Genome-wide analysis of a model-derived binge eating disorder phenotype identifies risk loci and implicates iron metabolism.

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.

An exploratory structural equation modelling (ESEM) of the Eating Disorders Examination Questionnaire (EDE-Q) in bariatric patients.

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.

An Initial Test of the Efficacy of a Digital Health Intervention for Bariatric Surgery Candidates.

BACKGROUND: Rigorous research on smartphone apps for individuals pursuing bariatric surgery is limited. A digital health intervention was recently developed using standard behavioral weight loss programs with specific modifications for bariatric surgery. The current study evaluated this intervention for improving diet, exercise, and psychosocial health over 8 weeks prior to surgery in an academic medical center. METHODS: Fifty patients were randomized to receive either the digital intervention or treatment as usual prior to a surgical procedure. Measures of anxiety, depression, stress, quality of life, physical activity, and diet were administered at baseline and at 8-week follow-up. Statistical power of 80% estimated for N = 50 to detect ES = 0.68 with alpha = 0.05. RESULTS: Results of intent-to-treat (N = 50 baseline, N = 36 follow-up) analyses indicated significant moderate differences in stress and anxiety (ES = - 0.58 to - 0.62) favoring the digital intervention. Effects of the program on total daily calories consumed, body mass index, quality of life, and eating disorder symptoms were small (ES = - 0.24 to 0.33) and not significant. Given small effects for these domains, the sample size of the study likely affected the ability to detect significant differences. CONCLUSIONS: The digital health intervention appears to significantly impact several measures of physical activity and emotional functioning in candidates for bariatric surgery, which could augment surgical outcomes.

Lessons learned developing and testing family-based interoceptive exposure for adolescents with low-weight eating disorders.

BACKGROUND: Anorexia nervosa (AN) usually develops in early adolescence and is characterized by high rates of morbidity and mortality. Family-based therapy (FBT) is the leading evidence-based treatment for adolescents with AN, but not all patients experience sufficient improvement. The purpose of this manuscript is to describe the development and subsequent experience with a Family-Based Interoceptive Exposure (FBT-IE) for adolescents with a broader form of low-weight eating disorders. METHODS: The novel IE-based behavioral intervention is a six-session family-based treatment module designed to directly target and modify disgust by altering the prefrontal regulation of the insula response to aversive stimuli by decreasing visceral sensitivity (e.g., bloating). Each session teaches a new skill regarding tolerating distress to visceral sensations associated with disgust and an in-vivo "IE exercise," in which the family is provided with a meal replacement shake of unknown content and caloric density. RESULTS: In this novel treatment, the patient learns to tolerate disgust in the context of a challenging food stimulus as a way to increase consumption of restricted foods outside of session. CONCLUSION: We discuss successes and challenges executing this treatment with patients with low-weight eating disorders and propose future directions for the intervention.

Relationship of estrogen synthesis capacity in the brain with obesity and self-control in men and women.

Gonadal hormones are linked to mechanisms that govern appetitive behavior and its suppression. Estrogens are synthesized from androgens by the enzyme aromatase, highly expressed in the ovaries of reproductive-aged women and in the brains of men and women of all ages. We measured aromatase availability in the amygdala using positron emission tomography (PET) with the aromatase inhibitor [11C]vorozole in a sample of 43 adult, normal-weight, overweight, or obese men and women. A subsample of 27 also completed personality measures to examine the relationship between aromatase and personality traits related to self-regulation and inhibitory control. Results indicated that aromatase availability in the amygdala was negatively associated with body mass index (BMI) (in kilograms per square meter) and positively correlated with scores of the personality trait constraint independent of sex or age. Individual variations in the brain's capacity to synthesize estrogen may influence the risk of obesity and self-control in men and women.

Applying the disgust conditioning model of food avoidance: A case study of acceptance-based interoceptive exposure.

OBJECTIVE: The current case report details the treatment of a 16-year-old adolescent with anorexia nervosa utilizing a novel adjunct, acceptance-based interoceptive exposure, prior to family-based treatment (FBT) for eating disorders. METHOD: The exposure-based module focused particularly on the tolerance of disgust. For six sessions, the clinician taught the client skills that could be used to tolerate distress to visceral sensations associated with disgust. These skills were to be used during in- and between-session exposures. Each session included exposure to physical sensations that occurred while drinking a milkshake. RESULTS: Across six sessions, the client reported improvement in symptoms in addition to gaining weight. Additionally, she consumed more calories of a test meal following the intervention. Within broader FBT, the client reached an established weight goal, was able to return to physical activity, and reported an increased ability to manage distress. DISCUSSION: Given the client's improvement on the Eating Disorders Examination-Questionnaire (EDE-Q) within six sessions, we believe IE may be a useful adjunct to FBT. Interoceptive exposure may augment the efficacy of FBT for anorexia nervosa as it provides clients with skills to utilize during the refeeding phase of treatment.

Defining the Construct of Synthetic Androgen Intoxication: An Application of General Brain Arousal.

Synthetic androgens (i. e., anabolic-androgenic steroids) are the primary component to the majority of problematic appearance and performance enhancing drug (APED) use. Despite evidence that these substances are associated with increased risk for aggression, violence, body image disturbances, and polypharmacy and can develop a pattern of chronic use consistent with drug dependence, there are no formal definitions of androgen intoxication. Consequently, the purpose of this paper is to establish a testable theory of androgen intoxication. We present evidence and theorize that synthetic androgen intoxication can be defined by a pattern of poor self-regulation characterized by increased propensity for a range of behaviors (e.g., aggression, sex, drug seeking, exercise, etc.) via androgen mediated effects on general brain arousal. This theory posits that androgens reduce threshold for emotional reactivity, motor response, and alertness to sensory stimuli and disrupt inhibitory control over the behaviors associated with synthetic androgen use. These changes result from alteration to basic neurocircuitry that amplifies limbic activation and reduces top-down cortical control. The implications for this definition are to inform APED specific hypotheses about the behavioral and psychological effects of APED use and provide a basis for establishing clinical, legal, and public health guidelines to address the use and misuse of these substances.

Suicidal Ideation and Behaviours Among Adolescents Receiving Bariatric Surgery: A Case-Control Study.

OBJECTIVE: This study examined the prevalence and correlates of suicidal ideation and behaviour (SI/B) among adolescents receiving bariatric surgery. METHOD: Charts of 206 adolescents receiving bariatric surgery were reviewed. Cases with SI/B (current/lifetime reported at baseline or event occurring in the programme n = 31, 15%) were case matched on gender, age and surgery type to 31 adolescents reporting current or past psychiatric treatment and 31 adolescents denying lifetime SI/B or psychiatric treatment. RESULTS: Before surgery, adolescents with SI/B reported significantly lower total levels of health-related quality of life (p = 0.01) and greater depressive symptoms (p = 0.004) in comparison with candidates who never received psychiatric treatment. No significant differences were found between groups for the change in depressive symptoms or body mass index following surgery. CONCLUSIONS: As in studies of adults, a notable subset of adolescents receiving bariatric surgery indicated pre-operative or post-operative SI/B. It is critical that clinicians evaluate and monitor adolescent patients undergoing bariatric surgery for risk of SI/B.

Predictors and correlates of follow-up visit adherence among adolescents receiving laparoscopic adjustable gastric banding.

BACKGROUND: Adherence behaviors have not been examined among adolescents undergoing laparoscopic adjustable gastric banding (LAGB). In addition, studies of youth receiving bariatric surgery have not considered the influence of psychopathology on postoperative adherence. The purpose of this study was to evaluate predictors and correlates of adherence to post-surgery visits among a sample of adolescents undergoing LAGB. METHODS: Postoperative visits with surgical staff were analyzed over the 2 years after surgery (n = 101 adolescents). Growth mixture modeling examined trends in adherence. RESULTS: A 3-class solution provided the best fit to the data. The classes from the final model were characterized by class 1 (61.6%) demonstrating high levels of adherence over the 24 months after LAGB, class 2 (28.5%) showing a more gradual decline in adherence, and class 3 (9.9%) with an accelerated decline in adherence. Higher levels of preoperative depressive symptoms and more preoperative episodes of loss of control overeating decreased the likelihood of adherence. Class 3 adolescents had significantly higher estimated 24-month body mass indices than classes 1 or 2. CONCLUSION: Variable patterns of follow-up visit adherence were identified among adolescents receiving LAGB, which were predicted by depressive symptoms and loss of control overeating. The trajectory characterized by a rapid decline in adherence to follow-up visits was also associated with less weight loss.

Stress and addiction.

Appetitive behaviors such as substance use and eating are under significant regulatory control by the hypothalamic-pituitary adrenal (HPA) and hypothalamic pituitary gonadal (HPG) axes. Recent research has begun to examine how these systems interact to cause and maintain poor regulation of these appetitive behaviors. A range of potential molecular, neuroendocrine, and hormonal mechanisms are involved in these interactions and may explain individual differences in both risk and resilience to a range of addictions. This manuscript provides a commentary on research presented during the International Society of Psychoneuroendocrinology's mini-conference on sex differences in eating and addiction with an emphasis on how HPG and HPA axis interactions affect appetitive behaviors in classic addictions and may be used to help inform the ongoing debate about the validity of food addiction.

Psychological outcomes and predictors of initial weight loss outcomes among severely obese adolescents receiving laparoscopic adjustable gastric banding.

OBJECTIVE: Elevated rates of psychopathology are noted among severely obese youth presenting for weight loss surgery. The role of mental health providers in this population is not well defined, and the selection of candidates is often the result of clinical judgment alone. The purpose of this study was to comprehensively evaluate psychiatric symptoms among a large sample of adolescents receiving laparoscopic adjustable gastric banding (LAGB) by (1) examining changes in depressive symptoms and quality of life in the year following surgery; (2) evaluating the interaction between patterns of change in depression, quality of life, and weight postsurgery; and (3) identifying presurgical psychological predictors of initial weight change. METHOD: Participants were 101 severely obese adolescents aged 14 to 18 years receiving LAGB at the Center for Adolescent Bariatric Surgery at the Morgan Stanley Children's Hospital of New York Presbyterian/Columbia University Medical Center between August 2006 and December 2009. Measures of height, weight, depressive symptoms, and quality of life were obtained in the first year following surgery. Changes in the Beck Depression Inventory (BDI), Pediatric Quality of Life Inventory (PedsQL), and body mass index were analyzed using latent growth curve modeling. RESULTS: Short-term changes in psychiatric symptoms and weight were analyzed using latent growth curve modeling. Significant changes in total BDI (ßslope = -0.885, SE = 0.279, P < .01; ßquadratic = 0.054, SE = 0.021, P < .001) and PedsQL (ßslope = -0.885, SE = 0.279, P < .001) scores were observed following LAGB, and comparable postoperative changes between psychosocial variables and body mass index were also noted (BDI: covariance [COV] = 0.21, SE = 0.06, P < .001; PedsQL: COV = -0.41, SE = 0.10, P < .01). Two variables (family conflict/loss of control eating) were found to be significant predictors of weight change over the year following surgery (P < .05). CONCLUSIONS: Adolescents experienced notable improvements in initial depressive symptoms and quality of life after LAGB, and measures of preoperative binge eating and family conflict affected postsurgery body mass index among youth. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01045499.

The diagnostic dilemma of pathological appearance and performance enhancing drug use.

Appearance and performance enhancing drug (APED) use includes the use of a range of pharmacologically distinct substances and concurrent investment in outward appearance or achievement, dietary control, and frequent exercise. A number of existing reviews and conceptual papers have defined pathological forms of APED use within the APED class of anabolic-androgenic steroids (AASs) and using the framework of AAS dependence. We review published data on APED use including human studies of AAS users and identified three defining phenomenological features associated with increased health risk and pathology. These features included (1) polypharmacy or the concurrent use of several pharmacologically distinct substances used to change outward appearance or increase likelihood of personal achievement; (2) significant body image disturbance; (3) rigid practices and preoccupations with diet and exercise. Investigations into the latent structure of APED use suggest these features cluster together in a homogenous group of APED users who have the highest health risk and most psychopathology. These features are discussed in the context of AAS dependence and problems with defining classic tolerance-withdrawal symptoms among APED users. Suggestions for a resolution and outline for future research needed to determine the best system for identifying and diagnosing pathological APED use are discussed.

Conceptualizing the role of estrogens and serotonin in the development and maintenance of bulimia nervosa.

Serotonergic dysregulation is thought to underlie much of the pathology in bulimia nervosa (BN). The purpose of this review is to expand the serotonergic model by incorporating specific and nonspecific contributions of estrogens to the development and maintenance of bulimic pathology in order to guide research from molecular genetics to novel therapeutics for BN. Special emphasis is given to the organizing theory of general brain arousal which allows for integration of specific and nonspecific effects of these systems on behavioral endpoints such as binge eating or purging as well as arousal states such as fear, novelty seeking, or sex. Regulation of the serotonergic system by estrogens is explored, and genetic, epigenetic, and environmental estrogen effects on bulimic pathology and risk factors are discussed. Genetic and neuroscientific research support this two-system conceptualization of BN with both contributions to the developmental and maintenance of the disorder. Implications of an estrogenic-serotonergic model of BN are discussed as well as guidelines and suggestions for future research and novel therapeutic targets.