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.

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.

Dorsolateral prefrontal cortex and amygdala function during cognitive reappraisal predicts weight restoration and emotion regulation impairment in anorexia nervosa.

BACKGROUND: Although deficits in affective processing are a core component of anorexia nervosa (AN), we lack a detailed characterization of the neurobiological underpinnings of emotion regulation impairment in AN. Moreover, it remains unclear whether these neural correlates scale with clinical outcomes. METHODS: We investigated the neural correlates of negative emotion regulation in a sample of young women receiving day-hospital treatment for AN (n = 21) and healthy controls (n = 21). We aimed to determine whether aberrant brain activation patterns during emotion regulation predicted weight gain following treatment in AN patients and were linked to AN severity. To achieve this, participants completed a cognitive reappraisal paradigm during functional magnetic resonance imaging. Skin conductance response, as well as subjective distress ratings, were recorded to corroborate task engagement. RESULTS: Compared to controls, patients with AN showed reduced activation in the dorsolateral prefrontal cortex (dlPFC) during cognitive reappraisal [pFWE<0.05, threshold-free cluster enhancement (TFCE) corrected]. Importantly, psycho-physiological interaction analysis revealed reduced functional connectivity between the dlPFC and the amygdala in AN patients during emotion regulation (pFWE<0.05, TFCE corrected), and dlPFC-amygdala uncoupling was associated with emotion regulation deficits (r = -0.511, p = 0.018) and eating disorder severity (r = -0.565, p = .008) in the AN group. Finally, dlPFC activity positively correlated with increases in body mass index (r = 0.471, p = 0.042) and in body fat mass percentage (r = 0.605, p = 0.008) following 12 weeks of treatment. CONCLUSIONS: Taken together, our findings indicate that individuals with AN present altered fronto-amygdalar response during cognitive reappraisal and that this response may serve as a predictor of response to treatment and be linked to clinical severity.

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.

What Difference Does it Make? Risk-Taking Behavior in Obesity after a Loss is Associated with Decreased Ventromedial Prefrontal Cortex Activity.

Altered activity in decision-making neural circuitry may underlie the maladaptive food choices found in obesity. Here, we aimed to identify the brain regions purportedly underpinning risk-taking behavior in individuals with obesity. Twenty-three adult women with obesity and twenty-three healthy weight controls completed the Risky Gains Task during functional magnetic resonance imaging (fMRI). This task allows participants to choose between a safe option for a small, guaranteed monetary reward and risky options with larger rewards. fMRI analyses comparing losing trials to winning trials found that participants with obesity presented decreased activity in the left anterior insula in comparison to controls (p < 0.05, AlphaSim corrected). Moreover, left insula activation during losses vs. wins was negatively correlated with UPPS-P questionnaire sensation seeking scores. During safe vs. risky trials following a loss, the control group exhibited increased activation in the ventromedial prefrontal cortex (vmPFC) (p < 0.05, AlphaSim corrected) in comparison to the OB group. Moreover, vmPFC response in the obesity group during post-loss trials was negatively correlated with risky choices on the task overall. As a whole, our findings support that diminished tuning of the insula towards interoceptive signals may lead to a lack of input to the vmPFC when weighing the costs and benefits of risky choices.

A multimodal MRI study of the neural mechanisms of emotion regulation impairment in women with obesity.

Maladaptive emotion regulation contributes to overeating and impedes weight loss. Our study aimed to compare the voluntary downregulation of negative emotions by means of cognitive reappraisal in adult women with obesity (OB) and female healthy controls (HC) using a data-driven, multimodal magnetic resonance imaging (MRI) approach. Women with OB (n = 24) and HC (n = 25) carried out an emotion regulation task during functional MRI scanning. Seed-to-voxel resting-state connectivity patterns derived from activation peaks identified by this task were compared between groups. Diffusion tensor imaging (DTI) was used to examine white matter microstructure integrity between regions exhibiting group differences in resting-state functional connectivity. Participants in the OB group presented reduced activation in the ventromedial prefrontal (vmPFC) cortex in comparison to the HC group when downregulating negative emotions, along with heightened activation in the extrastriate visual cortex (p < 0.05, AlphaSim-corrected). Moreover, vmPFC peak activity levels during cognitive reappraisal were negatively correlated with self-reported difficulties in emotion regulation. OB patients exhibited decreased functional connectivity between the vmPFC and the temporal pole during rest (peak-pFWE = 0.039). Decreased fractional white-matter track volume in the uncinate fasciculus, which links these two regions, was also found in participants with OB. Taken together, our findings are indicative of emotion regulation deficits in OB being underpinned by dysfunctional hypoactivity in the vmPFC and hyperactivity in the extrastriate visual cortex. Our results provide a potential target circuit for neuromodulatory interventions to improve emotion regulation skills and weight-loss intervention outcomes.

Food addiction and impaired executive functions in women with obesity.

BACKGROUND: Individuals with obesity (OB) often report suffering from addiction-like symptoms. As in addictions, deficits in executive function domains, such as decision-making and sustained attention, are found in OB. No study to date has examined the associations between food addiction, OB, and neuropsychological performance. METHOD: Thirty-three adult women with OB and 36 healthy weight controls completed the Yale Food Addiction Scale Version 2.0, a validated instrument used to assess food-related addictive behaviours. Additionally, participants completed computerized versions of the Iowa Gambling Task (IGT) and Conners' Continuous Performance Test, second edition (CPT-II) to examine decision-making and attentional control, respectively. RESULTS: Food addiction criteria were met in 24.2% of the participants with OB and in 2.8% of the control group. In the OB group, food addiction severity levels were negatively correlated with overall scores on the IGT. Participants with OB meeting criteria for food addiction committed more omissions and perseveration errors on the CPT-II compared with those without food addiction. CONCLUSIONS: Our results point to an association between food addiction severity levels and impairments in decision-making and attentional capacity in individuals with OB. Given the heterogeneity found in OB, it stands to reason that this subset of patients with food addiction could potentially benefit from interventions targeting neuropsychological deficits.

Delay discounting and impulsivity traits in young and older gambling disorder patients.

BACKGROUND: Impulsivity is understood to be a multidimensional construct involving aspects such as impulsive choice and impulsive traits. Delay discounting, the tendency to place greater value in immediate rewards over larger, long-term rewards, has been associated with maladaptive choices in gambling disorder (GD). Delay discounting is known to evolve with age; though no study to date has evaluated the interactions between impulsivity, GD severity and age in treatment-seeking patients. OBJECTIVES: We aimed to examine whether associations between delay discounting and impulsivity traits differed between younger and older-aged GD patients. Secondly, we sought to untangle the mediating role of impulsivity in determining gambling behavior in these two age groups. METHODS: GD patients (N=335) were evaluated using the UPPS-P Impulsive Behavior Scale and a delay discounting task. Structural Equation Modeling (SEM) was used to explore associations between impulsivity measures and gambling severity in young (18-30years) and old (31-70) GD patients. RESULTS: No differences in delay discounting were found between young and old GD patients. Significant correlations between delay discounting and urgency levels (the tendency to act rashly under emotional states) were identified only in the young GD group. Path analyses also revealed both positive and negative urgency to be a mediator of GD severity levels in young GD patients. DISCUSSION AND CONCLUSIONS: Significant associations between impulsive choice and positive urgency are only present in young gamblers, suggesting that positive urgency influence choice behavior to a greater degree at younger ages. Implications for targeted interventions are discussed.

Enduring Changes in Decision Making in Patients with Full Remission from Anorexia Nervosa.

BACKGROUND: Deficits in neuropsychological functioning have consistently been identified in patients with anorexia nervosa (AN). However, little is known on how decision making in AN patients evolves in response to treatment or whether impairments are reversible. METHOD: AN patients (n = 42) completed the Iowa Gambling Task (IGT) upon admission to a 3-month day-hospital treatment programme and at a 1-year follow-up. Patient IGT performance was compared to age-matched controls (n = 46). RESULTS: AN patients displayed poorer performance on the IGT at admission compared to controls (p < .001). Patients with full remission (n = 31; 73.9%) at the 1-year follow-up improved IGT performance (p = 0.007), and scores were similar compared to controls (p = 0.557). AN patients with partial/no remission at follow-up (n = 11; 26.1%) did not improve IGT scores (p = 0.867). CONCLUSIONS: These findings uphold that enduring remission from AN can reverse decision-making impairments, and they might be most likely explained by clinical state rather than a trait vulnerability. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

Surgery-Induced Weight Loss Is Associated With the Downregulation of Genes Targeted by MicroRNAs in Adipose Tissue.

CONTEXT: Molecular mechanisms associated with physiological variations in adipose tissue (AT) are not fully recognized. The most recent reports highlight the critical relevance of microRNAs (miRNAs) found in AT. OBJECTIVE: To identify changes in messenger RNA (mRNA) and miRNA expressions and their interaction in human AT before and after surgery-induced weight loss. Research Design and Setting: Genome-wide mRNA and miRNA expressions were assessed by microarrays in abdominal subcutaneous AT of 16 morbidly obese women before and 2 years after laparoscopic Roux-en-Y gastric bypass. The association of changes in miRNAs with their respective mRNA targets was studied. The results were replicated in publicly available microarray datasets. Validation was made by real-time polymerase chain reaction in additional fat samples from 26 age-matched lean women and in isolated human adipocytes. RESULTS: A total of 5018 different mRNA probe sets and 15 miRNAs were differentially expressed after surgery-induced weight loss. The clustering of similar expression patterns for gene products with related functions revealed molecular footprints that elucidate significant changes in cell cycle, development, lipid metabolism, and the inflammatory response. The participation of inflammation was demonstrated by results assessed in isolated adipocytes. Interestingly, when transcriptomes were analyzed taking into account the presence of miRNA target sites, miRNA target mRNAs were upregulated in obese AT (P value = 2 × 10(-181)) and inflamed adipocytes (P value = 4 × 10(-61)), according to the number of target sites harbored by each transcript. CONCLUSIONS: Current findings suggest impaired miRNA target gene expression in obese AT in close association with inflammation, both improving after weight loss.

Video game addiction in gambling disorder: clinical, psychopathological, and personality correlates.

OBJECTIVE: We studied the prevalences of video game use (VGU) and addiction (VGA) in gambling disorder (GD) patients and compared them with subjects with non-video game use (non-VGU) in relation to their gambling behavior, psychopathology, and personality characteristics. METHOD: A sample of 193 GD patients (121 non-VGU, 43 VGU, and 29 VGA) consecutively admitted to our pathological gambling unit participated in the study. Assessment. Measures included the video game dependency test (VDT), symptom checklist-90-revised, and the temperament and character inventory-revised, as well as a number of other GD indices. RESULTS: In GD, the observed prevalence of VG (use or addiction) was 37.3% (95% CI :30.7% ÷ 44.3),VGU 22.3% (95% CI :17.0% ÷ 28.7), and VGA 15% (95% CI :10.7% ÷ 20.7). Orthogonal polynomial contrast into logistic regression showed positive linear trends for VG level and GD severity and other measures of general psychopathology. After structural equation modeling, higher VG total scores were associated with younger age, general psychopathology, and specific personality traits, but not with GD severity. Patients' sex and age were involved in the mediational pathways between personality traits and VG impairment. CONCLUSIONS: GD patients with VG are younger and present more dysfunctional personality traits, and more general psychopathology. The presence of VG did not affect the severity of GD.