Noradrenergic control of neurobehavior in human binge-eating disorder and obesity (NOBEAD): A smartphone-supported behavioral emotion regulation intervention study protocol integrating molecular brain imaging.

OBJECTIVE: The neurobehavioral underpinnings of binge-eating disorder (BED), co-occurring with obesity (OB), are largely unknown. This research project conceptualizes BED as a disorder with dysfunctional emotion regulation (ER) linked with changes in central noradrenaline (NA) transmission and NA-modulated neuronal networks. METHODS: We expect abnormalities in NA activity in both BED and OB, but most pronounced in BED. We expect these abnormalities to be modifiable through state-of-the-art ER intervention, specifically in BED. To assess the role of NA transmission, we will quantify changes in NA transporter (NAT) availability using the highly NAT-specific [11 C]methylreboxetin (MRB) and positron emission tomography-magnetic resonance imaging (PET-MRI) that allows measuring molecular and neuronal changes before and after an ER intervention. Individual 12-session smartphone-supported acceptance-based behavioral therapy will be conducted to improve ER. Thirty individuals with OB and BED (OB + BED), 30 individuals with OB without BED (OB - BED), and 20 individuals with normal weight will undergo assessments of NAT availability and neuronal network activity under rest and stimulated conditions, clinical interviews, self-report questionnaires on eating behavior, ER, mental and physical health, and quality of life, and neuropsychological tests on executive function. Afterwards, in an experimental randomized-controlled design, individuals with OB + BED and OB - BED will be allocated to smartphone-supported ER intervention versus a waitlist and re-assessed after 10 weeks. DISCUSSION: By obtaining biological and behavioral markers, the proposed study will disentangle the involvement of NAT and the central NA system in the modulation of emotion-supporting neuronal networks that influence eating behavior. Neurobehavioral mechanisms of change during an ER intervention will be determined. TRIAL REGISTRATION: German Clinical Trials Register (DRKS): DRKS00029367. PUBLIC SIGNIFICANCE: This study investigates the central noradrenaline system by using hybrid brain imaging in conjunction with emotion regulation as a putative core biological mechanism in individuals with obesity with or without binge-eating disorder that is targeted by emotion regulation intervention. The results will provide a molecular signature beyond functional imaging biomarkers as a predictive biomarker toward precision medicine for tailoring treatments for individuals with binge-eating disorders and obesity.

Endocrinology-informed neuroimaging in eating disorders: GLP1, orexins, and psilocybin.

The neurobiology of eating disorders [EDs; anorexia nervosa (AN), bulimia nervosa (BN), and binge eating disorder (BED)] remains poorly understood. Here, I describe how neuroimaging, accompanied by peripheral endocrine measures, can provide insights into the neurobiological drivers of eating disorders. Orexins/hypocretins, glucagon-like peptide-1 receptor (GLP1R) agonists, and psilocybin are highlighted as avenues for investigation.

Aberrant reward-related neural activation: Dimensional correlate of binge-eating severity or categorical marker of binge eating?

Binge eating (BE) is characterized by consuming an objectively large amount of food in a short period of time and experiencing loss of control over one's eating. The neural underpinnings of monetary reward anticipation and their association with BE severity remain poorly understood. Fifty-nine women aged 18 to 35 (M = 25.67, SD = 5.11) with a range of average weekly BE frequency (M = 1.96, SD = 1.89, range = 0-7) completed the Monetary Incentive Delay Task during fMRI scanning. Mean percent signal change within the left and right nucleus accumbens (NAc) during anticipation of monetary gain (versus non-gain) was extracted from a priori-defined functional 5 mm spheres and correlated with average weekly BE frequency. Exploratory voxel-wise whole-brain analyses examined the association between neural activation during anticipation of monetary reward and average weekly BE frequency. Body mass index and depression severity were covariates of non-interest in analyses. Mean percent signal change in the left and right NAc inversely correlated with average weekly BE frequency. Whole-brain analysis revealed no significant associations between neural activation during reward anticipation and average weekly BE frequency. In exploratory case-control analyses, mean percent signal change in the right NAc was significantly lower in women with BE (n = 41) versus women without BE (n = 18), but whole-brain analyses revealed no significant group differences in neural activation during reward anticipation. Decreased right NAc activity during monetary reward anticipation may distinguish women with and without BE.

Aberrant functional connectivity between reward and inhibitory control networks in pre-adolescent binge eating disorder.

BACKGROUND: Behavioral features of binge eating disorder (BED) suggest abnormalities in reward and inhibitory control. Studies of adult populations suggest functional abnormalities in reward and inhibitory control networks. Despite behavioral markers often developing in children, the neurobiology of pediatric BED remains unstudied. METHODS: 58 pre-adolescent children (aged 9-10-years) with BED (mBMI = 25.05; s.d. = 5.40) and 66 age, BMI and developmentally matched control children (mBMI = 25.78; s.d. = 0.33) were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development (ABCD) Study. We investigated group differences in resting-state functional MRI functional connectivity (FC) within and between reward and inhibitory control networks. A seed-based approach was employed to assess nodes in the reward [orbitofrontal cortex (OFC), nucleus accumbens, amygdala] and inhibitory control [dorsolateral prefrontal cortex, anterior cingulate cortex (ACC)] networks via hypothesis-driven seed-to-seed analyses, and secondary seed-to-voxel analyses. RESULTS: Findings revealed reduced FC between the dlPFC and amygdala, and between the ACC and OFC in pre-adolescent children with BED, relative to controls. These findings indicating aberrant connectivity between nodes of inhibitory control and reward networks were corroborated by the whole-brain FC analyses. CONCLUSIONS: Early-onset BED may be characterized by diffuse abnormalities in the functional synergy between reward and cognitive control networks, without perturbations within reward and inhibitory control networks, respectively. The decreased capacity to regulate a reward-driven pursuit of hedonic foods, which is characteristic of BED, may in part, rest on this dysconnectivity between reward and inhibitory control networks.

Sex differences in regional gray matter density in pre-adolescent binge eating disorder: a voxel-based morphometry study.

BACKGROUND: Binge eating disorder (BED) is a pernicious psychiatric disorder which is linked with broad medical and psychiatric morbidity, and obesity. While BED may be characterized by altered cortical morphometry, no evidence to date examined possible sex-differences in regional gray matter characteristics among those with BED. This is especially important to consider in children, where BED symptoms often emerge coincident with rapid gray matter maturation. METHODS: Pre-adolescent, 9-10-year old boys (N = 38) and girls (N = 33) with BED were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development Study. We investigated sex differences in gray matter density (GMD) via voxel-based morphometry. Control sex differences were also assessed in age and body mass index and developmentally matched control children (boys N = 36; girls N = 38). Among children with BED, we additionally assessed the association between dorsolateral prefrontal (dlPFC) GMD and parent-reported behavioral approach and inhibition tendencies. RESULTS: Girls with BED uniquely demonstrate diffuse clusters of greater GMD (p < 0.05, Threshold Free Cluster Enhancement corrected) in the (i) left dlPFC (p = 0.003), (ii) bilateral dmPFC (p = 0.004), (iii) bilateral primary motor and somatosensory cortex (p = 0.0003) and (iv) bilateral precuneus (p = 0.007). Brain-behavioral associations suggest a unique negative correlation between GMD in the left dlPFC and behavioral approach tendencies among girls with BED. CONCLUSIONS: Early-onset BED may be characterized by regional sex differences in terms of its underlying gray matter morphometry.

The neurobiological reward system and binge eating: A critical systematic review of neuroimaging studies.

OBJECTIVE: Changes in reward processing are hypothesized to play a role in the onset and maintenance of binge eating (BE). However, despite an increasing number of studies investigating the neurobiological reward system in individuals who binge eat, no comprehensive systematic review exists on this topic. Therefore, this review has the following objectives: (1) identify structural and functional changes in the brain reward system, either during rest or while performing a task; and (2) formulate directions for future research. METHODS: A search was conducted of articles published until March 31, 2022. Neuroimaging studies were eligible if they wanted to study the reward system and included a group of individuals who binge eat together with a comparator group. Their results were summarized in a narrative synthesis. RESULTS: A total of 58 articles were included. At rest, individuals who binge eat displayed a lower striatal dopamine release, a change in the volume of the striatum, frontal cortex, and insula, as well as a lower frontostriatal connectivity. While performing a task, there was a higher activity of the brain reward system when anticipating or receiving food, more model-free reinforcement learning, and more habitual behavior. Most studies only included one patient group, used general reward-related measures, and did not evaluate the impact of comorbidities, illness duration, race, or sex. DISCUSSION: Confirming previous hypotheses, this review finds structural and functional changes in the neurobiological reward system in BE. Future studies should compare disorders, use measures that are specific to BE, and investigate the impact of confounding factors. PUBLIC SIGNIFICANCE STATEMENT: This systematic review finds that individuals who binge eat display structural and functional changes in the brain reward system. These changes could be related to a higher sensitivity to food, relying more on previous experiences when making decisions, and more habitual behavior. Future studies should use a task that is specific to binge eating, look across different patient groups, and investigate the impact of comorbidities, illness duration, race, and sex.

OBJETIVO: Se plantea la hipótesis de que los cambios en el procesamiento de la recompensa desempeñan un papel en el inicio y mantenimiento de los atracones (BE). Sin embargo, a pesar de un número creciente de estudios que investigan el sistema de recompensa neurobiológica en individuos que comen en atracones, no existe una revisión sistemática exhaustiva sobre este tema. Por lo tanto, esta revisión tiene los siguientes objetivos: (1) identificar cambios estructurales y funcionales en el sistema de recompensa cerebral, ya sea en reposo o mientras se realiza una tarea; (2) formular direcciones para futuras investigaciones. MÉTODOS: Se realizó una búsqueda de artículos publicados hasta el 31 de marzo de 2022. Los estudios de neuroimagen eran elegibles si querían estudiar el sistema de recompensa e incluían a un grupo de individuos que comían en atracón junto con un grupo de comparación. Sus resultados se resumieron en una síntesis narrativa. RESULTADOS: Se incluyeron un total de 58 artículos. En reposo, los individuos que comen en atracón mostraron una menor liberación de dopamina estriatal, un cambio en el volumen del cuerpo estriado, la corteza frontal y la ínsula, así como una menor conectividad frontostriatal. Al realizar una tarea, hubo una mayor actividad del sistema de recompensa cerebral al anticipar o recibir alimentos, más aprendizaje de refuerzo sin modelos y un comportamiento más habitual. La mayoría de los estudios sólo incluyeron un grupo de pacientes, utilizaron medidas generales relacionadas con la recompensa y no evaluaron el impacto de las comorbilidades, la duración de la enfermedad, la raza o el sexo. DISCUSIÓN: Confirmando hipótesis anteriores, esta revisión encuentra cambios estructurales y funcionales del sistema de recompensa neurobiológica en BE. Los estudios futuros deben comparar los trastornos, utilizar medidas que sean específicas para el comer en atracones e investigar el impacto de los factores de confusión.

Neural correlates of body image processing in binge eating disorder.

Although body image disturbances play a central role in the development, maintenance and relapse of binge eating disorder (BED), studies investigating the neural basis underlying body processing in BED are still missing. To address this gap, we conducted a preregistered (German Clinical Trials Register [Deutsches Register Klinischer Studien; DRKS], Registration DRKS00008107) combined functional magnetic resonance (fMRI)/eye tracking study in which 38 women with BED and 22 healthy controls weight-matched for overall equivalence processed images of their own bodies, an unfamiliar weight-matched body, and visually matched nonbody control stimuli while performing a one-back task. Women with BED responded with higher left fusiform body area (FBA) activity than controls during body image processing. Despite higher levels of self-reported body dissatisfaction, women with BED did not show overactivation in emotion-processing areas in response to their own body. The eye-tracking results indicated that visual attention toward the presented stimuli was associated with increased activity in the extrastriate body area (EBA) and FBA across groups. Our results thus provide evidence for an aberrant neural processing of body images in BED and highlight the importance of controlling for visual attention in future studies assessing neuronal body processing. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Regional gray matter abnormalities in pre-adolescent binge eating disorder: A voxel-based morphometry study.

BACKGROUND: Binge eating disorder (BED) is a pernicious psychiatric disorder which is linked with an array of multisystemic organ morbidity, broad psychiatric morbidity, and obesity. Despite behavioral markers often developing in early childhood, the neurobiological markers of early-onset BED remain understudied, and developmental pathophysiology remains poorly understood. METHODS: 71 preadolescent children (aged 9-10-years) with BED and 74 age, BMI and developmentally matched control children were extracted from the 3.0 baseline (Year 0) release of the Adolescent Brain Cognitive Development (ABCD) Study. We investigated group differences in gray matter density (GMD) via voxel-based morphometry (VBM). We additionally performed region of interest analyses, assessing the association between GMD in nodes of the reward (orbitofrontal cortex; OFC) and inhibitory control (dorsolateral prefrontal cortex; dlPFC) networks, and parent-reported behavioral inhibition and approach tendencies. RESULTS: Diffuse elevations in cortical GMD were noted in those with BED, which spanned prefrontal, parietal, and temporal regions. No areas of reduced GMD were noted in those with BED. No alterations in subcortical GMD were noted. Brain-behavioral associations suggest a distinct and negative relationship between GMD in the OFC and dlPFC, respectively, and self-reported markers of hedonic behavioral approach tendencies. CONCLUSIONS: Early-onset BED may be characterized by diffuse morphological abnormalities in gray matter density, suggesting alterations in cortical architecture which may reflect decreased synaptic pruning and arborization, or decreased myelinated fibers and therefore inter-regional afferents.

Subcortical brain volume and cortical thickness in adolescent girls and women with binge eating.

OBJECTIVE: Alterations in brain structure have been implicated in the onset and acute phases of several forms of psychopathology. However, there is a dearth of research investigating brain structure in persons with binge eating, contributing to poor understanding of mechanisms associated with binge eating. METHOD: Adolescent girls and women (aged 14-35 years) with binge eating (n = 56) and group age-matched girls and women without binge eating (n = 26) completed structural magnetic resonance imaging (MRI) scans and interview-based and self-report assessments of eating disorder and general psychopathology. MRI data were processed using FreeSurfer. Analysis of covariance tested mean differences in subcortical volume and cortical thickness of a priori selected regions of interest between binge-eating and non-binge-eating groups, controlling for age, body mass index, purging frequency, depression, and medication use. Exploratory partial correlations tested associations between brain structure and eating disorder symptoms within participants with binge eating. RESULTS: We did not observe differences in regional subcortical volume and cortical thickness between girls and women with and without binge eating. Within participants with binge eating, severity of attitudinal eating disorder symptoms was inversely associated with caudal middle frontal gyrus, right precentral gyrus, right postcentral gyrus, superior parietal, left inferior parietal thickness, and left accumbens volume; however, these associations would not survive multiple-comparison corrections. DISCUSSION: Correlations between attitudinal eating disorder symptoms and frontoparietal thinning may represent a state marker of binge eating. Future research could investigate whether frontoparietal thinning worsens with illness duration or persists beyond binge eating cessation.

Impulsivity and compulsivity in binge eating disorder: A systematic review of behavioral studies.

BACKGROUND: Binge eating disorder (BED) often includes impulsive and compulsive behaviors related to eating behavior and food. Impulsivity and compulsivity generally may contribute to the etiology and maintenance of multiple psychiatric disorders including BED. This review aimed to identify and synthesize available behavioral studies of impulsivity and compulsivity among individuals with BED. METHOD: A systematic search was performed focusing on BED and specific facets of impulsivity (rapid response and choice) and compulsivity (set-shifting, cognitive flexibility, and/or habit learning). All case-control studies comparing adults with either full-threshold or subthreshold BED to individuals with normal weight, overweight/obesity, or other eating disorders (e.g., bulimia nervosa) were included. RESULTS: Thirty-two studies representing 29 unique samples met inclusion criteria. Increased choice impulsivity was observed among individuals with BED relative to individuals with normal weight. There were mixed findings and/or a lack of available evidence regarding rapid response impulsivity and compulsivity. The presence of between-group differences was not dependent on sample characteristics (e.g., full or sub threshold BED diagnosis, or treatment-seeking status). Heterogeneity relating to covariates, task methodologies, and power limited conclusions. CONCLUSIONS: Literature supports a postive association between choice impulsivity and BED. More research is needed to determine if individuals with BED demonstrate elevated levels of either rapid response impulsivity or types of compulsivity. Careful selection of covariates and consideration of task methodologies and power would aid future research.

Reward learning in unmedicated women with bulimia nervosa: A pilot investigation.

Bulimia nervosa (BN) is characterized by recurrent engagement in eating disorder behaviors despite negative consequences, potentially reflecting aberrant stimulus-response or reward-learning processes. Indeed, frontostriatal circuitry involved in reward learning is altered in persons with BN and preliminary research suggests reward learning is impaired in persons with BN. Additional research on reward learning in BN and its association with eating disorder symptom expression is warranted to further the field's understanding of potential pathophysiological mechanisms of BN. To this end, the probabilistic reward learning task (PRLT) was administered to unmedicated women with BN (n = 15) and demographically matched psychiatrically healthy women (n = 18). Contrary to our hypotheses, results demonstrated that women with BN showed greater reward learning during the PRLT relative to healthy comparison women when covarying for symptoms of depression, social anxiety, and mania. Exploratory analyses showed that binge-eating frequency was inversely associated with reward learning in women with BN; however, results should be interpreted with caution due to the small sample size. Together, results suggest that women with BN do not have deficits in implicit reward learning. Given the preliminary nature of this investigation, larger-scale studies are needed to further examine reward learning in current BN and could compare reward learning using general (e.g., monetary) and disorder-specific (e.g., food) reinforcers. Further work is needed to confirm the inverse association between reward learning and binge eating.

Altered regional grey matter volume and appetite-related hormone levels in adolescent obesity with or without binge-eating disorder.

PURPOSE: Binge eating disorder (BED) is characterized by frequent and persistent overeating episodes of binge eating without compensatory behaviors. The aim was to evaluate regional gray matter volume (GMV) abnormalities and appetite-regulating hormone levels (NPY and Leptin) in obese subjects either with or without BED compared to healthy controls (HC). METHODS: Twenty-six obese patients with BED, 25 obese patients without BED and 27 healthy subjects as an age-matched control group with neuroimaging and appetite-regulating hormone levels were found eligible for regional GMV abnormalities. A structural magnetic resonance scan and timely blood samples were drawn to assess the appetite-regulating hormone levels. RESULTS: The BED obese patients had a greater GMVs of the right medial orbitofrontal cortex (OFC) and the left medial OFC compared to the non-BED obese patients. BED patients were characterized by greater GMV of the left medial OFC than HCs. Relative to the HCs, higher serum NPY levels were found in BED obese and non-BED obese groups. Serum leptin levels (pg/mL) had positively correlations with GMV in right medial OFC, left medial OFC, right lateral OFC, and left anterior cingulate cortex. CONCLUSION: Among the reward processing network, which is largely associated with feeding behaviours in individuals with obesity and binge eating disorder, the OFC volumes was correlated with serum leptin concentrations. The results of our study may provide a rationale for exploring the link between regional grey matter volumes and appetite-related hormone levels in people with BED. LEVEL OF EVIDENCE: Level III, case-control analytic study.

Resting State Hypoconnectivity of Reward Networks in Binge Eating Disorder.

The clinical presentation of binge eating disorder (BED) and data emerging from task-based functional neuroimaging research suggests that this disorder may be associated with alterations in reward processing. However, there is a dearth of research investigating the functional organization of brain networks that mediate reward in BED. To address this gap, 27 adults with BED and 21 weight-matched healthy controls (WMC) completed a multimodel assessment consisting of a resting functional magnetic resonance imaging scan, behavioral tasks measuring reward-based decision-making (i.e., delay discounting and reversal learning), and self-report assessing clinical symptoms. A seed-based approach was employed to examine the resting state functional connectivity (rsFC) of the striatum (nucleus accumbens [NAcc] and ventral and dorsal caudate), a collection of regions implicated in reward processing. Compared with WMC, the BED group exhibited lower rsFC of striatal seeds, with frontal regions mediating executive functioning (e.g., superior frontal gyrus [SFG]) and posterior, parietal, and temporal regions implicated in emotional processing. Lower NAcc-SFG rsFC was associated with more difficulties with reversal learning and binge eating frequency in the BED group. Results suggest that hypoconnectivity of striatal networks that integrate self-regulation and reward processing may promote the clinical phenomenology of BED. Interventions for BED may benefit from targeting these circuit-based disturbances.

Relationship between binge eating and associated eating behaviors with subcortical brain volumes and cortical thickness.

BACKGROUND: Binge eating disorder (BED) is the most prevalent eating disorder. We examined the presence of binge eating (BE) and three associated eating behaviors in relation to subcortical regional volumes and cortical thickness from brain scans. METHODS: We processed structural MRI brain scans for 466 individuals from the Nathan Kline Institute Rockland Sample using Freesurfer. We investigated subcortical volumes and cortical thicknesses among those with and without BE and in relation to the scores on dietary restraint, disinhibition, and hunger from the Three-Factor Eating Questionnaire (TFEQ). We conducted a whole-brain analysis and a region of analysis (ROI) using a priori regions associated with BE and with the three eating factors. We also compared scores on the three TFEQ factors for the BE and non-BE. RESULTS: The BE group had higher scores for dietary restraint (p = .013), disinhibition (p = 1.22E-07), and hunger (p = 5.88E-07). In the whole-brain analysis, no regions survived correction for multiple comparisons (FDR corrected p<0.01) for either BE group or interaction with TFEQ. However, disinhibition scores correlated positively with left nucleus accumbens (NAc) volume (p < 0.01 FDR corrected). In the ROI analysis, those with BE also had greater left NAc volume (p = 0.008, uncorrected) compared to non-BE. LIMITATIONS: Limitations include potential self-report bias on the EDE-Q and TFEQ. CONCLUSIONS: The findings show that BE and disinhibition scores were each associated with greater volumes in the left NAc, a reward area, consistent with a greater drive and pleasure for food.

A broad-spectrum review on multimodal neuroimaging in bulimia nervosa and binge eating disorder.

Bulimia nervosa (BN) and binge eating disorder (BED) are psychiatric conditions marked by emotional disorders managed through the ingestion of great amount of food, with consequent vomiting for avoiding weight gain. Such behavioral habits are dysfunctional and severely impact both psychological and physical health, also compromising neurobiological processes. In the present review, we focus on recent neuroimaging findings (2010-2019) that provide insight into the neural bases of BN and BED. We describe the role of different neuroimaging techniques (magnetic resonance imaging, both structural and functional, positron emission tomography, single-photon emission computerized tomography, electroencephalography and magnetoencephalography) in the delineation of pathophysiological aspects of BN and BED. Results highlight the main involvement of the frontal system and its relationships with temporal areas for reward and self-regulatory processes modulation. The network that regulates food-stimuli control seems to be widespread across the brain, catching the insula, precentral gyrus, frontal cortex and extending until the visual cortex for processing of body image. These results demonstrate diffuse brain vulnerability associated with BN and BED and can confirm that symptomatology maintenance results from several neurostructural and neurofunctional alterations.

Eating disorders: Do PET and SPECT have a role? A systematic review of the literature.

A systematic review was implemented according to PRISMA guidelines on Pubmed, Psychinfo, Medline, Embase to fill the existing literature gap on the effectiveness of using Positron Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) in Anorexia Nervosa (AN), Bulimia Nervosa (BN) and Binge Eating Disorder (BED). Twenty-two articles were included. Four studies reported an increased density in 5-hydroxytryptamine receptor (5-HT1A) in fronto-temporo-parietal regions in both affected and recovered AN as well as in BN. The 5-HT transporter (5-HTT) binding was increased or diminished in different specific cortical areas and in relation to Eating Disorder (ED) subtypes. Some evidences of blunted Dopamine (DA) release in the putamen in BN patients suggest that their DA function might be impaired as in addictive behaviours. Studies estimating the regional Cerebral Blood Flow (rCBF) with SPECT demonstrated that temporal areas seem to play a key role in ED corroborating the hypothesis of a cingulate-temporal cortical dysfunction in AN. In addition, alterations of both parietal and prefrontal cortex provide a possible common neural substrate in AN. Studies included in this review are heterogeneous preventing robust conclusions, however, our findings add knowledge on some of the neurotransmitters involved in ED.

Subcortical Shape Abnormalities in Bulimia Nervosa.

BACKGROUND: Bulimia nervosa (BN) is associated with functional abnormalities in frontostriatal and frontolimbic circuits. Although structural alterations in the frontal portions of these circuits have been observed, this is the first study of subcortical surface morphometry and the largest study of subcortical volume in BN. METHODS: Anatomical magnetic resonance scans were acquired from 62 female participants with full and subthreshold BN (mean age ± SD, 18.7 ± 4.0 years) and 65 group-matched healthy control participants (mean age ± SD, 19.3 ± 5.7 years). General linear models were used to compare groups and assess the significance of group-by-age interactions on the shape and total volume of 15 subcortical structures (p < .05, familywise error corrected). Associations with illness severity and duration were assessed in the BN group. RESULTS: Subcortical volumes did not differ across groups, but vertexwise analyses revealed inward shape deformations on the anterior surface of the pallidum in BN relative to control participants that were associated with binge-eating frequency and illness duration. Inward deformations on the ventrolateral thalamus and dorsal amygdala were more pronounced with advancing age in the BN group, and inward deformations on the caudate, putamen, and amygdala were associated with self-induced vomiting frequency. CONCLUSIONS: Our findings point to localized deformations on the surface of subcortical structures in areas that comprise both reward and cognitive control circuits. These deformations were more pronounced among older BN participants and among those with the most severe symptoms. Such precise localization of alterations in subcortical morphometry may ultimately aid in efforts to identify markers of risk and BN persistence.

Effect of lisdexamfetamine on emotional network brain dysfunction in binge eating disorder.

We examined the effects of lisdexamfetamine (LDX) treatment on ventral prefrontal cortex (VPFC) and striatal brain activation in binge eating disorder (BED). We hypothesized that participants with BED have an abnormal brain response to palatable food cues, and that VPFC and striatal regions would respond to such cues after LDX treatment. Twenty women with moderate to severe BED consented to a 12-week, open-label trial of LDX with fMRI before and after treatment. Twenty obese women without BED served as healthy controls and received one fMRI. LDX was started at 30 mg/d with a target of 70 mg/d at week 12. At baseline, women with BED showed greater activation in ventrolateral prefrontal cortex (VLPFC), striatum, and globus pallidus to food pictures and brain activation to food pictures predicted clinical outcome at 12 weeks. After 12 weeks of LDX treatment, BED women showed significant reductions in globus pallidus activation. Reductions in ventromedial prefrontal cortex (VMPFC) and thalamus activation specifically correlated with binge eating and obsessive-compulsive symptom reductions, respectively. Results suggest that BED is characterized by an abnormally large VPFC-subcortical brain response to palatable foods that LDX treatment helps modify. Moreover, VPFC-subcortical activation at baseline is a potential biomarker of LDX response.

Binge eating disorder and morbid obesity are associated with lowered mu-opioid receptor availability in the brain.

Both morbid obesity and binge eating disorder (BED) have previously been linked with aberrant brain opioid function. Behaviorally these two conditions are however different suggesting also differences in neurotransmitter function. Here we directly compared mu-opioid receptor (MOR) availability between morbidly obese and BED subjects. Seven BED and nineteen morbidly obese (non-BED) patients, and thirty matched control subjects underwent positron emission tomography (PET) with MOR-specific ligand [11C]carfentanil. Both subjects with morbid obesity and BED had widespread reduction in [11C]carfentanil binding compared to control subjects. However, there was no significant difference in brain MOR binding between subjects with morbid obesity and BED. Thus, our results indicate that there is common brain opioid abnormality in behaviorally different eating disorders involving obesity.

Binge-eating disorder: Clinical and therapeutic advances.

Binge-eating disorder (BED) is the most prevalent eating disorder with estimates of 2-5% of the general adult population. Nonetheless, its pathophysiology is poorly understood. Furthermore, there exist few therapeutic options for its effective treatment. Here we review the current state of binge-eating neurobiology and pharmacology, drawing from clinical therapeutic, neuroimaging, cognitive, human genetic and animal model studies. These studies, which are still in their infancy, indicate that while there are many gaps in our knowledge, several key neural substrates appear to underpin binge-eating and may be conserved between human and animals. This observation suggests that behavioral intermediate phenotypes or endophenotypes relevant to BED may be modeled in animals, facilitating the identification and testing of novel pharmacological targets. The development of novel, safe and effective pharmacological therapies for the treatment of BED will enhance the ability of clinicians to provide optimal care for people with BED.