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.
In November 2021, the COVID-19 pandemic death toll surpassed five million individuals. We applied Mendelian randomization including >3,000 blood proteins as exposures to identify potential biomarkers ...that may indicate risk for hospitalization or need for respiratory support or death due to COVID-19, respectively. After multiple testing correction, using genetic instruments and under the assumptions of Mendelian Randomization, our results were consistent with higher blood levels of five proteins GCNT4, CD207, RAB14, C1GALT1C1, and ABO being causally associated with an increased risk of hospitalization or respiratory support/death due to COVID-19 (ORs = 1.12-1.35). Higher levels of FAAH2 were solely associated with an increased risk of hospitalization (OR = 1.19). On the contrary, higher levels of SELL, SELE, and PECAM-1 decrease risk of hospitalization or need for respiratory support/death (ORs = 0.80-0.91). Higher levels of LCTL, SFTPD, KEL, and ATP2A3 were solely associated with a decreased risk of hospitalization (ORs = 0.86-0.93), whilst higher levels of ICAM-1 were solely associated with a decreased risk of respiratory support/death of COVID-19 (OR = 0.84). Our findings implicate blood group markers and binding proteins in both hospitalization and need for respiratory support/death. They, additionally, suggest that higher levels of endocannabinoid enzymes may increase the risk of hospitalization. Our research replicates findings of blood markers previously associated with COVID-19 and prioritises additional blood markers for risk prediction of severe forms of COVID-19. Furthermore, we pinpoint druggable targets potentially implicated in disease pathology.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Anorexia nervosa (AN) occurs nine times more often in females than in males. Although environmental factors likely play a role, the reasons for this imbalanced sex ratio remain unresolved. AN ...displays high genetic correlations with anthropometric and metabolic traits. Given sex differences in body composition, we investigated the possible metabolic underpinnings of female propensity for AN. We conducted sex‐specific GWAS in a healthy and medication‐free subsample of the UK Biobank (n = 155,961), identifying 77 genome‐wide significant loci associated with body fat percentage (BF%) and 174 with fat‐free mass (FFM). Partitioned heritability analysis showed an enrichment for central nervous tissue‐associated genes for BF%, which was more prominent in females than males. Genetic correlations of BF% and FFM with the largest GWAS of AN by the Psychiatric Genomics Consortium were estimated to explore shared genomics. The genetic correlations of BF%male and BF%female with AN differed significantly from each other (p < .0001, δ = −0.17), suggesting that the female preponderance in AN may, in part, be explained by sex‐specific anthropometric and metabolic genetic factors increasing liability to AN.
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.
Objective
Alterations in blood lipid concentrations in anorexia nervosa (AN) have been reported; however, the extent, mechanism, and normalization with weight restoration remain unknown. We conducted ...a systematic review and a meta‐analysis to evaluate changes in lipid concentrations in acutely‐ill AN patients compared with healthy controls (HC) and to examine the effect of partial weight restoration.
Method
A systematic literature review and meta‐analysis (PROSPERO: CRD42017078014) were conducted for original peer‐reviewed articles.
Results
Forty‐eight studies were eligible for review; 33 for meta‐analyses calculating mean differences (MD). Total cholesterol (MD = 22.7 mg/dL, 95% CI = 12.5, 33.0), high‐density lipoprotein (HDL; MD = 3.4 mg/dL, CI = 0.3, 7.0), low‐density lipoprotein (LDL; MD = 12.2 mg/dL, CI = 4.4, 20.1), triglycerides (TG; MD = 8.1 mg/dL, CI = 1.7, 14.5), and apolipoprotein B (Apo B; MD = 11.8 mg/dL, CI = 2.3, 21.2) were significantly higher in acutely‐ill AN than HC. Partially weight‐restored AN patients had higher total cholesterol (MD = 14.8 mg/dL, CI = 2.1, 27.5) and LDL (MD = 16.1 mg/dL, CI = 2.3, 30.0). Pre‐ versus post‐weight restoration differences in lipid concentrations did not differ significantly.
Discussion
We report aggregate evidence for elevated lipid concentrations in acutely‐ill AN patients compared with HC, some of which persist after partial weight restoration. This could signal an underlying adaptation or dysregulation not fully reversed by weight restoration. Although concentrations differed between AN and HC, most lipid concentrations remained within the reference range and meta‐analyses were limited by the number of available studies.
Resumen
Objetivo
En la anorexia nervosa (AN) han sido reportadas alteraciones en las concentraciones de lípidos sanguíneos; sin embargo, la extensión, mecanismo y normalización con la restauración del peso continúa aún desconocida. Hicimos una revisión sistemática y meta‐análisis para evaluar los cambios en las concentraciones de lípidos en pacientes agudamente enfermas de AN comparados con controles sanos (HC) y para examinar el efecto parcial de la restauración de peso.
Método
Una revisión sistemática de la literatura y meta‐análisis (PROSPERO: CRD42017078014) fueron llevados a cabo en artículos originales revisados por pares.
Resultados
Un total de cuarenta y ocho estudios fueron elegibles para revisión; 33 para meta‐análisis calculando las diferencias promedio (MD). Colesterol total (MD = 22.7 mg/dL, 95% CI = 12.5, 33.0), lipoproteína de alta densidad (HDL; MD = 3.4 mg/dL, CI = 0.3, 7.0), lipoproteína de baja densidad (LDL; MD = 12.2 mg/dL, CI = 4.4, 20.1), triglicéridos (TG; MD = 8.1 mg/dL, CI = 1.7, 14.5), y apolipoproteína B (Apo B; MD = 11.6 mg/dL, CI = 2.3, 21.2) fueron significativamente elevados en los pacientes agudamente enfermos de AN en comparación con los controles sanos (HC). Los pacientes con AN parcialmente recuperados de peso tuvieron niveles más elevados de colesterol total (MD = 14.8 mg/dL, CI = 2.1, 27.5) y de LDL (MD = 16.1 mg/dL, CI = 2.3, 30.0). Las diferencias pre‐ versus post‐ restauración de peso en las concentraciones de lípidos no difirieron significativamente.
Discusión
Reportamos evidencia agregada de concentraciones elevadas de lípidos en pacientes agudamente enfermos de AN comparados con controles sanos (HC), algunos de los cuales persisten después de la restauración parcial de peso. Esto podría señalar una adaptación subyacente o desregulación no completamente revertida por la restauración del peso. Aunque las concentraciones difirieron entre AN y HC, la mayoría de las concentraciones de lípidos permanecieron dentro del rango de referencia y los meta‐análisis fueron limitados por el número de estudios disponibles.
Background
Immune system dysfunction may be associated with eating disorders (ED) and could have implications for detection, risk assessment, and treatment of both autoimmune diseases and EDs. ...However, questions regarding the nature of the relationship between these two disease entities remain. We evaluated the strength of associations for the bidirectional relationships between EDs and autoimmune diseases.
Methods
In this nationwide population‐based study, Swedish registers were linked to establish a cohort of more than 2.5 million individuals born in Sweden between January 1, 1979 and December 31, 2005 and followed up until December 2013. Cox proportional hazard regression models were used to investigate: (a) subsequent risk of EDs in individuals with autoimmune diseases; and (b) subsequent risk of autoimmune diseases in individuals with EDs.
Results
We observed a strong, bidirectional relationship between the two illness classes indicating that diagnosis in one illness class increased the risk of the other. In women, the diagnoses of autoimmune disease increased subsequent hazards of anorexia nervosa (AN), bulimia nervosa (BN), and other eating disorders (OED). Similarly, AN, BN, and OED increased subsequent hazards of autoimmune diseases.Gastrointestinal‐related autoimmune diseases such as, celiac disease and Crohn's disease showed a bidirectional relationship with AN and OED. Psoriasis showed a bidirectional relationship with OED. The previous occurence of type 1 diabetes increased the risk for AN, BN, and OED. In men, we did not observe a bidirectional pattern, but prior autoimmune arthritis increased the risk for OED.
Conclusions
The interactions between EDs and autoimmune diseases support the previously reported associations. The bidirectional risk pattern observed in women suggests either a shared mechanism or a third mediating variable contributing to the association of these illnesses.
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.
Anxiety and depression symptoms are common in individuals with eating disorders. To study these co-occurrences, we need high-quality self-report questionnaires. The 19-item self-rated Comprehensive ...Psychopathological Rating Scale for Affective Syndromes (CPRS-S-A) is not validated in patients with eating disorders. We tested its factor structure, invariance, and differences in its latent dimensions.
Patients were registered by 45 treatment units in the Swedish nationwide Stepwise quality assurance database for specialised eating disorder care (n = 9509). Patients self-reported their anxiety and depression symptoms on the CPRS-S-A. Analyses included exploratory and confirmatory factor analyses (CFA) in split samples, and testing of invariance and differences in subscales across eating disorder types.
Results suggested a four-factor solution: Depression, Somatic and fear symptoms, Disinterest, and Worry. Multigroup CFA indicated an invariant factor structure. We detected the following differences: Patients with anorexia nervosa binge-eating/purging subtype scored the highest and patients with unspecified feeding and eating disorders the lowest on all subscales. Patients with anorexia nervosa or purging disorder show more somatic and fear symptoms than individuals with either bulimia nervosa or binge-eating disorder.
Our four-factor solution of the CPRS-S-A is suitable for patients with eating disorders and may help to identify differences in anxiety and depression dimensions amongst patients with eating disorders.
A recent study reported a positive genetic correlation between anorexia nervosa and insulin sensitivity using data from genome-wide association studies. Epidemiological studies have, on the other ...hand, suggested that bulimia nervosa and binge-eating disorder are associated with decreased insulin sensitivity. The aim of this study was to conduct a systematic review and meta-analysis of insulin sensitivity across the spectrum of eating disorders.
EMBASE, Medline, and PsycINFO were searched for all relevant studies published until January 2017, and retrieved studies were assessed for eligibility by two independent reviewers as per predefined inclusion criteria. The associations between eating disorder subtypes and insulin sensitivity were analysed separately. Individual effect sizes were standardized, and a meta-analysis was performed to calculate a pooled effect size using random effects.
Of 296 citations retrieved, 22 studies met the inclusion criteria, and 12 studies had appropriate data for meta-analysis. Using the random effects model, the pooled effect size (95% confidence interval) was 1.66 (0.79, 2.54) in people with anorexia nervosa (n = 340) and −0.57 (−0.80, −0.34) in people with bulimia nervosa (n = 120) and binge-eating disorders (n = 3241).
Anorexia nervosa is associated with increased insulin sensitivity whilst bulimia nervosa and binge-eating disorders are associated with decreased insulin sensitivity. The possible mechanism underpinning these findings needs to be determined.
Body composition is often altered in psychiatric disorders. Using genome-wide common genetic variation data, we calculate sex-specific genetic correlations amongst body fat %, fat mass, fat-free ...mass, physical activity, glycemic traits and 17 psychiatric traits (up to N = 217,568). Two patterns emerge: (1) anorexia nervosa, schizophrenia, obsessive-compulsive disorder, and education years are negatively genetically correlated with body fat % and fat-free mass, whereas (2) attention-deficit/hyperactivity disorder (ADHD), alcohol dependence, insomnia, and heavy smoking are positively correlated. Anorexia nervosa shows a stronger genetic correlation with body fat % in females, whereas education years is more strongly correlated with fat mass in males. Education years and ADHD show genetic overlap with childhood obesity. Mendelian randomization identifies schizophrenia, anorexia nervosa, and higher education as causal for decreased fat mass, with higher body fat % possibly being a causal risk factor for ADHD and heavy smoking. These results suggest new possibilities for targeted preventive strategies.
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