The human VGLUT3-pT8I mutation elicits uneven striatal DA signaling, food or drug maladaptive consumption in male mice.

Cholinergic striatal interneurons (ChIs) express the vesicular glutamate transporter 3 (VGLUT3) which allows them to regulate the striatal network with glutamate and acetylcholine (ACh). In addition, VGLUT3-dependent glutamate increases ACh vesicular stores through vesicular synergy. A missense polymorphism, VGLUT3-p.T8I, was identified in patients with substance use disorders (SUDs) and eating disorders (EDs). A mouse line was generated to understand the neurochemical and behavioral impact of the p.T8I variant. In VGLUT3T8I/T8I male mice, glutamate signaling was unchanged but vesicular synergy and ACh release were blunted. Mutant male mice exhibited a reduced DA release in the dorsomedial striatum but not in the dorsolateral striatum, facilitating habit formation and exacerbating maladaptive use of drug or food. Increasing ACh tone with donepezil reversed the self-starvation phenotype observed in VGLUT3T8I/T8I male mice. Our study suggests that unbalanced dopaminergic transmission in the dorsal striatum could be a common mechanism between SUDs and EDs.

Assessing biomarkers of remission in female patients with anorexia nervosa (REMANO): a protocol for a prospective cohort study with a nested case-control study using clinical, neurocognitive, biological, genetic, epigenetic and neuroimaging markers in a French specialised inpatient unit.

BACKGROUND: Anorexia nervosa (AN) is a severe psychiatric disorder associated with frequent relapses and variability in treatment responses. Previous literature suggested that such variability is influenced by premorbid vulnerabilities such as abnormalities of the reward system. Several factors may indicate these vulnerabilities, such as neurocognitive markers (tendency to favour delayed reward, poor cognitive flexibility, abnormal decision process), genetic and epigenetic markers, biological and hormonal markers, and physiological markers.The present study will aim to identify markers that can predict body mass index (BMI) stability 6 months after discharge. The secondary aim of this study will be focused on characterising the biological, genetic, epigenetic and neurocognitive markers of remission in AN. METHODS AND ANALYSIS: One hundred and twenty-five (n=125) female adult inpatients diagnosed with AN will be recruited and evaluated at three different times: at the beginning of hospitalisation, when discharged and 6 months later. Depending on the BMI at the third visit, patients will be split into two groups: stable remission (BMI≥18.5 kg/m²) or unstable remission (BMI<18.5 kg/m²). One hundred (n=100) volunteers will be included as healthy controls.Each visit will consist in self-reported inventories (measuring depression, anxiety, suicidal thoughts and feelings, eating disorders symptoms, exercise addiction and the presence of comorbidities), neurocognitive tasks (Delay Discounting Task, Trail-Making Test, Brixton Test and Slip-of-action Task), the collection of blood samples, the repeated collection of blood samples around a standard meal and MRI scans at rest and while resolving a delay discounting task.Analyses will mainly consist in comparing patients stabilised 6 months later and patients who relapsed during these 6 months. ETHICS AND DISSEMINATION: Investigators will ask all participants to give written informed consent prior to participation, and all data will be recorded anonymously. The study will be conducted according to ethics recommendations from the Helsinki declaration (World Medical Association, 2013). It was registered on clinicaltrials.gov on 25 August 2020 as 'Remission Factors in Anorexia Nervosa (REMANO)', with the identifier NCT04560517 (for more details, see https://clinicaltrials.gov/ct2/show/record/NCT04560517). The present article is based on the latest protocol version from 29 November 2019. The sponsor, Institut National de la Santé Et de la Recherche Médicale (INSERM, https://www.inserm.fr/), is an academic institution responsible for the monitoring of the study, with an audit planned on a yearly basis.The results will be published after final analysis in the form of scientific articles in peer-reviewed journals and may be presented at national and international conferences. TRIAL REGISTRATION NUMBER: clinicaltrials.govNCT04560517.

Body shape rather than facial emotion of others alters interpersonal distance in patients with anorexia nervosa.

OBJECTIVE: The study investigated interpersonal distance in patients with anorexia nervosa (AN), focussing on the role of other's facial expression and morphology, also assessing physiological and subjective responses. METHOD: Twenty-nine patients with AN and 30 controls (CTL) were exposed to virtual characters either with an angry, neutral, or happy facial expression or with an overweight, normal-weight, or underweight morphology presented either in the near or far space while we recorded electrodermal activity. Participants had to judge their preferred interpersonal distance with the characters and rated them in terms of valence and arousal. RESULTS: Unlike CTL, patients with AN exhibited heightened electrodermal activity for morphological stimuli only, when presented in the near space. They also preferred larger and smaller interpersonal distances with overweight and underweight characters respectively, although rating both negatively. Finally, and similar to CTL, they preferred larger interpersonal distance with angry than neutral or happy characters. DISCUSSION: Although patients with AN exhibited behavioural response to emotional stimuli similar to CTL, they lacked corresponding physiological response, indicating emotional blunting towards emotional social stimuli. Moreover, they showed distinct behavioural and physiological adjustments in response to body shape, confirming the specific emotional significance attached to body shape.

The capacity of cognitive tests to detect generalized anxiety disorder (GAD): A pilot study.

Cognitive impairment remains understudied in generalized anxiety disorder (GAD), despite the high prevalence and substantial burden associated with this disorder. We aimed to assess cognitive impairment in patients with GAD and evaluate the ability of cognitive tests to detect this disorder. Because of its high rate of comorbidity, we also examined how other anxiety disorders and current major depressive episodes affected our results. We tested 263 consecutive general practice outpatients. We used the GAD-7 and the Mini International Neuropsychiatric Interview (MINI) to detect anxiety and mood disorders. We assessed cognitive performance with the Stroop test, a facial emotion recognition test, and the trail-making test (TMT). Compared to patients without GAD, patients with GAD were significantly slower to complete the TMT(B-A) and faster to recognize emotions, especially negative ones such as disgust and anger. When controlling for other anxiety disorders and current major depressive episode, GAD retained a significant effect on the TMT(B-A), but not on the emotion recognition test. The TMT(B-A) could detect GAD with good accuracy (area under the curve (AUC) = 0.83, maximal Youden's index = 0.56), which was by no means comparable to the GAD-7 (AUC = 0.97, Youden's index = 0.81). While it is not efficient enough to replace the GAD-7 as a diagnostic tool, the capacity of the TMT(B-A) to detect GAD emphasizes the importance of cognitive flexibility impairment in GAD.

Trajectories and predictive factors of weight recovery in patients with anorexia nervosa completing treatment. A latent class mixed model approach.

BACKGROUND: Treatment of anorexia nervosa (AN) sometimes requires hospitalisation, which is often lengthy, with little ability to predict individual trajectory. Depicting specific profiles of treatment response and their clinical predictors could be beneficial to tailor inpatient management. The aim of this research was to identify clusters of weight recovery during inpatient treatment, and their clinical predictors. METHODS: A sample of 181 inpatients who completed a treatment programme for AN was included in a retrospective study. A latent class mixed model approach was used to identify distinct weight-gain trajectories. Clinical variables were introduced in a multinomial logistic regression model as predictors of the different classes. RESULTS: A four-class quadratic model was retained, able to correctly classify 63.7% of the cohort. It encompassed a late-rising, flattening, moderate trajectory of body mass index (BMI) increase (class 1), a late-rising, steady, high trajectory (class 2), an early-rising, flattening, high trajectory (class 3) and an early-rising, steady, high trajectory (class 4). Significant predictors of belonging to a class were baseline BMI (all classes), illness duration (class 2), and benzodiazepine prescription (class 3). CONCLUSION: Predicting different kinetics of weight recovery based on routinely collected clinical indicators could improve clinician awareness and patient engagement by enabling shared expectations of treatment response.

The value of plasma cell-free DNA levels as biomarker in patients with eating disorders: A preliminary study.

OBJECTIVE: Circulating cell-free DNA (cfDNA) holds promise as a rapid and convenient biomarker for identifying individuals with eating disorders. To investigate this hypothesis, we measured plasma cfDNA in patients with different eating disorders. METHODS: In this study, 110 participants (98 patients with eating disorders divided into 30 patients with bulimia nervosa, 33 patients with anorexia nervosa (AN) Restricting subtype, 35 patients with AN Binge-eating/purging subtype and 12 controls) were enrolled. We measured both cell-free nuclear DNA (cf-nDNA) and cell-free mitochondrial DNA (cf-mtDNA) from plasma using two specific droplet digital PCR assays each, referring to two amplicon sizes. RESULTS: Levels of plasma cf-nDNA and cf-mtDNA showed no significant differences between control participants and those with eating disorders. However, we observed a higher proportion of long cf-nDNA fragments in patients with eating disorders, suggesting its potential as a biomarker for eating disorders. CONCLUSION: This is the first study of cfDNA in patients with eating disorders. Our findings highlight the potential for qualitative exploration of cfDNA, although not of quantitative interest. Full characterization of cfDNA may serve as a valuable biomarker for eating disorders and provide some insights into the hidden mechanisms underlying the chronic development of these conditions. Future studies are needed to confirm or refute this hypothesis.

Measuring implicit associations between food and body stimuli in anorexia nervosa: a Go/No-Go Association Task.

PURPOSE: The present study aimed to explore the implicit associations between food and bodily stimuli in patients with anorexia nervosa (AN) and control subjects (HC). METHODS: A Go/No-Go Association Task was administrated to 55 participants (28 AN and 27 HC), using food stimuli (low-calorie food vs. high-calorie food) and body stimuli (underweight vs. overweight bodies). RESULTS: We evidenced an implicit association between food and body stimuli in the AN group, whereas the HC group only showed a tendency. AN and HC groups also exhibited different categorization strategies: the AN group tended to categorize stimuli as low-calorie foods and underweight bodies less than the HC group, and they tended to categorize stimuli as high-calorie foods and overweight bodies more than the HC group. CONCLUSION: The present study revealed for the first time specificities of the AN population's implicit association between food and body stimuli in terms of association strength and categorization strategy. Furthermore, the results suggest that combining implicit methodologies with other methods could contribute to a better characterization of the physiopathology of AN. LEVEL OF EVIDENCE: Level I, experimental study.

The role of dysregulated ghrelin/LEAP-2 balance in anorexia nervosa.

LEAP-2 is a ghrelin antagonist with an anorexigenic drive. This study investigates the evolution of plasma ghrelin and LEAP-2 concentrations in 29 patients with anorexia nervosa (AN) before and after refeeding and compares it to physiological adaptations during fasting in healthy controls or to mouse model of chronic food restriction and refeeding. Acute and chronic food restriction decrease LEAP-2 and increase ghrelin concentrations in both humans and mice, while patients with AN displayed higher ghrelin and LEAP-2 concentrations before than after refeeding (p = 0.043). After 6 months follow-up, patients with unstable weight gain (n = 17) had significantly decreased LEAP-2 concentrations after refeeding (p = 0.044), in contrast to patients with stable weight gain (n = 12). We provide evidence that the ghrelin/LEAP-2 system is not regulated according to the nutritional status in AN, in contrast to what is physiologically expected when coping with food restriction.

GWAS Meta-Analysis of Suicide Attempt: Identification of 12 Genome-Wide Significant Loci and Implication of Genetic Risks for Specific Health Factors.

OBJECTIVE: Suicidal behavior is heritable and is a major cause of death worldwide. Two large-scale genome-wide association studies (GWASs) recently discovered and cross-validated genome-wide significant (GWS) loci for suicide attempt (SA). The present study leveraged the genetic cohorts from both studies to conduct the largest GWAS meta-analysis of SA to date. Multi-ancestry and admixture-specific meta-analyses were conducted within groups of significant African, East Asian, and European ancestry admixtures. METHODS: This study comprised 22 cohorts, including 43,871 SA cases and 915,025 ancestry-matched controls. Analytical methods across multi-ancestry and individual ancestry admixtures included inverse variance-weighted fixed-effects meta-analyses, followed by gene, gene-set, tissue-set, and drug-target enrichment, as well as summary-data-based Mendelian randomization with brain expression quantitative trait loci data, phenome-wide genetic correlation, and genetic causal proportion analyses. RESULTS: Multi-ancestry and European ancestry admixture GWAS meta-analyses identified 12 risk loci at p values <5×10-8. These loci were mostly intergenic and implicated DRD2, SLC6A9, FURIN, NLGN1, SOX5, PDE4B, and CACNG2. The multi-ancestry SNP-based heritability estimate of SA was 5.7% on the liability scale (SE=0.003, p=5.7×10-80). Significant brain tissue gene expression and drug set enrichment were observed. There was shared genetic variation of SA with attention deficit hyperactivity disorder, smoking, and risk tolerance after conditioning SA on both major depressive disorder and posttraumatic stress disorder. Genetic causal proportion analyses implicated shared genetic risk for specific health factors. CONCLUSIONS: This multi-ancestry analysis of suicide attempt identified several loci contributing to risk and establishes significant shared genetic covariation with clinical phenotypes. These findings provide insight into genetic factors associated with suicide attempt across ancestry admixture populations, in veteran and civilian populations, and in attempt versus death.

Risk of non-fatal self-harm and premature mortality in the three years following hospitalization in adolescents and young adults with an eating disorder: A nationwide population-based study.

INTRODUCTION: Eating disorders (ED) are associated with high rates of suicide attempts and premature mortality. However, data in large samples of adolescents and young adults are limited. This study aims to assess the risk of self-harm and premature mortality in young people hospitalized with an ED. METHODS: Individuals aged 12 to 25 years old hospitalized in 2013-2014 in France with anorexia nervosa and/or bulimia nervosa as a primary or associated diagnosis were identified from French national health records. They were compared to two control groups with no mental disorders, and with any other mental disorder than ED. The main outcomes were any hospitalization for deliberate self-harm and mortality in the 3 years following hospitalization. Logistic regression models were used. RESULTS: This study included 5, 452 patients hospitalized with an ED, 14,967 controls with no mental disorder, and 14,242 controls with a mental disorder other than an ED. During the three-year follow-up, 13.0% were hospitalized for deliberate self-harm (vs. 0.2 and 22.0%, respectively) and 0.8% died (vs. 0.03 and 0.4%). After adjustment, hospitalization with an ED was associated with more self-harm hospitalizations (hazard ratio [HR] = 46.0, 95% confidence interval [32.3-65.3]) and higher all-cause mortality (HR = 12.6 [4.3-37.3]) relative to youths without any mental disorder; less self-harm hospitalizations (HR = 0.5 [0.5-0.6]) but higher mortality (HR = 1.6 [1.0-2.4]) when compared to youths with any other mental disorder. CONCLUSION: Young patients hospitalized with an ED are at high risk of self-harm and premature mortality. It is urgent to evaluate and implement the best strategies for post-discharge care and follow-up. PUBLIC SIGNIFICANCE: We found that the risk of being hospitalized for a suicide attempt is 46 times higher and mortality 13 times higher than the general population in adolescents and young adults during the 3 years following hospitalization with an eating disorder. Eating disorders are also associated with a 1.5 higher risk of premature mortality relative to other mental disorders. This risk is particularly high in the 6 months following hospitalization. It is therefore crucial to implement careful post-discharge follow-up in patients hospitalized for eating disorders.

A systematic literature review and meta-analysis of circulating nucleic acids as biomarkers in psychiatry.

Common mental disorders (CMDs) such as depression, anxiety and post-traumatic stress disorders account for 40% of the global burden of disease. In most psychiatric disorders, both diagnosis and monitoring can be challenging, frequently requiring long-term investigation and follow-up. The discovery of better methods to facilitate accurate and fast diagnosis and monitoring of psychiatric disorders is therefore crucial. Circulating nucleic acids (CNAs) are among these new tools. CNAs (DNA or RNA) can be found circulating in body biofluids, and can be isolated from biological samples such as plasma. They can serve as biomarkers for diagnosis and prognoses. They appear to be promising for disorders (such as psychiatric disorders) that involve organs or structures that are difficult to assess. This review presents an accurate assessment of the current literature about the use of plasma and serum cell-free DNA (cfDNA) as biomarkers for several aspects of psychiatric disorders: diagnosis, prognosis, treatment response, and monitor disease progression. For each psychiatric disorder, we examine the effect sizes to give insights on the efficacy of CNAs as biomarkers. The global effect size for plasma nuclear and mitochondrial cfDNA studies was generally moderate for psychiatric disorders. In addition, we discuss future applications of CNAs and particularly cfDNA as non-invasive biomarkers for these diseases.

Medical Students' Learning Process During Simulated Patient Consultations in Psychiatry: A Grounded Theory Study.

INTRODUCTION: Recent changes in psychiatric care and teaching, which limit patient contact for medical students, can be partially overcome by simulation-based education in psychiatry. The authors explored the learning processes of medical students during meetings with simulated patients to inform efforts to improve this teaching. METHODS: After recruiting 81 undergraduate medical students from 3 universities to participate in 6 simulation sessions in psychiatry, the authors purposively sampled 21 students to participate in face-to-face individual semistructured interviews analyzed with constructivist grounded theory. Integration of this analysis with those of the simulation consultation videotapes and the debriefing audiotapes improved the triangulation process. RESULTS: Three organizational themes were identified: developing and structuring representations of psychiatry; integrating subjectivity into learning; and refining and developing psychiatric praxis. Given the broad and in-depth learning that occurs, simulation in psychiatry should respect content validity of SP portrayals to ensure appropriate learning. However, psychological fidelity seems to provide adequate realism while retaining feasibility. Psychiatric simulation also requires the encouragement of student self-confidence and well-being. Within a reflective framework, simulation triggers cognitive reframing, which can alleviate fears and prejudice toward people with mental disorders. CONCLUSIONS: The holistic interactive learning process involved in simulation can address the complexity of the personal and interpersonal features needed in psychiatry.

The impact of a telephone hotline on suicide attempts and self-injurious behaviors in patients with borderline personality disorder.

Background: Borderline personality disorder is often associated with self-injurious behaviors that cause personal suffering, family distress, and substantial medical costs. Mental health hotlines exist in many countries and have been shown to be effective in some contexts, but none have been specifically designed for borderline patients. The aim of the present study is to evaluate the impact of a 24/7 hotline dedicated to patients with borderline personality disorder on suicide attempts and self-injurious behaviors. Methods: We conducted a single-blind, multicenter (9 French centers) clinical trial with stratified randomization (by age, sex and center). Patients (N = 315) with a diagnosis of borderline personality disorder (according to the SIDP-IV) were randomized into two groups with or without access to the hotline in addition to treatment as usual. The number of suicide attempts and self-injurious behaviors in each group within 12 month were analyzed in the "per protocol" population (Student's t-tests, 5% significance threshold), adjusting for possible confounders in a multivariate analysis (using Poisson regression). The percentage of patients with suicide attempts and with self-injurious behaviors (and other percentages) were analyzed in the per protocol population (χ2-tests or exact Fischer tests, 5% significance threshold). Results: The mean number of suicide attempts was 3 times lower in the hotline group (0.41 vs. 1.18, p = 0.005) and the mean number of self-injurious behaviors was 9 times lower (0.90 vs. 9.5, p = 0.006). Multivariate analysis confirmed the effectiveness of the hotline in reducing suicide attempts and self-harm. Conclusion: This study supports the effectiveness of hotlines in reducing self-aggressive behavior in patients with borderline personality disorder. Such support is easy to use, cheap and flexible, and therefore easy to implement on a large scale.

Vagus nerve stimulation allows to cease maintenance electroconvulsive therapy in treatment-resistant depression: a retrospective monocentric case series.

Context: The use of vagus nerve stimulation (VNS) to reduce or stop electroconvulsive therapy (ECT) in treatment-resistant depression seems promising. The aim of this study was to investigate the efficacy of VNS on the reduction of ECT sessions and mood stabilization. Methods: We conducted a monocentric retrospective case series of patients who suffered from treatment-resistant depression, treated with ECT and referred to our center for VNS. We investigated the number and the frequency of ECT sessions before and after VNS implantation. Secondary criteria consisted in the Montgomery Åsberg Depression Rating Scale (MADRS) score, number of medical treatments, dosage of the main treatment and length of hospital stays before and after VNS. Additionally, we sent an anonymous survey to psychiatrists and other physicians in our institution to investigate their knowledge and perception of VNS therapy to treat treatment-resistant depression. Results: Seven patients benefited from VNS: six (86%) were female (mean age of 51.7 +/- 16.0 years at surgery), and five (71%) suffered from bipolar depression (three type I and two type II). All patients were followed up at least 2 years post-implantation (range: 27-68 months). Prior to VNS, six patients were treated by maintenance ECT. After VNS, three (43%) patients did not require maintenance ECT anymore, and three (43%) patients required less frequent ECT session with a mean 14.7 +/- 9.8 weeks between sessions after VNS vs. 2.9 +/- 0.8 weeks before VNS. At last follow-up, 4 (57%) patients had stopped ECT. Five (71%) patients implanted with VNS were good responders (50% decrease relative to baseline MADRS). According to the survey, psychiatrists had a significantly better perception and knowledge of ECT, but a worse perception and knowledge of VNS compared to other physicians. Conclusion: VNS is a good option for treatment-resistant depression requiring maintenance ECT dependence. Larger on-going studies will help broaden the implanted patients while strengthening psychiatrists' knowledge on this therapy.

Common Genetic Variation and Age of Onset of Anorexia Nervosa.

Background: Genetics and biology may influence the age of onset of anorexia nervosa (AN). The aims of this study were to determine whether common genetic variation contributes to age of onset of AN and to investigate the genetic associations between age of onset of AN and age at menarche. Methods: A secondary analysis of the Psychiatric Genomics Consortium genome-wide association study (GWAS) of AN was performed, which included 9335 cases and 31,981 screened controls, all from European ancestries. We conducted GWASs of age of onset, early-onset AN (<13 years), and typical-onset AN, and genetic correlation, genetic risk score, and Mendelian randomization analyses. Results: Two loci were genome-wide significant in the typical-onset AN GWAS. Heritability estimates (single nucleotide polymorphism-h 2) were 0.01-0.04 for age of onset, 0.16-0.25 for early-onset AN, and 0.17-0.25 for typical-onset AN. Early- and typical-onset AN showed distinct genetic correlation patterns with putative risk factors for AN. Specifically, early-onset AN was significantly genetically correlated with younger age at menarche, and typical-onset AN was significantly negatively genetically correlated with anthropometric traits. Genetic risk scores for age of onset and early-onset AN estimated from independent GWASs significantly predicted age of onset. Mendelian randomization analysis suggested a causal link between younger age at menarche and early-onset AN. Conclusions: Our results provide evidence consistent with a common variant genetic basis for age of onset and implicate biological pathways regulating menarche and reproduction.

The Fitter I Am, the Larger I Feel-The Vicious Circle of Physical Exercise in Anorexia Nervosa.

Introduction: Body image distortion is a core symptom of anorexia nervosa (AN), embodying dissatisfaction and overvaluation of body appearance and weight. Body image distortion is an important factor in the maintenance of weight loss behaviours such as compulsive physical exercise. Conversely, physical exercise seems to have an aggravating effect on body image in patients with AN, but the evidence is still poor. The aim of this study was to examine the relationship between body image distortion and physical exercise in AN in order to understand whether physical exercise may play a specific role in body image distortion beyond psychopathological severity. Methods: Forty patients with AN and 21 healthy controls were tested for body image distortion and different proxies of physical exercise. Univariate correlations tested the relationship between body image distortion and physical exercise in AN and control groups. Then, to experimentally assess the effect of exercise on body image distortion, participants were invited to rate their body image before and after a standardised effort test. Results: In the AN group, a correlation was found between physical activity and body image distortion (p < 0.01), which was still significant after controlling for psychopathological severity. No correlation was found in healthy controls. After a standardised effort, patients with AN had higher increases in body image distortion than healthy controls (almost 4 kg/m2 vs. 0.8 kg/m2) (p < 0.01). Discussion: Physical exercise may contribute to the distortion of body image in anorexia nervosa and explain the paradoxical augmentation of unhealthy exercise despite ongoing weight loss.

Sinful Foods: Measuring Implicit Associations Between Food Categories and Moral Attributes in Anorexic, Orthorexic, and Healthy Subjects.

Recently, neurocognitive studies have shown that food categorization is sensitive to both the properties of the food stimuli (e.g., calorie content) and the individual characteristics of subjects (e.g., BMI, eating disorders) asked to categorize these stimuli. Furthermore, groups of patients with eating disorders (ED) were described as relying more on moral criteria to form food categories than were control subjects. The present studies built on these seminal articles and aimed to determine whether certain food properties might trigger moral categories preferentially in subjects suffering from ED and in the general population. Using a Go/No-Go Association Task, Study 1 focused on the extent to which food categories are laden with moral attributes in ED patients compared to control subjects. Study 2 was a follow-up with a different design (an Implicit Association Test), another food variable (calorie content), and two non-clinical subgroups (orthorexic and healthy control subjects). Results revealed for the first time implicit associations between food variables cueing for energy density and moral attributes in the general population, the population suffering from anorexia nervosa, and subjects suffering from disordered eating such as orthorexia nervosa. These findings suggest that moralization of food is a pervasive phenomenon that can be measured with methods reputed to be less vulnerable to self-presentation or social desirability biases.

Clinical meaning of body temperatures in anorexia nervosa and bulimia nervosa.

OBJECTIVE: Bradycardia is one of the common cardiac abnormalities in patients with eating disorders. It ensues from hypometabolism, which results from reduced caloric intake and consequential weight loss. Hypothermia is another consequence of hypometabolism. While at-rest metabolism and body mass index (BMI) are typically used to assess hypometabolism and estimate potential bradycardia, we hypothesised that body temperature, which is easy to measure, could also capture the presence of this threatening cardiovascular condition. METHOD: We monitored heart rate continuously for 72 h, measured resting energy expenditure (REE) and assessed body temperature in 12 body parts for 58 patients with anorexia nervosa (AN) and 29 patients with bulimia nervosa (BN). RESULTS: Palm temperature reflects bradycardia in both AN and BN, explaining 18% of its variance (p < 0.001), capturing this aspect even more efficiently than BMI. We also observe different correlations between palm temperature, abdominal temperature, BMI, REE and levels of physical activity. CONCLUSION: Palm temperature could be used as a warning of bradycardia, a serious cardiovascular condition which can be difficult to detect in short visits with outpatients. Further studies are needed to determine how useful bradycardia and palm temperature could be to assess severity and prognosis of the disorder.

Pupil psychosensory reflex in response to own and standardised silhouettes in patients with anorexia nervosa.

OBJECTIVE: This study aimed to assess the physiological response of patients with anorexia nervosa (AN) to different types of silhouettes using pupillometry. METHODS: We measured the pupil psychosensory reflex (PSR) of 42 patients with AN and 35 healthy controls in response to standardised body silhouettes and to pictures of their own silhouettes digitally modified to represent different body mass indices (BMI). Perceptual distortion and body dissatisfaction were assessed using Anamorphic Micro Software©. Twenty-three of the recruited patients were tested up to four times during an inpatient treatment programme to assess the impact of weight gain. RESULTS: PSR correlated with the subjective rating of emotional arousal in controls but not in patients. Own silhouettes and standardised silhouettes triggered a different pupil response both in patients with AN and in controls. With pictures of their own silhouettes, pupil response to underweight stimuli differed from pupil response to normal weight or overweight stimuli in both groups. Weight gain was associated with an increase in PSR, an improvement of ideal BMI and a decrease of body dissatisfaction, but no change in perceptual distortion. CONCLUSION: Our findings support the idea that pupillometry could be a useful tool to assess the physiological state of patients with AN.

Morphing analysis of facial emotion recognition in anorexia nervosa: association with physical activity.

PURPOSE: Anorexia Nervosa (AN) has been linked to emotion processing inefficiencies, social cognition difficulties and emotion dysregulation, but data on Facial Emotion Recognition (FER) are heterogenous and inconclusive. This study aims to explore FER in patients with AN using a dynamic and ecological evaluation, and its relationship with Physical Activity (PA), an important aspect of AN that could impact emotional processing. METHODS: Sixty-six participants (33 patients with AN and 33 healthy controls) performed a morphed facial emotional recognition task and 49 of them wore an accelerometer during seven days to assess PA. Axis-I disorders and depressive symptoms have been assessed. RESULTS: No difference was found regarding time to recognize facial emotions. However, patients with AN correctly recognize emotions more frequently than controls. This was specific to disgust, although there was also a tendency for sadness. Among patients, higher depressive scores are associated with a faster and more accurate recognition of disgust, while a higher level of PA is associated to decreased accuracy in recognizing sadness. CONCLUSION: Patients with AN are capable of recognizing facial emotions as accurately as controls, but could have a higher sensitivity in recognizing negative emotions, especially disgust and sadness. PA has opposite effects and, thus, could be considered as an emotional regulation strategy against negative affect. LEVEL OF EVIDENCE II: Controlled trial without randomization.