Diminished Adaptation, Satisfaction, and Neural Responses to Advantageous Social Signals in Anorexia Nervosa and Bulimia Nervosa.

BACKGROUND: Development and recurrence of 2 eating disorders (EDs), anorexia nervosa and bulimia nervosa, are frequently associated with environmental stressors. Neurobehavioral responses to social learning signals were evaluated in both EDs. METHODS: Women with anorexia nervosa (n = 25), women with bulimia nervosa (n = 30), or healthy comparison women (n = 38) played a neuroeconomic game in which the norm shifted, generating social learning signals (norm prediction errors [NPEs]) during a functional magnetic resonance imaging scan. A Bayesian logistic regression model examined how the probability of offer acceptance depended on cohort, block, and NPEs. Rejection rates, emotion ratings, and neural responses to NPEs were compared across groups. RESULTS: Relative to the comparison group, both ED cohorts showed less adaptation (p = .028, ηp2 = 0.060), and advantageous signals (positive NPEs) led to higher rejection rates (p = .014, ηp2 = 0.077) and less positive emotion ratings (p = .004, ηp2 = 0.111). Advantageous signals increased neural activations in the orbitofrontal cortex for the comparison group but not for women with anorexia nervosa (p = .018, d = 0.655) or bulimia nervosa (p = .043, d = 0.527). More severe ED symptoms were associated with decreased activation of dorsomedial prefrontal cortex for advantageous signals. CONCLUSIONS: Diminished neural processing of advantageous social signals and impaired norm adaptation were observed in both anorexia nervosa and bulimia nervosa, while no differences were found for disadvantageous social signals. Development of neurocognitive interventions to increase responsivity to advantageous social signals could augment current treatments, potentially leading to improved clinical outcomes for EDs.

Interpersonal attribution bias and social evaluation in adolescent eating disorders.

OBJECTIVE: Improved understanding of adolescent eating disorders (EDs), including identification and refinement of treatment and recovery targets, may help improve clinical outcomes. Interpersonal function is a proposed risk and maintenance factor that may be particularly relevant given the significance of adolescence for both psychosocial development and ED onset. This study examined self-referential thinking in adolescents with EDs compared to healthy adolescents. METHOD: Twenty-nine adolescents with EDs and 31 healthy controls completed a self-report measure of interpersonal attributions as well as a verbal appraisal task that required conducting direct and indirect evaluations about oneself and direct evaluations about others. RESULTS: The ED group had a more negative self-attribution bias than the control group (p = 0.006) even when controlling for depression severity. Additionally, the ED group exhibited less positive direct self (p < 0.001), direct social (p = 0.015), and social reflected self-appraisals (p = 0.011) than the healthy cohort. After including depression as a covariate in the verbal appraisal model, the model was no longer significant, suggesting group differences related to social appraisals may be mediated by depression. CONCLUSIONS: Adolescents with EDs have more negative interpersonal beliefs than comparison adolescents. Future studies are needed to determine how the constructs identified here relate to clinical course.

Social Processing in Eating Disorders: Neuroimaging Paradigms and Research Domain Organizational Constructs.

PURPOSE OF REVIEW: Social and environmental factors have been related to both symptom expression of disordered eating in individuals and changes in the prevalence of eating disorders (EDs) in populations. Neural differences in processing social information may contribute to EDs. This review assesses the evidence for aberrant neural responses during social processing in EDs. RECENT FINDINGS: This review examines how constructs within the social processing domain have been evaluated by neuroimaging paradigms in EDs, including communication, affiliation, and understanding of both oneself and others. Differences related to social processing in EDs include altered processing for self-relevant stimuli, in the context of identity, valence, expectations, and affiliative relationships. Future work is needed to integrate how differences in processing social stimuli relate to alterations in cognitive control and reward as well as specific disordered eating symptoms.

Elevated Neurobehavioral Responses to Negative Social Interactions in Women With Bulimia Nervosa.

BACKGROUND: Bulimia nervosa (BN) is a complex psychiatric illness that includes binge-purge behaviors and a belief that one's value as a person depends on body shape and weight. Social pressure strongly influences the development and maintenance of BN, but how this manifests neurobiologically within an individual remains unknown. We used a computational psychiatry approach to evaluate neural mechanisms underlying social interactions in BN. METHODS: Behavioral and functional magnetic resonance imaging data were collected from 24 women with BN and 26 healthy comparison women using an iterated social exchange game. Data were sorted round by round based on whether the mathematically computed social signals indicated an improving (positive reciprocity) or deteriorating (negative reciprocity) relationship for each participant. RESULTS: Social interactions with negative reciprocity resulted in more negative behavioral responses and stronger neural activations in both cortical and subcortical regions in women with BN than healthy comparison women. No behavioral or neural differences were observed for interactions demonstrating positive reciprocity, suggesting a very specific form of psychopathology in BN: amplification of negative self-relevant social interactions. Cortical activations (e.g., temporoparietal junction and dorsolateral prefrontal cortex) did not covary with mood symptoms, while subcortical activations (e.g., amygdala and dorsal striatum) were associated with acute psychopathology. CONCLUSIONS: These data provide a first step toward a mechanistic neuropsychological model of aberrant social processing in BN, demonstrating how a computational psychiatric approach can elucidate neural mechanisms for complex psychiatric illnesses. Future treatments for BN may include targeting neural regions that support these negative biases in social perceptions.

Neural processes related to negative self-concept in adult and adolescent anorexia nervosa.

OBJECTIVE: Negative self-concept is characteristic of anorexia nervosa (AN), but the neural processes mediating this component of AN is unknown. These studies investigated how valence and social perspectives impact neural processing in both adults and adolescents with AN. METHOD: In an fMRI task, participants evaluated positive and negative adjectives from three social perspectives. Two studies were completed, one in 59 women (healthy, with AN, recovered from AN) and one in 42 adolescents (healthy, with AN). Neural regions of interest (ROIs) related to valence were identified and activations compared across groups and social perspectives. RESULTS: Behaviourally, both adult and adolescent cohorts with AN were less positive during self-evaluations. In the adult study, neural differences related to clinical group and condition were observed in ROIs more responsive to positive social stimuli (medial prefrontal cortex, precuneus, left temporoparietal junction) but not in ROIs more responsive to negative social stimuli. No neural differences in relation to clinical group were observed in the adolescents. CONCLUSIONS: Behavioural differences related to negative self-concept are present in both adolescents and adults with AN, and neural differences, selective for positive social stimuli, were also observed in adults. AN may interfere with neurodevelopmental processes involved in positive self-concept.

The legacy of hope summit: a consensus-based initiative and report on eating disorders in the U.S. and recommendations for the path forward.

BACKGROUND: Several unsuccessful attempts have been made to reach a cross-disciplinary consensus on issues fundamental to the field of eating disorders in the United States (U.S.). In January 2020, 25 prominent clinicians, academicians, researchers, persons with lived experience, and thought leaders in the U.S. eating disorders community gathered at the Legacy of Hope Summit to try again. This paper articulates the points on which they reached a consensus. It also: (1) outlines strategies for implementing those recommendations; (2) identifies likely obstacles to their implementation; and (3) charts a course for successfully navigating and overcoming those challenges. METHODS: Iterative and consensual processes were employed throughout the Summit and the development of this manuscript. RESULTS: The conclusion of the Summit culminated in several consensus points, including: (1) Eating disorder outcomes and prevention efforts can be improved by implementing creative health education initiatives that focus on societal perceptions, early detection, and timely, effective intervention; (2) Such initiatives should be geared toward parents/guardians, families, other caretakers, and frontline healthcare providers in order to maximize impact; (3) Those afflicted with eating disorders, their loved ones, and the eating disorders community as a whole would benefit from greater accessibility to affordable, quality care, as well as greater transparency and accountability on the part of in-hospital, residential, and outpatient health care providers with respect to their qualifications, methodologies, and standardized outcomes; (4) Those with lived experience with eating disorders, their loved ones, health care providers, and the eating disorders community as a whole, also would benefit from the establishment and maintenance of treatment program accreditation, professional credentialing, and treatment type and levels of care guidelines; and (5) The establishment and implementation of effective, empirically/evidence-based standards of care requires research across a diverse range of populations, adequate private and government funding, and the free exchange of ideas and information among all who share a commitment to understanding, treating, and, ultimately, markedly diminishing the negative impact of eating disorders. CONCLUSIONS: Widespread uptake and implementation of these recommendations has the potential to unify and advance the eating disorders field and ultimately improve the lives of those affected. A cross-disciplinary group of eating disorder professionals, thought leaders, and persons with lived experience have come together and reached a consensus on issues that are fundamental to the battle against the life-threatening and life-altering illnesses that are eating spectrum disorders. Those issues include: (1) the need for early detection, intervention, prevention, and evidenced-based standards of care; (2) the critical need to make specialized care more accessible and affordable to all those in need; (3) the importance of developing uniform, evidenced-based standards of care; (4) the need for funding and conducting eating spectrum disorder research; and (5) the indispensability of advocacy, education, and legislation where these illnesses are concerned. During the consensus process, the authors also arrived at strategies for implementing their recommendations, identified likely obstacles to their implementation, and charted a course for successfully navigating and overcoming those challenges. Above all else, the authors demonstrated that consensus in the field of eating spectrum disorders is possible and achievable and, in doing so, lit a torch of hope that is certain to light the path forward for years to come.

Qualitative patient experiences from the Self-Blame and Perspective-Taking Intervention for eating disorders.

BACKGROUND: Problems in social cognition and social support contribute to eating disorders (ED). Group therapy provides an ideal format to create an experiential learning environment focused on understanding social interactions. This pilot study examined the qualitative content of the participants' experiences in the Self-Blame and Perspective-Taking Intervention (SBPI) for ED. METHODS: The SBPI was a 4-week group therapy intervention involving art therapy and psychoeducation that focused on social behaviors in ED patients. Participants received surveys immediately after the intervention and at 1 to 4 weeks after the post-intervention. Thematic analyses of qualitative feedback were performed using Braun and Clarke's thematic analysis framework. RESULTS: Inductive analyses revealed three main themes: (1) Developing self-acceptance through emotional reflection, (2) Changing expectations with neurosocial knowledge, and (3) Bonding and vulnerability in social interactions; all concepts intentionally targeted by the SBPI. Participants varied in their support of a guideline to exclude personal discussion of ED-related cognitions and behaviors in the group. CONCLUSIONS: As a whole, patients valued the combination of psychosocial education with group experientials focused on social behavior. Positive feedback from the SBPI suggests that adjunctive treatments that target mental-wellness constructs indirectly related to ED pathology may be helpful by allowing patients to see themselves as separable from the illness. Trial registration ClinicalTrials.gov, NCT0487758. Registered 7 May 2021-Retrospectively registered. https://clinicaltrials.gov/ct2/show/NCT04877158 .

Adult patients with eating disorders frequently report challenges in developing and maintaining supportive social relationships. A group therapy intervention utilizing structured art tasks in conjunction with psychoeducation about interpersonal relationships was piloted in twenty-four women with eating disorders. Participants provided written feedback about their experiences in the intervention. These responses were coded by three raters to identify consistent themes related to those experiences. Participants reported benefits related to self-acceptance and emotional regulation, valued learning about their brain and behaviors, and appreciated peer interactions in this setting. In sum, this adjunctive and structured outpatient group targeting social interactions was acceptable to outpatients with eating disorders.

Structural brain differences in recovering and weight-recovered adult outpatient women with anorexia nervosa.

BACKGROUND: Anorexia nervosa is a complex psychiatric illness that includes severe low body weight with cognitive distortions and altered eating behaviors. Brain structures, including cortical thicknesses in many regions, are reduced in underweight patients who are acutely ill with anorexia nervosa. However, few studies have examined adult outpatients in the process of recovering from anorexia nervosa. Evaluating neurobiological problems at different physiological stages of anorexia nervosa may facilitate our understanding of the recovery process. METHODS: Magnetic resonance imaging (MRI) images from 37 partially weight-restored women with anorexia nervosa (pwAN), 32 women with a history of anorexia nervosa maintaining weight restoration (wrAN), and 41 healthy control women were analyzed using FreeSurfer. Group differences in brain structure, including cortical thickness, areas, and volumes, were compared using a series of factorial f-tests, including age as a covariate, and correcting for multiple comparisons with the False Discovery Rate method. RESULTS: The pwAN and wrAN cohorts differed from each other in body mass index, eating disorder symptoms, and social problem solving orientations, but not depression or self-esteem. Relative to the HC cohort, eight cortical thicknesses were thinner for the pwAN cohort; these regions were predominately right-sided and in the cingulate and frontal lobe. One of these regions, the right pars orbitalis, was also thinner for the wrAN cohort. One region, the right parahippocampal gyrus, was thicker in the pwAN cohort. One volume, the right cerebellar white matter, was reduced in the pwAN cohort. There were no differences in global white matter, gray matter, or subcortical volumes across the cohorts. CONCLUSIONS: Many regional structural differences were observed in the pwAN cohort with minimal differences in the wrAN cohort. These data support a treatment focus on achieving and sustaining full weight restoration to mitigate possible neurobiological sequela of AN. In addition, the regions showing cortical thinning are similar to structural changes reported elsewhere for suicide attempts, anxiety disorders, and autistic spectrum disorder. Understanding how brain structure and function are related to clinical symptoms expressed during the course of recovering from AN is needed.

Anorexia nervosa is a life-threatening mental illness defined in part by an inability to maintain a body weight in the normal range. Malnutrition and low weight are factors typically present in the anorexia nervosa and can affect brain structure. We conducted a detailed analysis of brain structure using Freesurfer, focusing on regional cortical thicknesses, areas, and volumes, in adult outpatient women with anorexia nervosa. The study included both a partially weight-restored cohort with anorexia nervosa, a cohort sustaining a healthy body weight with history of anorexia nervosa, and a healthy comparison cohort. Reduced cortical thicknesses were observed in eight regions, primarily in the frontal lobe and cingulate for the cohort recently with anorexia nervosa but only one frontal region in the weight-maintained cohort. These data emphasize the importance of sustained weight-restoration for adult women with anorexia nervosa. Further, the impacted neural regions have been associated with impulsivity, attention, self-regulation, and social interactions in other clinical cohorts, suggesting that these neuropsychological processes may warrant study in patients recovering from anorexia nervosa. Future work should consider whether these factors have clinical relevance in the outpatient treatment of adults with anorexia nervosa.

Treatment Utilization and Medical Problems in a Community Sample of Adult Women With Anorexia Nervosa.

Anorexia nervosa (AN) has a prolonged course of illness, making both defining recovery and determining optimal outpatient treatments difficult. Here, we report the types of treatments utilized in a naturalistic sample of adult women with AN in Texas. Participants were recruited from earlier studies of women with AN (n = 28) and in weight recovery following AN (n = 18). Participants provided information about both their illness and treatments during their most severe period as well as during the 2-6 years following original assessments. Based upon their baseline and follow-up clinical status participants were classified as remaining ill (AN-CC, n = 17), newly in recovery (AN-CR, n = 11), and sustained weight-recovery (AN-WR, n = 18). Utilization of health care institutions and providers were compared across groups. There were no differences in groups related to symptoms or treatments utilized during the severe-period. During the follow-up period, intensive outpatient programs were utilized significantly more by the AN-CC group than the other groups, and dietitians were seen significantly less by the AN-WR group. Medical complications related to the ED were significantly more common in the AN-CC group. All groups maintained similar levels of contact with outpatient psychiatrists, therapists, and primary care physicians. Current treatments remain ineffective for a subset of AN participants. Future prospective studies assessing medical health and comorbidities in AN may provide additional insights into disease severity and predictors of clinical outcome.

Oxytocin Receptor Polymorphism Decreases Midline Neural Activations to Social Stimuli in Anorexia Nervosa.

Oxytocin is a neurotransmitter related to both feeding and social behavior; anorexia nervosa is a psychiatric illness defined by reduced food intake, weight loss, and problems in social perceptions. Oxytocin receptor single nucleotide polymorphisms rs2254298 or rs53576 and neural responses to social stimuli were evaluated in adult women with or recovered from anorexia nervosa using functional magnetic resonance imaging. Carriers of the A allele for OXTR rs2254298 (2 AA and 10 AG) showed significantly reduced activation of portions of the posterior cingulate cortex and medial prefrontal cortex for social stimuli as well as greater negative connectivity between the posterior cingulate and the occipital lobe relative to the GG subjects for rs2254298. Differences in the other OXTR SNP, rs53576, did not result in detectable neural differences in either whole brain or region of interest analyses. Development of a mechanistic, biological model of how social behavior is impacted by mental illness requires linking genes to functional brain activations in disease. This pilot study suggests that in anorexia nervosa, differences related to OXTR SNP rs2254298 may alter neural responses to social stimuli and disrupt the engagement and disengagement of the default mode network.

Mentalization and the left inferior frontal gyrus and insula.

OBJECTIVE: To determine if an interpersonal attribution bias associated with self-perception, the externalizing bias, was related to neural activations during mentalization. METHODS: A functional magnetic resonance imaging task involving verbal appraisals measured neural activations when thinking about oneself and others in 59 adults, including healthy women as well as women with and recovered from anorexia nervosa. Whole-brain regressions correlated brain function during mentalization with the externalizing bias measured using the Internal, Personal, and Situational Attributions Questionnaire. RESULTS: Women with anorexia nervosa had a lower externalizing bias, demonstrating a tendency to self-attribute more negative than positive social interactions, unlike the other groups. The externalizing bias was correlated with activation of the left inferior frontal gyrus and posterior insula, when comparing thinking about others evaluating oneself with direct self-evaluation. DISCUSSION: Externalizing biases may provide an office-based assay reflecting neurocognitive disturbances in social self-perception that are common during anorexia nervosa.

Neuropsychological and Cognitive Correlates of Recovery in Anorexia Nervosa.

OBJECTIVE: To identify clinical or cognitive measures either predictive of illness trajectory or altered with sustained weight recovery in adult women with anorexia nervosa. METHODS: Participants were recruited from prior studies of women with anorexia nervosa (AN-C) and in weight-recovery following anorexia nervosa (AN-WR). Participants completed a neuropsychological battery at baseline and clinical assessments at both baseline and follow-up. Groups based on clinical outcome (continued eating disorder, AN-CC; newly in recovery, AN-CR; sustained weight-recovery, AN-WR) were compared by using one-way ANOVAs with Bonferroni-corrected post hoc comparisons. RESULTS: Women with continued eating disorder had poorer neuropsychological function and self-competence at baseline than AN-CR. AN-CR showed changes in depression and externalizing bias, a measure of self-related attributions. AN-WR differed from both AN-CC and AN-CR at baseline in externalizing bias, but only from AN-CC at outcome. DISCUSSION: Neuropsychological function when recently ill may be a prognostic factor, while externalizing bias may provide a clinical target for recovery. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

Novel and ultra-rare damaging variants in neuropeptide signaling are associated with disordered eating behaviors.

OBJECTIVE: Eating disorders develop through a combination of genetic vulnerability and environmental stress, however the genetic basis of this risk is unknown. METHODS: To understand the genetic basis of this risk, we performed whole exome sequencing on 93 unrelated individuals with eating disorders (38 restricted-eating and 55 binge-eating) to identify novel damaging variants. Candidate genes with an excessive burden of predicted damaging variants were then prioritized based upon an unbiased, data-driven bioinformatic analysis. One top candidate pathway was empirically tested for therapeutic potential in a mouse model of binge-like eating. RESULTS: An excessive burden of novel damaging variants was identified in 186 genes in the restricted-eating group and 245 genes in the binge-eating group. This list is significantly enriched (OR = 4.6, p<0.0001) for genes involved in neuropeptide/neurotrophic pathways implicated in appetite regulation, including neurotensin-, glucagon-like peptide 1- and BDNF-signaling. Administration of the glucagon-like peptide 1 receptor agonist exendin-4 significantly reduced food intake in a mouse model of 'binge-like' eating. CONCLUSIONS: These findings implicate ultra-rare and novel damaging variants in neuropeptide/neurotropic factor signaling pathways in the development of eating disorder behaviors and identify glucagon-like peptide 1-receptor agonists as a potential treatment for binge eating.

Orthorexia Nervosa and Eating Disorder Symptoms in Registered Dietitian Nutritionists in the United States.

BACKGROUND: Registered dietitian nutritionists are trained to identify optimal food choices for clients based on medical state and lifestyle. Orthorexia nervosa (ON) is a proposed disorder related to obsessions about eating healthfully. Eating disorders (EDs) are serious mental illnesses with symptoms related to eating, body image, and self-esteem. Both ON and EDs are more common among RDNs than the general population. OBJECTIVE: This study examined the prevalence of ON and EDs in RDNs in the United States and, among this sample, assessed whether the presence of ON symptoms related to symptoms of EDs, including weight, shape, eating, and restraint. DESIGN: A cross-sectional design compared responses for participants after dividing into three groups: those scoring at-risk for ON, those with a current or past ED, and a comparison group. PARTICIPANTS: A sample of 2,500 RDNs were invited to complete surveys electronically; 636 responses were received. MAIN OUTCOME MEASURES: Scores on the Orthorexia Nervosa Questionnaire (ORTO-15) and Eating Disorder Examination Questionnaire (EDE-Q) determined prevalence of ON and EDs. Differences in these measures, and body mass index were compared among the three groups. STATISTICAL ANALYSES: Analysis of variance and χ2 analyses were used to compare the groups. RESULTS: For the entire sample, scores on the ORTO-15 suggested 49.5% were at risk for ON, and scores on the EDE-Q suggested 12.9% were at risk for an ED, with 8.2% of RDNs self-disclosing treatment for an ED. Both the group disclosing ED treatment and the group at risk for ON had a lower mean body mass index, lower scores on the ORTO-15, and higher scores on the EDE-Q and all its subscales than the comparison group. CONCLUSIONS: Clarifying the relationship between ON and EDs is warranted because ON symptoms appear to be associated not only with disturbances in eating, but also with elevated shape and weight concerns.

Neural activations are related to body-shape, anxiety, and outcomes in adolescent anorexia nervosa.

Anorexia nervosa (AN) is an illness that frequently begins during adolescence and involves weight loss. Two groups of adolescent girls (AN-A, weight-recovered following AN) and (HC-A, healthy comparison) completed a functional magnetic resonance imaging task involving social evaluations, allowing comparison of neural activations during self-evaluations, friend-evaluations, and perspective-taking self-evaluations. Although the two groups were not different in their whole-brain activations, anxiety and body shape concerns were correlated with neural activity in a priori regions of interest. A cluster in medial prefrontal cortex and the dorsal anterior cingulate correlated with the body shape questionnaire; subjects with more body shape concerns used this area less during self than friend evaluations. A cluster in medial prefrontal cortex and the cingulate also correlated with anxiety such that more anxiety was associated with engagement when disagreeing rather than agreeing with social terms during self-evaluations. This data suggests that differences in the utilization of frontal brain regions during social evaluations may contribute to both anxiety and body shape concerns in adolescents with AN. Clinical follow-up was obtained, allowing exploration of whether brain function early in course of disease relates to illness trajectory. The adolescents successful in recovery used the posterior cingulate and precuneus more for friend than self evaluations than the adolescents that remained ill, suggesting that neural differences related to social evaluations may provide clinical predictive value. Utilization of both MPFC and the precuneus during social and self evaluations may be a key biological component for achieving sustained weight-recovery in adolescents with AN.