Hunger, Satiety, and Their Vulnerabilities.

The psychological states of hunger and satiety play an important role in regulating human food intake. Several lines of evidence suggest that these states rely upon declarative learning and memory processes, which are based primarily in the medial temporal lobes (MTL). The MTL, and particularly the hippocampus, is unusual in that it is especially vulnerable to insult. Consequently, we examine here the impact on hunger and satiety of conditions that: (1) are central to ingestive behaviour and where there is evidence of MTL pathology (i.e., habitual consumption of a Western-style diet, obesity, and anorexia nervosa); and (2) where there is overwhelming evidence of MTL pathology, but where ingestive behaviour is not thought central (i.e., temporal lobe epilepsy and post-traumatic stress disorder). While for some of these conditions the evidence base is currently limited, the general conclusion is that MTL impairment is linked, sometimes strongly, to dysfunctional hunger and satiety. This focus on the MTL, and declarative learning and memory processes, has implications for the development of alternative treatment approaches for the regulation of appetite.

Myocardial mechanics in anorexia nervosa: a systematic review and meta-analysis of speckle tracking echocardiographic studies.

BACKGROUND: Clinical complications of anorexia nervosa (AN) include cardiac structural and functional alterations. Available evidence on impaired myocardial deformation in AN patients without overt systolic dysfunction as assessed by left ventricular ejection fraction (LVEF) is scanty and based on a few studies. The aim of the present meta-analysis was to provide comprehensive and updated information on this issue. METHODS: Following the PRISMA guidelines, systematic searches were conducted across bibliographic databases (Pub-Med, OVID, EMBASE and Cochrane library) to identify eligible studies from inception up to 31 January 2024. Searches were limited to clinical investigations published in English reporting data on left ventricular (LV) mechanics (i.e. global longitudinal strain) in patients with anorexia and controls. The statistical difference of the echocardiographic variables of interest between groups such as LVEF and global longitudinal strain (GLS) was calculated by standardized mean difference (SMD) with 95% confidence interval (CI) by using random-effects models. RESULTS: Five studies including 171 AN and 147 healthy normal-weight individuals were considered for the analysis. Pooled average LVEF values were 63.2 ±â€Š0.4% in the healthy control group and 64.6 ±â€Š1.0% in the AN group (SMD -0.08 ±â€Š0.11, CI: -0.15/0.30, P  = 0.51); the corresponding values of GLS were -20.1 ±â€Š0.9% and -20.2 ±â€Š0.9% (SMD 0.07 ±â€Š0.3, CI: -0.46/0.60, P  = 0.80). Unlike GLS, apical strain (data from three studies) was higher in AN than in controls (-23.1 ±â€Š1.8 vs. -21.3 ±â€Š1.8; SMD: -0.42 ±â€Š0.17, CI: -0.08/-0.76, P  = 0.01). CONCLUSIONS: The results of the present meta-analysis do not support the view that myocardial deformation as assessed by GLS is impaired in patients with AN and preserved LVEF. The role of STE in detecting subclinical cardiac damage in this clinical condition deserves to be evaluated in future studies including regional LV strain.

Extreme weight conditions impact on the relationship between risky decision-making and interoception.

Anorexia nervosa (AN) and obesity (OB) lie on the two ends of the broad spectrum of extreme weight conditions (EWC). Both disorders entail the constant risk to one's body integrity. Importantly, risk-taking is supported by internal signals, the perception of which is typically distorted in EWC. In this study, we sought to characterize in EWC: (i) risky decision-making by contrasting situations in which people process bodies or neutral objects and (ii) the relationship between interoceptive ability and risky decision-making. In a between-subject design, participants with AN restricting type, participants with class 2 OB, and two groups of matched healthy controls (HC) (total N = 160) were administered either the Balloon Analogue Risk Task (BART) or a modified version of it by using a body-related stimulus as a cue in the place of the balloon. Moreover, we collected a measure of interoceptive sensibility and a measure of interoceptive accuracy. Results showed that, when analysing the global population as a continuum based on the BMI, the risk propensity decreased as a function of increased BMI, only for the task involving a body-related stimulus. Moreover, while HC risk propensity toward a body-related stimulus correlated with interoceptive sensibility, such correlation was absent in participants with AN. Individuals with OB, on the opposite pole, showed mixed interaction between interoception and risky decision-making in both tasks. These findings add one more tile to understanding these complex pathologies in the EWC spectrum, opening up future differential rehabilitation scenarios.

Effects of repetitive transcranial magnetic stimulation of the right inferior parietal lobe on the body image perception in anorexia nervosa: A pilot randomized controlled study.

INTRODUCTION: Restrictive anorexia nervosa (AN) is associated with distorted perception of body shape, previously linked to hypoactivity and reduced excitability of the right inferior parietal lobe (rIPL). Here, we investigated the impact of high-frequency repetitive transcranial magnetic stimulation (HF rTMS) of the rIPL on body shape perception in patients with AN. METHODS: Seventeen patients with AN (median [Q1_Q3] age, 35 [27_39] years; disease duration, 12 [6_18] years) were randomly assigned to receive real or sham HF (10 Hz) rTMS of the rIPL over a period of 2 weeks, comprising 10 sessions. The primary outcome measure was the Body Shape Questionnaire (BSQ). Secondary outcomes included eating disorder symptoms, body mass index, mood, anxiety, and safety. Data collection were done at baseline, post-rTMS, and at 2 weeks and 3 months post-rTMS. RESULTS: Following both real and sham rTMS of the rIPL, no significant differences were observed in body shape perception or other parameters. Both real and sham rTMS interventions were deemed safe and well tolerated. Notably, serious adverse events were associated with the underlying eating and mood disorders, resulting in hospitalization for undernutrition (five patients) or suicidal attempts (two patients). CONCLUSION: This pilot study does not support the use of rTMS of the rIPL as an effective method for improving body shape perception in individuals with the restrictive form of AN. Further research is warranted to comprehensively explore both the clinical and neurophysiological effects of HF rTMS in this population.

Developmental activity-based anorexia alters hippocampal non-genomic stress response and induces structural instability and spatial memory impairment in female rats.

OBJECTIVE: Anorexia nervosa (AN) is characterized by hyperactivation of the hypothalamic-pituitary-adrenal axis and cognitive deficits. However, little is known about the rapid non-genomic stress response involvement. This study investigates the molecular, structural and behavioral signatures of the anorexic phenotype induction in female rats on stress-related mechanisms in the hippocampus. METHOD: Female adolescent rats, exposed to the combination of food restriction and wheel access, i.e., the activity-based anorexia (ABA) protocol, were sacrificed in the acute phase of the pathology (postnatal day [P]42) or following a 7-day recovery period (P49). RESULTS: ABA rats, in addition to body weight loss and increased wheel activity, alter their pattern of activity over days, showing increased food anticipatory activity, a readout of their motivation to engage in intense physical activity. Corticosterone plasma levels were enhanced at P42 while reduced at P49 in ABA rats. In the membrane fraction of the hippocampus, we found reduced glucocorticoid receptor levels together with reduced expression of caldesmon, n-cadherin and neuroligin-1, molecular markers of cytoskeletal stability and glutamatergic homeostasis. Accordingly, structural analyses revealed reduced dendritic spine density, a reduced number of mushroom-shaped spines, together with an increased number of thin-shaped spines. These events are paralleled by impairment in spatial memory measured in the spatial order object recognition test. These effects persisted even when body weight of ABA rats was restored. DISCUSSION: Our findings indicate that ABA induction orchestrates hippocampal maladaptive structural and functional plasticity, contributing to cognitive deficits, providing a putative mechanism that could be targeted in AN patients.

Assessing midbrain neuromelanin and its relationship to reward learning in anorexia nervosa: Stage 1 of a registered report.

INTRODUCTION: Anorexia nervosa (AN) is a debilitating and potentially chronic eating disorder, characterized by low hedonic drive toward food, which has been linked with perturbations in both reward processing and dopaminergic activity. Neuromelanin-sensitive magnetic resonance imaging (MRI) is an emerging method to index midbrain neuromelanin-a by-product of dopaminergic synthesis. The assessment of midbrain neuromelanin, and its association with AN psychopathology and reward-related processes, may provide critical insights into reward circuit function in AN. METHODS: This study will incorporate neuromelanin-sensitive MRI into an existing study of appetitive conditioning in those with AN. Specifically, those with acute and underweight AN (N = 30), those with weight-restored AN (N = 30), and age-matched healthy controls (N = 30) will undergo clinical assessment of current and previous psychopathology, in addition to structural neuromelanin-sensitive MRI, diffusion MRI, and functional MRI (fMRI) during appetitive conditioning. CONCLUSION: This study will be among the first to interrogate midbrain neuromelanin in AN-a disorder characterized by altered dopaminergic activity. Results will help establish whether abnormalities in the midbrain synthesis of dopamine are evident in those with AN and are associated with symptomatic behavior and reduced ability to experience pleasure and reward.

Superior facial emotion recognition in adolescents with anorexia nervosa - A replication study.

OBJECTIVE: Anorexia nervosa (AN) has been associated with alterations in the processing of socio-emotional information, including impairments in the recognition of emotions in other people's faces. However, adolescents with AN might not show the impairments found in adult patients. The present study investigated facial emotion recognition in adolescents with AN, aiming to replicate our previous results of superior emotion recognition abilities in adolescents with AN compared to adolescents without mental disorders. METHOD: Adolescent girls (12-18 years) with AN (n = 33) were compared to girls without mental disorders (n = 41). Participants completed one task requiring identification of emotions (happy, sad, afraid, angry, neutral) in faces and one control task. RESULTS: As expected, adolescents with AN showed superior emotion recognition, with higher accuracy rates specifically for afraid faces. CONCLUSION: This is the first study replicating previous results on basic emotion recognition in adolescents with AN using (almost) the same methodology. The results suggest that, in contrast to adults, adolescents with AN do not show impairments in facial emotion recognition. The impairments may arise in the longer course of the illness, however, longitudinal studies are necessary to confirm this assumption.

Bioelectrical Impedance Vector Analysis, Nutritional Ultrasound®, and Handgrip Strength as Innovative Methods for Monitoring Critical Anorexia Nervosa Physical Recovery: A Pilot Study.

Eating disorders (EDs) manifest as persistent disruptions in eating habits or related behaviors, significantly impacting physical health and psychosocial well-being. Nutritional assessment in ED patients is crucial for monitoring treatment efficacy. While dual-energy X-ray absorptiometry (DEXA) remains standard, interest in alternative methods such as bioelectrical impedance vector analysis (BIVA) and Nutritional Ultrasound® (NU) has risen due to their affordability and portability. Additionally, hand dynamometry offers a user-friendly approach to assessing grip strength (HGS), indicative of nutritional status. A prospective study was carried out to evaluate the utility of BIVA, NU®, and HGS in 43 female AN patients. Measurements were taken at baseline and hospital discharge. A total of 41 patients completed the study. After the intervention, numerous BIVA-related parameters such as fat (3.5 ± 2 kg vs. 5.3 ± 2.7 kg, p < 0.001) and free fat mass (33.9 ± 3.8 kg vs. 37.5 ± 4.1 kg, p < 0.001) were partially restored. Similarly, Nutritional Ultrasound® showed promising results in assessing body composition changes such as total abdominal fat tissue (0.5 ± 0.3 cm vs. 0.9 ± 0.3 cm, p < 0.05). In the same way, rectus femoris cross-sectional area values correlated with clinical outcomes such as free fat mass (0.883, p < 0.05) and appendicular muscle mass (0.965, p < 0.001). HGS reached the normality percentile after the intervention (21.6 ± 9.1 kg vs. 25.9 ± 12.3 kg, p < 0.05), demonstrating a significant association between grip strength and body composition parameters such as free fat mass (0.658, p < 0.001) and appendicular muscle mass (0.482, p < 0.001). Incorporating BIVA-, NU®-, and HGS-enhanced nutritional assessment into the treatment of AN patients offers cost-effective, portable, and non-invasive alternatives to DEXA. These techniques offer valuable insights into changes in body composition and nutritional status, which, in turn, facilitate treatment monitoring and contribute to improved patient outcomes.

Reduced dorsal fronto-striatal connectivity at rest in anorexia nervosa.

BACKGROUND: Anorexia nervosa (AN) is a serious psychiatric illness that remains difficult to treat. Elucidating the neural mechanisms of AN is necessary to identify novel treatment targets and improve outcomes. A growing body of literature points to a role for dorsal fronto-striatal circuitry in the pathophysiology of AN, with increasing evidence of abnormal task-based fMRI activation within this network among patients with AN. Whether these abnormalities are present at rest and reflect fundamental differences in brain organization is unclear. METHODS: The current study combined resting-state fMRI data from patients with AN (n = 89) and healthy controls (HC; n = 92) across four studies, removing site effects using ComBat harmonization. First, the a priori hypothesis that dorsal fronto-striatal connectivity strength - specifically between the anterior caudate and dlPFC - differed between patients and HC was tested using seed-based functional connectivity analysis with small-volume correction. To assess specificity of effects, exploratory analyses examined anterior caudate whole-brain connectivity, amplitude of low-frequency fluctuations (ALFF), and node centrality. RESULTS: Compared to HC, patients showed significantly reduced right, but not left, anterior caudate-dlPFC connectivity (p = 0.002) in small-volume corrected analyses. Whole-brain analyses also identified reduced connectivity between the right anterior caudate and left superior frontal and middle frontal gyri (p = 0.028) and increased connectivity between the right anterior caudate and right occipital cortex (p = 0.038). No group differences were found in analyses of anterior caudate ALFF and node centrality. CONCLUSIONS: Decreased coupling of dorsal fronto-striatal regions indicates that circuit-based abnormalities persist at rest and suggests this network may be a potential treatment target.

Longitudinal changes in brain-derived neurotrophic factor (BDNF) but not cytokines contribute to hippocampal recovery in anorexia nervosa above increases in body mass index.

BACKGROUND: Physical sequelae of anorexia nervosa (AN) include a marked reduction in whole brain volume and subcortical structures such as the hippocampus. Previous research has indicated aberrant levels of inflammatory markers and growth factors in AN, which in other populations have been shown to influence hippocampal integrity. METHODS: Here we investigated the influence of concentrations of two pro-inflammatory cytokines (tumor necrosis factor-alpha [TNF-α] and interleukin-6 [IL-6]) and brain-derived neurotrophic factor (BDNF) on the whole hippocampal volume, as well as the volumes of three regions (the hippocampal body, head, and tail) and 18 subfields bilaterally. Investigations occurred both cross-sectionally between acutely underweight adolescent/young adult females with AN (acAN; n = 82) and people recovered from AN (recAN; n = 20), each independently pairwise age-matched with healthy controls (HC), and longitudinally in acAN after partial renourishment (n = 58). Hippocampal subfield volumes were quantified using FreeSurfer. Concentrations of molecular factors were analyzed in linear models with hippocampal (subfield) volumes as the dependent variable. RESULTS: Cross-sectionally, there was no evidence for an association between IL-6, TNF-α, or BDNF and between-group differences in hippocampal subfield volumes. Longitudinally, increasing concentrations of BDNF were positively associated with longitudinal increases in bilateral global hippocampal volumes after controlling for age, age2, estimated total intracranial volume, and increases in body mass index (BMI). CONCLUSIONS: These findings suggest that increases in BDNF may contribute to global hippocampal recovery over and above increases in BMI during renourishment. Investigations into treatments targeted toward increasing BDNF in AN may be warranted.

A multi-modal assessment of fear conditioning in adolescent anorexia nervosa.

OBJECTIVE: Anorexia nervosa (AN) is a pernicious psychiatric disorder which is principally characterized by a fear of weight gain. Notwithstanding the centrality of fear in the psychopathology of AN, controlled assessments of negative valence systems are lacking. Herein we assess fear conditioning in adolescent females with AN. METHOD: Adolescent girls (Mage = 14.6 years, ±1.57) with DSM-5 diagnoses of AN (N = 25) and age-matched control girls (Mage = 14.8 years, ±1.46) with no DSM-5 diagnoses (N = 25) completed structured clinical interviews and participated in a classical three-phase Pavlovian fear conditioning paradigm. Participants with comorbid anxiety disorders were excluded. Skin conductance response (SCR) was measured, alongside self-reported fear, valence, and fear expectancy ratings. RESULTS: Both groups demonstrated significant differential acquisition across all four measures. Regarding group comparisons, no differences emerged for self-reported fear, valence, and fear expectancy ratings during acquisition, although for SCR, those with AN demonstrated reduced physiological arousal relative to controls. Both groups demonstrated significant differential extinction for unconditioned stimuli (US) expectancy, self-report fear, and self-report valence. No statistically significant group differences were evident during extinction to the conditioned stimuli (CS)+, on any outcome measure. However, controls reported more positive valence to the CS- than those with AN. CONCLUSIONS: Contrary to our hypotheses, our preliminary assessment did not find support for elevated fear responding among adolescent girls with AN with regards to fear acquisition or extinction. These data suggest that AN in adolescent girls may not be associated with a heightened propensity to acquire fear, but conversely, may suggest that exposure treatments for AN may be helpful, since extinction learning is intact in AN. PUBLIC SIGNIFICANCE: AN is characterized by fear-related symptoms, including food and weight-related fear, and behavioral avoidance, yet controlled studies assessing fear learning are limited. Our preliminary assessment of adolescent AN indicates no abnormalities in fear learning among adolescents with AN. These findings may inform existing mechanistic models of AN psychopathology, and the development of exposure-based treatments for AN.

Adverse childhood experiences, low self-esteem, and salient stimulus response in eating disorders.

BACKGROUND: Adverse childhood experiences (ACEs) are elevated in individuals with eating disorders (EDs), but how the neurobiology of EDs and ACEs interact is unclear. METHODS: Women 18-45 years old with anorexia nervosa (AN, n = 38), bulimia nervosa (BN, n = 32), or healthy controls (n = 60) were assessed for ACEs and ED behaviours and performed a taste-conditioning task during brain imaging. Mediation analyses tested relationships between ACE score, self-esteem, and ED behaviours. RESULTS: ACE scores were elevated in EDs and correlated positively with body mass index (p = 0.001), drive for thinness (p = 0.001), and body dissatisfaction (p = 0.032); low self-esteem mediated the relationship between ACEs and body dissatisfaction, drive for thinness, and bulimia severity. ACE scores correlated negatively (FDR-corrected) with unexpected, salient stimulus receipt in AN (substantia nigra) and BN (anterior cingulate, frontal and insular cortex, ventral striatum, and substantia nigra). When ACE scores were included in the model, unexpected stimulus receipt brain response was elevated in EDs in the anterior cingulate and ventral striatum. CONCLUSIONS: ACEs attenuate unexpected salient stimulus receipt response, which may be a biological marker for altered valence or hedonic tone perception in EDs. Low self-esteem mediates the relationships between ACEs and ED behaviours. Adverse childhood experiences should be assessed in biological studies, and their effects targeted in treatment.

Weight suppression at lowest weight as an indicator of eating disorder clinical severity: A retrospective cohort study.

OBJECTIVES: Weight suppression (WS) defines the difference between the highest weight in adulthood and the current weight. WS at lowest weight is the difference between the highest and the lowest ever weight. Weight rebound is the difference between the past lowest weight and current weight. The distinction in the capacities of WS, weight rebound, and WS at the lowest weight remains unclear regarding their efficacy in forecasting clinical endpoints. This study assessed the relationship between WS, WS at lowest weight and/or weight rebound and eating disorder (ED) clinical severity. METHODS: In this retrospective cohort study, adult participants were selected at the Outpatient Unit for multidisciplinary assessment of ED, Montpellier, France, between February 2012 and October 2014 and May 2017 and January 2020. ED clinical severity was evaluated using the Eating Disorder Examination Questionnaire (EDE-Q). RESULTS: The sample included 303 patients: 204 with anorexia nervosa (AN) and 99 with bulimia nervosa (BN). The EDE-Q total score was positively correlated with WS at lowest weight in patients with AN (Spearman's rho = 0.181, p = 0.015) and with BN (Spearman's rho = 0.377; p < 0.001). It was also positively correlated with weight rebound (Spearman's rho = 0.319; p = 0.003) in patients with BN. In the multivariate analysis, EDE-Q total score was associated with WS at lowest weight only in patients with BN (ß = 0.265; p = 0.03). CONCLUSION: WS at lowest weight seems to be a good measure of ED clinical severity. More research is needed for better understanding WS at lowest weight in assessment and treatment of patients with ED.

A transdiagnostic and translational framework for delineating the neuronal mechanisms of compulsive exercise in anorexia nervosa.

OBJECTIVE: The development of novel treatments for anorexia nervosa (AN) requires a detailed understanding of the biological underpinnings of specific, commonly occurring symptoms, including compulsive exercise. There is considerable bio-behavioral overlap between AN and obsessive-compulsive disorder (OCD), therefore it is plausible that similar mechanisms underlie compulsive behavior in both populations. While the association between these conditions is widely acknowledged, defining the shared mechanisms for compulsive behavior in AN and OCD requires a novel approach. METHODS: We present an argument that a better understanding of the neurobiological mechanisms that underpin compulsive exercise in AN can be achieved in two critical ways. First, by applying a framework of the neuronal control of OCD to exercise behavior in AN, and second, by taking better advantage of the activity-based anorexia (ABA) rodent model to directly test this framework in the context of feeding pathology. RESULTS: A cross-disciplinary approach that spans preclinical, neuroimaging, and clinical research as well as compulsive neurocircuitry and behavior can advance our understanding of when, why, and how compulsive exercise develops in the context of AN and provide targets for novel treatment strategies. DISCUSSION: In this article, we (i) link the expression of compulsive behavior in AN and OCD via a transition between goal-directed and habitual behavior, (ii) present disrupted cortico-striatal circuitry as a key substrate for the development of compulsive behavior in both conditions, and (iii) highlight the utility of the ABA rodent model to better understand the mechanisms of compulsive behavior relevant to AN. PUBLIC SIGNIFICANCE: Individuals with AN who exercise compulsively are at risk of worse health outcomes and have poorer responses to standard treatments. However, when, why, and how compulsive exercise develops in AN remains inadequately understood. Identifying whether the neural circuitry underlying compulsive behavior in OCD also controls hyperactivity in the activity-based anorexia model will aid in the development of novel eating disorder treatment strategies for this high-risk population.

Initial evidence of abnormal brain plasticity in anorexia nervosa: an ultra-high field study.

Anorexia Nervosa has been associated with white matter abnormalities implicating subcortical abnormal myelination. Extending these findings to intracortical myelin has been challenging but ultra-high field neuroimaging offers new methodological opportunities. To test the integrity of intracortical myelin in AN we used 7 T neuroimaging to acquire T1-weighted images optimized for intracortical myelin from seven females with AN (age range: 18-33) and 11 healthy females (age range: 23-32). Intracortical T1 values (inverse index of myelin concentration) were extracted from 148 cortical regions at ten depth-levels across the cortical ribbon. Across all cortical regions, these levels were averaged to generate estimates of total intracortical myelin concentration and were clustered using principal component analyses into two clusters; the outer cluster comprised T1 values across depth-levels ranging from the CSF boundary to the middle of the cortical regions and the inner cluster comprised T1 values across depth-levels ranging from the middle of the cortical regions to the gray/white matter boundary. Individuals with AN exhibited higher T1 values (i.e., decreased intracortical myelin concentration) in all three metrics. It remains to be established if these abnormalities result from undernutrition or specific lipid nutritional imbalances, or are trait markers; and whether they may contribute to neurobiological deficits seen in AN.

Editorial: The Altered Brain Network Architecture of Anorexia Nervosa.

A deeper understanding of neurobiological basis of disease is key to mental health research and clinical practice. This could lead to more targeted treatments, improved survival rates, and better outcomes. This is the challenge now undertaken by scientists around the globe who study the human brain in health and disease to identify brain systems involved in clinical syndromes. Several well-powered magnetic resonance imaging (MRI) studies have established the existence of differences in brain structure in several groups of patients compared to healthy individuals.1 Recent technological advances in network analyses allowing examination of whole-brain connectivity are moving the field forward, providing evidence that major psychiatric disorders arise from perturbations in a complex network of highly connected, anatomically distributed neural systems rather than dysfunctions of circumscribed brain regions.2.

Neural Representations of Food-Related Attributes in the Human Orbitofrontal Cortex during Choice Deliberation in Anorexia Nervosa.

Decisions about what to eat recruit the orbitofrontal cortex (OFC) and involve the evaluation of food-related attributes such as taste and health. These attributes are used differently by healthy individuals and patients with disordered eating behavior, but it is unclear whether these attributes are decodable from activity in the OFC in both groups and whether neural representations of these attributes are differentially related to decisions about food. We used fMRI combined with behavioral tasks to investigate the representation of taste and health attributes in the human OFC and the role of these representations in food choices in healthy women and women with anorexia nervosa (AN). We found that subjective ratings of tastiness and healthiness could be decoded from patterns of activity in the OFC in both groups. However, health-related patterns of activity in the OFC were more related to the magnitude of choice preferences among patients with AN than healthy individuals. These findings suggest that maladaptive decision-making in AN is associated with more consideration of health information represented by the OFC during deliberation about what to eat.SIGNIFICANCE STATEMENT An open question about the OFC is whether it supports the evaluation of food-related attributes during deliberation about what to eat. We found that healthiness and tastiness information was decodable from patterns of neural activity in the OFC in both patients with AN and healthy controls. Critically, neural representations of health were more strongly related to choices in patients with AN, suggesting that maladaptive overconsideration of healthiness during deliberation about what to eat is related to activity in the OFC. More broadly, these results show that activity in the human OFC is associated with the evaluation of relevant attributes during value-based decision-making. These findings may also guide future research into the development of treatments for AN.

High levels of physical activity in female adolescents with anorexia nervosa: medical and psychopathological correlates.

PURPOSE: While overexercise is commonly described in patients who experience anorexia nervosa (AN), it represents a condition still underestimated, especially in the paediatric population. METHOD: The present study aims at assessing the possible associations between levels of physical activity (PA) and clinical features, endocrinological data and psychopathological traits in a sample of 244 female adolescents hospitalised for AN subdivided into two groups according to PA levels (high PA vs. no/low PA). The two groups were compared through multivariate analyses, while multiple regression analysis was conducted to determine whether physical activity predict specific outcomes. RESULTS: No significant differences were found between the two groups in terms of last Body Mass Index (BMI) before illness, BMI at admission and disease duration, while a difference emerged in delta BMI(rapidity of weight loss), significantly higher in high-PA group (p = 0.021). Significant differences were observed in Free triiodothyronine- (p < 0.001), Free thyroxine (p = 0.046), Follicle-stimulating hormone (p = 0.019), Luteinising hormone (p = 0.002) levels, with values remarkably lower in high-PA group. Concerning psychopathological scales, the high-PA group showed worst Children's Global Assessment Scale (CGAS) scores (p = 0.035). Regression analyses revealed that higher PA predicts higher delta BMI (p = 0.021), presence of amenorrhea (p = 0.003), lower heart rate (p = 0.012), lower thyroid (Free triiodothyronine p < 0.001, Free thyroxine p = 0.029) and gynaecological hormones' levels (Follicle-stimulating hormone p = 0.023, Luteinising hormone p = 0.003, 17-Beta estradiol p = 0.041). Concerning psychiatric measures, HPA predicts worst scores at CGAS (p = 0.019), and at scales for evaluation of alexithymia (p = 0.028) and depression (p = 0.004). CONCLUSIONS: Results suggest that high levels of physical activity in acute AN associate with worst clinical conditions at admission, especially in terms of endocrinological and medical features. LEVEL OF EVIDENCE: Level III.

Nutrient Intake and Dietary Inflammatory Potential in Current and Recovered Anorexia Nervosa.

Anorexia nervosa (AN) is characterised by disrupted and restrictive eating patterns. Recent investigations and meta-analyses have found altered concentrations of inflammatory markers in people with current AN. We aimed to assess nutrient intake in participants with current or recovered AN, as compared to healthy individuals, and explore group differences in dietary inflammatory potential as a possible explanation for the observed alterations in inflammatory markers. We recruited participants with current AN (n = 51), those recovered from AN (n = 23), and healthy controls (n = 49). We used the Food Frequency Questionnaire (FFQ), to calculate a Dietary Inflammatory Index (DII®) score and collected blood samples to measure serum concentrations of inflammatory markers. In current AN participants, we found lower intake of cholesterol, compared to HCs, and lower consumption of zinc and protein, compared to HC and recovered AN participants. A one-way ANOVA revealed no significant group differences in DII score. Multivariable regression analyses showed that DII scores were significantly associated with tumour necrosis factor (TNF)-α concentrations in our current AN sample. Our findings on nutrient intake are partially consistent with previous research. The lack of group differences in DII score, perhaps suggests that diet is not a key contributor to altered inflammatory marker concentrations in current and recovered AN. Future research would benefit from including larger samples and using multiple 24-h dietary recalls to assess dietary intake.

Physical activity and sleep during the first week of anorexia nervosa inpatient care.

BACKGROUND: Individuals with Anorexia Nervosa are often described as restless, hyperactive and having disturbed sleep. The result reproducibility and generalisability of these results are low due to the use of unreliable methods, different measurement methods and outcome measures. A reliable method to measure both physical activity and sleep is through accelerometry. The main purpose of the study was to quantify the physical activity and sleeping behaviour of anorexia nervosa patients. Another purpose was to increase result reproducibility and generalisability of the study. MATERIAL AND METHODS: Accelerometer data were collected from the first week of treatment of anorexia nervosa at an inpatient ward. Raw data from the Axivity AX3© accelerometer was used with the open-source package GGIR for analysis, in the free statistical software R. Accelerometer measurements were transformed into euclidean norm minus one with negative values rounded to zero (ENMO). Physical activity measurements of interest were 24h average ENMO, daytime average ENMO, inactivity, light activity, moderate activity, and vigorous activity. Sleep parameters of interest were sleep duration, sleep efficiency, awakenings, and wake after sleep onset. The sleep duration of different age groups was compared to recommendations by the National Sleep Foundation using a Fisher's exact test. RESULTS: Of 67 patients, due to data quality 58 (93% female) were included in the analysis. Average age of participants was 17.8 (±6.9) years and body mass index was 15.5 (±1.9) kg/m2. Daytime average ENMO was 17.4 (±5.1) mg. Participants spent 862.6 (±66.2) min per day inactive, 88.4 (±22.6) min with light activities, 25.8 (±16.7) min with moderate activities and 0.5 (±1.8) min with vigorous activities. Participants slept for 461.0 (±68.4) min, waking up 1.45 (±1.25) times per night for 54.6 (±35.8) min, having an average sleep quality of 0.88 (±0.10). 31% of participants met sleep recommendations, with a significantly higher number of 6-13 year old patients failing to reach recommendations compared to 14-25 year old patients. CONCLUSION: The patient group spent most of their time inactive at the beginning of treatment. Most patients failed to reach sleep recommendations. The use of raw data and opensource software should ensure result reproducibility, enable comparison across points in treatment and comparison with healthy individuals.