Neuroendocrinological factors in binge eating disorder: A narrative review

Neuroendocrine mechanisms play a key role in the regulation of eating behavior. In individuals with binge eating disorder (BED), alterations in these mechanisms signaling hunger and satiety have been observed. It has been investigated that these alterations may underlie the development and maintenance of compulsive overeating in BED. The present narrative review examined the current literature related to the neurobiological processes involved in feeding dysregulation in BED with the aim of updating the most relevant aspects with special attention to neuroendocrine signaling. Studies have shown both central and peripheral endocrine dysfunctions in hormones participating in homeostatic and hedonic pathways in BED. Most studies have been especially focused on orexigenic signals, pointing out the existence of a hyperactivated mechanism promoting hunger. Fewer studies have explored anorexigenic pathways, but the findings so far seem to suggest an abnormal satiety threshold. Despite this, to date, it is unable to identify whether these alterations are typical of the BED patho-physiology or are related to an obesogenic pattern due to most studies included patients with BED and obesity. The identification of endophenotypes in BED may provide a new approach to aberrant eating behavior, favoring the implementation of biological therapeutic targets

Neuropsychological Learning Deficits as Predictors of Treatment Outcome in Patients with Eating Disorders

Eating disorders (EDs) are severe psychiatric illnesses that require individualized treatments. Decision-making deficits have been associated with EDs. Decision-making learning deficits denote a lack of strategies to elaborate better decisions that can have an impact on recovery and response to treatment. This study used the Iowa Gambling Task (IGT) to investigate learning differences related to treatment outcome in EDs, comparing between patients with a good and bad treatment outcome and healthy controls. Likewise, the predictive role of impaired learning performance on therapy outcome was explored. Four hundred twenty-four participants (233 ED patients and 191 healthy controls) participated in this study. Decision making was assessed using the Iowa Gambling Task before any psychological treatment. All patients received psychological therapy, and treatment outcome was evaluated at discharge. Patients with bad outcome did not show progression in the decision-making task as opposed to those with good outcome and the healthy control sample. Additionally, learning performance in the decision-making task was predictive of their future outcome. The severity of learning deficits in decision making may serve as a predictor of the treatment. These results may provide a starting point of how decision-making learning deficits are operating as dispositional and motivational factors on responsiveness to treatment in EDs

Food addiction and lifetime alcohol and illicit drugs use in specific eating disorders

Background and aims: Food addiction (FA) and substance use (SU) have frequently been reported in patients with eating disorders (EDs). Our study aimed to assess the prevalence rates of FA and/or lifetime problematic alcohol and illicit drug use among patients with specific ED, such as: bulimia nervosa (BN), binge eating disorder (BED), and other specified feeding and eating disorder (OSFED). We sought to identify clinical, psychopathological, and personality profiles involved in these addictive behavior-based phenotypes. Methods: The total sample was 527 patients (176 BN, 115 BED, and 236 OSFED). FA was assessed through the Yale Food Addiction Scale 2.0. To determine lifetime SU, a semi structured clinical interview was carried out. Results: Patients with BN had the highest rates of FA both with and without SU. No gender differences were obtained for the prevalence of current FA and/or lifetime SU. Patients reporting at least one addictive-related behavior exhibited increased clinical severity compared to those who reported none. Increased impulsivity (such as high lack of premeditation, sensation seeking, and positive urgency) and low self-directedness were differentiating factors for presenting one or two addictive behaviors. Discussion and Conclusions: Overall, patients presenting with at least one addictive-like behavior reported a poorer clinical status than those without. Also, patients with FA and SU exhibited a more dysfunctional profile characterized by high impulsivity and low selfdirectedness. These findings would support the need for targeted treatments to reduce impulsivity and increase self-directedness, especially in patients with any addictive-related behavior, as a step towards improving their treatment outcome

The role of food addiction and lifetime substance use on eating disorder treatment outcomes

Food addiction (FA) and substance use (SU) in eating disorders (ED) have been associated with a more dysfunctional clinical and psychopathological profile. However, their impact on treatment outcomes has been poorly explored. Therefore, this transdiagnostic study is aimed at examining whether the presence of FA and/or SU is associated with treatment outcomes in patients with different ED types. The results were not able to reveal significant differences in treatment outcomes between patients with and without FA and/or SU; however, the effect sizes suggest higher dropout rates in the group with both FA and SU. The predictive models of treatment outcomes showed different features associated with each group. High persistence (i.e., tendency to perseverance and inflexibility) was the personality trait most associated with poor treatment outcomes in patients without addictions. High harm avoidance and younger age at ED onset were the variables most related to poor outcomes in patients with FA or SU. Finally, in the group with both addictive behaviors (FA and SU), the younger patients presented the poorest outcomes. In conclusion, our results suggest that, regardless of presenting addictive behaviors, patients with ED may similarly benefit from treatment. However, it may be important to consider the differential predictors of each group that might guide certain treatment targets

Delay Discounting in Gambling Disorder: Implications in Treatment Outcome

Impulsive choice, measured by delay discounting (DD) tasks, has been shown in patients with gambling disorders (GD). However, the impact of DD and treatment outcome has been scarcely explored in GD patients. The aims of this study were: (1) to examine the baseline association between DD and clinical variables in GD patients depending on their age and gambling preferences (strategic vs. non-strategic); and (2) to estimate the predictive role of DD on poorer outcomes of cognitive-behavioral therapy (CBT) when considering also the effect of other clinical variables. 133 treatment-seeking male GD patients were evaluated at baseline with a DD task and measures of GD severity, personality traits and psychopathology. Treatment outcome was measured in terms of dropout from CBT and relapses. Results showed baseline associations between DD and GD severity (correlation coefficient R = 0.408 among strategic gamblers and R = 0.279 among mixed gamblers) and between DD and positive/negative urgency (R = 0.330 for the youngest patients, R = 0.244 for middle age, and around R = 0.35 for gamblers who reported preferences for strategic games). Other personality traits such as high harm avoidance and low cooperativeness were also related to DD at baseline (R = 0.606 among strategic gamblers). Regarding treatment outcome, a steeper discount rate predicted a higher risk of relapses in strategic gamblers (odds ratio OR = 3.01) and middle-age ones (OR = 1.59), and a higher risk of dropout in younger gamblers (OR = 1.89), non-strategic gamblers (OR = 1.70) and mixed gamblers (R = 4.74). GD severity mediated the associations between age, DD, personality traits and poor CBT outcome. In conclusion, impulsive choice affects treatment response in individuals with GD and may interfere with it to a significant extent. Considering DD in GD, patients seeking treatment could help control its impact on treatment adherence and relapses

Executive functions in binge spectrum eating disorders with comorbid compulsive buying

Objective: The aims were to explore if bulimic spectrum disorders (BSD) patients, who also present comorbid compulsive buying (CB), could represent a specific subtype considering its neuropsychological performance; to present a descriptive analysis of different clinical features; and to explore how these variables could influence treatment outcome. It was hypothesised that the comorbid group will present worse neuropsychological performance that will lead to a worse treatment outcome. Method: The study has a longitudinal design. Women (N = 75) diagnosed with BSD, BSD + CB and Healthy Controls (HC); completed an evaluation of: cognitive flexibility, decision making, eating disorder (ED) symptomatology, psychopathological state and personality traits. Results: BSD + CB was the group with the most severe clinical profile, worst treatment outcome and higher neuropsychological impairment, than other groups. Path-analysis evidenced that deficits in decision making were associated with bad treatment outcome, while deficits in flexibility with the presence of the comorbidity. Self-directedness and novelty seeking were associated with the neuropsychological performance and the comorbidity. Conclusion: BSD + CB exhibit a worse clinical and neuropsychological profile that seems to be related with the treatment outcome, which should be taken into account for the establishment of specific treatment approaches

Nucleus accumbens functional connectivity and circulating endocannabinoids levels in anorexia nervosa

Introduction: Neuroimaging findings have reported aberrant functional connectivity in brain regions involved reward system in individuals with anorexia nervosa (AN) altering hedonic processing over food. Likewise, endocannabinoids such as Anandamide (AEA) and 2-Arachidonoylglycerol (2-AG) have been involved in rewarding aspects of food intake. Objectives: To identify nucleus accumbens (NAcc) functional connectivity with whole-brain comparing between individuals with AN and controls. Furthermore, in a sub-study, to explore the interaction between NAcc functional connectivity and peripheral AEA and 2-AG levels

Dynamic fronto-amygdalar interactions underlying emotion-regulation deficits in women at higher weight

Objective: The regulation of negative emotions entails the modulation of subcortical regions, such as the amygdala, by prefrontal regions. There is preliminary evidence suggesting that individuals at higher weight may present with hypoactivity in prefrontal regulatory systems during emotional regulation, although the directionality of these pathways has not been tested. In this study, we compared fronto-amygdalar effective connectivity during cognitive reappraisal as a function of BMI in 48 adult women with obesity and 54 control participants. Methods: Dynamic causal modeling and parametric empirical Bayes were used to map effective connectivity between the dorsomedial prefrontal cortex, orbitofrontal cortex, dorsolateral prefrontal cortex, and the amygdala. Results: Difficulty in Emotion Regulation Scale scores were higher in the obesity group compared with control participants (p < 0.001). A top-down cortical model best explained our functional magnetic resonance imaging data (posterior probability = 86%). Participants at higher BMI were less effective at inhibiting activity in the amygdala via the orbitofrontal cortex and dorsomedial prefrontal cortex during reappraisal compared with those at lower BMI. In contrast, increased excitatory modulation of dorsolateral prefrontal cortex-to-amygdalar connectivity was found in participants at lower BMI. Conclusions: These findings support a framework involving alterations in fronto-amygdalar connectivity contributing to difficulties in regulating negative affect in individuals at higher weight

Obesity status and obesity-associated gut dysbiosis effects on hypothalamic structural covariance

Background: Functional connectivity alterations in the lateral and medial hypothalamic networks have been associated with the development and maintenance of obesity, but the possible impact on the structural properties of these networks remains largely unexplored. Also, obesity-related gut dysbiosis may delineate specific hypothalamic alterations within obese conditions. We aim to assess the effects of obesity, and obesity and gut-dysbiosis on the structural covariance differences in hypothalamic networks, executive functioning, and depressive symptoms. Methods: Medial (MH) and lateral (LH) hypothalamic structural covariance alterations were identified in 57 subjects with obesity compared to 47 subjects without obesity. Gut dysbiosis in the subjects with obesity was defined by the presence of high (n = 28) and low (n = 29) values in a BMI-associated microbial signature, and posthoc comparisons between these groups were used as a proxy to explore the role of obesity-related gut dysbiosis on the hypothalamic measurements, executive function, and depressive symptoms. Results: Structural covariance alterations between the MH and the striatum, lateral prefrontal, cingulate, insula, and temporal cortices are congruent with previously functional connectivity disruptions in obesity conditions. MH structural covariance decreases encompassed postcentral parietal cortices in the subjects with obesity and gut-dysbiosis, but increases with subcortical nuclei involved in the coding food-related hedonic information in the subjects with obesity without gut-dysbiosis. Alterations for the structural covariance of the LH in the subjects with obesity and gut-dysbiosis encompassed increases with frontolimbic networks, but decreases with the lateral orbitofrontal cortex in the subjects with obesity without gut-dysbiosis. Subjects with obesity and gut dysbiosis showed higher executive dysfunction and depressive symptoms. Conclusions: Obesity-related gut dysbiosis is linked to specific structural covariance alterations in hypothalamic networks relevant to the integration of somatic-visceral information, and emotion regulation

Obesity status and obesity-associated gut dysbiosis effects on hypothalamic structural covariance

[Background]: Functional connectivity alterations in the lateral and medial hypothalamic networks have been associated with the development and maintenance of obesity, but the possible impact on the structural properties of these networks remains largely unexplored. Also, obesity-related gut dysbiosis may delineate specific hypothalamic alterations within obese conditions. We aim to assess the effects of obesity, and obesity and gut-dysbiosis on the structural covariance differences in hypothalamic networks, executive functioning, and depressive symptoms.[Methods]: Medial (MH) and lateral (LH) hypothalamic structural covariance alterations were identified in 57 subjects with obesity compared to 47 subjects without obesity. Gut dysbiosis in the subjects with obesity was defined by the presence of high (n = 28) and low (n = 29) values in a BMI-associated microbial signature, and posthoc comparisons between these groups were used as a proxy to explore the role of obesity-related gut dysbiosis on the hypothalamic measurements, executive function, and depressive symptoms.[Results]: Structural covariance alterations between the MH and the striatum, lateral prefrontal, cingulate, insula, and temporal cortices are congruent with previously functional connectivity disruptions in obesity conditions. MH structural covariance decreases encompassed postcentral parietal cortices in the subjects with obesity and gut-dysbiosis, but increases with subcortical nuclei involved in the coding food-related hedonic information in the subjects with obesity without gut-dysbiosis. Alterations for the structural covariance of the LH in the subjects with obesity and gut-dysbiosis encompassed increases with frontolimbic networks, but decreases with the lateral orbitofrontal cortex in the subjects with obesity without gut-dysbiosis. Subjects with obesity and gut dysbiosis showed higher executive dysfunction and depressive symptoms.[Conclusions]: Obesity-related gut dysbiosis is linked to specific structural covariance alterations in hypothalamic networks relevant to the integration of somatic-visceral information, and emotion regulation.This study has been funded by the Project Grant IRONMET (PI15/01934) from the ISCIII, and the Project ThinkGut (EFA345/19) 65% co-financed by the European Regional Development Fund (ERDF) through the Interreg V-A Spain-France-Andorra program (POCTEFA 2014–2020) (JM Fernández-Real). Partial support was also obtained by the Ministerio de Economia y Competitividad, Spain, reference MTM2015-64465-C2-1-R (ML Calle). O Contreras-Rodriguez is funded by a “PERIS” postdoctoral fellowship (SLT006/17/00236) from the Health Department of the Catalan Government and by a “Miguel Servet” contract (CP20/00165) from the ISCIII. M Arnoriaga-Rodríguez is funded by a predoctoral Rio Hortega contract (CM19/00190) co-funded by European Social Fund “Investigating in your future” from the ISCIII.Peer reviewe