CBFß-SMMHC Inhibition Triggers Apoptosis by Disrupting MYC Chromatin Dynamics in Acute Myeloid Leukemia.

The fusion oncoprotein CBFß-SMMHC, expressed in leukemia cases with chromosome 16 inversion, drives leukemia development and maintenance by altering the activity of the transcription factor RUNX1. Here, we demonstrate that CBFß-SMMHC maintains cell viability by neutralizing RUNX1-mediated repression of MYC expression. Upon pharmacologic inhibition of the CBFß-SMMHC/RUNX1 interaction, RUNX1 shows increased binding at three MYC distal enhancers, where it represses MYC expression by mediating the replacement of the SWI/SNF complex component BRG1 with the polycomb-repressive complex component RING1B, leading to apoptosis. Combining the CBFß-SMMHC inhibitor with the BET inhibitor JQ1 eliminates inv(16) leukemia in human cells and a mouse model. Enhancer-interaction analysis indicated that the three enhancers are physically connected with the MYC promoter, and genome-editing analysis demonstrated that they are functionally implicated in deregulation of MYC expression. This study reveals a mechanism whereby CBFß-SMMHC drives leukemia maintenance and suggests that inhibitors targeting chromatin activity may prove effective in inv(16) leukemia therapy.

The explore/exploit trade-off: An ecologically valid and translational framework that can advance mechanistic understanding of eating disorders.

The explore/exploit trade-off is a decision-making process that is conserved across species and balances exploring unfamiliar choices of unknown value with choosing familiar options of known value to maximize reward. This framework is rooted in behavioral ecology and has traditionally been used to study maladaptive versus adaptive non-human animal foraging behavior. Researchers have begun to recognize the potential utility of understanding human decision-making and psychopathology through the explore/exploit trade-off. In this article, we propose that explore/exploit trade-off holds promise for advancing our mechanistic understanding of decision-making processes that confer vulnerability for and maintain eating pathology due to its neurodevelopmental bases, conservation across species, and ability to be mathematically modeled. We present a model for how suboptimal explore/exploit decision-making can promote disordered eating and present recommendations for future research applying this framework to eating pathology. Taken together, the explore/exploit trade-off provides a translational framework for expanding etiologic and maintenance models of eating pathology, given developmental changes in explore/exploit decision-making that coincide in time with the emergence of eating pathology and evidence of biased explore/exploit decision-making in psychopathology. Additionally, understanding explore/exploit decision-making in eating disorders may improve knowledge of their underlying pathophysiology, informing targeted clinical interventions such as neuromodulation and pharmacotherapy. PUBLIC SIGNIFICANCE STATEMENT: The explore/exploit trade-off is a cross-species decision-making process whereby organisms choose between a known option with a known reward or sampling unfamiliar options. We hypothesize that imbalanced explore/exploit decision-making can promote disordered eating and present preliminary data. We propose that explore/exploit trade-off has significant potential to advance understanding of the neurocognitive and neurodevelopmental mechanisms of eating pathology, which could ultimately guide revisions of etiologic models and inform novel interventions.

El balance entre explorar y explotar es un proceso de toma de decisiones que se conserva a través de las especies y equilibra la exploración de opciones desconocidas de valor desconocido con la elección de opciones familiares de valor conocido para maximizar la recompensa. Este marco está arraigado en la ecología del comportamiento y tradicionalmente se ha utilizado para estudiar el comportamiento de forrajeo no adaptativo versus adaptativo en animales no humanos. Los investigadores han comenzado a reconocer la utilidad potencial de entender la toma de decisiones humanas y la psicopatología a través del balance entre explorar y explotar. En este artículo, proponemos que el balance entre explorar y explotar ofrece promesas para avanzar en nuestra comprensión mecanicista de los procesos de toma de decisiones que confieren vulnerabilidad y mantienen la patología alimentaria debido a sus bases neurodesarrolladoras, su conservación a través de las especies y su capacidad de ser modelado matemáticamente. Presentamos un modelo de cómo la toma de decisiones subóptima entre explorar y explotar puede promover la alimentación disfuncional y presentamos recomendaciones para futuras investigaciones que apliquen este marco a la patología alimentaria. En conjunto, el balance entre explorar y explotar proporciona un marco translacional para expandir los modelos etiológicos y de mantenimiento de la patología alimentaria, dadas los cambios en el desarrollo de la toma de decisiones entre explorar y explotar que coinciden en el tiempo con la aparición de la patología alimentaria y la evidencia de una toma de decisiones entre explorar y explotar sesgada en la psicopatología. Además, comprender la toma de decisiones entre explorar y explotar en los trastornos alimentarios puede mejorar el conocimiento de su fisiopatología subyacente, informando intervenciones clínicas dirigidas como la neuromodulación y la farmacoterapia.

Naturalistic symptom trajectories of atypical anorexia nervosa, anorexia nervosa, and bulimia nervosa in a prospective cohort study of United States college students.

OBJECTIVE: Research on the natural course of symptoms of atypical anorexia nervosa (AN) relative to AN and bulimia nervosa (BN) is limited yet needed to inform nosology and improve understanding of atypical AN. This study aimed to 1) characterize trajectories of eating disorder and internalizing (anxiety, depression) symptoms in college students with and without a history of atypical AN, AN, and BN; and 2) compare sex and race/ethnicity distributions across groups. METHOD: United States college students who participated in Spit for Science™, a prospective cohort study, were classified as having a history of atypical AN (n = 125), AN (n = 160), BN (n = 617), or as non-eating-disorder controls (NCs, n = 5876). Generalized and linear mixed-effects models assessed group differences in eating and internalizing symptom trajectories, and logistic regression compared groups on sex and race/ethnicity distributions. RESULTS: Atypical AN participants demonstrated elevated eating disorder and internalizing symptoms compared to NCs during college, but less severe symptoms than AN and BN participants. Although all eating disorder groups showed signs of improvement in fasting and driven exercise, purging and depression remained elevated. Atypical AN participants showed increasing anxiety and stable binge-eating trajectories compared to AN and/or BN participants. The atypical AN group comprised significantly more people of color than the AN group. DISCUSSION: Findings underscore that atypical AN is a severe psychiatric disorder. As atypical AN may present as less severe than AN and BN and disproportionately affects people of color, clinicians should be mindful of biases that could delay diagnosis and care. PUBLIC SIGNIFICANCE: College students with histories of atypical AN, AN, and BN demonstrated improvements in fasting and driven exercise and stable purging and depression levels. Atypical AN students showed worsening anxiety and stable binge-eating trajectories compared to favorable changes among AN and BN students. A higher percentage of atypical AN (vs. AN) students were people of color. Findings may improve the detection of atypical AN in college students.

Eating disorder symptom non-endorsers in hospitalised patients with anorexia nervosa: Who are they?

OBJECTIVE: Impaired insight and illness denial are common in anorexia nervosa (AN). Missing an AN diagnosis may delay treatment and negatively impact outcomes. METHOD: The current retrospective study examined the prevalence and characteristics of AN symptom non-endorsement (i.e., scoring within the normal range on the Eating Disorder Examination Questionnaire [EDE-Q] or the Eating Disorder Examination [EDE] interview) in three independent samples of hospitalised patients with AN (N1 = 154; N2 = 300; N3 = 194). A qualitative chart review of a subsample of non-endorsers (N4 = 32) extracted reports of disordered eating behaviours observed by the treatment team. RESULTS: The prevalence of non-endorsement ranged from 11% to 34% across sites. Non-endorsers were more likely to be diagnosed with AN restricting type (AN-R) and reported fewer symptoms of co-occurring psychopathology than endorsers. Groups benefitted equally from treatment. The qualitative chart review indicated that objective symptoms of AN were recorded by staff in over 90% of non-endorsers. CONCLUSIONS: Eating disorder symptom assessments using the EDE-Q or EDE may miss symptomatology in up to a third of individuals hospitalised with AN. This study highlights the potential utility of multi-modal assessment including patient interviews, collateral informants, and behavioural observation to circumvent non-endorsement.

Understanding outcomes in family-based treatment for adolescent anorexia nervosa: a network approach.

BACKGROUND: Family-based treatment (FBT) is the first-line treatment for adolescent anorexia nervosa (AN). Yet, remission is not achieved for about half of adolescents with AN receiving FBT. Understanding patient- and parent-level factors that predict FBT response may inform treatment development and improve outcomes. METHODS: Network analysis was used to identify the most central symptoms of AN in adolescents who completed the Eating Disorder Examination (EDE) prior to FBT (N = 409). Bridge pathways between adolescent AN and parental self-efficacy in facilitating their child's recovery from AN were identified in a subset of participants (n = 184). Central and bridge symptoms were tested as predictors of early response (⩾2.4 kg weight gain by the fourth session of FBT) and end-of-treatment weight restoration [⩾95% expected body weight (EBW)] and full remission (⩾95% EBW and EDE score within 1 standard deviation of norms). RESULTS: The most central symptoms of adolescent AN included desiring weight loss, dietary restraint, and feeling fat. These symptoms predicted early response, but not end-of-treatment outcomes. Bridge symptoms were parental beliefs about their responsibility to renourish their child, adolescent discomfort eating in front of others, and adolescent dietary restraint. Bridge symptoms predicted end-of-treatment weight restoration, but not early response nor full remission. CONCLUSIONS: Findings highlight the prognostic utility of core symptoms of adolescent AN. Parent beliefs about their responsibility to renourish their child may maintain associations between parental self-efficacy and AN psychopathology. These findings could inform strategies to adapt FBT and improve outcomes.

A systematic review comparing atypical anorexia nervosa and anorexia nervosa.

OBJECTIVE: A description of atypical anorexia nervosa (atypical AN) was provided in DSM-5 in 2013 and a sizable literature has since developed describing the clinical features of individuals with atypical AN and comparing them to those of individuals with anorexia nervosa (AN) and those of healthy individuals. The purpose of this study was to conduct a systematic review of this literature. METHOD: A systematic review following PRISMA guidelines was conducted of studies published since 2013 that compared the clinical characteristics of individuals with atypical AN to those of individuals with AN and/or healthy controls. Meta-analyses were conducted when similar measures were reported in three or more studies. RESULTS: Twenty-four publications met criteria for inclusion. Their results indicated that the level of eating disorder-specific psychopathology is significantly higher among individuals with atypical AN than among controls and as high or higher as among individuals with AN while levels of non-eating disorder psychopathology are similar. Individuals with atypical AN experience many of the physiological complications associated with AN, but some complications appear less frequent. DISCUSSION: The psychological symptoms and physiological complications of individuals with atypical AN are generally similar to those of individuals with AN, although there may be differences in the frequency of some physical complications. Little information is available on the course, outcome, and treatment response of individuals with atypical AN. In addition, full diagnostic criteria for atypical AN have not been developed, and the nosological relationship of atypical AN to established eating disorders such as bulimia nervosa is unclear. PUBLIC SIGNIFICANCE: Atypical anorexia nervosa as described in the DSM-5 identifies individuals with many of the psychological characteristics of typical anorexia nervosa who, despite significant weight loss, are not underweight. The current systematic review found that the psychological symptoms and physiological characteristics of individuals with atypical AN are generally similar to those of individuals with AN, although there may be differences in the frequency of some physical complications.

OBJETIVO: En 2013 se realizó una descripción de la anorexia nerviosa atípica (ANA) en el DSM-5 y desde entonces se ha desarrollado una literatura considerable que describe las características clínicas de los individuos que padecen anorexia nerviosa atípica y los compara con los de los individuos que padecen anorexia nerviosa (AN) y los de individuos sanos. El propósito de este estudio fue realizar una revisión sistemática de esta literatura. MÉTODO: Se realizó una revisión sistemática siguiendo las guías PRISMA de estudios publicados desde 2013 que compararon las características clínicas de individuos que padecen anorexia nerviosa atípica con las de individuos que padecen anorexia nerviosa y/o controles sanos. Se realizaron metaanálisis cuando se reportaron medidas similares en tres o más estudios. RESULTADOS: Veinticuatro publicaciones cumplieron con los criterios de inclusión. Sus resultados indicaron que el nivel de psicopatología específica del trastorno de conducta alimentaria es significativamente mayor entre los individuos que padecen anorexia nerviosa atípica que entre los controles y tan alto o más alto como entre los individuos que padecen anorexia nerviosa, mientras que los niveles de psicopatología del no trastorno de la conducta alimentaria son similares. Los individuos que padecen anorexia nerviosa atípica experimentan muchas de las complicaciones fisiológicas asociadas con la anorexia nerviosa, pero algunas complicaciones parecen menos frecuentes. DISCUSIÓN: Los síntomas psicológicos y las complicaciones fisiológicas de los individuos que padecen anorexia nerviosa atípica son generalmente similares a los de los individuos que padecen anorexia nerviosa, aunque puede haber diferencias en la frecuencia de algunas complicaciones físicas. Hay poca información disponible sobre el curso, el resultado y la respuesta al tratamiento de los individuos que padecen AN atípica. Además, no se han desarrollado criterios diagnósticos completos para la anorexia nerviosa atípica, y la relación nosológica de la anorexia nerviosa atípica con los trastornos de la conducta alimentaria establecidos, como la bulimia nerviosa, no está clara.

Predictors of family-based treatment for adolescent eating disorders: Do family or diagnostic factors matter?

OBJECTIVE: Misconceptions around which patients will and will not benefit from family-based treatment (FBT) for adolescent eating disorders (EDs) limit referrals and access to this treatment modality. The present study explored whether common demographic and clinical factors that may prevent referral to FBT predict treatment outcomes in adolescent anorexia nervosa (AN) and bulimia nervosa (BN). METHOD: The following predictors of treatment outcomes were assessed: baseline family and diagnostic factors (socioeconomic status, comorbidity, illness duration, parent feelings of self-efficacy, family status, prior treatment, sex and prior hospitalizations) in a combined sample of adolescents receiving FBT compared to those randomized to other treatment conditions, across six clinical trials in the United States and Canada (total n = 724, ages 12-18, 90% female across both diagnoses). AN and BN samples were examined separately. RESULTS: Any prior ED treatment emerged as the only predictor of outcome in AN and BN, such that having no prior treatment predicted better outcomes in FBT for AN, and in both FBT and other treatment modalities for BN. No other sociodemographic or clinical variables predicted outcomes for AN or BN in FBT or in other evidence-based treatment modalities. CONCLUSIONS: The findings of this exploratory analysis suggest that commonly assumed factors do not predict outcome in FBT. Specifically socioeconomic and demographic factors or clinical variability in families seeking treatment do not predict treatment outcomes in FBT, or other evidence-based treatment modalities, with the exception of prior treatment. Providers should consider referring to FBT even when these factors are present. PUBLIC SIGNIFICANCE: This manuscript reports that commonly assumed family, sociodemographic and diagnostic factors do not predict outcome in FBT or other evidence-based treatment modalities, with the exception of prior treatment. This data may be helpful for providers when considering referrals to FBT in the context of variability in these variables.

Generalized network psychometrics of eating-disorder psychopathology.

OBJECTIVE: As network models of eating disorder (ED) psychopathology become increasingly popular in modeling symptom interconnectedness and identifying potential treatment targets, it is necessary to contextualize their performance against other methods of modeling ED psychopathology and to evaluate potential ways to optimize and capitalize on their use. To accomplish these goals, we used generalized network psychometrics to estimate and compare latent variable models and network models, as well as hybrid models. METHOD: We tested the structure of the Eating Pathology Symptoms Inventory (EPSI) and Eating Disorder Examination-Questionnaire (EDE-Q) in Recovery Record, Inc. mobile phone application users (N = 6856). RESULTS: Although all models fit well, results favored a hybrid latent variable and network framework, which showed that ED symptoms fit best when modeled as higher-order constructs, rather than direct symptom-to-symptom connections, and when the relationships between those constructs are described as a network. Hybrid models in which latent factors were modeled as nodes within a network showed that EPSI Purging, Binge Eating, Cognitive Restraint, Body Dissatisfaction, and Excessive Exercise had high importance in the network. EDE-Q Eating Concern and Shape Concern were also important nodes. Results showed that the EPSI network was highly stable and replicable, whereas the EDE-Q network was not. DISCUSSION: Integrating latent variable and network model frameworks enables tests of centrality to identify important latent variables, such as purging, that may promote the spread of ED psychopathology throughout a network, allowing for the identification of future treatment targets.

Subcortical brain volume and cortical thickness in adolescent girls and women with binge eating.

OBJECTIVE: Alterations in brain structure have been implicated in the onset and acute phases of several forms of psychopathology. However, there is a dearth of research investigating brain structure in persons with binge eating, contributing to poor understanding of mechanisms associated with binge eating. METHOD: Adolescent girls and women (aged 14-35 years) with binge eating (n = 56) and group age-matched girls and women without binge eating (n = 26) completed structural magnetic resonance imaging (MRI) scans and interview-based and self-report assessments of eating disorder and general psychopathology. MRI data were processed using FreeSurfer. Analysis of covariance tested mean differences in subcortical volume and cortical thickness of a priori selected regions of interest between binge-eating and non-binge-eating groups, controlling for age, body mass index, purging frequency, depression, and medication use. Exploratory partial correlations tested associations between brain structure and eating disorder symptoms within participants with binge eating. RESULTS: We did not observe differences in regional subcortical volume and cortical thickness between girls and women with and without binge eating. Within participants with binge eating, severity of attitudinal eating disorder symptoms was inversely associated with caudal middle frontal gyrus, right precentral gyrus, right postcentral gyrus, superior parietal, left inferior parietal thickness, and left accumbens volume; however, these associations would not survive multiple-comparison corrections. DISCUSSION: Correlations between attitudinal eating disorder symptoms and frontoparietal thinning may represent a state marker of binge eating. Future research could investigate whether frontoparietal thinning worsens with illness duration or persists beyond binge eating cessation.

Longitudinal trajectories of behavior change in a national sample of patients seeking eating-disorder treatment.

OBJECTIVE: Rapid response to treatment, indicated by substantial decreases in eating-disorder (ED) symptoms within the first 4-6 weeks of treatment, is the most reliable predictor of treatment outcomes for EDs. However, there is limited research evaluating short-term longitudinal trajectories of ED symptoms during treatment. Thus, it is difficult to know which aspects of ED psychopathology are slow or fast to change. The purpose of this study was to elucidate three-month trajectories of ED psychopathology during treatment and test whether ED diagnosis influenced the direction and rate of change. METHOD: Participants were Recovery Record users seeking treatment for an ED (N = 4,568; 86.8% female). Participants completed the Eating Pathology Symptoms Inventory once per month for 3 months. RESULTS: Latent growth curve models indicated that ED diagnosis influenced the rate of ED behavior change. Anorexia nervosa was associated with faster reductions in cognitive restraint, excessive exercise, restricting, yet slower reductions in body dissatisfaction, and binge eating. Bulimia nervosa was associated with faster reductions in binge eating, cognitive restraint, excessive exercise, and purging. Binge-eating disorder was associated with faster reductions in body dissatisfaction and binge eating, yet slower reductions in restricting. CONCLUSIONS: Our results have implications for future research by providing initial information about the direction and rate of ED change over the course of treatment. If clinicians and researchers know which ED symptoms are slow to change, on average, across diagnostic groups, treatment protocols could be adjusted to target slow changing symptoms more quickly, and therefore improve ED treatment outcomes.

A systematic review and meta-analysis of attentional bias toward food in individuals with overweight and obesity.

Attentional bias to food stimuli may contribute to the etiology and/or maintenance of overweight and obesity. We conducted a literature review and meta-analysis per the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify the effect size associated with attentional bias to palatable food in persons with overweight/obesity across the age spectrum. Included studies measured attentional bias to food stimuli using two reaction-time tasks (dot-probe, emotional Stroop), eye-tracking methodology, and/or event-related potentials. Meta-analysis showed that persons with overweight/obesity did not differ from persons with a healthy weight on any of the following: automatic and maintained attention to food stimuli measured by the dot-probe task (Hedge's gautomatic = -0.355, 95% CI = -0.383, 0.486; and Hedge's gmaintained = 0.006, 95% CI = -0.187, 0.199); attentional bias to food stimuli measured by the emotional Stroop task (Hedge's g = 0.184, 95% CI = -0.283, 0.651); and attentional bias to food images on gaze-direction and gaze-duration bias eye-tracking metrics (Hedge's gdirection = 0.317, 95% CI = -0.096, 0.729; and Hedge's gduration = 0.056, 95% CI = -0.296, 0.407). Systematic review of preliminary event-related potentials research suggested automatic, but not maintained, attention to food images in persons with overweight/obesity. Limitations of past attentional bias research in overweight/obesity, such as poor reliability of measures and lack of consideration of moderators, such as binge eating and degree of overweight/obesity, preclude the ability to draw firm conclusions. We recommend implementation of empirically based methods for improving psychometric properties of attentional bias measures and examination of potential moderators so that the field can understand whether attentional bias to food is truly greater in overweight/obesity.

A new approach to eating-disorder classification: Using empirical methods to delineate diagnostic dimensions and inform care.

OBJECTIVE: Despite changes to the diagnostic criteria for eating disorders (EDs) in the DSM-5, the current diagnostic system for EDs has limited ability to inform treatment planning and predict outcomes. Our objective was to test the clinical utility of a novel dimensional approach to understanding the structure of ED psychopathology. METHOD: Participants (N = 243; 82.2% women) were community-recruited adults with a DSM-5 ED assessed at baseline, 6-month, and 1-year follow-up. Hierarchical factor analysis was used to identify a joint hierarchical-dimensional structure of eating, mood, and anxiety symptoms. Exploratory structural equation modeling was used to test the ability of the dimensional model to predict outcomes. RESULTS: At the top of the hierarchy, we identified a broad Internalizing factor that reflected diffuse symptoms of eating, mood, and anxiety disorders. Internalizing branched into three subfactors: distress, fear-avoidance (fears of certain stimuli and behaviors to neutralize fears, including ED behaviors designed to reduce fear of weight gain), and body dissatisfaction, which was nested within distress. The lowest level of the hierarchy was characterized by 15 factors. The hierarchical model predicted 60.1% of the variance in outcomes at 6-month follow-up, whereas all DSM eating, mood, and anxiety disorders combined predicted 35.8% of the variance in outcomes. DISCUSSION: A dimensional approach to understanding and diagnosing EDs improved the ability to prospectively predict clinical course above-and-beyond the traditional categorical (DSM-based) approach. Our findings have implications for endeavors to improve the prediction of ED prognosis and course, and to develop more effective trans-diagnostic treatments.

The Athletes' Relationships with Training scale (ART): A self-report measure of unhealthy training behaviors associated with eating disorders.

OBJECTIVE: Several studies indicate that eating-disorder (ED) psychopathology is elevated in athletes compared to non-athletes. The assessment of excessive exercise among athletes is a challenge because, compared to non-athletes, athletes are required to train at higher intensities and for longer periods of time. However, individuals participating in competitive sports are still susceptible to unhealthy physical-activity patterns. Most ED assessments were developed and normed in non-athlete samples and, therefore, do not capture the nuances of athletes' training experiences. The purpose of the current study was to develop and validate a clinically useful, self-report measure of unhealthy training behaviors and beliefs in athletes, the Athletes' Relationships with Training Scale (ART). METHOD: The initial item pool was administered to N = 267 women collegiate athletes who were participating in an ED prevention program study and N = 65 women athletes who were in ED treatment. RESULTS: Factor analyses indicated the ART had a four-factor structure. Factorial and construct validity of the ART were demonstrated. ART scores significantly predicted health care utilization and differed between athletes with an ED versus athletes without an ED. For athletes in ED treatment, ART scores significantly decreased from treatment admission to discharge. DISCUSSION: The ART showed evidence of strong psychometric properties and clinical utility. The ART could be helpful for clinicians and athletic trainers to help gauge whether athletes are engaging in unhealthy training practices that may warrant clinical attention and for tracking clinical outcomes in athletes with EDs who are receiving treatment.

New Horizons in Measurement: a Review of Novel and Innovative Approaches to Eating-Disorder Assessment.

PURPOSE OF REVIEW: Eating disorders are serious mental-health concerns that will affect over 30 million individuals in the USA at some point in their lives. Eating disorders occur across the lifespan, in a variety of ethnicities and races, in both men and women, and across the socioeconomic spectrum. Given the prevalence and severity of eating disorders, it is important that clinicians and researchers have access to appropriate assessment tools to aid in the early identification and treatment referral, differential diagnosis, treatment planning, and progress monitoring, and to ensure valid research findings. In this review, we describe novel and innovative assessment tools that were developed within the past 5 years for utilization in research and/or clinical practice with individuals with eating disorders. RECENT FINDINGS: We identified six multidimensional assessments for eating disorders, all of which can be administered online (with some also offering paper-and-pencil versions). Strengths of the measures included good internal consistency, test-retest reliability, and convergent validity. However, in part, due to problematic scale construction methods, certain scales had poor discriminant validity and most were developed and validated in mostly female samples. There are promising new eating disorder measures from which to choose; however, many measures continue to be limited by poor discriminant validity and need additional validation prior to incorporation into routine research and clinical practice.

Incremental validity of weight suppression in predicting clinical impairment in bulimic syndromes.

Research has shown that weight suppression (WS; the difference between a person's highest and current body weight in pounds) is a robust predictor of weight gain and eating-disorder (ED) symptoms among individuals with bulimic syndromes. Given the important prognostic role that WS plays in ED course and outcome, we hypothesized that WS would represent a clinically useful indicator of impairment for bulimic syndromes. We further posited that WS would demonstrate incremental validity above-and-beyond other proposed indicators in explaining clinical impairment in bulimic syndromes. Participants were community-recruited adults (N = 101; 80.2% female) with full-threshold (n = 51) or subthreshold (n = 50) bulimia nervosa. Other indicators of impairment included body mass index, frequency of inappropriate compensatory behaviors, lifetime history of any internalizing disorder, and multiple purging. Clinical impairment was assessed with the clinical impairment assessment (CIA). Hierarchical linear regression tested whether WS added to the explanation of CIA score variance above-and-beyond other indicators of bulimic-syndrome impairment. WS was significantly associated with clinical impairment (p = .011), but did not demonstrate incremental validity over other independent variables in predicting CIA scores. WS explained an additional 1.7% of the variance in CIA scores above-and-beyond other variables and the independent effect of WS on CIA scores represented a medium-sized effect (Cohen's d = 0.521). Results suggested that WS may be an indicator of ED-related clinical impairment. Inquiring about WS could be an informative component of routine bulimic-syndrome assessment, given that WS explains some of the variance in clinical impairment in bulimic syndromes.

Characterizing severe and enduring anorexia nervosa: An empirical approach.

Targeted approaches for the treatment of severe and enduring anorexia nervosa (SE-AN) have been recommended, but there is no consensus definition of SE-AN to inform research and clinical practice. This study aimed to take initial steps toward developing an empirically based definition of SE-AN by characterizing associations among putative indicators of severity and chronicity in eating disorders. Patients with AN (N = 355) completed interviews and questionnaires at treatment admission and discharge; height and weight were assessed to calculate body mass index (BMI). Structural equation mixture modeling was used to test whether associations among potential indicators of SE-AN (illness duration, treatment history, BMI, binge eating, purging, quality-of-life) formed distinct subgroups, a single group with one or more dimensions, or a combination of subgroups and dimensions. A three-factor (dimensional), two-profile (categorical) mixture model provided the best fit to the data. Factor 1 included eating disorder behaviors; Factor 2 comprised quality-of-life domains; Factor 3 was characterized by illness duration, number of hospitalizations, and admission BMI. Profiles differed on eating disorder behaviors and quality-of-life, but not on indicators of chronicity or BMI. Factor scores, but not profile membership, predicted outcome at discharge from treatment. Data suggest that patients with AN can be classified on the basis of eating disorder behaviors and quality-of-life, but there was no evidence for a chronic subgroup of AN. Rather, indices of chronicity varied dimensionally within each class. Given that current definitions of SE-AN rely on illness duration, these findings have implications for research and clinical practice.

Understanding eating disorders within internalizing psychopathology: A novel transdiagnostic, hierarchical-dimensional model.

BACKGROUND: Several problems with the classification and diagnosis of eating disorders (EDs) have been identified, including proliferation of 'other specified' diagnoses, within-disorder heterogeneity, and frequent diagnostic migration over time. Beyond problems within EDs, past research suggested that EDs fit better in a spectrum of internalizing psychopathology (characterized by mood and anxiety disorders) than in a separate diagnostic class. PURPOSE: To develop a transdiagnostic, hierarchical-dimensional model relevant to ED psychopathology that: 1) reduces diagnostic heterogeneity, 2) includes important dimensions of internalizing psychopathology that are often excluded from ED diagnostic models, and 3) predicts clinical impairment. PROCEDURES: Goldberg's (2006) method and exploratory structural equation modeling were used to identify a hierarchical model of internalizing in community-recruited adults with EDs (N=207). FINDINGS: The lowest level of the hierarchy was characterized by 15 factors that defined specific aspects of eating, mood, and anxiety disorders. At the two-factor level, Internalizing bifurcated into Distress (low well-being, body dissatisfaction, suicidality, dysphoria, ill temper, traumatic intrusions) and Fear-Avoidance (claustrophobia, social avoidance, panic symptoms, dietary restricting, excessive exercise, and compulsions). Results showed that the lowest level of the hierarchy predicted 67.7% of the variance in clinical impairment. In contrast, DSM eating, mood, and anxiety disorders combined predicted 10.6% of the variance in impairment secondary to an ED. CONCLUSIONS: The current classification model represents an improvement over traditional nosologies for predicting clinically relevant outcomes for EDs.

Do emotion regulation difficulties when upset influence the association between dietary restraint and weight gain among college students?

Obesity is a significant public health concern that affects more than one-fifth of adolescents aged 12-19 in the United States. Theoretical models suggest that prolonged dietary restraint leads to binge-eating behaviors, which in turn increases individuals' risk for weight gain or obesity. Results from the literature indicate a potential role for negative urgency (the tendency to act rashly when distressed) as a mediating variable that explains the link between dietary restraint and binge-eating episodes. The current study tested short-term, prospective longitudinal associations among dietary restraint, binge eating, negative urgency, and weight gain among college students - a population at increased risk for the development of overweight and obesity. We hypothesized that dietary restraint and weight gain would be mediated by negative urgency and binge eating, but only among participants with overweight and obesity. College students (N = 227) completed the Eating Pathology Symptoms Inventory, UPPS-P Impulsivity Scale, and self-reported weight and height to calculate body mass index. Results showed that the association between dietary restraint and weight gain was mediated by negative urgency and binge eating, but only among participants with overweight and obesity. Our findings indicated that negative urgency might represent a mechanism that explains why dietary restraint leads to future binge-eating episodes and weight gain among college students with overweight and obesity. Results suggest that future treatment and prevention programs for overweight and obesity may benefit from incorporating strategies to improve emotion regulation as a way to reduce binge eating and to prevent additional weight gain among 'at-risk' populations.

Low Overlap and High Heterogeneity Across Common Measures of Eating Disorder Pathology: A Content Analysis.

This study evaluated symptoms assessed in common measures of eating disorder pathology and tested overlap to evaluate the extent to which measures may be interchangeable. Six measures were included: Bulimia Test-Revised, Eating Attitudes Test-26, Eating Disorder Diagnostic Scale, Eating Disorder Examination Questionnaire, Eating Pathology Symptoms Inventory, and Questionnaire for Eating Disorder Diagnoses. Content overlap was quantitatively estimated using the Jaccard Index. Mean overlap was low (.195), likely due to the wide range of symptoms (87) assessed. The mean overlap of each measure with all others was .117 - .267, and the overlap among individual measures was .083 - .382. Implications of low overlap among measures include variable characterization of eating disorder phenotypes and the risk for lower generalizability of findings due to measurement variability.