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Introduction Even though international guidelines suggest that psychoeducation for carers should be provided systematically, it remains insufficiently available in psychiatry (1), including for eating disorders (EDs). The complicated interplay of factors contributing to the maintenance of EDs, including family/carer influences, highlights the importance of carer interventions within ED treatment (2). Carer interventions demonstrate positive outcomes for carers themselves, though are also hypothesised to benefit the patient indirectly. The BREF programme is a short, early and systematic single-family psycho-educational programme. The BREF programme is already proven to be effective for other mental disorders (3) Objectives The aim of this study is to adapt the BREF programme to the specific needs of carers of patients eating disorders (ED).The main objective was to identify the issues in the experience of the disorder that are most important to carers and which should be the focus of the BREF programme for cares of patients with eating disorders. Methods Twenty-eight topics relating to difficulties commonly encountered by carers of patients with eating disorders were identified by a group including mental health professionals with expertise in these disorders, patients and their relatives. The topics tested are illustrated by 2 decks of cards presented to the participants; the first concerns the problems frequently encountered by users living with ED and the other the problems frequently encountered by their carers. The 2 decks were tested by the participants to the first 15 sessions of the BREF ED programme run from January to July 2023 as part of the pilot conducted in a university-hospital department specialised in eating disorders. Results 30 participants participanted in the study. The 10 most frequently selected topics relating to patient problems were, in descending order: relative’s fear and anxiety; relative’s false-self functioning; ambivalence towards care; dysmorphophobia; food restrictions; relative’s hyperactivity; eating disorders; denial of symptoms; perfectionism; malnutrition. The 10 most frequently selected topics concerning the issues of carers were: social withdrawal; difficulty navigating care; fatigue/helplessness; disruption to family life as a result of the illness; guilt; right attitude to have with the ill relative; fear for your loved one’s future; fragility of the relative; not knowing/understanding the care their relative is receiving; cost of care and food expenses. Conclusions The priority topics highlighted in this study helped to identify relevant content for the BREF programme adapted to the context of eating disorders. This programme appears to be a promising way of responding to the concerns and information needs of carers of patients with ED. In this regard, it addresses a major shortcoming in the organisation of mental health services. Disclosure of Interest None Declared

Introduction Anorexia nervosa (AN) is a severe and chronic psychiatric disorder, resulting from a voluntary food restriction, vomiting, use of laxatives and excessive exercises, leading in dramatic weight loss and high mortality. AN is a multifactorial disease involving genetic and epigenetic factors supporting that AN is a metabo-psychiatric disorder. The molecular mechanisms involved in the etiology of AN remain unclear. One work reported gene expression by RNA sequencing in peripheral blood before and after weight restoration in 6 AN patients (Kim 2013), and one RNA sequencing in human iiPSC-derived neurons from 4 patients and 4 controls (Negraes 2017). To date, the profile of expression of genes and proteins in AN is undetermined. Objectives In this study, our goal is to identify specific gene expression signatures from circulating blood nuclear cells to decipher the pathophysiology of AN and characterize biomarkers that can be used for diagnostic or prognostic of AN. Methods All consented participants are recruited at Sainte-Anne Hospital, Paris, France, using DSM5 criteria. They had a blood draw in Paxgene tube for the collection of RNAs. Total RNA was extracted from peripheral blood mononuclear cells of 15 patients suffering of AN and 15 healthy controls. All messenger RNAs are sequenced on a Novaseq plateform. Reads are aligned to the human genome 19 and statistical analyses on the read counts for differentially expressed genes are computed with DESeq2. Results The total RNA sequencing allows us to identify 673 dysregulates genes (p adjusted value 1,5). Among them, 248 are down-regulated and 425 are up-regulated genes in AN patients compared to controls. From them, 151 transcripts are annotated as pseudogene and 45 are referenced as antisense RNA. Of the 522 remaining transcripts, 424 correspond to a transcript or protein annotated by HGNC and ENSEMBL and 93 are known pseudogenes. A large number of proteins resulting from the expression of deregulated genes interact with each other and form a statistically enriched network impacting biological processes. They are mainly increased and acting in the cellular machinery allowing protein synthesis (biological process: transcription, ribosome, spliceosome and mitochondria). In contrast, down-regulated genes present an enrichment in genes involved in immunity pathways. Finally, several genes are also expressed in the brain. We observed a significant enrichment of genes expressed in the blood and brain tissues. Conclusions We identify specific profiles of gene expression in AN. Several genes are both blood and brain tissue expression. Some genes are good candidates for biomarker of the diagnostic in AN that need to be investigated in a longitudinal study to evaluate their useful as prognostic biomarker of AN. This work is supported by Fondation de France & Fédération Recherche sur le Cerveau. Disclosure of Interest None Declared

Introduction Anorexia nervosa (AN) is a complex mental disorder mainly characterized by a voluntary food restriction and excessive physical activity resulting in dramatic weight loss. Changes in the brain-derived neurotropic factor (BDNF) have been reported in AN patients compared to controls. According to meta-analysis, functional variant rs6265 Val66Met of the BDNF gene has been found genetically associated to AN. We also reported an association of this functional variant and electrodermal response to images of thinness suggesting an association between rs6265 and a reward effect of weight loss in AN. In animal models, BDNF modulates negatively the central control of food intake and its injection in rodents induces weight loss and anorexia. Thus, besides its function on neuronal survival, synaptic plasticity and mood, BDNF was also reported to have a metabolic effect via both central nervous system and peripheral organs, which makes BDNF a good candidate for AN diagnosis biomarker. Objectives Our study investigates the levels of expression of Bdnf, gene and protein, taking advantage of the mouse AN-like model by measuring Bdnf levels in specific brain areas and blood in food-restricted and refeed animals. Methods We used a mouse AN-like model combining a phase of chronic food restriction (50%) during 15 days followed by an ad libitum refeeding period of one week. Female mice have or not access to a running with wheel to create a similar metabolic environment that those patients suffering from AN during restriction and recovery once hospitalised. The Bdnf mRNA and protein levels were measured in samples of blood and brain regions (prefrontal cortex, hippocampus, hypothalamus, dorsal striatum, nucleus Accumbens, ventral tegmental area and amygdala) using quantitative PCR and ELISA methods in the different groups of mice (ad libitum, ad libitum with wheel, food restriction and food restriction with wheel). Statistical analysis will compare the measures for different samples by one-way or two-way ANOVAs depending the group of animals or brain regions and blood. Results To date, no difference of the level of transcription for Bdnf was observed between the different groups of mice (ad libitum, ad libitum with wheel, food restriction and food restriction with wheel) in the prefrontal cortex, hippocampus and hypothalamus. We expect significant differences of Bdnf expression in the other brain regions of interest for the food restricted animals with or without the wheel compared to ad libitum animals. We expect also differences in the level of expression of Bdnf in fasted animals compared to the refeed animals. Conclusions The BDNF could represent a potential biomarker of AN for the diagnostic and the prognosis in the evolution to the remission when weight recover and thus will allow a better understanding of the aetiology of AN. This study is supported by Fédération pour la Recherche sur le Cerveau. Disclosure of Interest None Declared

Introduction Anorexia nervosa (AN) is a complex psychiatric disorder characterized by a persistant decrease in food intake leading to dramatic weight loss and energy deficit. The ghrelin system is a key regulator of appetite and food intake across species. LEAP-2, a recently discovered ghrelin antagonist, appears to be up-regulated in obesity and opposes to the orexigenic drive of ghrelin. The evolution of LEAP-2 levels could be an interesting insight to reflect the regulation of appetite in eating disorders such as anorexia nervosa (AN). Objectives We tested this hypothesis and here provide the first study exploring the ghrelin and LEAP-2 regulation in long-term food restriction followed by refeeding in both mice and patients suffering from AN. Methods Using a translational strategy, we compared the regulation of ghrelin and LEAP-2 concentrations in blood during food restriction and after refeeding i/ in female mice exposed to a 14 days protocol combining quantitative food restriction and running wheel activity followed by 10 days of progressive refeeding; ii/ in an ongoing longitudinal study of patients with AN evaluated before and after refeeding (n=30) as well as 6 months after hospital discharge to evaluate if the weight gain was stable (n=7) or unstable (n=10). Plasma concentrations of ghrelin and LEAP-2 were measured with selective immunoassays. Results Long-term food restriction in mice was associated with increased ghrelin (p

Abstract Body representation distortion (BRD) is a core criterion of Anorexia Nervosa (AN), and is usually assessed subjectively, focusing on body shape. We aimed to develop a new assessment to evaluate body representation independently from socially-mediated body image, on a body part with low emotional salience (hands). In a monocentric open label pilot study, we measured hand representations based on explicit (verbal) and implicit (tactile) instructions. Participants, with eyes closed, had to point targeted locations (knuckles and nails of each finger) based on verbal instructions and tactile stimulations to evaluate body representations respectively. Ratios between hand width and finger length were compared between AN (n = 31) and controls (n = 31) and correlated with current body mass index, AN subtype and disease duration. To control that hand distortion was specific to body representation, we also assessed object representation. Hand representation’s width/length ratio was significantly increased in patients with AN, whereas no difference was found in object representation. We found no correlation between hand wideness and clinical traits related to eating disorders. Our results propose that BRD is not limited to body parts with high emotional salience, strengthening the hypothesis that anorexia nervosa is associated with profound unspecific BRD.

The growing interest concerning the role of metabolic sensors in various eating disorders requires the implementation of a strict methodology to collect, store and process blood samples in clinical studies. In particular, measurement of isoforms of the appetite-stimulating hormone, ghrelin, has been challenging in clinical settings. Indeed the acyl ghrelin (AG) isoform is rapidly degraded into desacyl ghrelin (DAG) by blood esterases, thus optimal conditions for the conservation of AG and accurate determination of AG/DAG ratio should be used. Here, we compared different protease inhibitors (Aprotinin, PHMB, AEBSF) during blood collection, increasing delays (0–180 min) before centrifugation, plasma supplementation with various HCl concentrations, storage durations of frozen plasma (8 and 447 days) and immunoenzyme-assay procedures (one-step versus sequential) in healthy subjects. Optimal conditions were obtained by collecting blood with aprotinin and supplementation of plasma with 0.1 N HCl with subsequent freezing for at least 8 days and using one-step assay. Under such conditions, different patterns of secretion of ghrelin isoforms were characterized in patients with restrictive-type anorexia nervosa (AN-R) before and after nutritional recovery. We illustrate the pulsatile variations of ghrelin isoforms according to the time around a meal and hunger rates in 3 patients with AN-R. This study offers a comprehensive comparison of various conditions using selective and specific immunoassays for both ghrelin isoforms in order to optimize assay sensitivity and consistency among procedures. These assay conditions could therefore be widely used to elucidate precisely the role of ghrelin isoforms on eating behavior in physiological and pathological situations.

Introduction Art-therapy (encompassing plastic arts, music, theather and writing) is a promising and acceptable management strategy of eating disorders (ED). It has the potential to improve well-being and therapeutic alliance, targeting psychological dimensions of ED, and dealing with difficulties of expression and rationalization of patients. Nevertheless, the efficacy of this approach is difficult to evaluate because of the lack of studies in this area. Objectives We sought to provide an overview on the efficacy of art therapy in the management of ED, by a systematic review of all controlled trials using art therapy on patients with ED. Methods This systematic review included all controlled trials using art-therapy on a population of adolescent and adult patients with ED. The effect of art therapy on clinical indicators such as anthropometric variables, symptoms and dimensions of ED was evaluated. Results Of the 1286 screened records, only four respected inclusion criteria. These four trials evaluated plastic art therapy, music therapy, writing therapy, and dance-movement therapy. A large number of bias and strong heterogeneity of inclusion criteria, techniques and variables prevented any attempt of quantitative synthesis. Music therapy appeared to have a significant effect on post-prandial anxiety, while dance-movement therapy showed an effect on body dissatisfaction. Conclusions The generalizability of the results found is weakened by the high heterogeneity of trials. Replication studies and a rigorous methodologies are necessary for more reliable conclusions. Art therapy could help improving some specific dimensions of ED. Disclosure No significant relationships.

Introduction Patients with anorexia nervosa (AN) show impaired decision-making ability, but it is still unclear if this is a trait marker, i.e. a stable endophenotype of AN, or a state parameter, i.e. being explained by present symptoms and associated comorbidity. Objectives We aimed to determine whether decision-making impairment is an endophenotype of AN. We hypothesized that decision-making alteration would not respect the criteria of an endophenotype, and that these alterations would have a relationship with illness severity. Methods Ninety-one patients with acute AN (A-AN), 90 unaffected relatives (UR), 23 patients remitted from AN (R-AN) and 204 healthy controls (HC) underwent the Iowa Gambling Task (IGT) and psychometric assessments. Prospective Valence Learning model (PVL) was employed to distinguish the cognitive dimensions underlying the decision-making process. Performance at the IGT was compared between the four groups and then analysed according to clinical and psychometric variables. Results Patients with A-AN scored worse than UR and HC at the IGT (p

Four sets of arguments are supporting the idea that compulsory admissions should be possible in anorexia nervosa, as much as it is other in psychiatric disorders. Indeed, if nobody challenges the use of compulsory treatments for patients with acutte schizophrenia or a manic episodes, it is because the usual rational for compulsory admission relies on (1) the severity of the disorder (a need), (2) the capacity of hospitalisation to really improve patients and prognosis (a utility), associated to the fact that (3) the disorder alters the capacity to spontaneously ask for care (a rational), and (4) the possible danger of the present medical conditions for others (a protection). We will explain that these four points are clearly being equivalent for anorexia nervosa compared to other psychiatric disorders, with some subtilities that modify their expression, but not the spirit of these rationals. We will then propose that a much easier way to understand the paicity of use of this hospitalisation modalities is related to the strange position of anorexia nervosa, a metabo-psychiatric disorder, namely a complex disorder at the interface of somatic and psychiatric disorder. We will conclude in promoting a step-by-step procedure to reuce the risk of abuse, and facilitate the paradoxical “acceptance” of a “forced” hospitalisation.

Introduction Anorexia nervosa (AN) is a chronic psychiatric disorder resulting from abnormal eating habits with a high prevalence (0.5%). AN involves genetic and epigenetic factors supporting that AN is a metabo-psychiatric disorder. One candidate gene for AN, validated by meta-analyzes, is BDNF which encodes the brain-derived neurotrophic factor. BDNF negatively modulates the central control of food intake and its injection in rodents induces weight loss and anorexia. In humans, we observed an association of its functional variant Val66Met/rs6265 and electrodermal response to images of thinness suggesting an association between rs6265 and a reward effect of weight loss in AN. Objectives This work study the impact of the functional polymorphism at risk rs6265, epigenetic variations in DNA methylation of BDNF gene and consequences on the concentrations of BDNF in AN patients. Methods DNA was isolated from 24 AN patients and 48 controls. DNA methylation was measured for sites spanning the BDNF gene using Infinium HumanMethylation450 BeadChip technology. The genotyping of rs6265 was performed by Taqman-SNP assay. The BDNF was dosaged by ELISA from plasmas. Results We observe that several sites are significantly hypermethylated in AN patients compared to controls. AN patients show significantly higher BDNF levels than controls. Finally, this BDNF concentration is significantly higher in AN carrying the risk Met66 allele. Conclusions This work demonstrates the effects of genetic and epigenetic variations of BDNF, which could constitute relevant diagnostic biomarkers of AN, and their likely consequences in the pathophysiology of AN. This work was supported by the Nestlé Foundation. Disclosure No significant relationships.

Background: Measuring and interpreting outcome is challenging in mental health services than in some other areas of health care. Objectives: The aims of this study were to (1) explore results of Patient-Reported Outcome Measures (PROMs) and Patient-Reported Experience Measures (PREMs) in psychiatric hospital settings, (2) describe the relation between generic PROMs (measure of well-being) and specific PROMs (disorder-specific symptom assessments), (3) describe the congruence between patients and clinicians evaluation of the care experience (based on Patients reported experience measures and Clinician reported experience measures). Methods: A total of 269 consecutive patients participated in this study. Results: (1) Subjective experience of well-being (outcome) improved after hospitalisation (+15%, avg). High satisfaction with subjective experience of care (85%, avg). (2) Significant correlation between patients’ assessment of subjective well-being (generic PROMs) and clinical improvement (specific PROMs) (p

Introduction Gambling Disorder (GD) is considered a multifactorial behavioral addictive disorder, leading to severe psychological, social and economic consequences. Previous studies have investigated genetic mechanisms underlying GD. Growing literature showed a possible link between addiction-related disorders and neurotrophic factors (NTF), involved in synaptic plasticity and neuronal survival. Thus, the study of NTF genes emerged as promising targets in the field of GD. Objectives To evaluate genetic implications of the NTF family in the pathophysiology GD. We hypothesized the involvement of some NTF genes polymorphisms in the onset and progression of GD as potential biological risk factors. Methods The sample was composed by 166 individuals with GD and 191 healthy controls. 36 Single nucleotide polymorphisms (SNPs) from NTF (NGF, NGFR, NTRK1, BDNF, NTRK2, NTF3, NTRK3, NTF4, CNTF and CNTFR) were selected and genotyped. Linkage disequilibrium and haplotype constructions were assessed, related to the presence of GD. Moreover, regulatory elements overlapping the identified SNPs variants associated with GD was also analyzed. Results 6 SNPs were potentially associated to GD after the comparisons of allele frequencies between groups. Single and multiple-marker analyses showed a strong association between both NTF3 and NTRK2 genes, and GD. Conclusions This study suggests the implication of NTF genes in the development of GD, being the altered cross-regulation of some NTF factors signalling pathways, a potential biological vulnerability factor in GD. Fundings and Acknowledgements: Ministerio de Ciencia, Innovación y Universidades (RTI2018-101837-B-100) Delegación del Gobierno para el Plan Nacional sobre Drogas (2017I067, 2019I47), Instituto Salud Carlos III (ISCIII) (PI17/01167, PI20/00132) and CIBERObn, an initiative of ISCIII. Disclosure No significant relationships.

Introduction Pediatric acute bacterial meningitis is a life-threatening illness that results from bacterial infection of the meninges and leaves some survivors with significant sequelae. Given the potential trauma induced by the disease itself and the hospitalization, it is important to have an insight on how the parents cope with this aversive event, and especially how they give sense to this experience. Objectives (1) To explore the lived experience of close family ascendants whose child or grandchild had survived acute bacterial meningitis (2) To investigate how they give meaning to this specific experience. Methods Participants were recruited through two association of persons affected by meningitis. Convenience sample of eleven family ascendants. Their family descendants were aged between 0.2 and 20 years old at the time of the meningitis diagnosis (M= 4.1, SD= 7.3). In average, 9.4 years had passed between the onset of illness and the relative’s interview (SD= 5.4). Results 6 superordinate themes and 2 meaning-making processes were identified: 1. Sick child becoming a “hero” (comparison with other children). 2. Engaged action/attitude: finding the “positive” of the traumatic experience and engaged action to improve the care system. Conclusions This is one of the first studies exploring the first-hand experience of family ascendants confronted to acute bacterial meningitis. Findings highlighted factors characterising the disease experience and the psychological adjustment of meningitis survivors’ families. They demonstred (1) the multidimensional impact of the disease on family ascendants and their need for professional psychological support, (2) the importance of direct involvement of parents in identifying key aspects of care.

Introduction With increasing prevalence, eating disorders (EDs) constitute a public health problem. Access to treatment is limited and often delayed for the majority of patients. Such obstacles might be mitigated via the development of virtual treatments. Objectives Conducted during COVID-19 lockdown, this pilot study aimed to explore the feasibility and preliminary clinical outcomes associated with treatment of EDs by means of a remote psychoeducational (PE) programme. Methods Eleven patients who fulfilled DSM‐5 criteria for anorexia nervosa, bulimia nervosa, or binge eating disorder completed assessments, including ED symptoms, anxiety and depression, as well as motivation to change measures at the beginning and end of the time-limited (4 weeks) specialized treatment. It consisted in receiving 4 PE documents by email (1 per week), which was completed by a 15-20 minutes phone call with each participant (1 per week). Results Data showed significant improvements of several self‐reported eating disorder symptoms, including body dissatisfaction and intensity of bulimic episodes. Conclusions Our findings suggest that a time-limited remote PE intervention produces clinically meaningful changes in ED symptoms. Thus, it might be worth developing such interventions in a clinical context, especially when performed prior to higher level of care. Further research is required to evaluate optimised interventions using a more diverse sample from a plurality of treatment facilities and context of care, as well as research in a non-pandemic setting which may have impacted these exploratory study results. Disclosure No significant relationships.

Introduction Anorexia Nervosa (AN) is a severe mental illness characterized by weight reducing strategies such as food restriction, purging behaviours and excessive physical exercise. The persistence of physical exercise despite underweight and its maintaining factors are poorly understood. Objectives The aim of this study is to explore the attitudes towards physical exercise and its effects on mood, body image perception and cognitive functioning in patients with AN, and to assess if these effects are associated with trait, or state. Methods Eighty-eight patients with AN, 30 unaffected relatives and 89 healthy controls were compared about their attitudes towards three aspects of physical exercise, namely the Exercise Dependence Scale (EDS), the Godin Leisure Time Exercise Questionnaire (GLTEQ) and a standardized effort test. Evaluations of positive and negative affects, cognitive rigidity and body image distortion were repeated at baseline and after the effort test to assess for correlations between the exercise measures and exercise-induced modifications in the three groups. Results Patients with AN showed higher scores on the EDS, the GLTEQ and used more effort in the standardized effort test (p

AbstractBackgroundThis study aimed to investigate the effectiveness of mindfulness-based cognitive therapy (MBCT) as a complementary approach in patients with bulimia nervosa (BN) or binge eating disorder (BED), and to assess how the reduction of the cognitive load of words related to eating disorders (ED) could constitute an intermediate factor explaining its global efficacy.MethodsEighty-eight women and men participated in clinical assessments upon inscription, prior to and following 8-week group MBCT. Mindfulness skills were assessed using the five facet mindfulness questionnaire; eating behaviors were assessed using the Three Factor Eating Questionnaire (TFEQ); comorbid pathologies were assessed using the beck depression index and the state-trait anxiety inventory. The cognitive load of words associated with ED was assessed through a modified version of the Stroop color naming task.ResultsMindfulness skills improved significantly (p

The concept of “race” and consequently of racism is not a recent phenomenon, although it had profound effects on the lives of populations over the last several hundred years. Using slaves and indentured labor from racial groups designated to be “the others,” who was seen as inferior and thus did not deserve privileges, and who were often deprived of the right to life and basic needs as well as freedoms. Thus, creation of “the other” on the basis of physical characteristics and dehumanizing them became more prominent. Racism is significantly related to poor health, including mental health. The impact of racism in psychiatric research and clinical practice is not sufficiently investigated. Findings clearly show that the concept of “race” is genetically incorrect. Therefore, the implicit racism that underlies many established “scientific” paradigms need be changed. Furthermore, to overcome the internalized, interpersonal, and institutional racism, the impact of racism on health and on mental health must be an integral part of educational curricula, from undergraduate levels through continuing professional development, clinical work, and research. In awareness of the consequences of racism at all levels (micro, meso, and macro), recommendations for clinicians, policymakers, and researchers are worked out.

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values

BackgroundThe Collaborative Outcome study on Health and Functioning during Infection Times (COH-FIT; www.coh-fit.com) is an anonymous and global online survey measuring health and functioning during the COVID-19 pandemic. The aim of this study was to test concurrently the validity of COH-FIT items and the internal validity of the co-primary outcome, a composite psychopathology "P-score".MethodsThe COH-FIT survey has been translated into 30 languages (two blind forward-translations, consensus, one independent English back-translation, final harmonization). To measure mental health, 1-4 items ("COH-FIT items") were extracted from validated questionnaires (e.g. Patient Health Questionnaire 9). COH-FIT items measured anxiety, depressive, post-traumatic, obsessive-compulsive, bipolar and psychotic symptoms, as well as stress, sleep and concentration. COH-FIT Items which correlated r ≥ 0.5 with validated companion questionnaires, were initially retained. A P-score factor structure was then identified from these items using exploratory factor analysis (EFA) and confirmatory factor analyses (CFA) on data split into training and validation sets. Consistency of results across languages, gender and age was assessed.ResultsFrom >150,000 adult responses by May 6th, 2022, a subset of 22,456 completed both COH-FIT items and validated questionnaires. Concurrent validity was consistently demonstrated across different languages for COH-FIT items. CFA confirmed EFA results of five first-order factors (anxiety, depression, post-traumatic, psychotic, psychophysiologic symptoms) and revealed a single second-order factor P-score, with high internal reliability (ω = 0.95). Factor structure was consistent across age and sex.ConclusionsCOH-FIT is a valid instrument to globally measure mental health during infection times. The P-score is a valid measure of multidimensional mental health.

BackgroundGenetics 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.MethodsA 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 (

BackgroundSuicide 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.MethodsWe 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.ResultsTwo 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.ConclusionsOur 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.

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.

Characterized primarily by a low body-mass index, anorexia nervosa is a complex and serious illness1, affecting 0.9-4% of women and 0.3% of men2-4, with twin-based heritability estimates of 50-60%5. Mortality rates are higher than those in other psychiatric disorders6, and outcomes are unacceptably poor7. 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.

ObjectiveThe authors conducted a genome-wide association study of anorexia nervosa and calculated genetic correlations with a series of psychiatric, educational, and metabolic phenotypes.MethodFollowing uniform quality control and imputation procedures using the 1000 Genomes Project (phase 3) in 12 case-control cohorts comprising 3,495 anorexia nervosa cases and 10,982 controls, the authors performed standard association analysis followed by a meta-analysis across cohorts. Linkage disequilibrium score regression was used to calculate genome-wide common variant heritability (single-nucleotide polymorphism [SNP]-based heritability [h2SNP]), partitioned heritability, and genetic correlations (rg) between anorexia nervosa and 159 other phenotypes.ResultsResults were obtained for 10,641,224 SNPs and insertion-deletion variants with minor allele frequencies >1% and imputation quality scores >0.6. The h2SNP of anorexia nervosa was 0.20 (SE=0.02), suggesting that a substantial fraction of the twin-based heritability arises from common genetic variation. The authors identified one genome-wide significant locus on chromosome 12 (rs4622308) 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 cholesterol, and significant negative genetic correlations were observed between anorexia nervosa and body mass index, insulin, glucose, and lipid phenotypes.ConclusionsAnorexia nervosa is a complex heritable phenotype for which this study has uncovered the first genome-wide significant locus. Anorexia nervosa also has large and significant genetic correlations with both psychiatric phenotypes and metabolic traits. The study results encourage a reconceptualization of this frequently lethal disorder as one with both psychiatric and metabolic etiology.

BackgroundAntidepressant-worsening suicidal ideation is a rare but serious phenomenon. This study aimed to test for association between antidepressant-worsening suicidal ideation and polymorphisms of BDNF/NTRK2 neurotrophin pathway genes, known to be involved in depression and suicide.MethodsThis was a case-control study comparing patients with antidepressant-worsening suicidal ideation to patients without. Patients were collected from the GENESE cohort (3771 depressed tianeptine-treated outpatients). Antidepressant-worsening suicidal ideation was defined by an increase of at least 2 points on the Montgomery-Åsberg Depression Rating Scale-item10 during treatment. Controls were matched for age, sex, and baseline Montgomery-Åsberg Depression Rating Scale-item10 score. Thirteen single nucleotide polymorphisms covering 5 BDNF/NTRK2 pathway genes were genotyped.ResultsA total 78 cases and 312 controls were included. Two NTRK2 single nucleotide polymorphisms were associated to antidepressant-worsening suicidal ideation: rs1439050 (P=.01) and rs1867283 (P=.04). Association with rs1439050 remained significant after adjustment for potentially confounding factors, including previous suicide attempts (P

AbstractBackground.Compulsory admission procedures of patients with mental disorders vary between countries in Europe. The Ethics Committee of the European Psychiatric Association (EPA) launched a survey on involuntary admission procedures of patients with mental disorders in 40 countries to gather information from all National Psychiatric Associations that are members of the EPA to develop recommendations for improving involuntary admission processes and promote voluntary care.Methods.The survey focused on legislation of involuntary admissions and key actors involved in the admission procedure as well as most common reasons for involuntary admissions.Results.We analyzed the survey categorical data in themes, which highlight that both medical and legal actors are involved in involuntary admission procedures.Conclusions.We conclude that legal reasons for compulsory admission should be reworded in order to remove stigmatization of the patient, that raising awareness about involuntary admission procedures and patient rights with both patients and family advocacy groups is paramount, that communication about procedures should be widely available in lay-language for the general population, and that training sessions and guidance should be available for legal and medical practitioners. Finally, people working in the field need to be constantly aware about the ethical challenges surrounding compulsory admissions.

Anorexia nervosa (AN) is a complex and heritable eating disorder characterized by dangerously low body weight. Neither candidate gene studies nor an initial genome-wide association study (GWAS) have yielded significant and replicated results. We performed a GWAS in 2907 cases with AN from 14 countries (15 sites) and 14 860 ancestrally matched controls as part of the Genetic Consortium for AN (GCAN) and the Wellcome Trust Case Control Consortium 3 (WTCCC3). Individual association analyses were conducted in each stratum and meta-analyzed across all 15 discovery data sets. Seventy-six (72 independent) single nucleotide polymorphisms were taken forward for in silico (two data sets) or de novo (13 data sets) replication genotyping in 2677 independent AN cases and 8629 European ancestry controls along with 458 AN cases and 421 controls from Japan. The final global meta-analysis across discovery and replication data sets comprised 5551 AN cases and 21 080 controls. AN subtype analyses (1606 AN restricting; 1445 AN binge-purge) were performed. No findings reached genome-wide significance. Two intronic variants were suggestively associated: rs9839776 (P=3.01 × 10(-7)) in SOX2OT and rs17030795 (P=5.84 × 10(-6)) in PPP3CA. Two additional signals were specific to Europeans: rs1523921 (P=5.76 × 10(-)(6)) between CUL3 and FAM124B and rs1886797 (P=8.05 × 10(-)(6)) near SPATA13. Comparing discovery with replication results, 76% of the effects were in the same direction, an observation highly unlikely to be due to chance (P=4 × 10(-6)), strongly suggesting that true findings exist but our sample, the largest yet reported, was underpowered for their detection. The accrual of large genotyped AN case-control samples should be an immediate priority for the field.