This chapter discusses the treatment of eating disorders, focusing on the treatment of anorexia nervosa (AN), bulimia nervosa (BN), and binge-eating disorder (BED) in adolescents. It highlights the effectiveness of family-based therapy, which has shown significant benefits for adolescents with AN, particularly those with a shorter illness duration. The chapter also examines pharmacological treatments. While evidence for the effectiveness of medications in adolescents with eating disorders is limited, treatments like antidepressants and atypical antipsychotics show promise for enhancing recovery. It emphasizes early intervention, specialized care, and individualized treatment approaches for this vulnerable population. Finally, the chapter stresses the importance of ongoing research and evaluation to refine treatment methods and improve long-term outcomes for adolescents with eating disorders.

BACKGROUND:Family-Based Treatment (FBT) is evidence based for patients younger than 18 with anorexia nervosa; however, continued refinement of FBT is needed to increase response and remission rates. AIMS:This study aimed to compare traditional FBT with an interoceptive exposure (IE) intervention that targets visceral sensitivity and autonomous eating in a family context. We hypothesized that IE would reduce food avoidance to a greater degree than FBT, as measured by laboratory feeding independent of weight gain. METHODS:Adolescents diagnosed with a low-weight eating disorder (LWED) were randomized to six sessions of FBT or IE. Before and after the intervention, patients completed interviews and self-report questionnaires, laboratory test meals (single and multi-item), and functional magnetic resonance imaging. Healthy controls provided a comparison group for these assessments. The study was registered as follows: clinicaltrials.gov NCT02795455 (https://clinicaltrials.gov/study/NCT02795455?term=NCT02795455&rank=1), GCO 15-0939 Reward Systems and Food Avoidance in Eating Disorders. RESULTS:Adolescents receiving IE (n = 30) consumed significantly more energy (kcal) during the post-treatment single item (Mdiff = 98.12 kcal, SDpooled = 119.84, d = 0.82) and multi-item meals (Mdiff = 137.11 kcal, SDpooled = 301.85, d = 0.45) than the FBT group (n = 30). No significant differences were found for age and sex adjusted % expected body weight between groups. Adolescents with LWED reported significantly more symptoms on all clinical measures than controls (n = 27). CONCLUSIONS:Six sessions of a novel form of IE yielded significant changes in eating behavior, namely an approximately two-fold increase in energy consumed in both multi-item and single-item meals among those randomized to IE. Additional research using a fully expanded version of these treatments is needed.

This chapter outlines a comprehensive research agenda aimed at advancing understanding, diagnosis, and treatment of eating disorders in adolescents. It calls for evaluation of DSM-5 and alternative diagnostic frameworks, increased genomic studies to uncover biological mechanisms, and large-scale epidemiological research to clarify prevalence across diverse populations. The chapter highlights the need to investigate comorbidities, diagnostic migration, and medical complications, and urges development of evidence-based psychological and pharmacological treatments, relapse prevention strategies, and effective interventions across levels of care. It emphasizes exploring culturally relevant factors, the impact of social determinants, and disparities in access to care among marginalized groups. Finally, the chapter recommends refining prevention strategies by distinguishing risk factors for symptom onset, escalation, and maintenance to design targeted and inclusive interventions that avoid inadvertently increasing eating disorder risk.

OBJECTIVE:Numerous publications utilize data from the Adolescent Brain and Cognitive Development (ABCD) Study. This review aimed to evaluate how data from the ABCD cohort contributes to understanding the pathophysiology of incipient eating disorders. METHOD:Searches were completed using PubMed and the ABCD Study research publications database. All available neuroimaging articles assessing prevalence and predictors of disordered eating/eating disorders were included. RESULTS:Thirty-eight articles met inclusion criteria, 10 of which presented neuroimaging results, all analyzing baseline brain data. The majority (n = 9) assessed brain structure and function in children with binge eating (BE)/binge eating disorder (BED). Results were inconsistent across imaging modalities. Structural MRI studies included widespread increases in gray matter density and reductions in cortical thickness associated with eating pathology. Task-based fMRI studies reported conflicting findings, with frontostriatal activation during reward processing in children with BE/BED reduced, increased, or not different compared to controls. Resting-state fMRI analyses consistently identified reduced functional connectivity in key frontal circuits, although patterns differed when samples were stratified by sex or BMI. Non-imaging studies showed positive associations between eating disorders/disordered eating and several sociodemographic, cognitive, behavioral, and biological correlates. DISCUSSION:Alterations in brain structure and function associated with binge eating are identified in neuroimaging analyses of baseline scans from the ABCD cohort, with inconsistent results. One potential pattern suggests alterations in reward system function, although the direction and exact location of such alterations are unclear. Consistency in methodological approaches is necessary to allow patterns in neural alterations to be more clearly identified. There is significant and ongoing potential for the ABCD Study dataset to quantify developmental aspects of binge eating. Recommendations for future analyses as the sample progresses through puberty and eating disorder prevalence increases are also presented.

Binge eating disorder (BED) is the most prevalent eating disorder. However, current diagnostic frameworks remain largely grounded in symptom-based criteria rather than underlying biological mechanisms, thereby limiting early detection and the development of biologically-informed interventions. Emerging studies have begun to investigate the neurobiological signatures of BED, yet their findings are often difficult to generalize due to the reliance on hypothesis-driven parametric models, single-modality analyses, and limited data diversity. Therefore, there is a critical need for advanced data-driven frameworks capable of modeling multimodal data to uncover generalizable and biologically meaningful signatures of BED. In this study, we propose the Interpretable Modality-Aware Mixture-of-Experts (IMA-MoE), a novel architecture designed to integrate heterogeneous neuroimaging, behavioral, hormonal, and demographic measures within a unified predictive framework. By encoding each measure as a distinct token, IMA-MoE enables flexible modeling of cross-modal dependencies while preserving modality-specific characteristics. We further introduce a token-importance mechanism to enhance interpretability by quantifying the contribution of each measure to model predictions. Evaluated on the large-scale Adolescent Brain Cognitive Development (ABCD) dataset, IMA-MoE demonstrates superior performance in differentiating BED from healthy controls compared with baseline methods, while revealing sex-specific predictive patterns, with hormonal measures contributing more prominently to prediction in females. Collectively, these findings highlight the promise of interpretable, data-driven multimodal modeling in advancing biologically-informed characterization of BED and facilitating more precise and personalized interventions in neuropsychiatric disorders.

Aim:Although a risk factor for the later development of eating disorders, few studies examine the neural underpinnings of binge eating (BE) in children. Preliminary evidence suggests a role of the corticostriatal system; the purpose of this study was to evaluate the role of the inhibitory control brain network for risk of BE in children. Methods:Data from 65 children with BE (57% girls) and 84 matched controls (52% girls) from the 4.0 baseline release of the Adolescent Brain Cognitive Development (ABCD) Study were included. Stop Signal Task-based fMRI data were analyzed using graph theoretic techniques. Global and nodal network properties (e.g. efficiency, betweenness-centrality) were compared for between-group differences and sex-by-group interactions. Results:Despite comparable behavioral performance, children with BE showed significantly increased nodal efficiency of the right postcentral gyrus and left middle frontal gyrus (MFG), and increased connectedness of the right postcentral gyrus compared to control children. Children with BE showed distinct network hubs including the right MFG and left insula, while controls had distinct hubs in the right orbitofrontal and left fusiform gyri. Group-specific sex differences were found in the functioning of insular and frontal cortices. Conclusion:Increased efficiency and connectedness in frontal and parietal nodes of the inhibitory control network functioning in children with BE may represent a vulnerability for overeating. Distinct sex differences in functioning in children with BE compared to control children may reflect specific vulnerabilities to BE in the inhibitory control system in boys and girls that may contribute to sex differences in prevalence.

OBJECTIVE:This randomized controlled study tested the effect of interoceptive exposure on anterior insula function and connectivity for the extinction of palatable and rotten food-cue associations in adolescent girls with low weight eating disorders (LWED). METHOD:A food-related conditioning paradigm was performed by 39 adolescent girls with LWED and 19 matched controls during functional magnetic resonance imaging (fMRI). Adolescents with LWED were then randomized to 6 sessions of either interoceptive exposure (n = 18) or family-based (n = 21) treatment, followed by a second functional magnetic resonance imaging scan. Whole-brain activation and insula-driven connectivity for the extinction of palatable and rotten food-cue associations were compared between groups, and changes over treatment were compared between the 2 therapies. RESULTS:Adolescents with LWED exhibited diminished bilateral anterior insula activation for the extinction of palatable food-cue associations compared with controls (t1,55 = 3.9-4.1, p < .001; Hedges g = 0.47-0.55). Brief interoceptive exposure treatment increased left anterior insula activation for the extinction of palatable food-cue associations (t1,37 = 5.10, p < .001; Hedges g = 1.59) and nonsignificantly improved palatability ratings for these associations during extinction compared with family-based treatment (β = -1.492, p = .087). There were no effects of group or therapy on connectivity or activation for rotten food-cue associations. CONCLUSION:These results suggest that targeting food avoidance in adolescent girls with LWED using interoceptive exposure engages anterior insula regions that mediate the visceral sensation of disgust and may underlie the resistance to extinction. The findings present a window into possible pathophysiological mechanisms of anorexia nervosa and other LWED PLAIN LANGUAGE SUMMARY: This randomized controlled study tested the effect of interoceptive exposure, which aims to reduce conditioned disgust responses to food. This treatment was compared to family-based treatment and the focus was on changes in anterior insula function. 39 adolescent girls with low-weight eating disorders (LWED) and 19 matched controls underwent food-related conditioning during functional magnetic resonance imaging, followed by interoceptive exposure or family-based treatment and a post-intervention imaging session. Key results showed that brief interoceptive exposure treatment increased left anterior insula activation for the extinction of palatable food-cue associations. These results offer new insights into the role of disgust and possible triggers and pathways to anorexia nervosa and other LWED. CLINICAL TRIAL REGISTRATION INFORMATION:Reward Systems and Food Avoidance in Eating Disorders; https://clinicaltrials.gov/study/NCT02795455.

The increased prevalence of binge eating during puberty is predominantly in girls, coinciding with a surge in pubertal hormones. This suggests that hormone-activated alterations in widespread brain networks, such as attention network, can contribute to the pathophysiology of the disorder in girls, while distinct mechanisms may exist in boys. This study proposed to examine the topological properties and their temporal dynamics of the sustained attention network in preadolescent children with binge eating symptoms (BE) and matched controls and to test the relation of these properties to circulating levels of pubertal hormones. Data from 77 children with BE and 104 group-matched controls were analyzed. In a static network comprising the entire task duration, the nodal topological properties, i.e., nodal efficiency, betweenness-centrality and degree, of the caudate nucleus, hippocampus and inferior parietal gyrus (IPG) significantly differentiated children with and without BE; and that of left caudate were significantly associated with pubertal hormone levels in girls with and without BE, but not in boys. During different substages of sustained attention processing, Variability of the topological properties in key network nodes, such as bilateral IPG, bilateral precentral gyrus and left hippocampus, demonstrated significant between-group differences and/or unique group-by-sex interactions. These results suggest that the association between pubertal hormones and network topological organization may contribute towards the specific rise of BE in girls, while neural mechanisms of BE in boys may alternatively link to suboptimal functional dynamics associated with precentral gyrus, during their interactions with other cortical and subcortical regions when sustained attention is performed.

Objective: Anorexia nervosa is characterized by decision-making that demonstrates an intolerance of uncertainty focused on food of unknown caloric content. This pilot study tested whether this intolerance of uncertainty involved distinct neural networks that process two conditions of uncertainty – risk and ambiguity.Method: Nine female adults with anorexia nervosa (mean age = 27.1 ± 6.7 years) and nine female adult controls (mean age = 27.5 ± 5.8 years) performed a validated lottery test of uncertainty during functional magnetic resonance imaging. Neuroeconomic models that predicted choice on each risk and ambiguity lottery based on the subjective value of the uncertain option versus the standard option were entered as parametric modulators of the neural response to the two types of lotteries.Results: Adult females with anorexia nervosa showed significantly greater activation of an extended network of cingulo-opercular-frontoparietal regions than controls despite similar choices of the ambiguous lottery tickets (T-value ≥ 2.57, p < 0.01, kappa > 50 voxels). In contrast, participants with anorexia nervosa were more risk averse and showed significantly reduced activation of prefrontal and temporoparietal regions than controls (T-value ≥ 2.57, p < 0.01, kappa > 50 voxels).Discussion: The preliminary findings of functional abnormalities in two distinct neural networks for decision-making under conditions of uncertainty in adult females with anorexia nervosa suggest that the intolerance of uncertainty that biases toward food avoidance may reflect aversions to both risk or probability-based decisions, and even more prominently, ambiguity or decisions based on uncertain outcomes.

BackgroundUnderstanding the emotional context of feeding behavior may help identify causal mechanisms of food avoidance among individuals with anorexia nervosa. Although predominant food avoidance models assume fear of fat drives feeding behavior, disgust may be more theoretically and proximally relevant to moment-to-moment experiences of feeding. This study, therefore, aimed to examine affect and food avoidance using automated affect analysis from facial response by measuring time-specific transitions in disgust during a laboratory eating paradigm. We hypothesized that phase transitions in disgust would distinguish temporally self-initiated eating from food avoidance.MethodsSixty-three adolescents with anorexia nervosa or another low-weight eating disorder (LWED) and 27 age- and sex-matched controls were recruited as part of a larger study; 45 patients and 22 controls provided data on autonomous eating and facial affect during a laboratory meal. Dynamic structural equation models quantified moment-to-moment relationships between disgust and feeding behavior.ResultsSelf-initiated eating was associated with greater increases in disgust, but not fear, intensity among those with LWED relative to control participants and greater disgust intensity predicted lower likelihood of self-initiated eating.DiscussionPhasic transitions in disgust provide moment-to-moment evidence of affective influence on self-initiated eating and lend credibility to the hypothesis that disgust contributes to food avoidance and initiation in individuals with LWED.

Objective: Few studies have considered the neural underpinnings of binge eating disorder (BED) in children, despite clinical and subclinical symptom presentation occurring in this age group. Symptom presentation at this age is of clinical relevance, as early onset of binge eating is linked to negative health outcomes. Studies in adults have highlighted dysfunction in the frontostriatal reward system as a potential candidate for binge eating pathophysiology, although the exact nature of such dysfunction is currently unclear. Method: Data from 83 children (mean age 9.9 years, SD = 0.60) with symptoms of BED (57% girls) and 123 control participants (mean age 10.0 years, SD = 0.60) (52% girls) were acquired from the 4.0 baseline release of the Adolescent Brain Cognitive Development Study. Task-based graph theoretic techniques were used to analyze data from anticipation trials of the monetary incentive delay task. Network and nodal properties were compared between groups. Results: The BED-S group showed alterations in topological properties associated with the frontostriatal subnetwork, such as reduced nodal efficiency in the superior frontal gyrus, nucleus accumbens, putamen, and in normal sex-difference patterns of these properties, such as diminished girls-greaterthan-boys pattern of betweenness-centrality in nucleus accumbens observed in controls. Conclusion: Distinct network properties and sex-difference patterns in preadolescent children with BED-S suggest dysregulation in the reward system compared to those of matched controls. For the first time, these results quantify this dysregulation in terms of systems-level properties during anticipation of monetary reward and significantly inform the early and sex-related brain markers of BED symptoms. Plain language summary: Binge eating disorder is the most common eating disorder. One factor that may contribute to binge eating is dysregulation of the reward system in the brain. This study analyzed brain activity during anticipation of monetary rewards in 83 youth with and 123 children without binge eating disorder symptoms from the Adolescent Brain Cognitive Development Study. The authors found specific alterations in the frontostriatal system, responsible for reward processing, in children with binge eating disorder symptoms, compared to the control group, suggesting dysregulation of the reward system.

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 the Million Veteran Program. We perform a genome-wide association study of individuals of African ( n = 77,574) and European ( n = 285,138) ancestry while controlling for body mass index to identify three independent loci near the HFE , MCHR2 and LRP11 genes and suggest APOE as a risk gene for BED. We identify shared heritability between BED and several neuropsychiatric traits, and implicate iron metabolism in the pathophysiology of BED. Overall, our findings provide insights into the genetics underlying BED and suggest directions for future translational research.

Several studies in clinical and non-clinical populations indicate differences between rationally and empirically derived subscales for the Eating Disorder Examination Questionnaire (EDE-Q), including samples of patients seeking bariatric surgery. This study aimed to use exploratory structural equation modelling (ESEM) to estimate the factor structure of the EDE-Q and assess for the additive value of alternative measurement of eating disorder symptoms. Adolescents and adults completed the EDE-Q and a psychiatric evaluation prior to bariatric surgery. Data from 330 participants were analysed using the original four-factor and modified three-factor structure of the EDE-Q using both confirmatory factor analysis (CFA) and exploratory structural equation modelling (ESEM). Age, ethnicity, and body mass index were examined as covariates in the best fitting model, and model subscales used to generate a predictive model of clinician screened DSM-5 eating disorder diagnoses for criterion validity. A CFA of the four-factor EDE-Q provided poor model fit for a pre-surgical bariatric population, but the three-factor EDE-Q and an ESEM of the four-factor EDE-Q provided excellent model fit. The Eating Concern subscale of the four-factor ESEM model significantly predicted eating disorder diagnosis and was positively correlated with age. Our results suggest the ESEM derived factors of the EDE-Q offered some improvements to the original empirically derived factor structure, as subscale scores based on the original items and cross-loading items yielded an adequate prediction of clinician diagnoses.

Background This pilot study outlines the development and psychometric evaluation of a therapist adherence coding measure for a novel treatment, Family-Based Treatment Interoceptive Exposure (FBT-IE). Methods The IE Adherence Coding Framework (IE-ACF) was developed from the FBT-IE Manual using an iterative process. Items on the IE-ACF were coded by two independent coders as either present or absent with therapists considered adherent if both independent coders coded the item as “present.” Videotaped sessions of FBT-IE of 30 adolescents with low-weight eating disorders (DSM-5 typical/atypical anorexia nervosa) and their families were coded. Participants received the FBT-IE intervention as part of a randomized controlled trial. Results Seventy FBT-IE videos were coded. The IE-ACF identified a mean (SD) rating of 80% (±5%) therapist adherence to the protocol across the six-session treatment, with a per item adherence ranging from 36–100%. Two independent coders demonstrated moderate to almost perfect inter-rater reliability (κ range 0.78–0.96) across the sessions. Conclusion IE-ACF measured therapist adherence to our novel FBT-IE treatment for adolescents with low-weight eating disorders. Through this study, we demonstrated that 1) our therapists were adherent to the FBT-IE manual in the context of an ongoing clinical trial and 2) that independent coders reliably coded sessions using our novel IE-ACF.

Objective: Conventional randomized controlled trials (RCTs) have long served as the foundation of research in clinical psychology; however, most treatments for eating disorders show only modest effects on reduction of symptoms and maintenance of long-term remission. New options for psychotherapy treatment development research, beyond continuing to pursue additive or subpopulation approaches, are needed.Methods: One option is to apply dose-response designs, which are commonplace in studies of pharmacology, toxicology, and medical research, and characterized by the evaluation of the amount of exposure (dose) to an intervention, and the resulting changes in body function or health (response).Results: Eating disorder interventions are particularly well-suited for dose-response treatment designs. The deadly nature of eating disorders makes it imperative that patients are not turned away for not being "ready" to engage with treatment. By identifying optimal doses, research will likely yield a more parsimonious course of treatment, which will lend itself to reduced costs, greater uptake, and reduced drop-out.Discussion: Limited use of within-subject designs in trials for patients with eating disorders has produced fast-track efficacy studies and omitted key elements in the treatment development pathway. To decrease reliance on RCT's, dose-response methods should be applied as an alternative study design.Public Significance: Eating disorders are associated with medical and psychiatric comorbidities, poor quality of life, and high mortality. Access to evidence-based services for patients with eating disorders is limited, and identifying additional effective treatment options can be difficult because of challenges inherent to randomized-controlled trials. This manuscript describes an alternative trial methodology to maximize the information that can be gathered prior to utilizing a standard large-scale efficacy design.

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 datasets. To address this limitation, we apply a supervised machine learning approach to estimate the probability of each individual having BED based on electronic medical records from the Million Veteran Program. We perform a genome-wide association study on individuals of African (n = 77,574) and European (n = 285,138) ancestry while controlling for body mass index to identify three independent loci near the HFE, MCHR2 and LRP11 genes, which are reproducible across three independent cohorts. We identify genetic association between BED and several neuropsychiatric traits and implicate iron metabolism in the pathophysiology of BED. Overall, our findings provide insights into the genetics underlying BED and suggest directions for future translational research.

BACKGROUND:Overweight and obesity are serious public health concerns. As the prevalence of excess weight among individuals continues to increase, there is a parallel need for inexpensive, highly accessible, and evidence-based weight loss programs. OBJECTIVE:This weight loss trial will aim to examine the efficacy of the Noom weight loss program in comparison to a digital control after a 6-month intervention phase and a 24-month maintenance phase, with assessments continuing for 2 years beyond the intervention (to 30 months-after the baseline). The secondary outcomes include quality of life, psychosocial functioning, sleep quality, physical activity, diet, and health status. This trial will also examine the severity of obesity-related functional impairment, weight loss history, and demographic moderators, along with adherence and self-efficacy as mediators of the outcome. METHODS:A total of 600 participants were randomized in a parallel-group, controlled trial to either Noom Healthy Weight Program (intervention) or Noom Healthy Weight Control (control) for a 6-month intervention. Both intervention and control groups include diet and exercise recommendations, educational content, daily logging capabilities, and daily weigh-in entries. The Noom Healthy Weight Program also includes a coach support for weight loss. Remote follow-up assessments of eating, physical activity, psychosocial factors, app use data, and weight will be conducted at 1, 4, 6, 12, 18, 24, and 30 months after baseline. Weight is measured at each follow-up point during a Zoom call using the participants' scales. RESULTS:Enrollment began in March 2021 and the 6-month intervention phase ended in March 2022. Data collection for the final assessment will be completed in March 2024. CONCLUSIONS:This study tests commercially available digital lifestyle interventions for individuals with overweight and obesity seeking weight loss support. Data obtained from the study will evaluate whether the Noom Healthy Weight Control Program can help individuals overcome weight loss, achieve long-term maintenance, adhere to lifestyle changes, and feature use barriers that are present in other traditional weight loss treatments. TRIAL REGISTRATION:ClinicalTrials.gov NCT04797169; https://clinicaltrials.gov/ct2/show/NCT04797169. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID):DERR1-10.2196/37541.