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Highlights d Three groups of highly genetically-related disorders among 8 psychiatric disorders d Identified 109 pleiotropic loci affecting more than one disorder d Pleiotropic genes show heightened expression beginning in 2 nd prenatal trimester d Pleiotropic genes play prominent roles in neurodevelopmental processes Authors Cross-Disorder Group of the Psychiatric Genomics Consortium

Objective To conduct a genome-wide association study (GWAS) of anorexia nervosa and to calculate genetic correlations with a series of psychiatric, educational, and metabolic phenotypes. Method Following uniform quality control and imputation using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, we performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression (LDSC) was used to calculate genome-wide common variant heritability [ hSNP2, partitioned heritability, and genetic correlations (rg)] between anorexia nervosa and other phenotypes. Results Results were obtained for 10,641,224 single nucleotide polymorphisms (SNPs) and insertion-deletion variants with minor allele frequency > 1% and imputation quality scores > 0.6. The hSNP2 of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. We identified one genome-wide significant locus on chromosome 12 (rs4622308, p=4.3×10−9) in a region harboring a previously reported type 1 diabetes and autoimmune disorder locus. Significant positive genetic correlations were observed between anorexia nervosa and schizophrenia, neuroticism, educational attainment, and high density lipoprotein (HDL) cholesterol, and significant negative genetic correlations between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes. Conclusions Anorexia nervosa is a complex heritable phenotype for which we have found the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. Our results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

Objective: the aim of this longitudinal study was to evaluate the impact of COVID-19 epidemic on Eating Disorders (EDs) patients, considering the role of pre-existing vulnerabilities. Method: 74 patients with Anorexia Nervosa (AN) or Bulimia Nervosa (BN) and 97 healthy controls (HCs) were evaluated before lockdown (T1) and during lockdown (T2). Patients were also evaluated at the beginning of treatment (T0). Questionnaires were collected to assess psychopathology, childhood trauma, attachment style, and COVID-19-related post-traumatic symptoms. Results: A different trend between patients and HCs was observed only for pathological eating behaviors. Patients experienced increased compensatory exercise during lockdown; BN patients also exacerbated binge eating. Lockdown interfered with treatment outcomes: the descending trend of ED-specific psychopathology was interrupted during the epidemic in BN patients. Previously remitted patients showed re-exacerbation of binge eating after lockdown. Household arguments and fear for the safety of loved ones predicted increased symptoms during the lockdown. BN patients reported more severe COVID-19-related post-traumatic symptomatology than AN and HCs, and these symptoms were predicted by childhood trauma and insecure attachment. Discussion: COVID-19 epidemic significantly impacted on EDs, both in terms of post-traumatic symptomatology and interference with the recovery process. Individuals with early trauma or insecure attachment were particularly vulnerable.

The present preliminary findings suggest that when motivation to eat is generated by the availability of highly palatable food and not by food deprivation, a peripheral activation of two endogenous rewarding chemical signals is observed. Future research should confirm and extend our results to better understand the phenomenon of hedonic eating, which influences food intake and, ultimately, body mass.

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Objective Research evidence suggests the need to identify treatments based on a more precise characterization of psychopathology and psychiatric comorbidity in anorexia nervosa. Network analysis provides a new method to conceptualize psychopathology. We use this approach to investigate the relationships between eating disorder and general psychiatric symptoms in adolescents with anorexia nervosa. Methods Four‐hundred and five adolescents with anorexia nervosa and illness duration less than 3 years were consecutively recruited from those admitted to inpatient treatment. They completed the following questionnaires: the Eating Disorder Inventory‐3, the Multidimensional Anxiety Scale for Children, the Children's Depression Inventory, and the Youth Self Report. A network analysis was conducted, including eating psychopathology measures, anxiety and depressive symptoms, and obsessive–compulsive and post‐traumatic stress problems. We employ a novel approach, the bridge function, to identify symptom clusters. Results Depression symptoms and personal alienation were the nodes with the highest centrality in the network, followed by asceticism, post‐traumatic stress problems, drive to thinness, low self‐esteem, and anxiety physical symptoms. Three symptom clusters (relative to eating disorder psychopathology, self‐esteem problems, and internalizing difficulties) were identified. Depression symptoms, personal alienation, low self‐esteem, and interoceptive deficits showed the highest bridge centrality. Besides eating disorder core symptoms, negative affect and internalizing symptoms seem to contribute to anorexia nervosa psychopathology independently from illness duration effects. Discussion These findings suggest that anorexia nervosa is characterized by a broad psychopathological spectrum rather than the mere eating disorder core symptoms, confirm the need to re‐conceptualize psychiatric comorbidity in this disorder, and provide intriguing diagnostic and therapeutic implications.

Objective Network theory considers mental disorders as the product of symptom interaction. A growing number of studies employing this methodology has been conducted in eating disorders (EDs). We aimed to review those studies to provide evidence and limitations for a novel conceptualisation of EDs. Methods According to PRISMA guidelines and PICOS criteria, studies eligible for inclusion were those employing network analysis in people with a clinically defined diagnosis of ED. Twenty‐five studies were included and were analysed in relation to diagnosis, comorbidity, and treatment outcome. Results Despite the central role of overvaluation of body shape and weight and cognitive restraint across ED diagnoses, ineffectiveness, interoceptive awareness and affective problems appear central symptoms. Ineffectiveness and interoceptive awareness emerge as bridge symptoms promoting comorbidity in people with anorexia nervosa and in mixed ED samples. Although few studies assessed treatment outcome, there is evidence supporting the predictive role of central network nodes. Conclusions Ineffectiveness, interoceptive ability and affective problems may be included in the core ED psychopathology, in addition to ED‐specific symptoms. Network analysis is a promising method to reconceptualize comorbidity. Future studies are recommended to include general psychopathology in ED networks, to assess connections with the external field and clinical meaning of network connectivity.