Genome-wide analysis of a model-derived binge eating disorder phenotype identifies risk loci and implicates iron metabolism.
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SUBMITTER: Burstein D
PROVIDER: S-EPMC10947608 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Genome-wide analysis of a model-derived binge eating disorder phenotype identifies risk loci and implicates iron metabolism.
Burstein David D Griffen Trevor C TC Therrien Karen K Bendl Jaroslav J Venkatesh Sanan S Dong Pengfei P Modabbernia Amirhossein A Zeng Biao B Mathur Deepika D Hoffman Gabriel G Sysko Robyn R Hildebrandt Tom T Voloudakis Georgios G Roussos Panos P
Nature genetics 20230807 9
Binge eating disorder (BED) is the most common eating disorder, yet its genetic architecture remains largely unknown. Studying BED is challenging because it is often comorbid with obesity, a common and highly polygenic trait, and it is underdiagnosed in biobank data sets. To address this limitation, we apply a supervised machine-learning approach (using 822 cases of individuals diagnosed with BED) to estimate the probability of each individual having BED based on electronic medical records from ...[more]
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Project description:Bipolar disorder (BD) is associated with binge eating behavior (BE), and both conditions are heritable. Previously, using data from the Genetic Association Information Network (GAIN) study of BD, we performed genome-wide association (GWA) analyses of BD with BE comorbidity. Here, utilizing data from the Mayo Clinic BD Biobank (969 BD cases, 777 controls), we performed a GWA analysis of a BD subtype defined by BE, and case-only analysis comparing BD subjects with and without BE. We then performed a meta-analysis of the Mayo and GAIN results. The meta-analysis provided genome-wide significant evidence of association between single nucleotide polymorphisms (SNPs) in PRR5-ARHGAP8 and BE in BD cases (rs726170 OR = 1.91, P = 3.05E-08). In the meta-analysis comparing cases with BD with comorbid BE vs. non-BD controls, a genome-wide significant association was observed at SNP rs111940429 in an intergenic region near PPP1R2P5 (p = 1.21E-08). PRR5-ARHGAP8 is a read-through transcript resulting in a fusion protein of PRR5 and ARHGAP8. PRR5 encodes a subunit of mTORC2, a serine/threonine kinase that participates in food intake regulation, while ARHGAP8 encodes a member of the RhoGAP family of proteins that mediate cross-talk between Rho GTPases and other signaling pathways. Without BE information in controls, it is not possible to determine whether the observed association reflects a risk factor for BE in general, risk for BE in individuals with BD, or risk of a subtype of BD with BE. The effect of PRR5-ARHGAP8 on BE risk thus warrants further investigation.
| S-EPMC5804024 | biostudies-literature
Project description:BackgroundBipolar disorder (BD) is a highly heritable disease. While genome-wide association (GWA) studies have identified several genetic risk factors for BD, few of these studies have investigated the genetic etiology of specific disease subtypes. In particular, BD is positively associated with eating dysregulation traits such as binge eating behavior (BE), yet the genetic risk factors underlying BD with comorbid BE have not been investigated.MethodsUtilizing data from the Genetic Association Information Network study of BD, which included 729,454 single nucleotide polymorphisms (SNPs) genotyped in 1001 European American bipolar cases and 1034 controls, we performed GWA analyses of bipolar subtypes defined by the presence or absence of BE history, and performed a case-only analysis comparing BD subjects with and without BE history. Association signals were refined using imputation, and network analysis was performed with Ingenuity Pathway Analysis software. Based on these results, candidate SNPs were selected for replication in an independent sample of 855 cases and 857 controls.ResultsTop ranking SNPs in the discovery set included rs6006893 in PRR5, rs17045162 in ANK2, rs13233490 near PER4, rs4665788 and rs10198175 downstream of APOB, rs2367911 in CACNA2D1, and rs7249968 near ZNF536. Rs10198175 in APOB also demonstrated evidence of association in the replication sample and a meta-analysis of the two samples.LimitationsWithout information of BE history in controls, it is not possible to determine whether the observed association with APOB reflects a risk factor for BE behavior in general or a risk factor for a subtype of BD with BE. Further longitudinal and functional studies are needed to determine the causal pathways underlying the observed associations.ConclusionsThis study identified new potential BD-susceptibility genes, highlighting the advantages of phenotypic sub-classification in genetic research and clinical practice.
| S-EPMC4224146 | biostudies-literature
Project description:To explore the relationship between binge eating disorder (BED) and obesity in patients with bipolar disorder (BP).717 patients participating in the Mayo Clinic Bipolar Biobank completed structured diagnostic interviews and questionnaires for demographic and illness-related variables. They also had weight and height measured to determine body mass index (BMI). The effects of BED and obesity (BMI?30 kg/m(2)), as well as their interaction, were assessed on one measure of general medical burden and six proxies of psychiatric illness burden.9.5% of patients received a clinical diagnosis of BED and 42.8% were obese. BED was associated with a significantly elevated BMI. Both BED and obesity were associated with greater psychiatric and general illness burden, but illness burden profiles differed. After controlling for obesity, BED was associated with suicidality, psychosis, mood instability, anxiety disorder comorbidity, and substance abuse comorbidity. After controlling for BED status, obesity was associated with greater general medical comorbidity, but lower substance abuse comorbidity. There were no significant interaction effects between obesity and BED, or BMI and BED, on any illness burden outcome.There may have been insufficient power to detect interactions between BED and obesity.Among patients with BP, BED and obesity are highly prevalent and correlated, but associated with different profiles of enhanced illness burden. As the association of BED with greater psychiatric illness burden remained significant even after accounting for the effect of obesity, BP with BED may represent a clinically important sub-phenotype.
| S-EPMC5551039 | biostudies-literature
Project description: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.
| S-EPMC9793802 | biostudies-literature
Project description:ObjectiveAlthough several effective behavioral treatments for binge-eating disorder (BED) exist, there are racial disparities in treatment access, with African-Americans and/or Black individuals having some of the lowest rates of access to care. Little is known about the experience and treatment of binge eating (BE) and BED among Black women.MethodThis systematic review, conducted according to PRISMA guidelines, synthesizes information related to BE and BED in Black women.ResultsA total of N = 38 studies met our eligibility criteria. We did not identify any systematic risk of bias across studies. The majority of included studies used cross-sectional survey methodology, and relied on interview (EDE) and self-report measures (particularly the Binge Eating Scale, BES) for the assessment of BE. Outcomes were inconsistently measured across trials, and there are limited data on the results of evidence-based treatments for BE/BED in Black women.DiscussionAlthough Black women have similar or higher rates of BE than White women, most research on BE and BED has focused on White women, with Black individuals underrepresented in clinical trials. Future research should examine evidence-based treatments to prevent and treat BED in this population.ObjetivoAunque existen varios tratamientos conductuales que son efectivos para el Trastorno de Atracones (BED, por sus siglas en inglés), existen disparidades raciales en el acceso a tratamiento, con individuos Afroamericanos y/o personas de color teniendo algunas de las tasas más bajas de acceso al cuidado de la salud. Se sabe muy poco acerca de la experiencia y tratamiento del comer en atracones (BE, por sus siglas en inglés) y BED entre mujeres afroamericanas y/o de color. MÉTODO: Esta revisión sistemática, realizada bajo lineamientos de las guías PRISMA, sintetiza información relacionada con BE y BED en mujeres afroamericanas y/o de color.ResultadosUn total de N = 38 estudios cumplieron con nuestros criterios de elegibilidad. No identificamos ningún riesgo sistemático de sesgo entre los estudios. La mayoría de los estudios incluidos utilizaron una metodología de encuesta transversal y se basaron en la entrevista (EDE) y las medidas de autoinforme (en particular, la Binge Eating Scale, BES) para la evaluación de BE. Los resultados se midieron de manera inconsistente entre los ensayos, y hay datos limitados sobre los resultados de los tratamientos basados en la evidencia para BE/BED en mujeres afroamericanas y/o de color. DISCUSIÓN: Aunque las mujeres afroamericanas y/o de color tienen tasas similares o más altas de BE que las mujeres blancas, la mayoría de las investigaciones sobre BE y BED se han centrado en las mujeres blancas, con individuos afroamericanos y/o de color subrepresentados en ensayos clínicos. La investigación futura debería examinar los tratamientos basados en la evidencia para prevenir y tratar el BED en esta población.
| S-EPMC8010989 | biostudies-literature
Project description:ContextInterpersonal psychotherapy (IPT) is an effective specialty treatment for binge eating disorder (BED). Behavioral weight loss treatment (BWL) and guided self-help based on cognitive behavior therapy (CBTgsh) have both resulted in short-term reductions in binge eating in obese patients with BED.ObjectiveTo test whether patients with BED require specialty therapy beyond BWL and whether IPT is more effective than either BWL or CBTgsh in patients with a high negative affect during a 2-year follow-up.DesignRandomized, active control efficacy trial.SettingUniversity outpatient clinics.ParticipantsTwo hundred five women and men with a body mass index between 27 and 45 who met DSM-IV criteria for BED. Intervention Twenty sessions of IPT or BWL or 10 sessions of CBTgsh during 6 months.Main outcome measuresBinge eating assessed by the Eating Disorder Examination.ResultsAt 2-year follow-up, both IPT and CBTgsh resulted in greater remission from binge eating than BWL (P < .05; odds ratios: BWL vs CBTgsh, 2.3; BWL vs IPT, 2.6; and CBTgsh vs IPT, 1.2). Self-esteem (P < .05) and global Eating Disorder Examination (P < .05) scores were moderators of treatment outcome. The odds ratios for low and high global Eating Disorder Examination scores were 2.8 for BWL, 2.9 for CBTgsh, and 0.73 for IPT; for self-esteem, they were 2.4 for BWL, 1.9 for CBTgsh, and 0.9 for IPT.ConclusionsInterpersonal psychotherapy and CBTgsh are significantly more effective than BWL in eliminating binge eating after 2 years. Guided self-help based on cognitive behavior therapy is a first-line treatment option for most patients with BED, with IPT (or full cognitive behavior therapy) used for patients with low self-esteem and high eating disorder psychopathology.Trial registrationclinicaltrials.gov Identifier: NCT00060762.
| S-EPMC3757519 | biostudies-literature
Project description:This report examined baseline affective response to binge eating as a predictor of binge-eating disorder (BED) treatment outcome. Baseline affective response was defined as: (1) each individual's average net change (i.e., area under the curve [AUC]) of positive affect (PA) or negative affect (NA) before and after binge-eating episodes and (2) post-binge eating slope of PA or NA across seven-days of ecological momentary assessment (EMA). Adults with BED completed Integrative Cognitive-Affective Therapy (ICAT-BED) or cognitive behavioral therapy guided self-help (CBTgsh). Individuals with greater net increases in PA (AUC) following binge eating at baseline exhibited better treatment response in ICAT-BED at end-of-treatment and follow-up. NA affective response was only significant at end-of-treatment; individuals with less rapid post-binge improvements in NA (slope) did better in ICAT-BED, while individuals with lower net improvements in NA (AUC) did better in CBTgsh. Affective response to binge eating may be a marker of BED treatment response.
| S-EPMC8579466 | biostudies-literature
Project description:IntroductionResearch on binge eating disorder continues to evolve and advance our understanding of recurrent binge eating.MethodsThis mixed-methods, cross-sectional survey aimed to collect information from experts in the field about clinical aspects of adult binge eating disorder pathology. Fourteen experts in binge eating disorder research and clinical care were identified based on receipt of relevant federal funding, PubMed-indexed publications, active practice in the field, leadership in relevant societies, and/or clinical and popular press distinction. Anonymously recorded semi-structured interviews were analyzed by ≥2 investigators using reflexive thematic analysis and quantification.ResultsIdentified themes included: (1) obesity (100%); (2) intentional/voluntary or unintentional/involuntary food/eating restriction (100%); (3) negative affect, emotional dysregulation, and negative urgency (100%); (4) diagnostic heterogeneity and validity (71%); (5) paradigm shifts in understanding binge eating disorder (29%); and (6) research gaps/future directives (29%).DiscussionOverall, experts call for a better understanding of the relationship between binge eating disorder and obesity, including a need for clarification around the extent to which the two health issues are separate vs. related/overlapping. Experts also commonly endorse food/eating restriction and emotion dysregulation as important components of binge eating disorder pathology, which aligns with two common models of binge eating disorder conceptualization (e.g., dietary restraint theory and emotion/affect regulation theory). A few experts spontaneously identified several paradigm shifts in our understanding of who can have an eating disorder (beyond the anorexi-centric "thin, White, affluent, cis-gendered neurotypical female" stereotype), and the various factors that can drive binge eating. Experts also identified several areas where classification issues may warrant future research. Overall, these results highlight the continual advancement of the field to better understand adult binge eating disorder as an autonomous eating disorder diagnosis.
| S-EPMC9971930 | biostudies-literature
Project description:BackgroundInefficient mechanisms of emotional regulation appear essential in understanding the development and maintenance of binge-eating disorder (BED). Previous research focused mainly on a very limited emotion regulation strategies in BED, such as rumination, suppression, and positive reappraisal. Therefore, the aim of the study was to assess a wider range of emotional regulation strategies (i.e. acceptance, refocusing on planning, positive refocusing, positive reappraisal, putting into perspective, self-blame, other-blame, rumination, and catastrophizing), as well as associations between those strategies and binge-eating-related beliefs (negative, positive, and permissive), and clinical variables (eating disorders symptoms, both anxiety, depressive symptoms, and alexithymia).MethodsWomen diagnosed with BED (n = 35) according to the DSM-5 criteria and healthy women (n = 41) aged 22-60 years were assessed using: the Eating Attitudes Test-26, the Eating Beliefs Questionnaire-18, the Hospital Anxiety and Depression Scale, the Toronto Alexithymia Scale-20, the Cognitive Emotion Regulation Questionnaire, and the Difficulties in Emotion Regulation Scale. Statistical analyses included: Student t - tests or Mann-Whitney U tests for testing group differences between BED and HC group, and Pearson's r coefficient or Spearman's rho for exploring associations between the emotion regulation difficulties and strategies, and clinical variables and binge-eating-related beliefs in both groups.ResultsThe BED group presented with a significantly higher level of emotion regulation difficulties such as: nonacceptance of emotional responses, lack of emotional clarity, difficulties engaging in goal-directed behavior, impulse control difficulties, and limited access to emotion regulation strategies compared to the healthy controls. Moreover, patients with BED were significantly more likely to use maladaptive strategies (rumination and self-blame) and less likely to use adaptive strategies (positive refocusing and putting into perspective). In the clinical group, various difficulties in emotion regulation difficulties occurred to be positively correlated with the level of alexithymia, and anxiety and depressive symptoms. Regarding emotion regulation strategies, self-blame and catastrophizing were positively related to anxiety symptoms, but solely catastrophizing was related to the severity of eating disorder psychopathology.ConclusionsOur results indicate an essential and still insufficiently understood role of emotional dysregulation in BED. An especially important construct in this context seems to be alexithymia, which was strongly related to the majority of emotion regulation difficulties. Therefore, it might be beneficial to pay special attention to this construct when planning therapeutic interventions, as well as to the maladaptive emotion regulation strategies self-blame and catastrophizing, which were significantly related to BED psychopathology.
| S-EPMC8504023 | biostudies-literature
Project description:BackgroundImpaired metabolic response such as blood glucose fast fluctuations may be hypothesized in binge eating disorder (BED) and food addiction (FA) by virtue of the repetitive consumption of highly processed food. Conversely, rapid changes in plasma glucose (i.e., hypoglycemia) may trigger craving for the same food products. The investigation of early glycemic disturbances in BED and FA could enhance the understanding of the metabolic mechanisms involved in the maintenance of the disorders. Present study investigated hypoglycemia events during a 5-h-long oral glucose tolerance test (OGTT) in people with BED, FA, and the comorbid phenotype. Further, the association between the severity of eating psychopathology and the variability in hypoglycaemia events was explored.MethodsTwo-hundred participants with high weight and no diabetes completed the extended OGTT and were screened for BED, FA, BED-FA, or no-BED/FA. The four groups were compared in hypoglycemia events, OGTT-derived measures, and eating psychopathology. The association between predictors (eating psychopathology), confounders (demographics, metabolic features), and the outcomes (hypoglycemia, early/late hypoglycemia, severe hypoglycemia, reactive hypoglycemia) was examined through logistic regression.ResultsHypoglycemia in general, and reactive hypoglycemia were highly frequent (79% and 28% of the sample, respectively). Hypoglycemia events (< 70 mg/dL) were equally experienced among groups, whilst severe hypoglycemia (< 54 mg/dL) was more frequent in BED at the late stage of OGTT (5 h; χ2 = 1.120, p = .011). The FA and BED groups exhibited significantly higher number of reactive hypoglycemia (χ2 = 13.898, p = .003), in different times by diagnosis (FA: 210'-240'; BED: at the 270'). FA severity was the only predictor of early and reactive hypoglycemia.ConclusionsPeople with BED or FA are prone to experiencing reactive hypoglycemia; FA severity may predict early and symptomatic hypoglycemia events. This can further reinforce disordered eating behaviours by promoting addictive responses, both biologically and behaviourally. These results inform professionals dealing with eating disorders about the need to refer patients for metabolic evaluation. On the other hand, clinicians dealing with obesity should screen for and address BED and FA in patients seeking care for weight loss.
| S-EPMC10507855 | biostudies-literature