Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group.

BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

Le trouble de l'accès hyperphagique: Aperçu actualisé à l'intention des professionnels des soins primaires.

OBJECTIF: Fournir aux professionnels des soins primaires un aperçu actualisé du trouble de l'accès hyperphagique (TAH), qui comporte des recommandations pertinentes. QUALITÉ DES DONNÉES: Une recension a été effectuée dans PubMed, PsycInfo et Google Scholar, sans restrictions temporelles, à l'aide des expressions clés en anglais binge eating disorder, treatment, review, guidelines, psychotherapy, primary care et pharmacotherapy. Le niveau des données probantes pour toutes les recommandations varie de I à III. MESSAGE PRINCIPAL: Le trouble de l'accès hyperphagique est associé à une grande détresse et à une incapacité considérable chez le patient, ainsi qu'à des comorbidités médicales et psychiatriques; il a été ajouté dans la 5e édition du Manuel diagnostique et statistique des troubles mentaux, en 2013. Les médecins de soins primaires sont bien placés pour le dépistage, le diagnostic et l'amorce du traitement du TAH. Une approche par étapes du traitement commence par un développement personnel guidé, suivi par l'ajout ou le changement de la pharmacothérapie, ou par une psychothérapie individuelle, au besoin. Les psychothérapies dont l'efficacité est le plus corroborée par la recherche sont la thérapie cognitivo-comportementale, la thérapie interpersonnelle et la thérapie comportementale dialectique. CONCLUSION: Cet aperçu présente des conseils sur le dépistage, le diagnostic et les approches thérapeutiques fondés sur les données probantes actuellement disponibles, de même les avis d'un groupe diversifié d'experts, pour aider à orienter les cliniciens lorsque les données probantes sont limitées.

The potential role of stimulants in treating eating disorders.

BACKGROUND: Many individuals with eating disorders remain symptomatic after a course of psychotherapy and pharmacotherapy; therefore, the development of innovative treatments is essential. METHOD: To learn more about the current evidence for treating eating disorders with stimulants, we searched for original articles and reviews published up to April 29, 2021 in PubMed and MEDLINE using the following search terms: eating disorders, anorexia, bulimia, binge eating, stimulants, amphetamine, lisdexamfetamine, methylphenidate, and phentermine. RESULTS: We propose that stimulant medications represent a novel avenue for future research based on the following: (a) the relationship between eating disorders and attention deficit/hyperactivity disorder (ADHD); (b) a neurobiological rationale; and (c) the current (but limited) evidence for stimulants as treatments for some eating disorders. Despite the possible benefits of such medications, there are also risks to consider such as medication misuse, adverse cardiovascular events, and reduction of appetite and pathological weight loss. With those risks in mind, we propose several directions for future research including: (a) randomized controlled trials to study stimulant treatment in those with bulimia nervosa (with guidance on strategies to mitigate risk); (b) examining stimulant treatment in conjunction with psychotherapy; (c) investigating the impact of stimulants on "loss of control" eating in youth with ADHD; and (d) exploring relevant neurobiological mechanisms. We also propose specific directions for exploring mediators and moderators in future clinical trials. DISCUSSION: Although this line of investigation may be viewed as controversial by some in the field, we believe that the topic warrants careful consideration for future research.

Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors.

BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders.

Time Course of Relapse Following Acute Treatment for Anorexia Nervosa.

OBJECTIVE: There is long-standing interest in how best to define stages of illness for anorexia nervosa, including remission and recovery. The authors used data from a previously published study to examine the time course of relapse over the year following full weight restoration. METHODS: Following weight restoration in an acute care setting, 93 women with anorexia nervosa were randomly assigned to receive fluoxetine or placebo and were discharged to outpatient care, where they also received cognitive-behavioral therapy for up to 1 year. Relapse was defined on the basis of a priori clinical criteria. Fluoxetine had no impact on the time to relapse. In the present analysis, for each day after entry into the study, the risk of relapse over the following 60 days and the following 90 days was calculated and a parametric function was fitted to approximate the Kaplan-Meier estimator. RESULTS: The risk of relapse rose immediately after entry into the study, reached a peak after approximately 60 days, and then gradually declined. There was no indication of an inflection point at which the risk of relapse fell precipitously after the initial peak. CONCLUSIONS: This analysis highlights the fact that adult patients with anorexia nervosa are at increased risk of relapse in the first months following discharge from acute care, suggesting a need for frequent follow-up and relapse prevention-focused treatment during this period. After approximately 2 months, the risk of relapse progressively decreases over time.

A retrospective chart review study of symptom onset, diagnosis, comorbidities, and treatment in patients with binge eating disorder in Canadian clinical practice.

PURPOSE: In the Canadian healthcare setting, there is limited understanding of the pathways to diagnosis and treatment for patients with binge eating disorder (BED). METHODS: This retrospective chart review examined the clinical characteristics, diagnostic pathways, and treatment history of adult patients diagnosed with BED. RESULTS: Overall, 202 charts from 57 healthcare providers (HCPs) were reviewed. Most patients were women (69%) and white (78%). Mean ± SD patient age was 37 ± 12.1 years. Comorbidities identified in > 20% of patients included obesity (50%), anxiety (49%), depression and/or major depressive disorder (46%), and dyslipidemia (26%). Discussions regarding a diagnosis of BED were typically initiated more often by HCPs than patients. Most patients (64%) received a diagnosis of BED ≥ 3 years after symptom onset. A numerically greater percentage of patients received (past or current) nonpharmacotherapy than pharmacotherapy (84% vs. 67%). The mean ± SD number of binge eating episodes/week numerically decreased from pretreatment to follow-up with lisdexamfetamine (5.4 ± 2.8 vs. 1.7 ± 1.2), off-label pharmacotherapy (4.7 ± 3.9 vs. 2.0 ± 1.13), and nonpharmacotherapy (6.3 ± 4.8 vs. 3.5 ± 6.0) Across pharmacotherapies and nonpharmacotherapies, most patients reported improvement in symptoms of BED (84-97%) and in overall well-being (80-96%). CONCLUSIONS: These findings highlight the importance of timely diagnosis and treatment of BED. Although HCPs are initiating discussions about BED, earlier identification of BED symptoms is required. Furthermore, these data indicate that pharmacologic and nonpharmacologic treatment for BED is associated with decreased binge eating and improvements in overall well-being. LEVEL OF EVIDENCE: IV, chart review.

Molecular neuroanatomy of anorexia nervosa.

Anorexia nervosa is a complex eating disorder with genetic, metabolic, and psychosocial underpinnings. Using genome-wide methods, recent studies have associated many genes with the disorder. We characterized these genes by projecting them into reference transcriptomic atlases of the prenatal and adult human brain to determine where these genes are expressed in fine detail. We found that genes from an induced stem cell study of anorexia nervosa cases are expressed at higher levels in the lateral parabrachial nucleus. Although weaker, expression enrichment of the adult lateral parabrachial is also found with genes from independent genetic studies. Candidate causal genes from the largest genetic study of anorexia nervosa to date were enriched for expression in the arcuate nucleus of the hypothalamus. We also found an enrichment of anorexia nervosa associated genes in the adult and fetal raphe and ventral tegmental areas. Motivated by enrichment of these feeding circuits, we tested if these genes respond to fasting in mice hypothalami, which highlighted the differential expression of Rps26 and Dalrd3. This work improves our understanding of the neurobiology of anorexia nervosa by suggesting disturbances in subcortical appetitive circuits.

A Behavioral Genetic Model of the Mechanisms Underlying the Link Between Obesity and Symptoms of ADHD.

Objective: The ADHD-obesity link has been suggested to result from a shared underlying basis of suboptimal dopamine (DA); however, this theory conflicts evidence that an amplified DA signal increases the risk for overeating and weight gain. A model was tested in which ADHD symptoms, predicted by hypodopaminergic functioning in the prefrontal cortex, in combination with an enhanced appetitive drive, predict hedonic eating and, in turn, higher body mass index (BMI). Method: DRD2 and DRD4 markers were genotyped. The model was tested using structural equation modeling in a nonclinical sample (N = 421 adults). Results: The model was a good fit to the data. Controlling for education, all parameter estimates were significant, except for the DRD4-ADHD symptom pathway. The significant indirect effect indicates that overeating mediated the ADHD symptoms-BMI association. Conclusion: Results support the hypothesis that overeating and elevated DA in the ventral striatum-representative of a greater reward response-contribute to the ADHD symptom-obesity relationship.

White matter microstructure in women with acute and remitted anorexia nervosa: an exploratory neuroimaging study.

Anorexia nervosa (AN) is a highly heritable psychiatric disorder characterized by starvation and emaciation and associated with changes in brain structure. The precise nature of these changes remains unclear, as does their developmental time course and capacity for reversal with weight restoration. In this exploratory neuroimaging study, we sought to characterize changes in white matter microstructure in women with acute and remitted AN. Diffusion-weighted MRI data was collected from underweight women with a current diagnosis of AN (acAN: n = 23), weight-recovered women with a past diagnosis of AN (recAN: n = 23), and age-matched healthy control women (HC: n = 24). Image processing and analysis were performed with Tract-Based Spatial Statistics, part of FSL, and group differences in voxelwise, brain-wide fractional anisotropy (FA) and mean diffusivity (MD), indices of white matter microstructure, were tested with nonparametric permutation and threshold-free cluster enhancement. No significant main effect of group on FA was identified. A significant main effect of group on MD was observed in a large cluster covering 9.2% of white matter and including substantial portions of the corpus callosum, corona radiata, internal capsule, and superior longitudinal fasciculus, and post hoc analyses revealed similar effects of group on axial diffusivity (AD) and radial diffusivity (RD). Clusterwise MD was significantly higher in acAN participants (+3.8%) and recAN participants (+2.9%) than healthy controls, and the same was true for clusterwise AD and RD. Trait-based increases in diffusivity, changes in which have been associated with atypical myelination and impaired axon integrity, suggest a link between altered white matter microstructure and vulnerability to AN, and evidence of reduced oligodendrocyte density in AN provides further support for this hypothesis. Potential mechanisms of action include atypical neurodevelopment and systemic inflammation.

Insula H-coil deep transcranial magnetic stimulation in severe and enduring anorexia nervosa (SE-AN): a pilot study.

INTRODUCTION: Anorexia nervosa (AN) is a complex disorder of unknown etiology, characterized by obsessions and compulsions around body shape, weight, and calorie intake. In the course of AN, 10%-30% will recover, while the rest will develop a treatment-resistant course with a high mortality rate due to AN-related complications. The insula is a region in the brain of considerable interest to its role in gustatory modulation, feeding behavior, and processing of interoceptive stimuli. OBJECTIVE: Recent advances in the neurophysiology of AN suggest insula dysfunction as a potential biomarker for people with severe and enduring AN (SE-AN). Deep transcranial magnetic stimulation (dTMS) is of particular interest in SE-AN because of its ability to target deep areas of the brain. DESIGN: We conducted a pilot study to investigate the feasibility and safety of insula dTMS in subjects with SE-AN. RESULTS: We found that dTMS is a safe and well-tolerated treatment. We also found a reduction in AN-related obsessions and compulsions, as well as depression and anxiety scores from baseline to the end of the trial. Due to small sample size, the results of this study should be interpreted with great caution. DISCUSSION: The results suggest that dTMS is safe and well tolerated and may be of some clinical interest in patients with SE-AN. However, to determine the true efficacy of dTMS for SE-AN, there is a need to conduct a randomized controlled trial comparing real versus sham dTMS in a larger number of AN subjects.

A randomized comparison of long acting methylphenidate and cognitive behavioral therapy in the treatment of binge eating disorder.

Cognitive behavioral therapy (CBT) is a well-established treatment for binge eating disorder (BED); however, this treatment is underutilized, highlighting the need for additional treatment alternatives. Dopamine neurotransmission has been associated with dysregulated eating, and pharmaceutical agents targeting the dopamine system are associated with decreased binge eating and weight. The primary objective of the current investigation was to evaluate the efficacy of psychostimulant medication versus current best practices in the treatment of BED symptoms, in a randomized trial of methylphenidate versus CBT for BED. The secondary objective was to evaluate the ability of impulsivity to predict treatment outcomes. Female outpatients with BED were randomized to receive methylphenidate (n = 22) or CBT (n = 27) for 12 weeks. The primary outcome was objective binge episode frequency; secondary outcomes included subjective binge episode frequency, body mass index (BMI), BED symptoms, and quality of life. Results showed that both treatments had a significant impact on primary and secondary outcomes. Methylphenidate and CBT were associated with decreases in subjective and objective binge episodes; methylphenidate was associated with greater decreases in BMI. Two impulsivity traits predicted clinical outcomes. Results provide preliminary support for the therapeutic benefit of methylphenidate in BED treatment, and prognostic utility of impulsivity in this context.

An investigation of indirect effects of personality features on anorexia nervosa severity through interoceptive dysfunction in individuals with lifetime anorexia nervosa diagnoses.

OBJECTIVE: This study examined a hypothesized pathway by which interoceptive dysfunction accounted for associations between personality features (harm avoidance, self-directedness, and perfectionism) and anorexia nervosa (AN) severity (indicated by drive for thinness, eating disorder-related preoccupations and rituals, and body mass index). METHOD: The study sample (n = 270, mean age = 28.47, 95.2% female, 98% White/Caucasian) consisted of probands and biological relatives who met DSM-IV criteria for lifetime diagnoses of AN (omitting criterion D, amenorrhea) drawn from the Price Foundation Anorexia Nervosa Affected Relative Pairs Study (AN-ARP). Participants completed measures assessing personality, interoceptive dysfunction, and eating pathology. RESULTS: Associations between personality features of low self-directedness and high perfectionism and indicators of AN severity (drive for thinness and eating disorder-related preoccupations and rituals) were significant, as were the hypothesized indirect pathways through interoceptive dysfunction. Neither harm avoidance nor body mass index was significantly related to other study variables, and the proposed indirect pathways involving these variables were not significant. DISCUSSION: Findings suggest that certain personality features may relate to AN severity, in part, through their associations with interoceptive dysfunction. Future research should examine prospective associations and the value of interventions targeting interoceptive dysfunction for interrupting the link between personality and AN severity.

Olanzapine Versus Placebo in Adult Outpatients With Anorexia Nervosa: A Randomized Clinical Trial.

OBJECTIVE: This study evaluated the benefits of olanzapine compared with placebo for adult outpatients with anorexia nervosa. METHODS: This randomized double-blind placebo-controlled trial of adult outpatients with anorexia nervosa (N=152, 96% of whom were women; the sample's mean body mass index [BMI] was 16.7) was conducted at five sites in North America. Participants were randomly assigned in a 1:1 ratio to receive olanzapine or placebo and were seen weekly for 16 weeks. The primary outcome measures were rate of change in body weight and rate of change in obsessionality, assessed with the Yale-Brown Obsessive Compulsive Scale (YBOCS). RESULTS: Seventy-five participants were assigned to receive olanzapine and 77 to receive placebo. A statistically significant treatment-by-time interaction was observed, indicating that the increase in BMI over time was greater in the olanzapine group (0.259 [SD=0.051] compared with 0.095 [SD=0.053] per month). There was no significant difference between treatment groups in change in the YBOCS obsessions subscale score over time (-0.325 compared with -0.017 points per month) and there were no significant differences between groups in the frequency of abnormalities on blood tests assessing potential metabolic disturbances. CONCLUSIONS: This study documented a modest therapeutic effect of olanzapine compared with placebo on weight in adult outpatients with anorexia nervosa, but no significant benefit for psychological symptoms. Nevertheless, the finding on weight is notable, as achieving change in weight is notoriously challenging in this disorder.

Severe and enduring anorexia nervosa: Can risk of persisting illness be identified, and prevented, in young patients?

OBJECTIVE: Long-term outcome studies of anorexia nervosa (AN) have demonstrated that up to 20% of cases will follow an unremitting course despite many attempts at symptom-based treatments. The objectives of this study are to identify in a younger age group with AN whether persistent illness can be identified early and prevented. METHODS: An extensive literature review of such studies published in Pubmed was conducted. RESULTS: This review revealed that these studies have generally been conducted in adult patients who have been chronically ill over many years. DISCUSSION: Despite that fact that there is little published evidence on severe and persistent illness in a younger rage group, there are important clinical questions to consider in such a group of AN individuals. This commentary attempts to answer these questions, often in the absence of research evidence. These questions include whether it is possible to identify those who will go on to develop a severe, enduring course; whether early intervention can prevent the development of a such a course; and whether a focus on quality of life rather symptom alleviation is appropriate for a younger age group of unremitted sufferers. In the absence of research that that clearly informs these questions, the authors are left to recommend answers to these question based on a case by case interrogation of relevant factors, including the presence of the risk architecture to which AN has been strongly linked, the age of the patient, the wishes of the family and importantly, the opinions of expert bioethicists and clinicians sufficiently knowledgeable about the psychopathology, natural history, and treatment of AN to be able to render an informed decision.

Associations between dimensions of anorexia nervosa and obsessive-compulsive disorder: An examination of personality and psychological factors in patients with anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) and obsessive-compulsive disorder (OCD) are highly comorbid. However, the factors that account for this comorbidity are poorly understood. We examined the core dimensions of AN and OCD and psychological and personality factors shared by both disorders. METHOD: In path analyses (N = 732 women with either current AN or recovered from AN), we examined which factors were uniquely and independently associated with the core dimensions of AN and OCD. We also examined recovery from AN as a moderator. RESULTS: When individuals with AN reported greater concern over mistakes, they endorsed more severity in both AN and OCD core dimensions. These unique associations existed above and beyond all other transdiagnostic personality and psychological factors and regardless of AN recovery status. CONCLUSIONS: Concern over mistakes partially accounts for severity in the core dimensions of both AN and OCD. Concern over mistakes may represent an important target in the aetiology of AN and OCD.

The Anorexia Nervosa Genetics Initiative (ANGI): Overview and methods.

BACKGROUND: Genetic factors contribute to anorexia nervosa (AN); and the first genome-wide significant locus has been identified. We describe methods and procedures for the Anorexia Nervosa Genetics Initiative (ANGI), an international collaboration designed to rapidly recruit 13,000 individuals with AN and ancestrally matched controls. We present sample characteristics and the utility of an online eating disorder diagnostic questionnaire suitable for large-scale genetic and population research. METHODS: ANGI recruited from the United States (US), Australia/New Zealand (ANZ), Sweden (SE), and Denmark (DK). Recruitment was via national registers (SE, DK); treatment centers (US, ANZ, SE, DK); and social and traditional media (US, ANZ, SE). All cases had a lifetime AN diagnosis based on DSM-IV or ICD-10 criteria (excluding amenorrhea). Recruited controls had no lifetime history of disordered eating behaviors. To assess the positive and negative predictive validity of the online eating disorder questionnaire (ED100K-v1), 109 women also completed the Structured Clinical Interview for DSM-IV (SCID), Module H. RESULTS: Blood samples and clinical information were collected from 13,363 individuals with lifetime AN and from controls. Online diagnostic phenotyping was effective and efficient; the validity of the questionnaire was acceptable. CONCLUSIONS: Our multi-pronged recruitment approach was highly effective for rapid recruitment and can be used as a model for efforts by other groups. High online presence of individuals with AN rendered the Internet/social media a remarkably effective recruitment tool in some countries. ANGI has substantially augmented Psychiatric Genomics Consortium AN sample collection. ANGI is a registered clinical trial: clinicaltrials.govNCT01916538; https://clinicaltrials.gov/ct2/show/NCT01916538?cond=Anorexia+Nervosa&draw=1&rank=3.

Subcortical volume and cortical surface architecture in women with acute and remitted anorexia nervosa: An exploratory neuroimaging study.

BACKGROUND: Anorexia nervosa (AN) is a highly heritable psychiatric disorder characterized by starvation and emaciation and associated with changes in brain structure. The precise nature of these changes remains unclear, as does their developmental time course and capacity for reversal with weight-restoration. In this comprehensive neuroimaging study, we sought to characterize these changes by measuring subcortical volume and cortical surface architecture in women with acute and remitted AN. METHODS: Structural magnetic resonance imaging data was acquired from underweight women with a current diagnosis of AN (acAN: n = 23), weight-recovered women with a past diagnosis of AN (recAN: n = 24), and female controls (HC: n = 24). Subcortical segmentation and cortical surface reconstruction were performed with FreeSurfer 6.0.0, and group differences in regional volume and vertex-wise, cortex-wide thickness, surface area, and local gyrification index (LGI), a measure of folding, were tested with separate univariate analyses of covariance. RESULTS: Mean hippocampal and thalamic volumes were significantly reduced in acAN participants, as was mean cortical thickness in four frontal and temporal clusters. Mean LGI was significantly reduced in acAN and recAN participants in five frontal and parietal clusters. No significant group differences in cortical surface area were detected. CONCLUSIONS: Reductions in subcortical volume, cortical thickness, and right postcentral LGI were unique to women with acute AN, indicating state-dependence and pointing towards cellular remodeling and sulcal widening as consequences of disease manifestation. Reductions in bilateral frontal LGI were observed in women with acute and remitted AN, suggesting a role of atypical neurodevelopment in disease vulnerability.

Binge Eating Disorder (BED) in Relation to Addictive Behaviors and Personality Risk Factors.

While there is good evidence that binge eating disorder (BED) is linked to higher-than-expected use of a broad range of addictive behaviors, mechanisms underlying this association are not well understood. Using a mediation-analytical approach with three age- and gender-matched groups - overweight/obese adults with (n = 42) and without (n = 104) BED, and normal-weight control participants (n = 73) - we tested the hypothesis that adults with BED would engage in more addictive behaviors and have higher scores on a personality-risk index than the two control groups. We also anticipated that the relationship between BED and addictive behaviors would be mediated by a high-risk personality profile. The predicted mediation effect was strongly supported. Contrary to expectation, BED participants did not engage in more addictive behaviors or have higher personality-risk scores than their weight-matched counterparts. However, both overweight/obese groups did have significantly higher scores than the normal-weight group. The relationships among personality risk, elevated body mass index (BMI), and addictive behaviors have important clinical implications, especially for treatments that target psycho-behavioral intervention for compulsive overeating and substance-use disorders.