Acute Anorexia Nervosa Research Articles

Attachment status is associated with grey matter recovery in adolescent anorexia nervosa: Findings from a longitudinal study.

The aim of the present study was to investigate whether grey matter (GM) reductions in acute anorexia nervosa (AN) are (i) valid for adolescents (age 14–18 years), (ii) reversible following short‐term psychotherapeutic and nutritional therapy and (iii) depend on psychological components like attachment trauma. 3T MRI including a high‐resolution T1 MPRAGE was performed in 22 female adolescents in the acute state of AN (age: 15.2 ± 1.2 years) and after weight restoration (duration: 2.6 ± 1 months, n = 18) and compared with 18 gender‐matched healthy controls. The Adult Attachment Projective Picture System was used to classify resolved and unresolved attachment patterns. GM decreases were localized in extensive cortical areas including the insula, prefrontal and cingulate cortices as well as subcortical regions during acute AN, which partially increased after therapy with a relative sparing of the hippocampus and parahippocampal gyrus. The resolved group showed more GM recovery in regions of the left hippocampus and parahippocampal gyrus, bilateral cerebellar regions, right precuneus and adjacent cingulate cortices relative to the unresolved pattern. Structural anomalies in adolescent AN that recovered after treatment may be primarily the consequence of malnutrition, whereas several regions did not display significant recovery. Attachment status seems to influence region‐specific GM recovery.

Intact neural and behavioral correlates of emotion processing and regulation in weight-recovered anorexia nervosa: a combined fMRI and EMA study

Altered emotion processing and regulation mechanisms play a key role in eating disorders. We recently reported increased fMRI responses in brain regions involved in emotion processing (amygdala, dorsolateral prefrontal cortex) in acutely underweight anorexia nervosa (AN) patients while passively viewing negatively valenced images. We also showed that patients’ ability to downregulate activity elicited by positively valenced pictures in a brain region involved in reward processing (ventral striatum) was predictive of worse outcomes (increased rumination and negative affect). The current study tries to answer the question of whether these alterations are only state effects associated with undernutrition or whether they constitute a trait characteristic of the disorder that persists after recovery. Forty-one individuals that were weight-recovered from AN (recAN) and 41 age-matched healthy controls (HC) completed an established emotion regulation paradigm using negatively and positively valenced visual stimuli. We assessed behavioral (arousal) and fMRI measures (activity in the amygdala, ventral striatum, and dorsolateral prefrontal cortex) during emotion processing and regulation. Additionally, measures of disorder-relevant rumination and affect were collected several times daily for 2 weeks after scanning via ecological momentary assessment. In contrast to our previous findings in acute AN patients, recAN showed no significant alterations either on a behavioral or neural level. Further, there were no associations between fMRI responses and post-scan momentary measures of rumination and affect. Together, these results suggest that neural responses to emotionally valenced stimuli as well as relationships with everyday rumination and affect likely reflect state-related alterations in AN that improve following successful weight-recovery.

Is decision-making impairment an endophenotype of anorexia nervosa?

Patients with anorexia nervosa (AN) show impaired decision-making ability, but it is still unclear if this is a trait marker (i.e., being associated with AN at any stage of the disease) or a state parameter of the disease (i.e., being present only in acutely ill patients), and if it has endophenotypic characteristics. The aim of this study was to determine the endophenotypic, and state- or trait-associated nature of decision-making impairment in AN. Ninety-one patients with acute AN (A-AN), 90 unaffected relatives (UR), 23 patients remitted from AN (R-AN), and 204 healthy controls (HC) carried out the Iowa gambling task (IGT). Prospective valence learning (PVL) model was employed to distinguish the cognitive dimensions underlying the decision-making process, that is, learning, consistency, feedback sensitivity, and loss aversion. IGT performance and decision-making dimensions were compared among groups to assess whether they had endophenotypic (i.e., being present in A-AN, UR, and R-AN, but not in HC) and/or trait-associated features (i.e., present in A-AN and R-AN but not in HC). Patients with A-AN had lower performance at the IGT (p<0.01), while UR, R-AN, and HC had comparable results. PVL-feedback sensitivity was lower in patients with R-AN and A-AN than in HC (p<0.01). Alteration of decision-making ability did not show endophenotypic features. Impaired decision-making seems a state-associated characteristic of AN, resulting from the interplay between trait-associated low feedback sensitivity and state-associated features of the disease.

White matter integrity is disrupted in adolescents with acute anorexia nervosa: A diffusion tensor imaging study

Anorexia nervosa (AN) is a highly debilitating mental illness with multifactorial etiology. It oftentimes begins in adolescence, therefore understanding the pathophysiology in this period is important. Few studies investigated the possible impact of the acute state of illness on white matter (WM) tissue properties in the developing adolescent brain. The present study expands our understanding of the implications of AN and starvation on WM integrity. 67 acutely ill adolescent patients suffering from AN restricting type were compared with 32 healthy controls using diffusion tensor imaging assessing fractional anisotropy (FA) and mean diffusivity (MD). We found widespread alterations in the vast majority of the WM regions with significantly decreased FA and increased MD in the AN group. In this highly selective sample in the acute stage of AN, the alterations are likely to be the consequence of starvation. Still, we cannot rule out that some of the affected regions might play a key role in AN-specific psychopathology.

Aberrant neural representation of food stimuli in women with acute anorexia nervosa predicts treatment outcome and is improved in weight restored individuals

Anorexia nervosa (AN) has been associated with altered reward processing. We recently reported greater neural response in secondary visual areas when processing visual food stimuli in acutely underweight AN patients (acAN). In order to examine whether the observed alterations are indicative of acute undernutrition or a potential trait marker of AN, we set out to assess neural responses in acAN and in individuals weight-recovered from AN (recAN). FMRI data were collected from a total of 126 female volunteers, 35 acAN, 33 recAN, and 58 age-matched healthy controls (HC) while they viewed streams of food, social and neutral stimuli. A standard general linear model (GLM) was used to interrogate neural responses to the different stimuli in recAN vs. age-matched HC. Moreover, within-subject multivoxel pattern analyses (MVPA) in the two matched samples (acAN/HC and recAN/HC) were used to estimate neural representation of food vs. neutral, and social vs. neutral stimuli. A multiple regression analysis was conducted to test associations between the accuracy of the neural representation and treatment outcome. The GLM revealed no group differences between recAN and HC. The MVPAs showed greater classification accuracy of food stimuli in the posterior fusiform gyrus in acAN but not recAN. Classification accuracy was associated with better treatment outcome. Our findings suggest that the neural representation of food stimuli is altered in secondary visual areas in acAN and normalizes with weight recovery. Possibly this altered representation reflects attentional engagement motivating food intake, which may promote the recovery process.

Reduced MIP-1β as a Trait Marker and Reduced IL-7 and IL-12 as State Markers of Anorexia Nervosa.

Alterations in certain inflammatory markers have been found in individuals with anorexia nervosa (AN). However, their relation to clinical characteristics has not been extensively explored, nor is it clear whether they are trait or state features of the disorder. This cross-sectional study measured serum concentrations of 36 inflammatory markers in people with acute AN (n = 56), recovered AN (rec-AN; n = 24) and healthy controls (HC; n = 51). The relationship between body mass index (BMI), eating disorder psychopathology, depression symptoms and inflammatory markers was assessed. Statistical models controlled for variables known to influence cytokine concentrations (i.e., age, ethnicity, smoking status and medication usage). Overall, most inflammatory markers including pro-inflammatory cytokines were unchanged in AN and rec-AN. However, in AN and rec-AN, concentrations of macrophage inflammatory protein (MIP)-1β were lower than HCs. Interleukin (IL)-7 and IL-12/IL-23p40 were reduced in AN, and concentrations of macrophage-derived chemokine, MIP-1α and tumor necrosis factor-α were reduced in rec-AN compared to HC. In conclusion, a reduction in MIP-1β may be a trait marker of the illness, whereas reductions in IL-7 and IL-12/IL-23p40 may be state markers. The absence of increased pro-inflammatory cytokines in AN is contradictory to the wider literature, although the inclusion of covariates may explain our differing findings.

Exploring the Mechanisms of Recovery in Anorexia Nervosa through a Translational Approach: From Original Ecological Measurements in Human to Brain Tissue Analyses in Mice.

Anorexia nervosa (AN) is a severe eating disorder where caloric restriction, excessive physical activity and metabolic alterations lead to life-threatening situations. Despite weight restoration after treatment, a significant part of patients experience relapses. In this translational study, we combined clinical and preclinical approaches. We describe preliminary data about the effect of weight gain on the symptomatology of patients suffering from acute AN (n = 225) and partially recovered (n = 41). We measured more precisely physical activity with continuous cardiac monitoring in a sub-group (n = 68). Using a mouse model, we investigated whether a long-term food restriction followed by nutritional recovery associated or not with physical activity may differentially impact peripheral and central homeostatic regulation. We assessed the plasma concentration of acyl ghrelin, desacyl ghrelin and leptin and the mRNA expression of hypothalamic neuropeptides and their receptors. Our data show an effect of undernutrition history on the level of physical activity in AN. The preclinical model supports an important role of physical activity in the recovery process and points out the leptin system as one factor that can drive a reliable restoration of metabolic variables through the hypothalamic regulation of neuropeptides involved in feeding behavior.

Sulcal characteristics patterns and gyrification gradient at different stages of Anorexia Nervosa: A structural MRI evaluation

Previous research evidenced alterations of different cortical parameters in patients with acute Anorexia Nervosa (AN), but no study to date investigated the morphology of individual sulci and their relationship with other structural indices. Our study aims at exploring the depth and width of 16 major cortical sulci in AN at different stages of the disorder and their relationships with the gyrification gradient. Two samples were included in the study. The first involved 38 patients with acute AN, 20 who fully recovered from AN, and 38 healthy women (HW); the second included 16 patients with AN and 16 HW. Sulcal width and depth were estimated for 16 sulci and outlined with a factorial analysis. An anterior-posterior gradient of gyrification was also extracted. Compared to HW, patients with acute AN displayed higher width and depth values in specific cortical sulci, and an altered gyrification gradient in areas encompassing the Central Sulcus, and Parieto-Temporal and Frontal Lobe regions. Sulcal width negatively correlated with gyrification gradient in areas where these values are altered in AN patients. Our results suggest the presence of alterations in sulcal morphology with a pattern similar to the gyrification gradient one and which seems to be related with malnutrition.

Anorexia nervosa-related cardiopathy in children with physical instability: prevalence, echocardiographic characteristics and reversibility at mid-term follow-up.

Prompt detection of cardiovascular abnormalities in children with anorexia nervosa and physical instability requiring hospitalization is essential to identify patients at higher cardiovascular risk. We studied all anorexia nervosa children requiring admission at Paediatric Institute in the period 2015-2019. Anorexia nervosa cardiopathy at admission was defined by the presence of at least two of the following clinical findings: pericardial effusion, mitral regurgitation, bradycardia, mitral billowing, aortic regurgitation, altered LV morphology and ECG abnormalities. Echocardiographic data were compared with those registered at 3-8-month follow-up and with data from a healthy population. Thirty-eight anorexia nervosa children were examined. Prevalence of anorexia nervosa cardiopathy at admission was 63% (24 patients). Pericardial effusion, bradycardia and mitral regurgitation were present together in 26% of patients. Most cardiovascular changes recovered at follow-up. Anorexia nervosa cardiopathy was associated with significantly lower left ventricle end-diastolic diameters and mass, and higher E wave, E/A and E/e' ratios and left ventricle sphericity index values vs healthy population and vs anorexia nervosa children without cardiopathy (p<0.05). Left ventricle global longitudinal strain was significantly reduced only in anorexia nervosa cardiopathy patients but recovered, whereas end-diastolic diameters, E/A ratio and sphericity index values remained impaired.Conclusion: Among anorexia nervosa children requiring hospitalization, those presenting several cardiac findings together express an acute anorexia nervosa cardiopathy which is characterized by worse LV filling, geometry and subclinical myocardial deformation impairment. Despite treatment, in those patients, some alterations persist at mid-term follow-up. What is Known: • Cardiac and electrocardiographic changes are present in anorexia nervosa children at diagnosis or during stable disease, and most recover after body-weight treatment. • It is unknown if anorexia nervosa children with more severe cardiac impairment during hospitalization present higher cardiovascular-risk profile despite treatment. What is New: • In anorexia nervosa children needing hospitalization for physical reasons, prevalence of acute anorexia nervosa cardiopathy at admission is high, around 60%. • By advanced echocardiography, children with anorexia nervosa cardiopathy at admission have a worse cardiac filling, impaired cardiac geometry and systolic deformation that only partially recover at mid-term follow-up.

Altered White Matter Connectivity in Young Acutely Underweight Patients With Anorexia Nervosa

Reductions of gray matter volume and cortical thickness in anorexia nervosa (AN) are well documented. However, findings regarding the integrity of white matter (WM) as studied via diffusion weighted imaging (DWI) are remarkably heterogeneous, and WM connectivity has been examined only in small samples using a limited number of regions of interest. The present study investigated whole-brain WM connectivity for the first time in a large sample of acutely underweight patients with AN. DWI data from predominantly adolescent patients with acute AN (n= 96, mean age= 16.3 years) and age-matched healthy control participants (n= 96, mean age= 17.2 years) were analyzed. WM connectivity networks were generated from fiber-tractography-derived streamlines connecting 233 cortical/subcortical regions. To identify group differences, network-based statistic was used while taking head motion, WM, and ventricular volume into account. Patients with AN were characterized by 6 WM subnetworks with abnormal architecture, as indicated by increased fractional anisotropy located primarily in parietal-occipital regions and accompanied by reduced radial diffusivity. Group differences based on number of streamlines reached only nominal significance. Our study reveals pronounced alterations in the WM connectome in young patients with AN. In contrast to known reductions in gray matter in the acutely underweight state of AN, this pattern does not necessarily indicate a deterioration of the WM network. Future studies using advanced MRI sequences will have to clarify interrelations with axonal packing or myelination, and whether the changes should be considered a consequence of undernutrition or a vulnerability for developing or maintaining AN.

Lower leptin level at discharge in acute anorexia nervosa is associated with early weight‐loss

Predictive values of acute phase metabolic abnormalities of anorexia nervosa (AN) have seldom been studied. As early postrestoration weight loss is associated with poor outcome, discharge biologic parameters were assessed to detect an association with 2-month follow-up weight loss as a proxy to poor outcome. Fasting plasma levels of leptin, acyl-ghrelin, obestatin, PYY, oxytocin and BDNF were measured in 26 inpatients, at inclusion, at discharge and 2 months later. A body mass index less than 18 2-month postdischarge was considered a poor outcome. Nineteen patients (73%) had a fair outcome and seven (27%) had a poor one with a mean loss of 0.69 versus 4.54kg, respectively. Only discharge leptin levels were significantly higher in fair versus poor outcome patients (14.1 vs. 7.0ng/ml, p=0.006). The logistic regression model using discharge leptin, acyl-ghrelin, obestatin, oxytocin, PYY and BDNF levels aspredictors of outcome disclosed a nearly significant effect of leptin (p<0.10). Receiver operating characteristic analysis showed 11.9ng/ml was the best value of threshold. Neither clinical variables differed according to outcome. Leptin level may be a biomarker of early weight relapse after acute inpatient treatment of AN. Its clinical usefulness in monitoring care in AN should further be determined.

Microbiome-metabolomics signature in anorexia nervosa (AN) before and after weight regain

IntroductionThe intestinal microbiota has been indicated to have a role in the pathophysiology of AN.ObjectivesAim of this study was to analyze fecal microbiome profiles of AN women before and after weight restoration and to combine them with fecal metabolomic profiles according to a multi-omics approach.MethodsThe gut microbiome and fecal metabolites were characterized in 21 underweight AN women and after weight restoration and compared with those of 20 healthy women. Microbiome data were correlated with the relevant fecal metabolites.ResultsAN subjects showed a decreased intra-individual bacterial richness, an increased Bacteroidetes-to-Firmicutes abundance ratio and significant changes in the relative abundances of several bacteria at different order levels in both the underweight and weight-restored condition compared to healthy women. The untargeted metabolomic procedure allowed the characterization of 224 metabolites involved in energy, lipid and amino acid metabolism. A genetic algorithm identified 49 relevant metabolites. The relationships among these fecal metabolites and bacteria genera showed structures of different complexity in the 3 groups. In particular, a quarter of those relationships showed a divergent direction in the acute phase of AN than in the weight-restored phase or normal controls. Finally, in acute AN 70% of those correlations showed a negative sign suggesting a prevalent metabolites consummation by gut microbiome.ConclusionsOur results provide a picture of the connections between gut bacteria and fecal metabolites in both the acute phase of AN and after short-term weight restoration. Further studies should aim to investigate the significance of gut microbiome perturbations in development and treatment of AN.

Recovery-Associated Resting-State Activity and Connectivity Alterations in Anorexia Nervosa

BackgroundPrevious studies provided controversial insight on the impact of starvation, disease status, and underlying gray matter volume (GMV) changes on resting-state functional magnetic resonance imaging alterations in anorexia nervosa (AN). Here, we adapt a combined longitudinal and cross-sectional approach to disentangle the effects of these factors on resting-state alterations in AN. MethodsOverall, 87 female subjects were included in the study: adolescent patients with acute AN scanned at inpatient admission (n = 22, mean age 15.3 years) and at discharge (n = 21), patients who recovered from AN (n = 21, mean age 22.3 years), and two groups of healthy age-matched control subjects (both n = 22, mean age 16.0 and 22.5 years, respectively). Whole-brain measures of resting-state activity and functional connectivity were computed (network-based statistics, global correlation, integrated local correlation, and fractional amplitude of low-frequency fluctuations) to assess resting-state functional magnetic resonance imaging alterations over the course of AN treatment before and after controlling for underlying GMV. ResultsPatients with acute AN displayed strong and widespread prefrontal, sensorimotor, parietal, temporal, precuneal, and insular reductions of resting-state connectivity and activity. All alterations were independent of GMV and were largely normalized in short-term recovered AN and absent in long-term recovered patients. ConclusionsResting-state functional magnetic resonance imaging alterations in AN constitute acute and GMV-independent, presumably starvation-related, phenomena. The majority of alterations found here normalized over the course of recovery without evidence for possible preexisting trait- or remaining “scar” effects.

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

While overexercise is commonly described in patients who experience anorexia nervosa (AN), it represents a condition still underestimated, especially in the paediatric population. 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. 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). 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 III.

Adverse Effects of Refeeding on the Plasma Lipidome in Young Individuals With Anorexia Nervosa?

Refeeding is the cornerstone of anorexia nervosa (AN) treatment, but little is known regarding the optimal pace and dietary composition or possible adverse effects of current clinical practices. Plasma lipids may be a moderating factor underlying unfavorable refeeding effects in AN, such as an abnormal central body fat distribution. The objective of this study was to analyze the plasma lipidome in the acutely underweight state of AN before and after refeeding. Using high-throughput quantitative mass spectrometry-based shotgun lipidomics, we measured 13 lipid classes and 204 lipid species or subspecies in the plasma of young female patients with acute AN, before (n= 39) and after (n= 23) short-term weight restoration during an intensive inpatient refeeding program (median body mass index [BMI] increase= 26.4%), in comparison to those in healthy control participants (n= 37). Before inpatient treatment, patients with AN exhibited increased concentrations of cholesterol and several other lipid classes. After refeeding, multiple lipid classes including cholesterol and ceramides, as well as certain ceramide species previously associated with obesity or overfeeding, showed increased concentrations, and a pattern of shorter and more saturated triacylgycerides emerged. A machine learning model trained to predict BMI based on the lipidomic profiles revealed a sizable overprediction in patients with AN after weight restoration. The results point toward a profound lipid dysregulation with similarities to obesity and other features of the metabolic syndrome after short-term weight restoration. Thus, this study provides evidence for possible short-term adverse effects of current refeeding practices on the metabolic state and should inspire more research on nutritional interventions in AN.

A Systematic Review and Meta-Analysis Finds Increased Blood Levels of All Forms of Ghrelin in Both Restricting and Binge-Eating/Purging Subtypes of Anorexia Nervosa.

Anorexia nervosa (AN) is a severe psychiatric condition associated with high mortality and chronicity. The hunt for state, trait, subtyping, and prognostic biomarkers is ongoing and the orexigenic hormone ghrelin and its different forms, acyl ghrelin and desacyl ghrelin, have been proposed to be increased in AN, especially in the restrictive subtype. A systematic literature search was performed using established databases up to 30 November 2020. Forty-nine studies met inclusion criteria for cross-sectional and longitudinal meta-analyses on total ghrelin, acyl ghrelin, and desacyl ghrelin. All forms of ghrelin were increased in the acute stage of anorexia nervosa during fasting compared to healthy controls. Previous notions on differences in ghrelin levels between AN subtypes were not supported by current data. In addition, a significant decrease in total ghrelin was observed pre-treatment to follow-up. However, total ghrelin levels at follow-up were still marginally elevated compared to healthy controls, whereas for acyl ghrelin, no overall effect of treatment was observed. Due to heterogeneity in follow-up designs and only few data on long-term recovered patients, longitudinal results should be interpreted with caution. While the first steps towards a biomarker in acute AN have been completed, the value of ghrelin as a potential indicator of treatment success or recovery status or its use in subtype differentiation are yet to be established.

Differential longitudinal changes of neuronal and glial damage markers in anorexia nervosa after partial weight restoration

Atrophic brain changes in acute anorexia nervosa (AN) are often visible to the naked eye on computed tomography or magnetic resonance imaging scans, but it remains unclear what is driving these effects. In neurological diseases, neurofilament light (NF-L) and tau protein have been linked to axonal damage. Glial fibrillary acidic protein (GFAP) has been associated with astroglial injury. In an attempt to shed new light on factors potentially underlying past findings of structural brain alterations in AN, the current study investigated serum NF-L, tau protein, and GFAP levels longitudinally in AN patients undergoing weight restoration. Blood samples were obtained from 54 acutely underweight, predominantly adolescent female AN patients and 54 age-matched healthy control participants. AN patients were studied in the severely underweight state and again after short-term partial weight restoration. Group comparisons revealed higher levels of NF-L, tau protein, and GFAP in acutely underweight patients with AN compared to healthy control participants. Longitudinally, a decrease in NF-L and GFAP but not in tau protein levels was observed in AN patients upon short-term partial weight restoration. These results may be indicative of ongoing neuronal and astroglial injury during the underweight phase of AN. Normalization of NF-L and GFAP but not tau protein levels may indicate an only partial restoration of neuronal and astroglial integrity upon weight gain after initial AN-associated cell damage processes.

Cortical thinning and associated connectivity changes in patients with anorexia nervosa

Structural brain abnormalities are a consistent finding in anorexia nervosa (AN) and proposed as a state biomarker of the disorder. Yet little is known about how regional structural changes affect intrinsic resting-state functional brain connectivity (rsFC). Using a cross-sectional, multimodal imaging approach, we investigated the association between regional cortical thickness abnormalities and rsFC in AN. Twenty-two acute AN patients and twenty-six age- and gender-matched healthy controls underwent a resting-state functional magnetic resonance imaging scan and cognitive tests. We performed group comparisons of whole-brain cortical thickness, seed-based rsFC, and network-based statistical (NBS) analyses. AN patients showed cortical thinning in the precuneus and inferior parietal lobules, regions involved in visuospatial memory and imagery. Cortical thickness in the precuneus correlated with nutritional state and cognitive functions in AN, strengthening the evidence for a critical role of this region in the disorder. Cortical thinning was accompanied by functional connectivity reductions in major brain networks, namely default mode, sensorimotor and visual networks. Similar to the seed-based approach, the NBS analysis revealed a single network of reduced functional connectivity in patients, comprising mainly sensorimotor- occipital regions. Our findings provide evidence that structural and functional brain abnormalities in AN are confined to specific regions and networks involved in visuospatial and somatosensory processing. We show that structural changes of the precuneus are linked to nutritional and functional states in AN, and future longitudinal research should assess how precuneus changes might be related to the evolution of the disorder.

Hair endocannabinoid concentrations in individuals with acute and weight-recovered anorexia nervosa

BackgroundThe endocannabinoid system has been suggested to modulate energy metabolism and stress response and could be an important factor in the pathophysiology of anorexia nervosa (AN). In the context of AN, excessive physical activity may influence endocannabinoid concentrations. The objective of this study was to investigate hair endocannabinoid concentrations at different stages of the disorder. Measurement in hair allows for a cumulative assessment of endocannabinoid concentrations independent of circadian rhythms. MethodsIn a combined cross-sectional and longitudinal design, we measured hair concentrations of the endocannabinoids anandamide and 2-arachidonoylglycerol and the endocannabinoid-related compounds palmitoylethanolamide, oleoylethanolamide, and stearoylethanolamide in female underweight patients with acute AN (n = 67, reassessment of n = 47 after short-term weight restoration with a body mass index increase of at least 14%), individuals long-term recovered from AN (n = 27), and healthy control participants (n = 84). ResultsHair concentrations of anandamide and all endocannabinoid-related compounds were elevated in acute AN and decreased over the course of short-term weight restoration. Anandamide concentrations remained elevated in long-term recovered AN patients. In long-term recovered patients, physical activity correlated positively with the concentrations of all endocannabinoid-related compounds. ConclusionThe current study provides evidence for a significant alteration of the endocannabinoid system in acute AN, which may partly persist into long-term recovery. The endocannabinoid system may be a possible target for pharmaceutical interventions in AN, which should be explored in further preclinical and subsequently clinical randomized controlled trials.

Evaluation of Metabolic Profiles of Patients with Anorexia Nervosa at Inpatient Admission, Short- and Long-Term Weight Regain-Descriptive and Pattern Analysis.

Acute anorexia nervosa (AN) constitutes an extreme physiological state. We aimed to detect state related metabolic alterations during inpatient admission and upon short- and long-term weight regain. In addition, we tested the hypothesis that metabolite concentrations adapt to those of healthy controls (HC) after long-term weight regain. Thirty-five female adolescents with AN and 25 female HC were recruited. Based on a targeted approach 187 metabolite concentrations were detected at inpatient admission (T0), after short-term weight recovery (T1; half of target-weight) and close to target weight (T2). Pattern hunter and time course analysis were performed. The highest number of significant differences in metabolite concentrations (N = 32) were observed between HC and T1. According to the detected main pattern, metabolite concentrations at T2 became more similar to those of HC. The course of single metabolite concentrations (e.g., glutamic acid) revealed different metabolic subtypes within the study sample. Patients with AN after short-term weight regain are in a greater “metabolic imbalance” than at starvation. After long-term weight regain, patients reach a metabolite profile similar to HC. Our results might be confounded by different metabolic subtypes of patients with AN.