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.

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.

Vagus nerve stimulation as a potential modulator of periictal psychotic episodes: A report of four cases.

Drug resistant epilepsy (DRE) has been associated with a high incidence of psychotic disorders. Patients can develop psychosis after starting a new antiseizure medication, after undergoing resective surgery, or after implantation of a vagus nerve stimulation (VNS) system. The aim of this study was to investigate the modulation effect of VNS on psychotic episodes in DRE patients with a pre-existing history of periictal psychotic episodes (PPE). We retrospectively report the outcome of four patients from a single tertiary center with PPE prior to implantation. None of the implanted patients developed de novo PPE after VNS therapy. Regarding seizure outcome, all patients demonstrated a response to VNS with two who experienced who status epilepticus and three patients wtih a change in semiology with after VNS implantation. PPE disappeared in all the study patients, two of them at 6 months post-implantation and in the others after 2 and 3 years, respectively. 18F-FDG-PET results showed hypermetabolism in both anterior insular and medial frontal lobes which disappeared in the 18F -FDG-PET 4 years post-implantation. Based on the results of this series of cases we suggest that VNS therapy may be useful to modulatet PPE in patients with DRE, though effectiveness may be time-dependent.

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.

Emotional intelligence in non-psychotic first-degree relatives of people with schizophrenia.

UNLABELLED: Subtle social cognitive deficits in unaffected relatives of schizophrenia patients have received increasing attention over the last few years, supporting their potential endophenotypic role for this disorder. The current study assessed non-psychotic first-degree relatives' performance on a multidimensional measure of emotional intelligence (EI): the Mayer-Salovey-Caruso Emotional Intelligence Test 2.0 (MSCEIT). Endorsed by the National Institute of Mental Health, the MSCEIT is a valid and reliable instrument for detecting emotion-processing deficits among schizophrenia patients and people high in schizotypy. METHOD: Thirty-seven first-degree relatives, 37 schizophrenia outpatients and 37 healthy controls completed the MSCEIT, which comprises eight subscales aimed to assess the four branches of EI: Identifying, Facilitating, Understanding and Managing Emotions. Potential associations with cognitive function and schizotypy levels, measured with the Schizotypal Personality Questionnaire-Brief, were further evaluated. RESULTS: Relatives had significantly lower MSCEIT total scores than controls and also significantly lower scores on the Identifying emotions branch. Nevertheless, schizophrenia patients still had the poorest global EI performance. The strongest positive correlations were found in relatives and controls with measures of executive function, processing speed and general intelligence. A higher level of schizotypy correlated significantly with lower MSCEIT scores among controls, but not among relatives. CONCLUSIONS: Contrary to expectations in the general population, the current study observed subtle EI impairment in non-psychotic first-degree relatives of schizophrenia patients. These findings support the hypothesis that these EI deficiencies may be potential endophenotypes located between the clinical phenotype and the genetic predisposition for schizophrenia.

Orexin and sleep quality in anorexia nervosa: Clinical relevance and influence on treatment outcome.

BACKGROUND AND AIMS: Orexins/hypocretins are orexigenic peptides implicated in the regulation of feeding behavior and the sleep/wake cycle. Little is known about the functioning of these peptides in anorexia nervosa (AN). The aims of the current study were to evaluate the extent to which orexin-A might be linked to sleep and treatment outcome in AN. METHOD: Fasting plasma orexin-A concentrations were measured in 48 females with AN at the start of a day hospital treatment and in 98 normal-eater/healthy-weight controls. The Pittsburgh Sleep Quality Index was administered at the beginning of the treatment as a measure of sleep quality. Other psychopathological variables were evaluated with the Symptom Checklist-Revised (SCL90R) and the Eating Disorder Inventory-2 (EDI). Patients were assessed at the start and end of treatment by means of commonly used diagnostic criteria and clinical questionnaires. RESULTS: The AN patients presented more sleep disturbances and poorer overall sleep quality than did the healthy controls (p=.026) but there were no global differences between groups in plasma orexin-A concentrations (p=.071). In the AN sample, orexin-A concentrations were associated with greater sleep disturbances (|r|=.30), sleep inefficiency (|r|=.22) and poorer overall sleep (|r|=.22). Structural Equation Modeling (SEM) showed that both elevated orexin-A concentrations and inadequate sleep predicted poorer treatment outcome. CONCLUSION: Plasma orexin-A concentrations contribute to poor sleep quality in AN, and both of these variables are associated with therapy response.

Changes in Body Composition in Anorexia Nervosa: Predictors of Recovery and Treatment Outcome.

The restoration of body composition (BC) parameters is considered to be one of the most important goals in the treatment of patients with anorexia nervosa (AN). However, little is known about differences between AN diagnostic subtypes [restricting (AN-R) and binge/purging (AN-BP)] and weekly changes in BC during refeeding treatment. Therefore, the main objectives of our study were twofold: 1) to assess the changes in BC throughout nutritional treatment in an AN sample and 2) to analyze predictors of BC changes during treatment, as well as predictors of treatment outcome. The whole sample comprised 261 participants [118 adult females with AN (70 AN-R vs. 48 AN-BP), and 143 healthy controls]. BC was measured weekly during 15 weeks of day-hospital treatment using bioelectrical impedance analysis (BIA). Assessment measures also included the Eating Disorders Inventory-2, as well as a number of other clinical indices. Overall, the results showed that AN-R and AN-BP patients statistically differed in all BC measures at admission. However, no significant time×group interaction was found for almost all BC parameters. Significant time×group interactions were only found for basal metabolic rate (p = .041) and body mass index (BMI) (p = .035). Multiple regression models showed that the best predictors of pre-post changes in BC parameters (namely fat-free mass, muscular mass, total body water and BMI) were the baseline values of BC parameters. Stepwise predictive logistic regressions showed that only BMI and age were significantly associated with outcome, but not with the percentage of body fat. In conclusion, these data suggest that although AN patients tended to restore all BC parameters during nutritional treatment, only AN-BP patients obtained the same fat mass values as healthy controls. Put succinctly, the best predictors of changes in BC were baseline BC values, which did not, however, seem to influence treatment outcome.

Treatment outcome of patients with comorbid type 1 diabetes and eating disorders.

BACKGROUND: Co-morbidity between Type 1 Diabetes Mellitus (T1DM) and eating disorders (ED) has been previously described; however the effect of this illness on the outcomes for conventional ED treatments has not been previously investigated. This study aims to compare clinical, psychopathological and personality features between two samples of ED individuals: those with comorbid T1DM and those without (No-DM); and to identify differences in treatment outcomes between the groups. METHODS: This study compares treatment outcome, dropouts, ED psychopathology and personality characteristics for 20 individuals with ED and T1DM and 20 ED patients without diabetes, matched for diagnostic and treatment type. RESULTS: The study found higher dropout rates from therapy in individuals with T1DM and worse treatment outcome in spite of having no significant differences in eating disorder psychopathology, although individuals with T1DM report misusing insulin. CONCLUSIONS: The low levels of motivation to change, and insulin abuse in T1DM patients, may suggest that treatment for patients with ED and T1DM should consider the individual's personality and role of insulin abuse when determining the appropriate intervention.

Pathological gambling in eating disorders: prevalence and clinical implications.

OBJECTIVE: Pathological gambling (PG) and eating disorders (ED) rarely co-occur. We explored the prevalence of lifetime PG in ED, compared severity of ED symptoms, personality traits, and psychopathological profiles across individuals with ED and PG (ED+PG) and without PG (ED-PG). Finally, we assessed the incremental predictive value of gender on the presentation of a comorbid PG. METHOD: A total sample of 1681 consecutively admitted ED patients (1576 females and 105 males), participated in the current study (25 ED+PG and 1656 ED-PG). All participants were diagnosed according to DSM-IV criteria. Assessment measures included the Symptom Checklist and the Temperament and Character Inventory-Revised, as well as other clinical and psychopathological indices. RESULTS: The observed lifetime prevalence of PG was 1.49%. ED subtype was associated with lifetime PG (p=.003), with PG being more frequent in binge eating disorder (5.7%). ED+PG was more prevalent in males than in females (16% vs. 1.26%, respectively). Additionally, ED+PG patients exhibited more impulsive behaviours, lower impulse regulation and higher novelty seeking. Best predictors of ED+PG were novelty seeking (OR 1.030, p=.035), sex (OR 3.295, p=.048) and BMI (OR 1.081, p=.005). CONCLUSIONS: Some personality traits (novelty seeking), being male and higher BMI are strongly related to the presence of lifetime PG in specific ED subtypes (namely binge eating disorder).

Efficacy of functional remediation in bipolar disorder: a multicenter randomized controlled study.

OBJECTIVE The authors sought to assess the efficacy of functional remediation, a novel intervention program, on functional improvement in a sample of euthymic patients with bipolar disorder. METHOD In a multicenter, randomized, rater-blind clinical trial involving 239 outpatients with DSM-IV bipolar disorder, functional remediation (N=77) was compared with psychoeducation (N=82) and treatment as usual (N=80) over 21 weeks. Pharmacological treatment was kept stable in all three groups. The primary outcome measure was improvement in global psychosocial functioning, measured blindly as the mean change in score on the Functioning Assessment Short Test from baseline to endpoint. RESULTS At the end of the study, 183 patients completed the treatment phase. Repeated-measures analysis revealed significant functional improvement from baseline to endpoint over the 21 weeks of treatment (last observation carried forward), suggesting an interaction between treatment assignment and time. Tukey's post hoc tests revealed that functional remediation differed significantly from treatment as usual, but not from psychoeducation. CONCLUSIONS Functional remediation, a novel group intervention, showed efficacy in improving the functional outcome of a sample of euthymic bipolar patients as compared with treatment as usual.

Comparison between immigrant and Spanish native-born pathological gambling patients.

The study compared clinical, psychopathological, and personality profiles between immigrants and Spanish native-born pathological gambling patients. A total of 1,601 native-born and 133 immigrant patients attending treatment at a specialized hospital unit were administered a battery of questionnaires during clinical assessment. Outcome measures were compared between both groups and the incremental predictive accuracy of the area of origin was examined using a regression model. Native-born Spaniards showed a mean 2.6 yr. greater duration of the disorder, while immigrants scored higher on South Oaks Gambling Screen, frequency of going to casinos, and total money spent (in a single day and/or to recover losses). General psychopathology and personality scores did not differ between the cohorts. However, immigration from Asia had a statistically significantly incremental validity for pathological gambling in South Oaks Gambling Screen scores. Both cohorts shared more similarities than differences in their gambling profiles.

Gambling on the stock market: an unexplored issue.

OBJECTIVE: Stock market investment (SMI) is one of the most socially acceptable types of gambling, which, however, can turn into a gambling problem. Because it is barely examined, we compared a series of clinical, psychopathologic, and personality variables in SMI gambling patients (both as primary and secondary problem) with a group of traditional pathologic gamblers (PGs). METHOD: A total sample of 1470 PGs (1376 patients without SMIs [PG-SMI], 76 patients with SMI as a secondary gambling problem [PG+SMI], and 18 patients with SMI as a primary gambling problem [SMI+PG]) participated in this study. All participants were diagnosed according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. The following instruments were used: the South Oaks Gambling Screen, the Symptom Check List-90 Items-Revised, the Temperament and Character Inventory-Revised, and other clinical and psychopathologic indices. RESULTS: The 3 patient groups' profiles were statistically similar in psychometrical measures. The risk of having SMI increased for patients with higher education, and the presence of SMI as a primary problem in PGs increased with university study level and higher scores on the personality trait of cooperativeness. CONCLUSIONS: The results of this study indicate comparability of SMI gamblers with PGs in their general clinical profile and in psychopathology and personality.