Acute Anorexia Nervosa Research Articles

Changes in the Firmicutes to Bacteriodetes ratio in the gut microbiome in individuals with anorexia nervosa following inpatient treatment: A systematic review and a case series.

Anorexia nervosa has the highest mortality rate among psychiatric illnesses. Current treatments remain ineffective for a large fraction of patients. This may be due to unclear mechanisms behind its development and maintenance. Studies exploring the role of the gut microbiome have revealed inconsistent evidence of dysbiosis. This article aims to investigate changes in the gut microbiome, particularly, mean differences in the Firmicutes to Bacteroidetes ratio, in adolescent and adult individuals with anorexia nervosa following inpatient treatment. Longitudinal studies investigating gut microbiome composition in inpatient populations of anorexia nervosa before and after treatment were systematically reviewed. Additionally, gut microbiome compositions were characterized in three acute anorexia nervosa inpatients early after admission and after 4-12weeks of treatment. Review results indicated an increase in the Firmicutes to Bacteroidetes ratio in individuals with anorexia nervosa after treatment. These however did not match values of their healthy counterparts. In the case-series samples, the reverse occurred with samples taken 4weeks after treatment. In the patient who provided an extra sample 12weeks after treatment, similar results to the studies included in the review were observed. Furthermore, Firmicutes to Bacteroidetes ratio values in the case-series samples were notably higher in the two patients who had chronic anorexia nervosa. Differences in methodologies, small sample sizes, and insufficient data limited the generalizability of the outcomes of the reviewed studies. Results suggest a potentially unique microbiome signature in individuals with chronic anorexia nervosa, which may explain different outcomes in this group of patients.

Updating Prospective Self-Efficacy Beliefs About Cardiac Interoception in Anorexia Nervosa: An Experimental and Computational Study.

Patients with anorexia nervosa (AN) typically hold altered beliefs about their body that they struggle to update, including global, prospective beliefs about their ability to know and regulate their body and particularly their interoceptive states. While clinical questionnaire studies have provided ample evidence on the role of such beliefs in the onset, maintenance, and treatment of AN, psychophysical studies have typically focused on perceptual and 'local' beliefs. Across two experiments, we examined how women at the acute AN (N = 86) and post-acute AN state (N = 87), compared to matched healthy controls (N = 180) formed and updated their self-efficacy beliefs retrospectively (Experiment 1) and prospectively (Experiment 2) about their heartbeat counting abilities in an adapted heartbeat counting task. As preregistered, while AN patients did not differ from controls in interoceptive accuracy per se, they hold and maintain 'pessimistic' interoceptive, metacognitive self-efficacy beliefs after performance. Modelling using a simplified computational Bayesian learning framework showed that neither local evidence from performance, nor retrospective beliefs following that performance (that themselves were suboptimally updated) seem to be sufficient to counter and update pessimistic, self-efficacy beliefs in AN. AN patients showed lower learning rates than controls, revealing a tendency to base their posterior beliefs more on prior beliefs rather than prediction errors in both retrospective and prospective belief updating. Further explorations showed that while these differences in both explicit beliefs, and the latent mechanisms of belief updating, were not explained by general cognitive flexibility differences, they were explained by negative mood comorbidity, even after the acute stage of illness.

Cognitive and emotional empathy in acute and remitted anorexia nervosa: a systematic review

BackgroundImpairments in empathy are well established in anorexia nervosa (AN). It is unclear, however, whether these deficits only occur in the acute phases of AN due to neurocognitive impacts of starvation (often referred to as context-dependent, or state-like), or if deficits remain once remission has been achieved (trait-like). This debate is commonly referred to as the ‘state vs trait’ debate.ObjectiveThis systematic review aims to summarise existing literature regarding empathy in AN, and to investigate whether empathy deficits in AN are state- or trait-based.MethodA total of 1014 articles were identified, and seven articles remained after the screening process. These seven articles, comparing empathy across three groups (acute AN, remission of AN, and non-clinical controls), were evaluated and summarised in accordance with PRISMA guidelines. Articles were required to have included all three groups and report on either cognitive empathy and/or emotional empathy.ResultsThe majority of studies were of satisfactory quality. The results identified were inconsistent, with few articles lending some support to the ‘state’ hypothesis and others producing nonsignificant results.ConclusionsThere is minimal literature comparing empathy in acute and remission phases of AN. While there were some inconsistencies in included articles, some data indicate that there may be slight improvements to emotional and cognitive empathy following recovery of AN. Further research is needed to better enrich knowledge regarding the role of state vs trait with regard to neurocognitive difficulties experienced by individuals with AN.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335669, identifier CRD42022335669.

Differential longitudinal changes of hippocampal subfields in patients with anorexia nervosa.

Anorexia nervosa (AN) is a mental disorder characterized by dietary restriction, fear of gaining weight, and distorted body image. Recent studies indicate that the hippocampus, crucial for learning and memory, may be affected in AN, yet subfield-specific effects remain unclear. We investigated hippocampal subfield alterations in acute AN, changes following weight restoration, and their associations with leptin levels. T1-weighted magnetic resonance imaging scans were processed using FreeSurfer. We compared 22 left and right hemispheric hippocampal subfield volumes cross-sectionally and longitudinally in females with acute AN (n = 165 at baseline, n = 110 after partial weight restoration), healthy female controls (HCs; n = 271), and females after long-term recovery from AN (n = 79) using linear models. We found that most hippocampal subfield volumes were significantly reduced in patients with AN compared with HCs (~-3.9%). Certain areas such as the subiculum exhibited no significant reduction in the acute state of AN, while other areas, such as the hippocampal tail, showed strong decreases (~-9%). Following short-term weight recovery, most subfields increased in volume. Comparisons between participants after long-term weight-recovery and HC yielded no differences. The hippocampal tail volume was positively associated with leptin levels in AN independent of body mass index. Our study provides evidence of differential volumetric differences in hippocampal subfields between individuals with AN and HC and almost complete normalization after weight rehabilitation. These alterations are spatially inhomogeneous and more pronounced compared with other major mental disorders (e.g. major depressive disorder and schizophrenia). We provide novel insights linking hypoleptinemia to hippocampal subfield alterations hinting towards clinical relevance of leptin normalization in AN recovery.

Fibre-specific white matter changes in anorexia nervosa

A large body of literature exists on white matter (WM) abnormalities in individuals with anorexia nervosa (AN). However, these studies have primarily relied on the diffusion tensor imaging (DTI), a technique known for its limited ability to resolve complex WM fibre arrangements. To overcome limitations of DTI, this study employed fixel-based analysis (FBA) to investigate fibre-specific WM abnormalities in AN. FBA, which incorporates information on connectivity and crossing-fibres, offers greater anatomical specificity and interpretability than DTI. Twenty-six acute AN patients and thirty-one healthy controls underwent diffusion-weighted imaging scanning, and FBA and DTI metrics were compared between groups. Results revealed significant reductions in fibre-bundle cross-section within the anterior corona radiata and genu of corpus callosum, indicating morphological atrophy in AN patients. These specific tracts, identified by FBA, connect brain regions involved in the symptomatology of AN. DTI showed increased axial diffusivity in the cerebellar peduncles of AN patients but did not show significant differences in other metrics. Notably, there was no overlap between findings of FBA and DTI analyses. Overall, this study highlights the potential of FBA to detect WM abnormalities not accounted for by DTI and suggests that myelin loss contributes to the observed clinical picture in AN patients.

Similarities and differences regarding acute anorexia nervosa and semi-starvation: does behavioral thermoregulation play a central role?

To clarify the association between acute anorexia nervosa (AN) and semi-starvation (SS) by focusing on similarities and differences in physiology, mood, and behavior. A comparison of published literature between these two groups. Both groups show similar hormonal and metabolic changes in response to caloric restriction and extreme weight loss (~25%). Associated changes result in a reduced body temperature (Tcore-low). Maintenance of body temperature within a specific range is crucial to survival. However, both groups cannot activate autonomic strategies to maintain their Tcore-low, such as increasing metabolic rate, constricting skin blood vessels, or shivering. Furthermore, Tcore-low increases the individuals' "coldness sensations" throughout the body, hence the frequent reports from ANs and SSs of "feeling cold." To eliminate these uncomfortable "coldness sensations" and, importantly, to maintain Tcore-low, ANs, and SSs "select" different thermoregulatory behavioral strategies. It is proposed that the primary differences between AN and SS, based on genetics, now manifest due to the "selection" of different thermo-regulatory behaviors. AN patients (ANs) "select" hyperactive behavior (HyAc), which increases internal metabolic heat and thus assists with maintaining Tcore-low; in harmony with hyperactive behavior is a lively mood. Also related to this elevated arousal pattern, ANs experience disrupted sleep. In contrast, SS individuals "select" a passive thermo-behavioral strategy, "shallow torpor," which includes reduced activity, resulting in energy conservation. In addition, this inactivity aids in the retention of generated metabolic heat. Corresponding to this lethargic behavior, SS individuals display a listless mood and increased sleep. Initial similarities between the two are attributable to physiological changes related to extreme weight loss. Differences are most likely attributable to genetically programmed "selection" of alternate thermoregulatory strategies, primarily to maintain Tcore-low. However, if acute AN is prolonged and evolves into a chronic condition, AN will more closely align with starvation and more precisely reflect SS symptomology.

Intra-individual cortical networks in Anorexia Nervosa: Evidence from a longitudinal dataset.

This work investigates cortical thickness (CT) and gyrification patterns in Anorexia Nervosa (AN) before and after short-term weight restoration using graph theory tools. 38 female adolescents with AN underwent structural magnetic resonance imaging scans at baseline and after - on average-3.5months following short-term weight restoration while 53 age-matched healthy controls (HCs) were scanned once. Graph measures were compared between groups and longitudinally within the AN group. Associations with clinical measures such as age of onset, duration of illness, BMI standard deviation score (BMI-SDS), and longitudinal weight changes were tested via stepwise regression. Cortical thickness graphs of patients with acute AN displayed lower modularity and small-world index (SWI) than HCs. Modularity recovered after weight gain. Reduced global efficiency and SWI were observed in patients at baseline compared to HCs based on gyrification networks. Significant associations between local clustering of CT at admission and BMI-SDS, and clustering/global efficiency of gyrification and duration of illness emerged. Our results indicate a shift towards less organised CT networks in patients with acute AN. After weight recovery, the disarrangement seems to be partially reduced. However, longer-term follow-ups are needed to determine whether cortical organizational patterns fully return to normal.

Dynamic Amygdala Nuclei Alterations in Relation to Weight Status in Anorexia Nervosa Are Mediated by Leptin

The amygdaloid complex is a subcortical limbic group of distinct nuclei. In a previous patient-control study, differential amygdala nuclei alterations were found in acute anorexia nervosa (AN); rostral-medial nuclei involved in fear and reward processing were substantially reduced in volume and associated with hypoleptinemia, a key neuroendocrine characteristic of AN. Here, longitudinal amygdala nuclei alterations in AN were investigated in relation to weight status and their associations with leptin levels. T1-weighted structural magnetic resonance imaging scans were longitudinally processed with FreeSurfer. Amygdala nuclei volumes in young female patients with acute AN before and after short-term weight restoration (n= 110, >14% body mass index increase over 3 months) and female participants with a history of AN (n= 79, long-term [mean 5 years] weight recovered) were compared with female healthy control participants (n= 271) using linear mixed effects models. Rostral-medially clustered amygdala nuclei volumes, accessory basal, cortical, medial nuclei, and corticoamygdaloid transition, increased during short-term weight restoration (Cohen's d range 0.18-0.30). However, volumetric normalization across nuclei was heterogeneous. Right cortical, medial nuclei, bilateral corticoamygdaloid transitions, and anterior amygdaloid areas were only partially normalized following short-term weight restoration. Right anterior amygdaloid area remained reduced after long-term weight recovery compared with control participants (d= 0.36). Leptin increase, accompanying short-term weight restoration, mediated the effect of weight gain on volumetric increase in left corticoamygdaloid transition and bilateral medial nuclei. Rostral-medially clustered amygdala nuclei show pronounced volumetric increase but incomplete normalization in AN during and after short-term weight restoration. Leptin increase may be relevant for the recovery of specific amygdala nuclei in addition to nutritional rehabilitation, indicating links between amygdala substructure and leptin dynamics of potential pathophysiological and clinical relevance in AN. The amygdala plays a critical role in processing fearful and rewarding stimuli, and alterations in the amygdala are associated with anorexia nervosa. In this study, the authors measured amygdala nuclei volumes in female patients with acute anorexia nervosa undergoing weight-restoration treatment (n = 110), long-term weight-recovered individuals with anorexia (n = 79), and healthy control participants (n = 271). Structural magnetic resonance imaging revealed that volumes of specific nuclei, clustered in the rostral-medial amygdala, were substantially reduced in acute anorexia nervosa and only partially normalized following weight restoration treatment. Residual reductions in volume persisted even after long-term weight-recovery, compared to healthy control participants. Short-term weight restoration was associated with increases in the neurohormone leptin, and increasing leptin levels were found to mediate the positive impact of weight gain on increased amygdala volume over the treatment course. We worked to ensure race, ethnic, and/or other types of diversity in the recruitment of human participants. We worked to ensure that the study questionnaires were prepared in an inclusive way. One or more of the authors of this paper received support from a program designed to increase minority representation in science. We actively worked to promote sex and gender balance in our author group. We actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our author group. While citing references scientifically relevant for this work, we also actively worked to promote sex and gender balance in our reference list. While citing references scientifically relevant for this work, we also actively worked to promote inclusion of historically underrepresented racial and/or ethnic groups in science in our reference list. The author list of this paper includes contributors from the location and/or community where the research was conducted who participated in the data collection, design, analysis, and/or interpretation of the work.

The role of mindfulness on the psychological aspects of anorexia nervosa.

Emotion regulation, perfectionism, and rumination are perpetuating factors in anorexia nervosa (AN). Mindfulness can be protective and therapeutic. We aimed to understand the relationship between these factors and mindfulness in AN. 20 adolescent girls in the acute phase of the AN, 16 in remission, and 40 in the control group were evaluated. Mindfulness was lowest in the acute AN group. The difference in the acute AN group regarding body dissatisfaction, emotion dysregulation, perfectionism, and mindfulness disappeared after controlling for the effects of depression and anxiety. The predictors of disordered eating in the entire study population were body dissatisfaction and depressive symptoms. Emotion regulation and perfectionism were the predictors of mindfulness in the acute AN group and the entire study population. When mindfulness decreased, concerns about body shape increased in both acute AN and remission groups, while dietary restriction and disordered eating behaviors increased only in the remission group. Emotion regulation difficulties in acute AN could be related to depression and anxiety. Mindfulness interventions for emotion regulation could be used for depression during the acute phase while for perfectionism in remission. Early intervention for depression and body dissatisfaction seems protective, and mindfulness could be an appropriate intervention.

Triangulating brain alterations in anorexia nervosa: a multimodal investigation of magnetic resonance spectroscopy, morphometry and blood-based biomarkers

The acute state of anorexia nervosa (AN) is associated with widespread reductions in cortical gray matter (GM) thickness and white matter (WM) volume, suspected changes in myelin content and elevated levels of the neuronal damage marker neurofilament light (NF-L), but the underlying mechanisms remain largely unclear. To gain a deeper understanding of brain changes in AN, we applied a multimodal approach combining advanced neuroimaging methods with analysis of blood-derived biomarkers. In addition to standard measures of cortical GM thickness and WM volume, we analyzed tissue-specific profiles of brain metabolites using multivoxel proton magnetic resonance spectroscopy, T1 relaxation time as a proxy of myelin content leveraging advanced quantitative MRI methods and serum NF-L concentrations in a sample of 30 female, predominately adolescent patients with AN and 30 age-matched female healthy control participants. In patients with AN, we found a reduction in GM cortical thickness and GM total N-acetyl aspartate. The latter predicted higher NF-L levels, which were elevated in AN. Furthermore, GM total choline was elevated. In WM, there were no group differences in either imaging markers, choline levels or N-acetyl aspartate levels. The current study provides evidence for neuronal damage processes as well as for increased membrane lipid catabolism and turnover in GM in acute AN but no evidence for WM pathology. Our results illustrate the potential of multimodal research including tissue-specific proton magnetic resonance spectroscopy analyses to shed light on brain changes in psychiatric and neurological conditions, which may ultimately lead to better treatments.

Food induced distractibility in restrictive anorexia nervosa: Different motor patterns for different foods as revealed by a mouse tracker evaluation.

An altered automatic processing of food stimuli may contribute to the maintenance of calorie restriction in patients with restrictive Anorexia Nervosa (AN-R). The present study aimed to assess whether task-irrelevant food distractors elicited a different interference effect in the motor actions of patients with AN-R compared to healthy controls (HC). 40 patients with acute AN-R and 40 HC performed an irrelevant distractor task in which they were required to perform a reaching movement from a starting point to a green dot, while an irrelevant distractor (a high-calorie food, low-calorie food, or neutral object) was presented in the middle of the screen. Mouse trajectories and response times (RT) were recorded. The analyses conducted on the kinematic variables revealed that while the trajectories of HC veered similarly toward the three categories of stimuli, AN-R patients showed an increased deviation toward low-calorie foods and a reduced deviation toward high-calorie foods compared to neutral objects. No significant results emerged as regards RT. The pattern of responses observed in patients with AN-R (deviation increased toward low-calorie and reduced toward high-calorie) is consistent with their eating habits and may thus represent an implicit mechanism sustaining calorie restriction in patients with AN-R.

Serum neurofilament light concentrations are associated with cortical thinning in anorexia nervosa.

Anorexia nervosa (AN) is characterized by severe emaciation and drastic reductions of brain mass, but the underlying mechanisms remain unclear. The present study investigated the putative association between the serum-based protein markers of brain damage neurofilament light (NF-L), tau protein, and glial fibrillary acidic protein (GFAP) and cortical thinning in acute AN. Blood samples and magnetic resonance imaging scans were obtained from 52 predominantly adolescent, female patients with AN before and after partial weight restoration (increase in body mass index >14%). The effect of marker levels before weight gain and change in marker levels on cortical thickness (CT) was modeled at each vertex of the cortical surface using linear mixed-effect models. To test whether the observed effects were specific to AN, follow-up analyses exploring a potential general association of marker levels with CT were conducted in a female healthy control (HC) sample (n = 147). In AN, higher baseline levels of NF-L, an established marker of axonal damage, were associated with lower CT in several regions, with the most prominent clusters located in bilateral temporal lobes. Tau protein and GFAP were not associated with CT. In HC, no associations between damage marker levels and CT were detected. A speculative interpretation would be that cortical thinning in acute AN might be at least partially a result of axonal damage processes. Further studies should thus test the potential of serum NF-L to become a reliable, low-cost and minimally invasive marker of structural brain alterations in AN.

Dynamic changes in the central autonomic network of patients with anorexia nervosa.

Autonomic cardiac dysfunction is a common complication in patients with anorexia nervosa (AN). Despite its high prevalence, physicians often overlook this clinical condition, and little research has been dedicated so far. To probe the functional role of the neurocircuitry underpinning the poorly understood autonomic cardiac dysfunction, we examined dynamic functional differences in the central autonomic network (CAN) between 21 acute AN individuals and 24 age, sex and heart rate-matched healthy controls (HC). We assessed functional connectivity (FC) changes in CAN using seeds in the ventromedial prefrontal cortex, left and right anterior insular cortex, left and right amygdala and dorsal anterior cingulate cortex. The overall FC between the six investigated seeds is reduced in AN individuals compared to HC, although no changes were observed for single connections. Moreover, AN exhibited higher complexity in the FC time series of such CAN regions. Contrary to HC, we found that the degree of complexity between FC and heart rate (HR) series did not correlate in AN, suggesting a shift from central to peripheral control of the heart in AN individuals. Using dynamic FC analysis, we showed that the CAN transits across five functional states with no preference for any. Strikingly, at the state of weakest connectivity, the entropy significantly diverges between healthy and AN individuals, reaching its minimum and maximum values, respectively. Overall, our findings provide evidence that core regions of the CAN engaged in cardiac regulation are functionally affected in acute AN.

Volume and complexity of the thalamus in Anorexia Nervosa: An exploratory evaluation.

Recent neuroscientific findings have highlighted the role of the thalamus in several cognitive functions, ranging from perception to cognitive flexibility, memory, and body representation. Since some of these functions may be involved in the pathophysiology of Anorexia Nervosa (AN), this study aims at exploring thalamic structure in different phases of the disorder. The sample included 38 patients with acute AN, 20 patients who fully recovered from AN (recAN), and 38 healthy controls (HC), all female. All participants underwent high-resolution MRI. The volumes of the whole thalamus and 25 thalamic nuclei were extracted using an automated segmentation algorithm, and thalamic fractal dimension was estimated using the calcFD toolbox. Patients with acute AN, compared to HC, displayed reduced thalamic volume and complexity both at the whole level and at the level of specific nuclei. In patients recAN, instead, alterations were observed only at the level of the right laterodorsal and central lateral nuclei. In the acute phase of the disorder patients with AN present a widespread reduction in thalamic volume and complexity. However, these alterations seem to normalise almost completely following weight restoration, thus suggesting the involvement of malnutrition-related mechanisms.

Increased Habit Frequency in the Daily Lives of Patients with Acute Anorexia Nervosa.

Strict eating routines and frequent rigid behavior patterns are commonly observed in patients with anorexia nervosa (AN). A recent theory proposes that while these behaviors may have been reinforced initially, they later become habitual. To date, however, research has been overly focused on eating-disorder (ED)-related habits. Over the course of seven days, we applied an ecological momentary assessment (EMA) to investigate the habit frequency and strength of ED-specific (food intake) and ED-unspecific (hygiene) habits in the daily lives of a sample of n = 57 AN and n = 57 healthy controls (HC). The results of the hierarchical models revealed that habits were significantly more likely in patients compared with HC for both categories, independently. Furthermore, a lower body mass index (BMI) was associated with increased habit frequency in AN. Our study strengthens the habit theory of AN by showing the relevance of habits beyond ED-specific behavioral domains. This also supports the development of innovative therapeutic interventions targeting habitual behavior in EDs.

Influence of eating disorder psychopathology and general psychopathology on the risk of involuntary treatment in anorexia nervosa.

We explored associations between clinical factors, including eating disorder psychopathology and more general psychopathology, and involuntary treatment in patients with anorexia nervosa. Our intention was to inform identification of patients at risk of involuntary treatment. This was a retrospective cohort study combining clinical data from a specialized eating disorder hospital unit in Denmark with nationwide Danish register-based data. A sequential methodology yielding two samples (212 and 278 patients, respectively) was adopted. Descriptive statistics and regression analyses were used to explore associations between involuntary treatment and clinical factors including previous involuntary treatment, patient cooperation, and symptom-level psychopathology (Eating Disorder Inventory-2 (EDI-2) and Symptom Checklist-90-Revised (SCL-90-R)). Somatization (SCL-90-R) (OR = 2.60, 95% CI 1.16-5.81) and phobic anxiety (SCL-90-R) (OR = 0.43, 95% CI 0.19-0.97) were positively and negatively, respectively, associated with the likelihood of involuntary treatment. Furthermore, somatization (HR = 1.77, 95% CI 1.05-2.99), previous involuntary treatment (HR = 5.0, 95% CI 2.68-9.32), and neutral (HR = 2.92, 95% CI 1.20-7.13) or poor (HR = 3.97, 95% CI 1.49-10.59) patient cooperation were associated with decreased time to involuntary treatment. Eating disorder psychopathology measured by the EDI-2 was not significantly associated with involuntary treatment. Clinical questionnaires of psychopathology appear to capture specific domains relevant to involuntary treatment. Poor patient cooperation and previous involuntary treatment being associated with shorter time to involuntary treatment raise important clinical issues requiring attention. Novel approaches to acute anorexia nervosa care along with unbiased evaluation upon readmission could mitigate the cycle of repeat admissions with involuntary treatment. Level III, cohort study.

Liver and vitamin B12 parameters in patients with anorexia nervosa before and after short-term weight restoration

Hepatic involvement in anorexia nervosa (AN) has been previously reported, but a link to elevated vitamin B12 concentrations, which can be a sign for liver damage, has not been thoroughly examined. We measured liver enzymes (alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase) and vitamin B12 parameters (total B12, holotranscobalamin, methylmalonic acid) in the plasma of young female patients with acute AN (n=77) and after short-term weight restoration (n=58, median body mass increase=25%), in comparison to healthy control participants (n=63). For a comprehensive assessment of vitamin B12 status, the combined marker cB12 was calculated. In acute AN, activities of alanine aminotransferase and gamma-glutamyltransferase as well as holotranscobalamin concentrations were elevated, and alanine aminotransferase activities positively correlated with total B12, holotranscobalamin and cB12 in patients with elevated liver enzyme activities. After weight restoration, alanine aminotransferase activities and holotranscobalamin concentrations were elevated, and cB12 increased above the level of the healthy control group. The present study provides further evidence for a hepatic involvement in acute AN in concert with vitamin B12 parameters and points to refeeding-associated alterations of liver and vitamin B12 parameters. Future studies should include non-invasive methods to characterize hepatic involvement and evaluate vitamin B12 status as a potential marker of liver damage/irritation.

Is decision-making impairment an endophenotype of Anorexia Nervosa?

IntroductionPatients with anorexia nervosa (AN) show impaired decision-making ability, but it is still unclear if this is a trait marker, i.e. a stable endophenotype of AN, or a state parameter, i.e. being explained by present symptoms and associated comorbidity.ObjectivesWe aimed to determine whether decision-making impairment is an endophenotype of AN. We hypothesized that decision-making alteration would not respect the criteria of an endophenotype, and that these alterations would have a relationship with illness severity.MethodsNinety-one patients with acute AN (A-AN), 90 unaffected relatives (UR), 23 patients remitted from AN (R-AN) and 204 healthy controls (HC) underwent the Iowa Gambling Task (IGT) and psychometric assessments. Prospective Valence Learning model (PVL) was employed to distinguish the cognitive dimensions underlying the decision-making process. Performance at the IGT was compared between the four groups and then analysed according to clinical and psychometric variables.ResultsPatients with A-AN scored worse than UR and HC at the IGT (p<.01). PVL-feedback sensitivity parameter was lower in patients with R-AN and A-AN than in the two other groups (p<.01) and PVL-loss aversion parameter was lower in A-AN than in UR and R-AN (p<.01). Decision-making style, in particular learning and loss aversion parameters, accounted for a significant part of variance of psychopathology in patients with AN (p<.01).ConclusionsImpaired decision-making represents a state-associated, cognitive hallmark of AN. The aggravation of reward modulation along with illness progression may explain the persistence of symptoms despite their consequences on health. Reversal of decision-making impairment should not be limited by inherited vulnerability.DisclosureNo significant relationships.

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group

BackgroundThe pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. MethodsWe analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). ResultsIn AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen’s d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. ConclusionsThe effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

Atypical Sensory Processing Is Associated With Lower Body Mass Index and Increased Eating Disturbance in Individuals With Anorexia Nervosa.

Background:Elevated autism spectrum disorder (ASD) traits are associated with anorexia nervosa (AN). Conversely, eating disturbances, which are core characteristics of AN, are common in ASD. Among individuals with ASD, atypical sensory processing is associated with eating disturbance. Because AN and ASD appear to overlap, it would be crucial to understand whether sensory processing atypicality exist also in AN. Further, it would be essential to find if atypical sensory processing is associated with eating disturbances in individuals with AN, since treatment modifications may be needed. We therefore aimed to examine whether atypical sensory processing is associated with AN and its core characteristics.MethodsParticipants of the current study included 42 individuals with AN and 40 healthy controls (HCs). All participants were adult women. Sensory processing, other ASD traits, and eating disorder symptoms were assessed with self-report questionnaires.ResultsIndividuals with AN reported lower registration, decreased sensation seeking, increased sensory sensitivity, and increased sensation avoiding compared to HCs. When analyzing groups with restrictive AN (AN-R) and binge-purge type AN (AN-BP) separately, only individuals with AN-R exhibited decreased sensation seeking, and only those with AN-BP exhibited lower registration. After controlling for body mass index as a covariate, group differences remained significant only in sensory sensitivity between individuals with AN and HCs. Increased atypical sensory processing predicted lower body mass index and increased disordered eating.ConclusionResults suggest that sensory processing appears to differ between AN and HC women, and AN subtypes may exhibit distinct sensory processing atypicality. Sensory sensitivity may be stable traits whereas other aspects of atypical sensory processing may be related to acute AN. Atypical sensory processing may contribute to the severity of AN, and thus it is crucial to recognize sensory processing differences when treating individuals with AN.