Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.

Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.

Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).

Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.

In England, a range of mental health crisis care models and approaches to organising crisis care systems have been implemented, but characteristics associated with their effectiveness are poorly understood.

To (a) develop a typology of catchment area mental health crisis care systems and (b) investigate how crisis care service models and system characteristics relate to psychiatric hospital admissions and detentions.

Crisis systems data were obtained from a 2019 English national survey. Latent class analyses were conducted to identify discernible typologies, and mixed-effects negative binomial regression models were fitted to explore associations between crisis care models and admissions and detention rates, obtained from nationally reported data.

No clear typology of catchment area crisis care systems emerged. Regression models suggested that provision of a crisis telephone service within the local crisis system was associated with a 11.6% lower admissions rate and 15.3% lower detention rate. Provision of a crisis cafe was associated with a 7.8% lower admission rates. The provision of a crisis assessment team separate from the crisis resolution and home treatment service was associated with a 12.8% higher admission rate.

The configuration of crisis care systems varies considerably in England, but we could not derive a typology that convincingly categorised crisis care systems. Our results suggest that a crisis phone line and a crisis cafe may be associated with lower admission rates. However, our findings suggest crisis assessment teams, separate from home treatment teams, may not be associated with reductions in admission and detentions.

To determine the safety and feasibility of over-expansion of right ventricle to pulmonary artery conduits during transcatheter pulmonary valve placement.

Transcatheter pulmonary valve placement is an alternative to surgical pulmonary valve replacement. Traditionally, it was thought to be unsafe to expand a conduit to >110% of its original size.

This retrospective cohort study from two centers includes patients with right ventricle to pulmonary artery conduits with attempted transcatheter pulmonary valve placement from 2010 to 2017. Demographic, procedural, echocardiographic and follow-up data, and complications were evaluated in control and overdilation (to >110% original conduit size) groups.

One hundred and seventy-two patients (51 overdilation and 121 control) had attempted transcatheter pulmonary valve placement (98% successful). The overdilation group was younger (11.2 versus 16.7 years, p < 0.001) with smaller conduits (15 versus 22 mm, p < 0.001); however, the final valve size was not significantly different (19.7 versus 20.2 mm, p = 0.2). Baseline peak echocardiographic gradient was no different (51.8 versus 55.6 mmHg, p = 0.3). Procedural complications were more frequent in overdilation (18%) than control (7%) groups (most successfully addressed during the procedure). One patient from each group required urgent surgical intervention, with no procedural mortality. Follow-up echocardiographic peak gradients were similar (24.1 versus 26 mmHg, p = 0.5).

Over-expansion of right ventricle to pulmonary artery conduits during transcatheter pulmonary valve placement can be performed successfully. Procedural complications are more frequent with conduit overdilation, but there was no difference in the rate of life-threatening complications. There was no difference in valve function at most recent follow-up, and no difference in rate of reintervention. The long-term outcomes of transcatheter pulmonary valve placement with conduit over-expansion requires further study.

Anorexia nervosa (AN) is a psychiatric disorder with complex etiology, with a significant portion of disease risk imparted by genetics. Traditional genome-wide association studies (GWAS) produce principal evidence for the association of genetic variants with disease. Transcriptomic imputation (TI) allows for the translation of those variants into regulatory mechanisms, which can then be used to assess the functional outcome of genetically regulated gene expression (GReX) in a broader setting through the use of phenome-wide association studies (pheWASs) in large and diverse clinical biobank populations with electronic health record phenotypes.

Here, we applied TI using S-PrediXcan to translate the most recent PGC-ED AN GWAS findings into AN-GReX. For significant genes, we imputed AN-GReX in the Mount Sinai BioMe™ Biobank and performed pheWASs on over 2000 outcomes to test the clinical consequences of aberrant expression of these genes. We performed a secondary analysis to assess the impact of body mass index (BMI) and sex on AN-GReX clinical associations.

Our S-PrediXcan analysis identified 53 genes associated with AN, including what is, to our knowledge, the first-genetic association of AN with the major histocompatibility complex. AN-GReX was associated with autoimmune, metabolic, and gastrointestinal diagnoses in our biobank cohort, as well as measures of cholesterol, medications, substance use, and pain. Additionally, our analyses showed moderation of AN-GReX associations with measures of cholesterol and substance use by BMI, and moderation of AN-GReX associations with celiac disease by sex.

Our BMI-stratified results provide potential avenues of functional mechanism for AN-genes to investigate further.

Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.

We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.

In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).

AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.

Centenarians have survived into very late life, but whether they reach very old age in good health remains unclear. The purpose of this study was to compare the cardiovascular health status and cognitive functioning of centenarians in the United States with centenarians in Japan.

This cross-national design compared centenarians from the United States and Japan. The sample of U.S. centenarians was recruited from the Georgia Centenarian Study and included 287 centenarians. The sample of Japanese centenarians was recruited from the Tokyo Centenarian Study and included 304 centenarians.

Cognitive functioning was assessed with a mental status questionnaire, and cardiovascular disease by a health history assessment, blood pressure, and selected blood parameters.

The results suggest that Tokyo centenarians had lower disease experiences and BMI values, when compared to Georgia centenarians, but blood pressure was higher among Japanese centenarians. Lower levels of hemoglobin in Japanese centenarians and higher levels of C-reactive protein in Georgia were also found. The positive association of hypertension and albumin levels with cognitive functioning and the negative association of stroke occurrence with cognitive functioning were replicated in both countries. Differential effects were obtained for heart problems, BMI, and C-reactive protein (with positive effects for Tokyo centenarians, except for C-reactive protein).

For extremely old individuals, some markers of cardiovascular disease are replicable across countries, whereas differential effects for cardiovascular health also need to be considered in cardiovascular health.