Exploring the influence of circulating endocannabinoids and nucleus accumbens functional connectivity on anorexia nervosa severity.

Anorexia nervosa (AN) is a severe psychiatric disorder characterized by a harmful persistence of self-imposed starvation resulting in significant weight loss. Research suggests that alterations in the nucleus accumbens (NAcc) and circulating endocannabinoids (eCBs), such as anandamide (AEA) and 2-arachidonoylglycerol (2-AG), may contribute to increased severity and maladaptive behaviors in AN, warranting an examination of the interplay between central reward circuitry and eCBs. For this purpose, we assessed NAcc functional connectivity and circulating AEA and 2-AG concentrations in 18 individuals with AN and 18 healthy controls (HC) to test associations between circulating eCBs, NAcc functional connectivity, and AN severity, as defined by body mass index (BMI). Decreased connectivity was observed between the NAcc and the right insula (NAcc-insula; pFWE < 0.001) and the left supplementary motor area (NAcc-SMA; pFWE < 0.001) in the AN group compared to HC. Reduced NAcc-insula functional connectivity mediated the association between AEA concentrations and BMI in the AN group. However, in HC, NAcc-SMA functional connectivity had a mediating role between AEA concentrations and BMI. Although no significant differences in eCBs concentrations were observed between the groups, our findings provide insights into how the interaction between eCBs and NAcc functional connectivity influences AN severity. Altered NAcc-insula and NAcc-SMA connectivity in AN may impair the integration of interoceptive, somatosensory, and motor planning information related to reward stimuli. Furthermore, the distinct associations between eCBs concentrations and NAcc functional connectivity in AN and HC could have clinical implications for weight maintenance, with eCBs being a potential target for AN treatment.

Probiotic and prebiotic interventions in eating disorders: A narrative review.

AIMS: The review aimed to summarise and discuss findings focused on therapeutic probiotic and prebiotic interventions in eating disorders (ED). METHODS: Using PubMed/MEDLINE, Cochrane Library, and Web of Science all published studies were retrieved until February 2023, following PRISMA guidelines. From the 111 initial studies, 5 met the inclusion criteria for this review. RESULTS: All studies included in this narrative review were focused on anorexia nervosa (AN). Three longitudinal, randomised, controlled trials aimed to evaluate interventions with probiotics (Lactobacillus reuteri, yoghurt with Lactobacillus, and Streptococcus) in children and adolescents. These studies primarily emphasised medical outcomes and anthropometric measures following the administration of probiotics. However, the findings yielded mixed results in terms of short-term weight gain or alterations in specific immunological parameters. With a lower level of evidence, supplementation with synbiotics (probiotic + prebiotic) has been associated with improvements in microbiota diversity and attenuation of inflammatory responses. CONCLUSIONS: Research on probiotics and prebiotics in ED is limited, primarily focussing on anorexia nervosa (AN). Their use in AN regarding medical and anthropometric outcomes needs further confirmation and future research should be warranted to assess their impact on psychological and ED symptomatology, where there is a notable gap in the existing literature.

Applying psycho-behavioural phenotyping in obesity characterization.

Individual differences in obesity, beyond being explained by metabolic and medical complications, are understood by alterations in eating behaviour which underlie psychological processes. From this psychological perspective, studies have identified several potential characteristic features at the psycho-behavioural level that could additionally explain the maintenance of chronic excess weight or the unsuccessful results of current treatments. To date, despite the growing evidence, the heterogeneity of the psychological evidence associated with obesity has made it challenging to generate consensus on whether these psycho-behavioural phenotypes can be a complement to improve outcomes of existing interventions. For this reason, this narrative review is an overview focused on summarizing studies describing the psycho-behavioural phenotypes associated with obesity. Based on the literature, three psychological constructs have emerged: reward dependence, cognitive control, and mood and emotion. We discuss the clinical implications of stratifying and identifying these psycho-behavioural profiles as potential target for interventions which may ensure a better response to treatment in individuals with obesity. Our conclusions pointed out a considerable overlap between these psycho-behavioural phenotypes suggesting bidirectional interactions between them. These findings endorse the complexity of the psycho-behavioural features associated with obesity and reinforce the need to consider them in order to improve treatment outcomes.

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.

Risk and protective factors for anxiety and obsessive-compulsive disorders: an umbrella review of systematic reviews and meta-analyses.

BACKGROUND: A multitude of risk/protective factors for anxiety and obsessive-compulsive disorders have been proposed. We conducted an umbrella review to summarize the evidence of the associations between risk/protective factors and each of the following disorders: specific phobia, social anxiety disorder, generalized anxiety disorder, panic disorder, and obsessive-compulsive disorder, and to assess the strength of this evidence whilst controlling for several biases. METHODS: Publication databases were searched for systematic reviews and meta-analyses examining associations between potential risk/protective factors and each of the disorders investigated. The evidence of the association between each factor and disorder was graded into convincing, highly suggestive, suggestive, weak, or non-significant according to a standardized classification based on: number of cases (>1000), random-effects p-values, 95% prediction intervals, confidence interval of the largest study, heterogeneity between studies, study effects, and excess of significance. RESULTS: Nineteen systematic reviews and meta-analyses were included, corresponding to 216 individual studies covering 427 potential risk/protective factors. Only one factor association (early physical trauma as a risk factor for social anxiety disorder, OR 2.59, 95% CI 2.17-3.1) met all the criteria for convincing evidence. When excluding the requirement for more than 1000 cases, five factor associations met the other criteria for convincing evidence and 22 met the remaining criteria for highly suggestive evidence. CONCLUSIONS: Although the amount and quality of the evidence for most risk/protective factors for anxiety and obsessive-compulsive disorders is limited, a number of factors significantly increase the risk for these disorders, may have potential prognostic ability and inform prevention.

Neuroendocrinological mechanisms underlying impulsive and compulsive behaviors in obesity: a narrative review of fMRI studies.

Impulsivity and compulsivity are multidimensional constructs that are increasingly considered determinants of obesity. Studies using functional magnetic resonance imaging (fMRI) have provided insight on how differences in brain response during tasks exploring facets of impulsivity and compulsivity relate to the ingestive behaviors that support the etiology and maintenance of obesity. In this narrative review, we provide an overview of neuroimaging studies exploring impulsivity and compulsivity factors as they relate to weight status. Special focus will be placed on studies examining the impulsivity-related dimensions of attentional bias, delayed gratification and emotion regulation. Discussions of compulsivity within the context of obesity will be restricted to fMRI studies investigating habit formation and response flexibility under shifting contingencies. Further, we will highlight neuroimaging research demonstrating how alterations in neuroendocrine functioning are linked to excessive food intake and may serve as a driver of the impulsive and compulsive behaviors observed in obesity. Research on the associations between brain response with neuroendocrine factors, such as insulin, peptide YY (PYY), leptin, ghrelin and glucagon-like peptide 1 (GLP-1), will be reviewed.

Eating disorders and obesity: bridging clinical, neurobiological, and therapeutic perspectives.

Eating disorders (EDs) and obesity are complex health conditions sharing various risk and maintenance factors, intensified in cases of comorbidity. This review explores the similarities and connections between these conditions, examining different facets from a multidisciplinary perspective, among them comorbidities, metabolic and psychological factors, neurobiological aspects, and management and therapy implications. We aim to investigate the common characteristics and complexities of weight and EDs and explore their interrelationships in individuals who experience both. The rising prevalence of EDs in people with obesity necessitates integrated approaches to study this comorbidity and to identify and analyze both common and distinct features of these conditions. This review may offer new opportunities for simultaneous prevention and management approaches, as well as future lines of research.

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 pathophysiology 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.

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.

Cognitive flexibility and DSM-5 severity criteria for eating disorders: assessing drive for thinness and duration of illness as alternative severity variables.

BACKGROUND: The severity criteria for eating disorders (EDs) proposed in the DSM-5 have been established without sufficient empirical support. Drive for thinness (DT) and duration of illness have been proposed as two alternative severity measures, however their empirical evidence is also limited. To date, no research has assessed the validity of current eating disorder (ED) severity criteria regarding cognitive flexibility factors. Cognitive flexibility is often impaired in EDs, becoming a possible severity symptom. The current study assessed for the first time (1) whether the severity indexes for EDs proposed in the DSM-5 were associated with deficits in cognitive flexibility and, (2) whether drive for thinness and illness duration, acted as an alternative, more meaningful severity indices for deficiencies in cognitive flexibility. METHODS: Participants were 161 patients diagnosed with an ED, who were categorized according to DSM-5 severity categories, DT and duration of illness. Discriminative capacity of each classification was assessed for cognitive flexibility measured by Wisconsin card sorting test (WCST). RESULTS: The findings for the DSM-5 classification comprised: (a) In the anorexia nervosa (AN) group, patients with moderate severity showed better scores in WCST than patients with mild and severe/extreme severity. Also, patients with moderate severity showed lower percentage of cognitive flexibility deficits than the other two severity categories; (b) For the binge spectrum disorders (BSD) group, the patients with mild severity showed a higher percentage of cognitive flexibility deficits than did the moderate and severe/extreme categories. When assessing the alternative severity index of DT, no differences were found in cognitive flexibility in any of the groups. Regarding illness duration, in the AN group the task performance of the patients with longer illness duration was worse than the performance of the short duration group and, in the BSD group, patients with longer duration also showed more deficits in cognitive flexibility than the patients with shorter duration of illness. CONCLUSIONS: Our findings point out the limitations of the DSM-5 severity criteria to categorize cognitive flexibility in EDs and support illness duration as an alternative severity approach for EDs.

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.

Association of anandamide and 2-arachidonoylglycerol concentrations with clinical features and body mass index in eating disorders and obesity.

BACKGROUND: Anandamide (AEA) and 2-arachidonoylglycerol (2-AG) play a pivotal role in stimulating motivational behavior toward food and energy metabolism. Aberrant functioning of the endocannabinoid system has been observed in extreme weight conditions (EWCs), suggesting it may influence pathophysiology. Then, we aimed to analyze fasting AEA and 2-AG plasma concentrations among individuals with EWC (i.e., anorexia nervosa [AN] and obesity with and without eating disorders [EDs]) compared with healthy controls (HCs), and its association with clinical variables and body mass index (BMI). METHODS: The sample included 113 adult women. Fifty-seven belonged to the obesity group, 37 without EDs (OB-ED) and 20 with ED (OB+ED classified within the binge spectrum disorders), 27 individuals from the AN group, and 29 from the HC group. Peripheral blood samples, several clinical variables, and BMI were evaluated. RESULTS: Unlike 2-AG, AEA concentrations showed significant differences between groups (p < 0.001). Increased AEA was observed in the OB-ED and OB+ED compared with both HC and AN group, respectively. Likewise, AEA was differentially associated with emotional dysregulation, general psychopathology, food addiction, and BMI in all clinical groups. CONCLUSIONS: These results support the interaction between biological and clinical factors contributing to delineating vulnerability pathways in EWC that could help fit personalized therapeutic approaches.

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 self-directedness. 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.

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.

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.

Clinical factors predicting impaired executive functions in eating disorders: The role of illness duration.

Poor performance in executive functions is observed in individuals with eating disorders (EDs). These impairments have usually been associated with the presence of comorbid psychopathology or with higher severity of EDs. However, few studies have explored the interaction between illness duration and deficits in executive functions. The present study investigates the association between ED duration and performance in decision-making, inhibitory control, and cognitive flexibility in the anorexia nervosa restrictive subtype (AN-R), bulimic/purging subtype (AN-BP), and binge spectrum disorders (BSDs) (namely, bulimia nervosa and binge eating disorder) among 116 women with EDs compared with 123 women healthy controls (HCs). Using cumulative survival analysis, we estimated the risk of deficits related to illness duration. Predictors of executive dysfunctions were assessed by regression analysis, including as potential predictors illness duration, severity of general psychopathology, and ED symptomatology. Results showed poor decision-making and cognitive flexibility in participants with EDs compared with HCs. ED duration was associated with poor inhibitory control in the AN-BP group and poor cognitive flexibility in the BSD group. The illness duration increased the risk of presenting early deficits in executive function. In decision-making and inhibitory control, the AN-R group showed the earliest deficits, whereas in cognitive flexibility it was the BSD group. ED duration predicted impaired cognitive flexibility in the BSD group and impaired inhibitory control in the AN-BP group, whereas the severity of general psychopathological symptoms was a predictor of impaired cognitive flexibility in individuals with AN-R. These results highlight the relevance of illness duration in executive dysfunctions in EDs.

The neural correlates of delay discounting in obesity and binge eating disorder.

BACKGROUND AND AIMS: Increased delay discounting is associated with obesity and binge eating disorder (BED). Although BED and obesity frequently co-occur, the neural mechanisms underlying delay discounting in these conditions remain poorly understood. METHODS: Thirtyfive women with obesity, including 10 participants with obesity and BED and 31 controls completed a monetary delay discounting task during functional magnetic resonance imaging. RESULTS: We identified that increased discounting rates were associated with decreased activity in the left anterior insula in participants with obesity compared to controls when choosing immediate rewards over delayed rewards (PFWE < 0.05). An exploratory analysis comparing the BED subsample to the other groups did not detect significant differences. DISCUSSION AND CONCLUSIONS: Our findings suggest decreased activity in the anterior insula may underlie heightened delay discounting in individuals with obesity, contributing the probability of choosing immediate rewards over delayed rewards based on emotional states. Future studies including larger, more diverse samples are required to confirm these effects.

Obesity Impairs Short-Term and Working Memory through Gut Microbial Metabolism of Aromatic Amino Acids.

The gut microbiome has been linked to fear extinction learning in animal models. Here, we aimed to explore the gut microbiome and memory domains according to obesity status. A specific microbiome profile associated with short-term memory, working memory, and the volume of the hippocampus and frontal regions of the brain differentially in human subjects with and without obesity. Plasma and fecal levels of aromatic amino acids, their catabolites, and vegetable-derived compounds were longitudinally associated with short-term and working memory. Functionally, microbiota transplantation from human subjects with obesity led to decreased memory scores in mice, aligning this trait from humans with that of recipient mice. RNA sequencing of the medial prefrontal cortex of mice revealed that short-term memory associated with aromatic amino acid pathways, inflammatory genes, and clusters of bacterial species. These results highlight the potential therapeutic value of targeting the gut microbiota for memory impairment, specifically in subjects with obesity.