Diana L. Williams

Background: Formation of Diagnostic and Statistical Manual of Mental Disorders (DSM) subcommittees combined with recently approved coding designations for bulimia nervosa (BN) in partial remission highlights the need to examine the validity of the threshold that distinguishes BN from other specified feeding or eating disorders (OSFED) BN of low frequency and/or limited duration (OSFED‐BN). Methods: Women ( N = 344) who met DSM‐5 criteria for BN ( n = 153) or OSFED‐BN ( n = 118) or had no lifetime eating disorder symptoms ( n = 78) completed assessments of height, weight, weight history, percent body fat, structured clinical interviews for DSM‐5 disorders, suicidality, trauma, and treatment histories, and self‐report questionnaires covering a range of validators related to eating disorders, psychological traits, and general psychopathology. Comparisons across groups tested the validity of OSFED‐BN and whether prior history of DSM‐5 BN impacted evidence of its clinical significance and distinctiveness. Results: Lower frequency of binge eating was the primary reason for diagnosis of OSFED‐BN vs. BN; more than 80% of those with OSFED‐BN met or exceeded frequency and duration criteria for inappropriate compensatory behaviors. The current DSM‐5 threshold distinguishing BN from its OSFED variant or from BN in partial remission produced few differences relative to several large differences observed for comparisons of these diagnostic groups and non‐eating disorder controls. Discussion: Despite being associated with distinct DSM‐5 diagnostic codes, BN, BN in partial remission, and OSFED‐BN appear to represent a single condition that may, at most, capture some dimensional differences in severity. Findings support lowering the current minimum frequency thresholds for diagnosing BN.

Background: Weight suppression represents the difference between highest and current body weight and predicts maintenance of bulimia nervosa and related syndromes (BN-S). This study tested a biobehavioral model of binge-eating severity in which greater weight suppression links to reduced leptin, which links to reduced glucagon-like peptide 1 (GLP-1) release, which links to both decreased reward satiation and increased reward valuation, which link, respectively, to excessive food intake and loss of control while eating – the defining features of DSM-5 binge-eating episodes. Methods: Women (N = 399) who met DSM-5 criteria for bulimia nervosa or another eating disorder with binge eating (n = 321) or had no lifetime eating disorder symptoms (n = 78) participated in a multi-visit protocol, including structured clinical interviews, height, weight, weight history, percent body fat, fasting leptin, post-prandial GLP-1 response to a fixed meal, and self-report and behavioral assessments of food reward satiation (ad lib meal) and food and nonfood reward valuation (progressive ratio tasks). Results: A structural equation model (SEM) demonstrated excellent fit to data with significant pathways from greater weight suppression to lower leptin, to blunted GLP-1 response, to lower reward satiation, to larger eating/binge-eating episode size, with significant indirect paths through leptin, GLP-1, and reward satiation. SEM with paths via reward valuation to loss of control eating demonstrated inadequate fit. Conclusions: Findings specifically link reduced GLP-1 response to severity of binge-episode size and support weight history assessment in eating disorders, DSM-5 over ICD-11 criteria for binge eating, and may inform future clinical trials of GLP-1 agonists for BN-S.

Background: Bulimia nervosa and related syndromes (BN-S) characterized by binge eating vary considerably in illness severity and course. Using the Research Domain Criteria framework of the National Institute of Mental Health, we developed a model positing that the same set of physiological consequences of weight suppression (WS; defined as the difference between the highest and current adult body weight) contribute to binge-eating severity and maintenance by (1) increasing the drive or motivation to consume food (reward valuation effort [RVE]) and (2) decreasing the ability for food consumption to lead to a state of satiation or satisfaction (reward satiation). Objective: Our funded project aimed to test concurrent associations among WS, physiological factors (leptin concentrations and postprandial glucagon-like peptide 1 [GLP-1] response), behavioral indicators of RVE (breakpoint on progressive ratio tasks) and reward satiation (ad-lib test meal intake), self-report of these core constructs, and binge-eating severity in BN-S (aim 1); test prospective associations to determine whether WS predicts BN-S maintenance in longitudinal models and whether posited mediators also predict BN-S maintenance (aim 2); and determine whether associations between WS and BN-S severity and maintenance are mediated by alterations in leptin levels, GLP-1 response, RVE, and reward satiation (aim 3). Methods: We aimed to recruit a sample of 320 women with BN-S or noneating disorder controls, with BMI from 16 kg/m2 to 35 kg/m2, for our study. The study included diagnostic interviews; questionnaires; height, weight, and percentage of body fat measurements; weight history; fasting leptin level; postprandial GLP-1 and insulin responses to a fixed meal; and ad-lib meal and progressive ratio tasks to behaviorally measure reward satiation and RVE, respectively, at baseline, with at least 78.1% (250/320) of the participants providing data at 6- and 12-month follow-up visits. Data will be analyzed using structural equation models to test posited pathways. Results: Data collection began in November 2016 and ended in April 2023, pausing in-person data collection from March 2020 to February 2021 due to the COVID-19 pandemic. Of 399 eligible women enrolled, 290 (72.7%) provided clinical, behavioral, and biological data at baseline, and 249 (62.4%) provided follow-up data. Measures demonstrated strong psychometric properties. Conclusions: We seek to identify biobehavioral predictors to inform treatments that target key factors influencing the severity and course of binge eating. These data, supported solely through federal funding, can inform questions emerging from recent interest and controversy surrounding the use of GLP-1 agonists for binge eating. International Registered Report Identifier (IRRID): RR1-10.2196/66554

BACKGROUND Bulimia nervosa and related syndromes (BN-S) characterized by binge eating vary considerably in illness severity and course. Using the Research Domain Criteria framework of the National Institute of Mental Health, we developed a model positing that the same set of physiological consequences of weight suppression (WS; defined as the difference between the highest and current adult body weight) contribute to binge-eating severity and maintenance by (1) increasing the drive or motivation to consume food (reward valuation effort [RVE]) and (2) decreasing the ability for food consumption to lead to a state of satiation or satisfaction (reward satiation). OBJECTIVE Our funded project aimed to test concurrent associations among WS, physiological factors (leptin concentrations and postprandial glucagon-like peptide 1 [GLP-1] response), behavioral indicators of RVE (breakpoint on progressive ratio tasks) and reward satiation (ad-lib test meal intake), self-report of these core constructs, and binge-eating severity in BN-S (aim 1); test prospective associations to determine whether WS predicts BN-S maintenance in longitudinal models and whether posited mediators also predict BN-S maintenance (aim 2); and determine whether associations between WS and BN-S severity and maintenance are mediated by alterations in leptin levels, GLP-1 response, RVE, and reward satiation (aim 3). METHODS We aimed to recruit a sample of 320 women with BN-S or noneating disorder controls, with BMI from 16 kg/m2 to 35 kg/m2, for our study. The study included diagnostic interviews; questionnaires; height, weight, and percentage of body fat measurements; weight history; fasting leptin level; postprandial GLP-1 and insulin responses to a fixed meal; and ad-lib meal and progressive ratio tasks to behaviorally measure reward satiation and RVE, respectively, at baseline, with at least 78.1% (250/320) of the participants providing data at 6- and 12-month follow-up visits. Data will be analyzed using structural equation models to test posited pathways. RESULTS Data collection began in November 2016 and ended in April 2023, pausing in-person data collection from March 2020 to February 2021 due to the COVID-19 pandemic. Of 399 eligible women enrolled, 290 (72.7%) provided clinical, behavioral, and biological data at baseline, and 249 (62.4%) provided follow-up data. Measures demonstrated strong psychometric properties. CONCLUSIONS We seek to identify biobehavioral predictors to inform treatments that target key factors influencing the severity and course of binge eating. These data, supported solely through federal funding, can inform questions emerging from recent interest and controversy surrounding the use of GLP-1 agonists for binge eating. INTERNATIONAL REGISTERED REPORT RR1-10.2196/66554

Glucagon‐like peptide 1 (GLP‐1) is well known as a gut hormone and also acts as a neuropeptide, produced in a discrete population of caudal brainstem neurons that project widely throughout the brain. GLP‐1 receptors are expressed in many brain areas of relevance to energy balance, and stimulation of these receptors at many of these sites potently suppresses food intake. This review surveys the current evidence for effects mediated by GLP‐1 receptors on feeding behaviour at a wide array of brain sites and discusses behavioural and neurophysiological mechanisms for the effects identified thus far. Taken together, it is clear that GLP‐1 receptor activity in the brain can influence feeding by diverse means, including mediation of gastrointestinal satiation and/or satiety signalling, suppression of motivation for food reward, induction of nausea and mediation of restraint stress‐induced hypophagia, but many questions about the organization of this system remain.LINKED ARTICLES: This article is part of a themed issue on GLP1 receptor ligands (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.4/issuetoc

Objective: Intermittent (INT) access to a high‐fat diet (HFD) can induce excessive‐intake phenotypes in rodents. This study hypothesized that impaired satiation responses contribute to elevated intake in an INT‐HFD access model.Methods: First, this study characterized the intake and meal patterns of female rats that were subjected to an INT HFD in which a 45% HFD was presented for 20 hours every fourth day. To examine nutrient‐induced satiation, rats received intragastric infusions of saline or Ensure Plus prior to darkness‐onset food access. A similar design was used to examine sensitivity to the satiating effect of amylin. This study then examined whether an INT HFD influences amylin‐induced c‐Fos in feeding‐relevant brain areas.Results: Upon INT HFD access, rats consumed meals of larger size. The anorexic response to intragastric Ensure infusion and exogenous amylin treatment was blunted in INT rats on both chow‐only and INT‐HFD days of the diet regimen, compared with chow‐maintained and continuous‐HFD rats. An INT HFD did not influence amylin‐induced c‐Fos in the area postrema, nucleus of the solitary tract, and lateral parabrachial nucleus.Conclusions: Impaired satiation responses, mediated in part by reduced sensitivity to amylin, may explain the elevated intake observed upon INT HFD access and may play a role in disorders of INT overconsumption, including binge eating.