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The predictive performance of polygenic scores (PGS) is largely dependent on the number of samples available to train the PGS. Increasing the sample size for a specific phenotype is expensive and takes time, but this sample size can be effectively increased by using genetically correlated phenotypes. We propose a framework to generate multi-PGS from thousands of publicly available genome-wide association studies (GWAS) with no need to individually select the most relevant ones. In this study, the multi-PGS framework increases prediction accuracy over single PGS for all included psychiatric disorders and other available outcomes, with prediction R 2 increases of up to 9-fold for attention-deficit/hyperactivity disorder compared to a single PGS. We also generate multi-PGS for phenotypes without an existing GWAS and for case-case predictions. We benchmark the multi-PGS framework against other methods and highlight its potential application to new emerging biobanks. Polygenic scores (PGS) have high potential for clinical use but are currently underpowered for many applications. Here, the authors develop an approach that leverages an agnostic library of hundreds of PGS to increase prediction of complex diseases and other traits. This multi-PGS framework is ideal for emerging biobank data.

Eating disorders (anorexia nervosa, bulimia nervosa and binge-eating disorder) are a heterogeneous class of complex illnesses marked by weight and appetite dysregulation coupled with distinctive behavioral and psychological features. Our understanding of their genetics and neurobiology is evolving thanks to global cooperation on genome-wide association studies, neuroimaging, and animal models. Until now, however, these approaches have advanced the field in parallel, with inadequate cross-talk. This review covers overlapping advances in these key domains and encourages greater integration of hypotheses and findings to create a more unified science of eating disorders. We highlight ongoing and future work designed to identify implicated biological pathways that will inform staging models based on biology as well as targeted prevention and tailored intervention, and will galvanize interest in the development of pharmacologic agents that target the core biology of the illnesses, for which we currently have few effective pharmacotherapeutics. Eating disorders are prevalent and, in far too many cases, fatal. This review covers advances in genetics, neuroimaging, and animal models, and encourages a more unified science of eating disorders.

Individuals with ADHD are at increased risk for poor occupational outcomes. Educational attainment and psychiatric comorbidity may be important contributing factors for these outcomes, but the role of these factors is not well characterized. This study aimed to investigate the associations between ADHD and occupational outcomes, and to examine the influence of educational attainment, comorbid developmental disorders and intellectual disability on these associations. We linked the Swedish population graduating from compulsory school 1998-2008 (N = 1.2 millions) to population-wide register-based data on clinical psychiatric diagnoses and medications, objective annual measures of educational, and occupational outcomes. Individuals were followed for between 6 to 16 years after graduation. Individuals with ADHD had annually on average 17 percent lower income, ratio = 0.83 (95% CI 0.83-0.84), 12.19 (11.89-12.49) more days of unemployment, and a higher likelihood of receiving disability pension, odds-ratio = 19.0 (18.4-19.6), compared to controls. Comorbid diagnoses of intellectual disability and developmental disorder explained most of the association between ADHD and disability pension, while lifetime educational attainment partially explained associations between ADHD and all occupational outcomes. Analyses of occupational trajectories found that income was lower and unemployment elevated relative to controls with the same educational attainment. Higher educational attainment correlated with higher income similarly among individuals with ADHD and controls after accounting for individual background factors. The occupational burden associated with ADHD is substantial. Comorbid developmental disorders, intellectual disability and educational difficulties (e.g., failing grades) from childhood to adulthood are important factors to consider when designing interventions to improve occupational outcomes in individuals with ADHD.

Individual-level longitudinal data on biological, behavioural, and social dimensions are becoming increasingly available. Typically, these data are analysed using mixed effects models, with the result summarised in terms of an average trajectory plus measures of the individual variations around this average. However, public health investigations would benefit from finer modelling of these individual variations which identify not just one average trajectory, but several typical trajectories. If evidence of heterogeneity in the development of these variables is found, the role played by temporally preceding (explanatory) variables as well as the potential impact of differential trajectories may have on later outcomes is often of interest. A wide choice of methods for uncovering typical trajectories and relating them to precursors and later outcomes exists. However, despite their increasing use, no practical overview of these methods targeted at epidemiological applications exists. Hence we provide: (a) a review of the three most commonly used methods for the identification of latent trajectories (growth mixture models, latent class growth analysis, and longitudinal latent class analysis); and (b) recommendations for the identification and interpretation of these trajectories and of their relationship with other variables. For illustration, we use longitudinal data on childhood body mass index and parental reports of fussy eating, collected in the Avon Longitudinal Study of Parents and Children.

Background Eating disorders (EDs) are common amongst women; however, no research has specifically investigated the lifetime/12-month prevalence of eating disorders amongst women in mid-life (i.e., fourth and fifth decade of life) and the relevant longitudinal risk factors. We aimed to investigate the lifetime and 12-month prevalence of EDs and lifetime health service use and to identify childhood, parenting, and personality risk factors. Methods This is a two-phase prevalence study, nested within an existing longitudinal community-based sample of women in mid-life. A total of 5658 women from the UK Avon Longitudinal Study of Parents and Children (ALSPAC; enrolled 20 years earlier) participated. ED diagnoses were obtained using validated structured interviews. Weighted analyses were carried out accounting for the two-phase methodology to obtain prevalence figures and to carry out risk factor regression analyses. Results By mid-life, 15.3% (95% confidence intervals, 13.5–17.4%) of women had met criteria for a lifetime ED. The 12-month prevalence of EDs was 3.6%. Childhood sexual abuse was prospectively associated with all binge/purge type disorders and an external locus of control was associated with binge-eating disorder. Better maternal care was protective for bulimia nervosa. Childhood life events and interpersonal sensitivity were associated with all EDs. Conclusions By mid-life a significant proportion of women will experience an ED, and few women accessed healthcare. Active EDs are common in mid-life, both due to new onset and chronic disorders. Increased awareness of the full spectrum of EDs in this stage of life and adequate service provision is important. This is the first study to investigate childhood and personality risk factors for full threshold and sub-threshold EDs and to identify common predictors for full and sub-threshold EDs. Further research should clarify the role of preventable risk factors on both full and sub-threshold EDs.

This study examined associations between the composition and diversity of the intestinal microbiota and measures of depression, anxiety, eating disorder psychopathology, stress, and personality in a group of healthy adult females. Female participants (n = 91) ages 19-50 years with BMI 18.5-25 kg/m2 were recruited from central North Carolina between July 2014 and March 2015. Participants provided a single fecal sample and completed an online psychiatric questionnaire that included five measures: (i) Beck Anxiety Inventory; (ii) Beck Depression Inventory-II; (iii) Eating Disorder Examination-Questionnaire; (iv) Perceived Stress Scale; and (v) Mini International Personality Item Pool. Bacterial composition and diversity were characterized by Illumina sequencing of the 16S rRNA gene, and associations were examined using Kendall's tau-b correlation coefficient, in conjunction with Benjamini and Hochberg's False Discovery Rate procedure. We found no significant associations between microbial markers of gut composition and diversity and scores on psychiatric measures of anxiety, depression, eating-related thoughts and behaviors, stress, or personality in a large cohort of healthy adult females. This study was the first specifically to examine associations between the intestinal microbiota and psychiatric measures in healthy females, and based on 16S rRNA taxonomic abundances and diversity measures, our results do not suggest a strong role for the enteric microbe-gut-brain axis in normal variation on responses to psychiatric measures in this population. However, the role of the intestinal microbiota in the pathophysiology of psychiatric illness may be limited to more severe psychopathology.

Binge eating disorder (BED) is characterized by regular binge eating episodes during which individuals ingest comparably large amounts of food and experience loss of control over their eating behaviour. The worldwide prevalence of BED for the years 2018–2020 is estimated to be 0.6–1.8% in adult women and 0.3–0.7% in adult men. BED is commonly associated with obesity and with somatic and mental health comorbidities. People with BED experience considerable burden and impairments in quality of life, and, at the same time, BED often goes undetected and untreated. The aetiology of BED is complex, including genetic and environmental factors as well as neuroendocrinological and neurobiological contributions. Neurobiological findings highlight impairments in reward processing, inhibitory control and emotion regulation in people with BED, and these neurobiological domains are targets for emerging treatment approaches. Psychotherapy is the first-line treatment for BED. Recognition and research on BED has increased since its inclusion into DSM-5; however, continuing efforts are needed to understand underlying mechanisms of BED and to improve prevention and treatment outcomes for this disorder. These efforts should also include screening, identification and implementation of evidence-based interventions in routine clinical practice settings such as primary care and mental health outpatient clinics.Binge eating disorder is an eating disorder that is characterized by loss of control of eating behaviour and episodes of eating very large amounts of food. This Primer discusses the epidemiology, mechanisms, diagnosis and treatment of binge eating disorder.

The current obesity epidemic is a major worldwide health concern. Despite the consensus that the brain regulates energy homeostasis, the neural adaptations governing obesity are unknown. Using a combination of high-throughput single-cell RNA sequencing and longitudinal in vivo two-photon calcium imaging, we surveyed functional alterations of the lateral hypothalamic area (LHA)–a highly conserved brain region that orchestrates feeding–in a mouse model of obesity. The transcriptional profile of LHA glutamatergic neurons was affected by obesity, exhibiting changes indicative of altered neuronal activity. Encoding properties of individual LHA glutamatergic neurons were then tracked throughout obesity, revealing greatly attenuated reward responses. These data demonstrate how diet disrupts the function of an endogenous feeding suppression system to promote overeating and obesity.

Eating disorders are complex heritable conditions influenced by both genetic and environmental factors. Given the progress of genomic discovery in anorexia nervosa, with the identification of the first genome-wide significant locus, as well as animated discussion of epigenetic mechanisms in linking environmental factors with disease onset, our goal was to conduct a systematic review of the current body of evidence on epigenetic factors in eating disorders to inform future directions in this area. Following PRISMA guidelines, two independent authors conducted a search within PubMed and Web of Science and identified 18 journal articles and conference abstracts addressing anorexia nervosa (n = 13), bulimia nervosa (n = 6), and binge-eating disorder (n = 1), published between January 2003 and October 2017. We reviewed all articles and included a critical discussion of field-specific methodological considerations. The majority of epigenetic analyses of eating disorders investigated methylation at candidate genes (n = 13), focusing on anorexia and bulimia nervosa in very small samples with considerable sample overlap across published studies. Three studies used microarray-based technologies to examine DNA methylation across the genome of anorexia nervosa and binge-eating disorder patients. Overall, results were inconclusive and were primarily exploratory in nature. The field of epigenetics in eating disorders remains in its infancy. We encourage the scientific community to apply methodologically sound approaches using genome-wide designs including epigenome-wide association studies (EWAS), to increase sample sizes, and to broaden the focus to include all eating disorder types.

Eating behaviours in childhood are considered as risk factors for eating disorder behaviours and diagnoses in adolescence. However, few longitudinal studies have examined this association. We investigated associations between childhood eating behaviours during the first ten years of life and eating disorder behaviours (binge eating, purging, fasting and excessive exercise) and diagnoses (anorexia nervosa, binge eating disorder, purging disorder and bulimia nervosa) at 16 years. Data on 4760 participants from the Avon Longitudinal Study of Parents and Children were included. Longitudinal trajectories of parent-rated childhood eating behaviours (8 time points, 1.3-9 years) were derived by latent class growth analyses. Eating disorder diagnoses were derived from self-reported, parent-reported and objectively measured anthropometric data at age 16 years. We estimated associations between childhood eating behaviours and eating disorder behaviours and diagnoses, using multivariable logistic regression models. Childhood overeating was associated with increased risk of adolescent binge eating (risk difference, 7%; 95% CI 2 to 12) and binge eating disorder (risk difference, 1%; 95% CI 0.2 to 3). Persistent undereating was associated with higher anorexia nervosa risk in adolescent girls only (risk difference, 6%; 95% CI, 0 to 12). Persistent fussy eating was associated with greater anorexia nervosa risk (risk difference, 2%; 95% CI 0 to 4). Our results suggest continuities of eating behaviours into eating disorders from early life to adolescence. It remains to be determined whether childhood eating behaviours are an early manifestation of a specific phenotype or whether the mechanisms underlying this continuity are more complex. Findings have the potential to inform preventative strategies for eating disorders.