Disentangling the links between gastric emptying and binge eating v. purging in eating disorders using a case-control design.

BACKGROUND: Prior work supports delayed gastric emptying in anorexia nervosa and bulimia nervosa (BN) but not binge-eating disorder, suggesting that neither low body weight nor binge eating fully accounts for slowed gastric motility. Specifying a link between delayed gastric emptying and self-induced vomiting could offer new insights into the pathophysiology of purging disorder (PD). METHODS: Women (N = 95) recruited from the community meeting criteria for DSM-5 BN who purged (n = 26), BN with nonpurging compensatory behaviors (n = 18), PD (n = 25), or healthy control women (n = 26) completed assessments of gastric emptying, gut peptides, and subjective responses over the course of a standardized test meal under two conditions administered in a double-blind, crossover sequence: placebo and 10 mg of metoclopramide. RESULTS: Delayed gastric emptying was associated with purging with no main or moderating effects of binge eating in the placebo condition. Medication eliminated group differences in gastric emptying but did not alter group differences in reported gastrointestinal distress. Exploratory analyses revealed that medication caused increased postprandial PYY release, which predicted elevated gastrointestinal distress. CONCLUSIONS: Delayed gastric emptying demonstrates a specific association with purging behaviors. However, correcting disruptions in gastric emptying may exacerbate disruptions in gut peptide responses specifically linked to the presence of purging after normal amounts of food.

The organizational role of ovarian hormones during puberty on risk for binge-like eating in rats.

Puberty is a high-risk period for the development of dysregulated eating, including binge eating. While risk for binge eating in animals and humans increases in both males and females during puberty, the increased prevalence is significantly greater in females. Emerging data suggest that the organizational effects of gonadal hormones may contribute to the female preponderance of binge eating. In this narrative review, we discuss studies conducted in animals that have examined these organizational effects as well as the neural systems that may serve as intermediary mechanisms. Relatively few studies have been conducted, but data thus far suggest that pubertal estrogens may organize risk for binge eating, potentially by altering key circuits in brain reward pathways. These promising results highlight the need for future studies to directly test organizational effects of pubertal hormones using hormone replacement techniques and circuit-level manipulations that can identify pathways contributing to binge eating across development.

Examination of onset trajectories and persistence of binge-like eating behavior in mice after intermittent palatable food exposure.

Binge eating is a persistent behavior associated with a chronic course of illness and poor treatment outcomes. While clinical research is unable to capture the full course of binge eating, preclinical approaches offer the opportunity to examine binge-like eating from onset through chronic durations, allowing identification of factors contributing to binge eating persistence. The present study quantified the trajectories of binge-like eating onset and modeled cycles of abstinence/relapse to develop a translational model for binge eating persistence. Adult male and female C57Bl6/J mice were randomized to a binge-like palatable food access schedule (daily 2-hr, 3×/week) or continuous, nonbinge like palatable food access for 12 days (Experiment 1). Persistence of palatable food consumption in both binge-like palatable food access groups was then examined across three cycles of forced abstinence and reexposure to palatable food (incubation) to model the persistence of binge eating in clinical populations. Mice with daily 2-hr palatable food access escalated their intake more than mice in the 3×/week or continuous groups (Experiment 1). This pattern was more pronounced in females. In addition, this pattern of palatable food intake reemerged across multiple cycles of behavioral incubation (Experiment 2). These findings provide a model of binge-like eating in mice that can be used in future studies examining both environmental factors and neural mechanisms contributing to binge eating persistence. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Corticostriatal dynamics underlying components of binge-like consumption of palatable food in mice.

Binge eating (BE) is a maladaptive repetitive feeding behavior present across nearly all eating disorder diagnoses. Despite the substantial negative impact of BE on psychological and physiological health, its underlying neural mechanisms are largely unknown. Other repetitive behavior disorders (e.g., obsessive compulsive disorder) show dysfunction within corticostriatal circuitry. However, to date, no work has investigated the in vivo neural dynamics underlying corticostriatal activity during BE episodes. The aim of the current study was to longitudinally examine in vivo neural activity within corticostriatal regions - the infralimbic cortex (IL) and dorsolateral striatum (DLS)- in a robust pre-clinical model for BE. Female C57BL6/J mice (N = 32) were randomized to receive: 1) intermittent (daily, 2-h) binge-like access to palatable food (sweetened condensed milk) (BE), or 2) continuous, non-intermittent (24-h) access to palatable food (control). In vivo calcium imaging was performed via fiber photometry at baseline and after chronic (4 weeks) engagement in the model for BE. Specific consummatory behaviors (feeding bout onset/offset) during recordings were captured using lickometers which generated TTL outputs for precise alignment of behavior to neural data. IL showed no specific changes in neural activity related to BE. However, BE animals showed decreased DLS activity at feeding onset and offset at the chronic timepoint when compared to activity at the baseline timepoint. Additionally, BE mice had significantly lower DLS activity at feeding onset and offset at the chronic timepoint compared to control mice. These results point to a role for DLS hypofunction in chronic BE, highlighting a potential target for future treatment intervention.

Breaking It Down: Investigation of Binge Eating Components in Animal Models to Enhance Translation.

Binge eating (BE) is a core eating disorder behavior that is present across nearly all eating disorder diagnoses (e. g., bulimia nervosa, binge eating disorder, anorexia nervosa binge/purge subtype), and is also widely present in the general population. Despite the prevalence of BE, limited treatment options exist and there are often high rates of relapse after treatment. There is evidence showing that genetic factors contribute to the heritability of BE and support for biological contributions to BE. However, more work is needed to fully understand neurobiological mechanisms underlying BE. One approach to target this problem is to separate BE into its distinct clinical components that can be more easily modeled using pre-clinical approaches. To date, a variety of animal models for BE have been used in pre-clinical studies; but there have been challenges translating this work to human BE. Here, we review these pre-clinical approaches by breaking them down into three clinically-significant component parts (1) consumption of a large amount of food; (2) food consumption within a short period of time; and (3) loss of control over eating. We propose that this rubric identifies the most frequently used and effective ways to model components of BE behavior using pre-clinical approaches with the strongest clinical relevance. Finally, we discuss how current pre-clinical models have been integrated with techniques using targeted neurobiological approaches and propose ways to improve translation of pre-clinical work to human investigations of BE that could enhance our understanding of BE behavior.

The effects of puberty and ovarian hormone removal on developmental trajectories of palatable food and chow intake in female rats.

OBJECTIVE: Palatable food (PF) intake is significantly greater in females than males and increases during adolescence. Previous data suggest that puberty and ovarian hormones may contribute to these sex and developmental differences, but few studies have examined this possibility. The aim of the current study was to address these gaps by examining trajectories of PF and chow intake during pre-puberty, puberty, and adulthood in intact female rats (Study 1) as well as in those receiving pre-pubertal ovariectomies (P-OVX) (Study 2). METHOD: We examined our study aims using archival data from 66 intact Sprague-Dawley female rats (Study 1) and 77 P-OVX and 79 intact Sprague-Dawley female rats (Study 2). PF and chow intake were measured using a free-choice, intermittent exposure paradigm in which rats were exposed to both food types starting in pre-puberty and continuing into adulthood. RESULTS: Mixed linear models revealed a specific effect of puberty on PF intake in both studies. PF intake increased substantially during puberty in all rats, but increases were particularly pronounced in P-OVX rats in Study 2. By contrast, chow intake increased significantly during pre-puberty (rather than puberty) in both studies, and these increases were relatively unaffected by P-OVX. DISCUSSION: Findings confirm a specific effect of puberty and ovarian hormone removal on PF intake in female rats. Differential trajectories of PF versus chow intake highlight potential reward-based processes in pubertal and ovarian hormone effects on PF intake in females.

The Disruptive Effects of Estrogen Removal before Puberty on Risk for Binge Eating in Female Rats.

Recent research suggests that estrogen is protective against binge eating in adult females, and that pubertal estrogen may be critical for these effects. Nonetheless, to date, no study has examined the role of pubertal estrogen in adult binge eating phenotypes in females, potentially due to difficulties experimentally manipulating estrogen in humans to examine causal effects. We used a novel animal model to examine whether estrogen removal prior to puberty (via pre-pubertal ovariectomy (P-OVX)) increases rates of binge eating prone (BEP) phenotypes in adulthood in females. A total of 77 P-OVX and 79 intact rats were followed from pre-puberty into adulthood and phenotyped for BEP status in adulthood. Results showed significantly increased rates (~2-8x higher) of adult BEP phenotypes in P-OVX as compared to intact rats. Findings confirm that estrogen removal substantially increases later risk for binge eating in females, potentially by disrupting typical adolescent brain development.

Exploring reward system responsivity in the nucleus accumbens across chronicity of binge eating in female rats.

OBJECTIVE: Research has highlighted the importance of reward-based processes in binge eating (BE). However, both increased and decreased activation have been observed in reward related brain regions for BE. Differences may be similar to addiction research, where the reward system is initially hyper-responsive at early stages of use, but becomes hypo-responsive with prolonged drug/alcohol use. This study was the first to examine differences in reward system responsivity at early versus chronic BE stages. METHOD: Using an animal model, Sprague-Dawley female rats were identified as BE prone (BEP) or BE resistant (BER) and randomly assigned to an early or chronic stage group. Neural activation (via Fos protein) was quantified in the nucleus accumbens core (NAC) and shell (NAS). RESULTS: Early stage BEP rats had the highest levels of Fos expression of all of the study groups. By contrast, chronic stage BEP rats exhibited decreased activation in the NAS and NAC that was similar to the activation in chronic stage BER rats. DISCUSSION: Findings are significant in suggesting hyper-neural activation to reward in the early stages of BE and decreased activation in later stages of BE. Additional studies are needed to elucidate how these differences may impact risk for and maintenance of BE.

Perinatal testosterone contributes to mid-to-post pubertal sex differences in risk for binge eating in male and female rats.

Exposure to testosterone early in life may contribute to sex differences and pubertal changes in risk for eating pathology (i.e., females > males, after pubertal onset). Specifically, perinatal testosterone permanently alters brain structure/function and drives the masculinization of several sex-differentiated behaviors. However, the effects of perinatal testosterone are often not evident until puberty when increases in gonadal hormones activate the expression of sex typical behavior, including eating behaviors (e.g., chow intake; saccharin preference) in rodents. Despite perinatal testosterone's masculinizing effects on general feeding behavior, it remains unknown if perinatal testosterone exposure contributes to sex differences in pathological eating. The current study addressed this gap by examining whether perinatal testosterone exposure decreases risk for binge eating proneness after pubertal onset in male and female rats. Sprague-Dawley rats (n = 40 oil-treated control females; n = 39 testosterone-treated females; n = 40 oil-treated control males) were followed longitudinally across pre-to-early puberty, mid-to-late puberty, and adulthood. The binge eating prone (BEP)/binge eating resistant (BER) rodent model was used to identify individual differences in binge eating proneness across the dimensional spectrum. As expected, testosterone-treated females and control males showed masculinized (i.e., lower) risk for binge eating as compared to control females, but only after midpuberty. These animal data are significant in suggesting that perinatal testosterone exposure may protect against binge eating and underlie sex differences in binge eating prevalence during and after puberty. (PsycINFO Database Record

Disturbance of gut satiety peptide in purging disorder.

OBJECTIVE: Little is known about biological factors that contribute to purging after normal amounts of food-the central feature of purging disorder (PD). This study comes from a series of nested studies examining ingestive behaviors in bulimic syndromes and specifically evaluated the satiety peptide YY (PYY) and the hunger peptide ghrelin in women with PD (n = 25), bulimia nervosa-purging (BNp) (n = 26), and controls (n = 26). Based on distinct subjective responses to a fixed meal in PD (Keel, Wolfe, Liddle, DeYoung, & Jimerson, ), we tested whether postprandial PYY response was significantly greater and ghrelin levels significantly lower in women with PD compared to controls and women with BNp. METHOD: Participants completed structured clinical interviews, self-report questionnaires, and laboratory assessments of gut peptide and subjective responses to a fixed meal. RESULTS: Women with PD demonstrated a significantly greater postprandial PYY response compared to women with BNp and controls, who did not differ significantly. PD women also endorsed significantly greater gastrointestinal distress, and PYY predicted gastrointestinal intestinal distress. Ghrelin levels were significantly greater in PD and BNp compared to controls, but did not differ significantly between eating disorders. Women with BNp endorsed significantly greater postprandial hunger, and ghrelin predicted hunger. DISCUSSION: PD is associated with a unique disturbance in PYY response. Findings contribute to growing evidence of physiological distinctions between PD and BNp. Future research should examine whether these distinctions account for differences in clinical presentation as this could inform the development of specific interventions for patients with PD.

Preliminary evidence of sex differences in behavioral and neural responses to palatable food reward in rats.

The female bias in eating disorder prevalence is the largest in all of psychiatry. Binge eating on palatable food (PF) is a core, maladaptive symptom that cuts across all major types of eating disorders and can be studied via animal models. Using an individual differences rat model of binge eating that identifies binge eating prone (BEP) and binge eating resistant (BER) phenotypes, we previously showed that, compared with males, females consume more PF and are more likely to be classified as BEP. One potential explanation for this sex difference is that PF is inherently more rewarding to females, leading to higher rates of binge eating. Here we tested the hypothesis that females have more robust behavioral and neural responses to PF reward than males. Adult male (N=18) and female (N=17) Sprague-Dawley rats were exposed to the Conditioned Place Preference paradigm using PF as the unconditioned stimulus. Select males (N=9) and females (N=9) were video-recorded during three of the PF-paired conditioning sessions to score feeding behavior. Following CPP, 13 male and 12 female rats were exposed to PF just prior to sacrifice to induce expression of the neural activation marker Fos, and Fos expression was quantified in mesocorticolimbic, hypothalamic, and amygdalar circuits. In the CPP paradigm, females displayed a more robust shift in preference for the chamber paired with PF compared with males, and behavioral analyses revealed that average duration of individual feeding bouts during pairing sessions was longer in females than in males. Fos expression was significantly higher in females vs. males in select regions of the mesocorticolimbic reward circuit, with no sex differences in hypothalamic or amygdalar regions. These results provide initial evidence that PF may be more rewarding to females than to males, possibly due to heightened responsiveness of neural substrates that mediate the hedonic and motivational responses to PF, which in part, may underlie sex differences in binge eating proneness.

Differential Effects of Estrogen and Progesterone on Genetic and Environmental Risk for Emotional Eating in Women.

Recent data show shifts in genetic and environmental influences on emotional eating across the menstrual cycle, with significant shared environmental influences during pre-ovulation, and primarily genetic effects during post-ovulation. Factors driving differential effects are unknown, although increased estradiol during pre-ovulation and increased progesterone during post-ovulation are thought to play a role. We indirectly investigated this possibility by examining whether overall levels of estradiol and progesterone differentially impact genetic and environmental risk for emotional eating in adult female twins (N = 571) drawn from the MSU Twin Registry. Emotional eating, estradiol levels, and progesterone levels were assessed daily and then averaged to create aggregate measures for analysis. As predicted, shared environmental influences were significantly greater in twins with high estradiol levels, whereas additive genetic effects increased substantially across low versus high progesterone groups. Results highlight significant and differential effects of ovarian hormones on etiologic risk for emotional eating in adulthood.

The effects of ovarian hormones and emotional eating on changes in weight preoccupation across the menstrual cycle.

OBJECTIVE: Previous research has shown that fluctuations in ovarian hormones (i.e., estradiol and progesterone) predict the changes in binge eating and emotional eating across the menstrual cycle. However, the extent to which other eating disorder symptoms fluctuate across the menstrual cycle and are influenced by ovarian hormones remains largely unknown. This study sought to examine whether the levels of weight preoccupation vary across the menstrual cycle and whether the changes in ovarian hormones and/or other factors (i.e., emotional eating and negative affect) account for menstrual cycle fluctuations in this eating disorder phenotype. METHOD: For 45 consecutive days, 352 women (age, 15-25 years) provided daily ratings of weight preoccupation, negative affect, and emotional eating. Saliva samples were also collected on a daily basis and assayed for levels of estradiol and progesterone using enzyme immunoassay techniques. RESULTS: Weight preoccupation varied significantly across the menstrual cycle, with the highest levels in the premenstrual and menstrual phases. However, ovarian hormones did not account for within-person changes in weight preoccupation across the menstrual cycle. Instead, the most significant predictor of menstrual cycle changes in weight preoccupation was the change in emotional eating. DISCUSSION: Fluctuations in weight preoccupation across the menstrual cycle appear to be influenced primarily by emotional eating rather than ovarian hormones. Future research should continue to examine the relationships among ovarian hormones, weight preoccupation, emotional eating, and other core eating disorder symptoms (e.g., body dissatisfaction, compensatory behaviors) in an effort to more fully understand the role of these biological and behavioral factors for the full spectrum of eating pathology.

Differential strain vulnerability to binge eating behaviors in rats.

Binge eating is a significantly heritable phenotype, but efforts to detect specific risk genes have fallen short. Identification of animal strain differences in risk for binge eating could highlight genetic differences across individuals of the same species that can be exploited in future animal and molecular genetic research. The current study aimed to explore strain differences in risk for binge eating in Sprague-Dawley versus Wistar female rats using the Binge Eating Resistant/Binge Eating Prone model. A sample of male Sprague-Dawley rats, a known low-risk group for binge eating, was included as a comparison group. A total of 83 rats (23 Wistar females, 30 Sprague-Dawley females, 30 Sprague-Dawley males) completed a protocol of intermittently administered, palatable food. Binge eating prone (BEP) and binge eating resistant (BER) rats were identified using a tertile approach. Sprague-Dawley female rats consumed the highest amount of palatable food and were more likely to be classified as BEP compared to Wistar female and Sprague-Dawley male rats. Wistar female rats were not significantly different from Sprague-Dawley male rats in their palatable food intake and tendency to be classified as BER rather than BEP. Sprague-Dawley female rats appear to be a particularly vulnerable genotype for binge eating. Comparisons between this group and others could help identify specific genetic/biological factors that differentiate it from lower risk groups. The reward system, linked to binge eating in humans, is a possible candidate to explore. Strain differences in the reward system could help increase understanding of individual differences in risk for binge eating in humans.