Abstract Background Bulimia nervosa (BN) is a serious mental illness with impulsivity as a cardinal symptom. Impulsivity contributes to various other, often comorbid, mental disorders, such as attention deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD). The aim of this study was to explore comorbidities of BN with ADHD and BPD as well as the contribution of impulsivity as an underlying trait linking these disorders. Methods Hundred and fifteen females with BN and 98 healthy matched controls (HC) (age range between 16 and 48 years) were assessed regarding adult and childhood-ADHD, personality disorders and impulsivity. Results Patients with BN were more impulsive (p < 0.001) and more often fulfilled criteria of childhood/adulthood ADHD (p < 0.001) than HC, and criteria of BPD than expected in the general population. Childhood-ADHD (p = 0.009) and BPD (p = 0.017) both were significant positive predictors for impulsivity scores found in patients with BN. Conclusion Comorbidity with ADHD and BPD often is prevalent in BN and associated with an increase in impulsivity, the latter being a relevant transdiagnostic trait. It might be beneficial to explore impulsivity as well as comorbidities in the clinical care of patients with BN. Level of evidence III Evidence obtained from well-designed cohort or case–control analytic studies.

OBJECTIVE:Assessment of the longer-term outcome of anorexia nervosa (AN) in female adolescent inpatients (N = 132). METHOD:A follow-up (mean 8.2 years) after treatment was conducted. A subsample of 39 patients with at least 10 years of follow-up (mean 14 years) was defined. RESULTS:Over the 8-year follow-up period, the body mass index (BMI) increased from 14.33 (1.65) to 19.04 kg/m2 (2.97; t[112] = 17.33, p < 0.001, d = 1.63), and BMI percentiles increased from 0.50 (1.14) to 24.96 (26.81; t[112] = 9.83, p < 0.001, d = 0.92). Remission was found in 32.5% (8-year total sample) and 48.6% (14-year subsample). In the 8-year total sample, 15.1% still had AN or had relapsed (8.1% in the 14-year subsample). A cross-over from AN to binge-eating disorder was rare. The main cross-over occurred from AN to an eating disorder not otherwise specified (37.5% and 27.0%, respectively). The standardized mortality ratio was 21.7. DISCUSSION:In the long run, eating disorder diagnoses decreased significantly. Although a considerable proportion of patients recovered from their eating disorder, the number of recovered patients remained limited, with long-term negative consequences in a large proportion of patients. Standardized mortality was excessive, calling for ever-better therapies. Additional studies are needed to show if improved therapies lead to a better long-term outcome.

OBJECTIVE:The new ICD-11 eating disorders (ED) guidelines are similar to the DSM-5 criteria. One difference to the DSM-5 is the inclusion of subjective binges in the definition of bulimia nervosa (BN) and binge-eating disorder (BED). The aim of this study was to identify differences between the ICD-11 guidelines and DSM-5 ED criteria, which could impact access to medical care and early treatment.METHOD:Data of 3863 ED inpatients who completed the Munich Eating and Feeding Disorder Questionnaire were analyzed using standardized diagnostic algorithms for DSM-5 and ICD-11.RESULTS:Agreement of diagnoses was high (Krippendorff's α = .88, 95% CI [.86, .89]) for anorexia nervosa (AN; 98.9%), BN (97.2%) and BED (100%), and lower for other feeding and eating disorders (OFED; 75.2%). Of the 721 patients with a DSM-5 OFED, 19.8% were diagnosed with AN, BN or BED by the ICD-11 diagnostic algorithm, reducing the number of OFED diagnoses. One-hundred and twenty-one patients received an ICD-11 diagnosis of BN or BED because of subjective binges.DISCUSSION:For over 90% of patients, applying either DSM-5 or ICD-11 diagnostic criteria/guidelines resulted in the same full-threshold ED diagnosis. Sub-threshold and feeding disorders exhibited a discrepancy of 25%.PUBLIC SIGNIFICANCE STATEMENT:For about 98% of inpatients, the ICD-11 and DSM-5 agree on the same specified eating disorder diagnosis. This is important when comparing diagnoses made by different diagnostic systems. Including subjective binges in the definition of bulimia nervosa and binge-eating disorder contributes to improved ED diagnoses. Clarifying the wording of diagnostic criteria at several places could further increase this agreement.

OBJECTIVE The objective of this study is to report on the 5.5-years outcome of anorexia nervosa (AN) in male adolescent inpatients and compare it to the outcome of female adolescent inpatients with AN. METHOD Diagnostic eating disorder outcome was assessed by the Structured Inventory of Anorexic and Bulimic Syndromes (DSM-IV) in 20 males and 20 females matched for AN diagnosis, age at treatment, and length of follow-up. For documentation, follow-up scores of the Eating Disorder Inventory and the Brief Symptom Inventory are reported. RESULTS Diagnostic outcome did not differ between sexes. Four male and six female participants had AN at follow-up. One male and four females had crossed to bulimia nervosa, and five males and three females to eating disorder not otherwise specified. Remission was found in 10 males and 7 females. Effect sizes were mostly small. At follow-up females had higher scores than males with large effect sizes for drive for thinness (Cohen's d = 0.86) and body dissatisfaction (d = 1.07). DISCUSSION Few significant sex differences were found. Additional research involving larger samples of males and a broader range of assessed outcomes (e.g., drive for muscularity) in both sexes is urgently needed.

Objective To assess the ability of psychotherapists to predict the future outcome for inpatients with anorexia nervosa (AN) and bulimia nervosa (BN). Method Psychotherapists rated the prognosis of the patient's eating disorder on a five point Likert scale on several dimensions at the end of inpatient treatment. Actual outcome was assessed about 10 years after treatment. The sample comprised 1,065 patients treated for AN, and 1,192 patients treated for BN. Results Psychotherapists' rating of their patient's prognosis was not better than chance for good outcome in AN and BN and for poor outcome in BN. Prediction of poor outcome in AN was somewhat better with approximately two thirds of correct predictions. In logistic regression analysis, psychotherapists' rating of the patients' prognosis for AN contributed to the explained variance of long-term outcome, increasing the variance explained from 7% (by conventional predictors) to 8% after including psychotherapists' prognosis. In BN, there was no significant contribution of psychotherapists' prognosis to overall prediction. Discussion Our current knowledge of risk and protective factors for the course of eating disorders is unsatisfying. More specialized research is urgently needed.

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

An overview of eating and feeding disorders according to the future criteria of the International Classification of Diseases (ICD-11) is presented, including information on differential diagnosis, epidemiology, etiology, pathogenesis as well as therapy. Binge-eating disorder is new and the most frequent eating disorder. While anorexia nervosa and bulimia nervosa mostly affect women, the gender ratio in binge-eating disorder is more balanced. Concerning etiology, socio-cultural, biological and psychological factors are discussed. Cognitive behavioral psychotherapy is the best-validated treatment for all three eating disorders. According to the German guidelines for treatment (2019), focal psychodynamic psychotherapy is also a treatment option for anorexia nervosa. Evidence for the positive effect of psychopharmacologic drugs in the treatment of anorexia nervosa is still lacking. Fluoxetine has been shown to have a limited effect in the treatment of bulimia nervosa.

Beim Jahreskongresses der Deutschen Gesellschaft für Psychiatrie, Psychotherapie, Psychosomatik und Nervenheilkunde (DGPPN) traf sich eine Arbeitsgruppe gerontologisch erfahrener Vertreterinnen und Vertreter aus Psychiatrie, psychosomatischer Medizin, Psychotherapie und Sozialmedizin zum Thema des Altersstereotyps. Die Ergebnisse der Beratung wurden in dem vorliegenden Positionspapier zusammengefasst.

BACKGROUND: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche.METHODS: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (,13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses.RESULTS: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early-and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early -onset AN.CONCLUSIONS: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.

Eating disorders and substance use disorders frequently co-occur. Twin studies reveal shared genetic variance between liabilities to eating disorders and substance use, with the strongest associations between symptoms of bulimia nervosa and problem alcohol use (genetic correlation [rg ], twin-based = 0.23-0.53). We estimated the genetic correlation between eating disorder and substance use and disorder phenotypes using data from genome-wide association studies (GWAS). Four eating disorder phenotypes (anorexia nervosa [AN], AN with binge eating, AN without binge eating, and a bulimia nervosa factor score), and eight substance-use-related phenotypes (drinks per week, alcohol use disorder [AUD], smoking initiation, current smoking, cigarettes per day, nicotine dependence, cannabis initiation, and cannabis use disorder) from eight studies were included. Significant genetic correlations were adjusted for variants associated with major depressive disorder and schizophrenia. Total study sample sizes per phenotype ranged from ~2400 to ~537 000 individuals. We used linkage disequilibrium score regression to calculate single nucleotide polymorphism-based genetic correlations between eating disorder- and substance-use-related phenotypes. Significant positive genetic associations emerged between AUD and AN (rg = 0.18; false discovery rate q = 0.0006), cannabis initiation and AN (rg = 0.23; q < 0.0001), and cannabis initiation and AN with binge eating (rg = 0.27; q = 0.0016). Conversely, significant negative genetic correlations were observed between three nondiagnostic smoking phenotypes (smoking initiation, current smoking, and cigarettes per day) and AN without binge eating (rgs = -0.19 to -0.23; qs < 0.04). The genetic correlation between AUD and AN was no longer significant after co-varying for major depressive disorder loci. The patterns of association between eating disorder- and substance-use-related phenotypes highlights the potentially complex and substance-specific relationships among these behaviors.

OBJECTIVE:To report on the long-term mortality of eating disorders in male inpatients.METHOD:Crude mortality rates (CMR) and standardized mortality ratios (SMR) were computed for a large sample of males (147 anorexia nervosa [AN], 81 bulimia nervosa [BN], 110 eating disorder not otherwise specified [ED-NOS]; DSM-IV). In addition, a survival analysis from onset of eating disorder to death or end of observation was computed.RESULTS:CMR was 12.9% in AN, 11.1% in BN, and 6.4% in ED-NOS. Standardized mortality was significantly elevated in males with AN (SMR = 5.91; 95% confidence interval 3.56-9.23) as well as ED-NOS (SMR = 3.40; 95% confidence interval 1.37-7.01) but not in males with BN (SMR = 1.88; 95% confidence interval 0.86-3.58). Males with AN died sooner after onset of eating disorder than males with BN or ED-NOS.DISCUSSION:Mortality in male inpatients with eating disorder is high, especially in AN. There is need for developing more effective treatments to achieve better outcome.

Anorexia Nervosa (AN) is a serious mental illness that often has an onset during adolescence. AN is characterized by emaciation, fear of gaining weight despite being underweight, and the highest mortality rate of all psychiatric illnesses. AN is highly heritable and recent meta-analyses in 3,495 anorexia nervosa cases and 10,982 controls has identified a region on chromosome 12 at genome-wide significance, significant common genetic heritability, and genetic correlations with both psychiatric and metabolic traits. AN symptoms and personality traits tend to be present in unaffected family members of the patients, suggesting that certain shared genetic factors within each family may contribute to the unique risk underlying an affected individual's phenotype. To gain insight into the role that unique, family-specific variants may play in the development of AN, we performed whole genome sequencing analysis (Complete Genomics) and extensive annotation of high quality variants (Cypher Genomics, SG-Advisor, ANNOVAR) to search for genetic variants that may influence AN risk in six individuals, consisting of two maternally-linked cousins with severe AN and their parents. We focused on maternally-inherited shared segments; the preferred transmission model for variant filtering was the dominant model. We reviewed results from the Psychiatric Genomic Consortium AN GWAS and other -omic databases at identified genes. Of the approximately 5.3 million variants per individual that were analyzed, 494,712 were shared Identical-By-Descent (IBD) by the cousin pair based on maternally derived haplotypes. Based on extensive genetic variant annotations within maternally inherited shared segments, we identified variants in TTC22, MRPS9, DNAJC30, HEPACAM2, USP20, ESF1, and CDK5RAP1. Multiple prediction methods suggest that six of these variants are likely to affect protein function. The region proximal to MRPS9 exhibits an excess of nominally significant findings in the PGC AN GWAS, and eQTLs to MRPS9 and to an uncharacterized antisense gene in many tissues. MRPS9 SNPs are associated in blood with 4-androsten-3beta,17beta-diol disulfate 2 and dehydroisoandrosterone sulfate (a metabolite and a precursor of steroid sex hormones, respectively). By capitalizing on the homogeneity of the disease presentation and the genomic makeup among two cousins with a diagnosis of restricting-type AN, we exploited whole genome sequence analysis and variant annotation approaches to identify a set of novel variants and genes that may influence AN. Our results suggest that there may be utility in whole genome sequencing of families with affected individuals to detect variants that contribute to a complex disease such as AN.

Genetic influences on psychiatric disorders transcend diagnostic boundaries, suggesting substantial pleiotropy of contributing loci. However, the nature and mechanisms of these pleiotropic effects remain unclear. We performed analyses of 232,964 cases and 494,162 controls from genome-wide studies of anorexia nervosa, attention-deficit/hyper-activity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, and Tourette syndrome. Genetic correlation analyses revealed a meaningful structure within the eight disorders, identifying three groups of inter-related disorders. Meta-analysis across these eight disorders detected 109 loci associated with at least two psychiatric disorders, including 23 loci with pleiotropic effects on four or more disorders and 11 loci with antagonistic effects on multiple disorders. The pleiotropic loci are located within genes that show heightened expression in the brain throughout the lifespan, beginning prenatally in the second trimester, and play prominent roles in neurodevelopmental processes. These findings have important implications for psychiatric nosology, drug development, and risk prediction.

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness(1), affecting 0.9-4% of women and 0.3% of men(2-4), with twin-based heritability estimates of 50-60%(5). Mortality rates are higher than those in other psychiatric disorders(6), and outcomes are unacceptably poor(7). Here we combine data from the Anorexia Nervosa Genetics Initiative (ANGI)(8,9) and the Eating Disorders Working Group of the Psychiatric Genomics Consortium (PGC-ED) and conduct a genome-wide association study of 16,992 cases of anorexia nervosa and 55,525 controls, identifying eight significant loci. The genetic architecture of anorexia nervosa mirrors its clinical presentation, showing significant genetic correlations with psychiatric disorders, physical activity, and metabolic (including glycemic), lipid and anthropometric traits, independent of the effects of common variants associated with body-mass index. These results further encourage a reconceptualization of anorexia nervosa as a metabo-psychiatric disorder. Elucidating the metabolic component is a critical direction for future research, and paying attention to both psychiatric and metabolic components may be key to improving outcomes.

OBJECTIVE:This study examined a hypothesized pathway by which interoceptive dysfunction accounted for associations between personality features (harm avoidance, self-directedness, and perfectionism) and anorexia nervosa (AN) severity (indicated by drive for thinness, eating disorder-related preoccupations and rituals, and body mass index).METHOD:The study sample (n = 270, mean age = 28.47, 95.2% female, 98% White/Caucasian) consisted of probands and biological relatives who met DSM-IV criteria for lifetime diagnoses of AN (omitting criterion D, amenorrhea) drawn from the Price Foundation Anorexia Nervosa Affected Relative Pairs Study (AN-ARP). Participants completed measures assessing personality, interoceptive dysfunction, and eating pathology.RESULTS:Associations between personality features of low self-directedness and high perfectionism and indicators of AN severity (drive for thinness and eating disorder-related preoccupations and rituals) were significant, as were the hypothesized indirect pathways through interoceptive dysfunction. Neither harm avoidance nor body mass index was significantly related to other study variables, and the proposed indirect pathways involving these variables were not significant.DISCUSSION:Findings suggest that certain personality features may relate to AN severity, in part, through their associations with interoceptive dysfunction. Future research should examine prospective associations and the value of interventions targeting interoceptive dysfunction for interrupting the link between personality and AN severity.