as diabetes and cardiovascular diseases. Obesity is also associated with deficits in executive function. Executive function (EF) is comprised of several distinct but interrelated abilities including working memory, planning, inhibition, and flexibility. Prior research suggests that obesity drives brain changes which implicate executive function structures. Our aim is to examine the relationship between childhood obesity and executive function in children with neurodevelopmental disorders.

These data are from an ongoing study on neural and behavioral phenotypes of executive functioning in children with developmental disabilities, primarily Attention-Deficit/Hyperactivity Disorder (ADHD) and Autism Spectrum Disorder (ASD). Only study participants with complete BMI and BRIEF data were included in these analyses (n = 184). 134 representing (72.8%) of the participants were Male, 49 representing (26.6%) were Female, and 1 representing (.5%) were Gender nonconforming. 50 representing (27.2%) of the participants were between 8-9 years, 55 representing (29.9%) were between 10-11 years, and 80 representing (43.0%) were between 12-13 years. Average age was 11 years. 11 representing (6.0%) of the participants were underweight, 115 representing (62.5%) were healthy, 29 representing (15.8%) were overweight, and 29 representing (15.8%) were obese. Average BMI was 19.0, ranging from 13.2 to 36.3. 106 representing (57.6%) of the participants identified as White, 65 representing (35.3%) identified as BIPOC (2 Asian, 31 Hispanic/Latinx, 32 Black) and 13 representing (4.4%) identified as other/unspecified. 114 representing (61.9%) of the participants had a diagnosis of ADHD, ASD, or comorbid ASD and ADHD, 70 representing (38.1%) had a diagnosis of other. Average FSIQ-2 score was 106.98. Parents were asked to complete the Behavior Rating Inventory of Executive Function (BRIEF-2) and the Inhibit, Shift, Working Memory (WM), Planning, and Global Executive Composite (GEC) scales were used as the dependent measure in analyses. BMI (kg/mA2) was calculated based on CDC 2000 growth charts and classified into 4 mutually exclusive categories—underweight, healthy, overweight, and obese. There was a prediction that higher BMI would be associated with lower executive function.

A one-way ANOVA revealed a statistically significant difference between groups (F(3,180) = 3.649, p = .014). A Tukey post hoc test revealed more Shift problems in the obese group (74.55 ± 11.7) compared to the overweight group (65.79 ± 11.6, p = .026). There was no statistically significant difference between the underweight/healthy and obese groups (p = .999/p = .054). There was no statistically significant difference in mean T-scores for the Inhibit, WM, Planning, or GEC scales.

Childhood obesity and executive function deficits are significant risk factors for adult health outcomes. Obesity and elevated executive function T-scores for flexibility are related in a group of children with neurodevelopmental disorders. Future investigation will explore the role of cortical thickness and medication in these data.