Although several types of risk factors for anorexia nervosa (AN) have been identified, including birth-related factors, somatic, and psychosocial risk factors, their interplay with genetic susceptibility remains unclear. Genetic and epidemiological interplay in AN risk were examined using data from Danish nationwide registers. AN polygenic risk score (PRS) and risk factor associations, confounding from AN PRS and/or parental psychiatric history on the association between the risk factors and AN risk, and interactions between AN PRS and each level of target risk factor on AN risk were estimated.

Participants were individuals born in Denmark between 1981 and 2008 including nationwide-representative data from the iPSYCH2015, and Danish AN cases from the Anorexia Nervosa Genetics Initiative and Eating Disorder Genetics Initiative cohorts. A total of 7003 individuals with AN and 45 229 individuals without a registered AN diagnosis were included. We included 22 AN risk factors from Danish registers.

Risk factors showing association with PRS for AN included urbanicity, parental ages, genitourinary tract infection, and parental socioeconomic factors. Risk factors showed the expected association to AN risk, and this association was only slightly attenuated when adjusted for parental history of psychiatric disorders or/and for the AN PRS. The interaction analyses revealed a differential effect of AN PRS according to the level of the following risk factors: sex, maternal age, genitourinary tract infection, C-section, parental socioeconomic factors and psychiatric history.

Our findings provide evidence for interactions between AN PRS and certain risk-factors, illustrating potential diverse risk pathways to AN diagnosis.

To examine associations between work and commute hours with food consumption and test whether neighbourhood type (20-minute neighbourhood (20MN)/non-20MN) moderate associations.

Cross-sectional analysis of the Places and Locations for Activity and Nutrition study (ProjectPLAN). Exposures were work hours (not working (0 h), working up to full-time (1–38 h/week), working overtime (> 38 h/week)), and among those employed, combined weekly work and commute hours (continuous). Outcomes were usual consumption of fruit, vegetables, takeaway food, snacks and soft drinks, and number of discretionary food types (takeaway, snacks and soft drinks) consumed weekly. Generalised linear models were fitted to examine associations between each exposure and outcome. The moderating role of neighbourhood type was examined through interaction terms between each exposure and neighbourhood type (20MN/non-20MN).

Melbourne and Adelaide, Australia, 2018–2019.

Adults ≥ 18 years old (n 769).

Although all confidence intervals contained the null, overall, patterns suggested non-workers and overtime workers have less healthy food behaviours than up-to-full-time workers. Among those employed, analysis of continuous work and commute hours data suggested longer work and commute hours were positively associated with takeaway consumption (OR = 1·014, 95 % CI 0·999, 1·030, P-value = 0·066). Patterns of better behaviours were observed across most outcomes for those in 20MN than non-20MN. However, differences in associations between work and commute hours with food consumption across neighbourhood type were negligible.

Longer work and commute hours may induce poorer food behaviours. There was weak evidence to suggest 20MN moderate associations between work and commute hours with food consumption, although behaviours appeared healthier for those in 20MN.

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.

Comorbidity with general medical conditions is common in individuals with eating disorders. Many previous studies do not evaluate types of eating disorder.

To provide relative and absolute risks of bidirectional associations between (a) anorexia nervosa, bulimia nervosa and eating disorders not otherwise specified and (b) 12 general medical conditions.

We included all people born in Denmark between 1977 and 2010. We collected information on eating disorders and considered the risk of subsequent medical conditions, using Cox proportional hazards regression. Absolute risks were calculated using competing risks survival analyses. We also considered risks for prior medical conditions and subsequent eating disorders.

An increased risk was seen for almost all disorder pairs (69 of 70). Hazard ratios for those with a prior eating disorder receiving a subsequent diagnosis of a medical condition ranged from 0.94 (95% CI 0.57−1.55) to 2.05 (95% CI 1.86−2.27). For those with a prior medical condition, hazard ratios for later eating disorders ranged from 1.35 (95% CI 1.26–1.45) to 1.98 (95% CI 1.71–2.28). Absolute risks for most later disorders were increased for persons with prior disorders, compared with reference groups.

This is the largest and most detailed examination of eating disorder–medical condition comorbidity. The findings indicate that medical condition comorbidity is increased among those with eating disorders and vice versa. Although there was some variation in comorbidity observed across eating disorder types, magnitudes of relative risks did not differ greatly.

During the Randomized Assessment of Rapid Endovascular Treatment (EVT) of Ischemic Stroke (ESCAPE) trial, patient-level micro-costing data were collected. We report a cost-effectiveness analysis of EVT, using ESCAPE trial data and Markov simulation, from a universal, single-payer system using a societal perspective over a patient’s lifetime.

Primary data collection alongside the ESCAPE trial provided a 3-month trial-specific, non-model, based cost per quality-adjusted life year (QALY). A Markov model utilizing ongoing lifetime costs and life expectancy from the literature was built to simulate the cost per QALY adopting a lifetime horizon. Health states were defined using the modified Rankin Scale (mRS) scores. Uncertainty was explored using scenario analysis and probabilistic sensitivity analysis.

The 3-month trial-based analysis resulted in a cost per QALY of $201,243 of EVT compared to the best standard of care. In the model-based analysis, using a societal perspective and a lifetime horizon, EVT dominated the standard of care; EVT was both more effective and less costly than the standard of care (−$91). When the time horizon was shortened to 1 year, EVT remains cost savings compared to standard of care (∼$15,376 per QALY gained with EVT). However, if the estimate of clinical effectiveness is 4% less than that demonstrated in ESCAPE, EVT is no longer cost savings compared to standard of care.

Results support the adoption of EVT as a treatment option for acute ischemic stroke, as the increase in costs associated with caring for EVT patients was recouped within the first year of stroke, and continued to provide cost savings over a patient’s lifetime.

Clinical Trial Registration: NCT01778335

To explore differences in proportion of food budget and total food expenditure by dwelling type.

A cross-sectional study using data from the Australian Bureau of Statistics 2015–2016 Household Expenditure Survey. Food expenditure was examined on multiple categories: fresh fruits, fresh vegetables, pre-prepared meals, meals in restaurants, hotels and clubs, and fast food and takeaway meals, using two-part models and zero-one inflated beta regression models. Dwelling types were categorised as separate house, semi-detached house, low-rise apartment and high-rise apartment.

Australia, 2015–2016.

Seven thousand three hundred and fifty-eight households from greater capital city areas.

Households living in high-rise apartments were estimated to allocate a greater proportion of their food budget to meals in restaurants, hotels and clubs, and to spend more (actual dollars) on that category, compared with other dwelling types. No substantial differences were estimated in the proportion of food budget allocated to the other food categories across dwelling types.

The dwelling type households live in may play a role in their food budget. Households living in a high-rise apartment may potentially spend more on meals in restaurants, hotels and clubs than those living in other dwelling types. Given the growth in urban population and the changes in living arrangements, findings point to the critical need for a better understanding of the influence of dwelling types on food expenditure and call for research investigating the relationship between the two.

Among the most disabling and fatal psychiatric illnesses, eating disorders (EDs) often manifest early in life, which encourages investigations into in utero and perinatal environmental risk factors. The objective of this study was to determine whether complications during pregnancy and birth and perinatal conditions are associated with later eating disorder risk in offspring and whether these associations are unique to EDs.

All individuals born in Denmark to Danish-born parents 1989–2010 were included in the study and followed from their 6th birthday until the end of 2016. Exposure to factors related to pregnancy, birth, and perinatal conditions was determined using national registers, as were hospital-based diagnoses of anorexia nervosa (AN), bulimia nervosa, and eating disorder not otherwise specified during follow-up. For comparison, diagnoses of depressive, anxiety, and obsessive-compulsive disorders were also included. Cox regression was used to compare hazards of psychiatric disorders in exposed and unexposed individuals.

1 167 043 individuals were included in the analysis. We found that similar to the comparison disorders, prematurity was associated with increased eating disorder risk. Conversely, patterns of increasing risks of EDs, especially in AN, with increasing parental ages differed from the more U-shaped patterns observed for depressive and anxiety disorders.

Our results suggest that pregnancy and early life are vulnerable developmental periods when exposures may influence offspring mental health, including eating disorder risk, later in life. The results suggest that some events pose more global transdiagnostic risk whereas other patterns, such as increasing parental ages, appear more specific to EDs.

Anorexia nervosa and bulimia nervosa are two severe eating disorders associated with high premature mortality, suicidal risk and serious medical complications. Transition between anorexia nervosa and bulimia nervosa over the illness course and familial co-aggregation of the two eating disorders imply aetiological overlap. However, genetic and environmental liabilities to the overlap are poorly understood. Quantitative genetic research using clinical diagnosis is needed.

We acquired a clinical diagnosis of anorexia nervosa (prevalence = 0.90%) and bulimia nervosa (prevalence = 0.48%) in a large population-based sample (N = 782 938) of randomly selected full-sisters and maternal half-sisters born in Sweden between 1970 and 2005. Structural equation modelling was applied to quantify heritability of clinically diagnosed anorexia nervosa and bulimia nervosa and the contributions of genetic and environmental effects on their overlap.

The heritability of clinically diagnosed anorexia nervosa and bulimia nervosa was estimated at 43% [95% confidence interval (CI) (36–50%)] and 41% (31–52%), respectively, in the study population, with the remaining variance explained by variance in unique environmental effects. We found statistically significant genetic [0.66, 95% CI (0.49–0.82)] and unique environmental correlations [0.55 (0.43–0.66)] between the two clinically diagnosed eating disorders; and their overlap was about equally explained by genetic and unique environmental effects [co-heritability 47% (35–58%)].

Our study supports shared mechanisms for anorexia nervosa and bulimia nervosa and extends the literature from self-reported behavioural measures to clinical diagnosis. The findings encourage future molecular genetic research on both eating disorders and emphasize clinical vigilance for symptom fluctuation between them.

Transition across eating disorder diagnoses is common, reflecting instability of specific eating disorder presentations. Previous studies have examined temporal stability of diagnoses in adult treatment-seeking samples but have not uniformly captured initial presentation for treatment. The current study examines transitions across eating disorder diagnostic categories in a large, treatment-seeking sample of individuals born in Sweden and compares these transitions across two birth cohorts and from initial diagnosis.

Data from Swedish eating disorders quality registers were extracted in 2013, including 9622 individuals who were seen at least twice from 1999 to 2013. Patterns of remission were examined in the entire sample and subsequently compared across initial diagnoses. An older (born prior to 1990) and younger birth cohort were also identified, and analyses compared these cohorts on patterns of diagnostic transition.

Although diagnostic instability was common, transition between threshold eating disorder diagnoses was infrequent. For all diagnoses, transition to remission was likely to occur following a diagnosis state that matched initial diagnosis, or through a subthreshold diagnostic state. Individuals in the younger cohort were more likely to transition to a state of remission than those in the older cohort.

Results indicate more temporal continuity in eating disorder presentations than suggested by previous research and highlight the importance of early detection and intervention in achieving remission.