Short-term Weight Restoration Research Articles

Effect of serum concentrations of IL-6 and TNF-α on brain structure in anorexia nervosa: a combined cross-sectional and longitudinal study.

Previous studies of brain structure in anorexia nervosa (AN) have reported reduced gray matter in underweight patients, which largely normalizes upon weight gain. One underlying biological mechanism may be glial cell alterations related to low-grade inflammation. Here, we investigated relationships between brain structure as measured by magnetic resonance imaging and serum concentrations of two pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor alpha) cross-sectionally in 82 underweight adolescent and young adult female patients (mean age 16.8 years; 59 of whom were observed longitudinally after short-term weight restoration; mean duration 2.8 months), 20 individuals long-term weight-recovered from AN (mean age 22.7 years) and 105 healthy control (HC) participants (mean age 17.2 years). We measured cortical thickness, subcortical volumes and local gyrification index, a measure of cortical folding. In contrast to most previous studies of cytokine concentrations in AN, we found no cross-sectional group differences (interleukin-6: p = 0.193, tumor necrosis factor alpha: p = 0.057) or longitudinal changes following weight restoration (interleukin-6: p = 0.201, tumor necrosis factor alpha: p = 0.772). As expected, widespread gray matter reductions (cortical thickness, subcortical volumes, cortical folding) were observed in underweight patients with AN compared to HC. However, we found no evidence of associations between cytokine concentrations and structural brain measures in any participant group. Furthermore, longitudinal changes in cytokine concentrations were unrelated to changes in gray matter. In conclusion, we did not identify any association between (sub-)inflammatory processes and structural brain changes in AN. Future studies are needed to elucidate which other factors besides nutritional status may contribute to brain morphological alterations.

Dynamic Changes in Local Brain Connectivity and Activity: A Longitudinal Study in Adolescent Anorexia Nervosa

BackgroundResting-state functional connectivity analysis has been used to study disruptions in neural circuitries underlying eating disorder symptoms. Research has shown resting-state functional connectivity to be altered during the acute phase of anorexia nervosa (AN), but little is known about the biological mechanisms underlying neural changes associated with weight restoration. The goal of the current study was to investigate longitudinal changes in regional homogeneity (ReHo) among neighboring voxels, degree centrality (DC) (a voxelwise whole brain correlation coefficient), voxel-mirrored homotopic connectivity (VMHC) (measuring the synchronization between hemispheres), and the fractional amplitude of low-frequency fluctuations associated with weight gain during AN treatment. MethodsResting-state functional connectivity data were acquired and analyzed from a sample of 174 female volunteers: 87 underweight patients with AN that were scanned before treatment and again after at least 12% body mass index increase, as well as 87 age-matched healthy control participants. ResultsLongitudinal changes in ReHo, DC, VMHC, and the fractional amplitude of low-frequency fluctuations were observed in most regions identified to differ between patients with AN before treatment and healthy control participants. However, the degree of normalization varied for each parameter, ranging from 9% of all clusters in DC to 66% in VMHC. Longitudinal changes in ReHo and VMHC showed a linear association weight gain. ConclusionsResting-state functional magnetic resonance imaging measures, including ReHo, DC, VMHC, and the fractional amplitude of low-frequency fluctuations, show varying degrees of recovery after short-term weight restoration. Although only some of these changes were related to weight gain, our results provide an overall positive message, suggesting that weight restoration is associated with changes in functional brain measures that point toward normalization.

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.

Hair-Based Assessment of Sex Steroid Hormones in Patients with Anorexia Nervosa.

Anorexia nervosa (AN) is a complex psychiatric disorder accompanied by a variety of endocrine effects. Altered levels of the sex steroid hormones progesterone and dehydroepiandrosterone (DHEA) have been shown to occur in patients with AN using short-term hormonal measurement methods based on blood, saliva, and urine samples. However, since sex steroid hormone levels fluctuate during the menstrual cycle, these measurement methods require a great deal of effort due to the need to collect multiple samples in order to correctly determine the basal level of sex hormones. In contrast, hair-based assessments provide a marker of accumulated longer-term hormone exposure using a single, non-invasive sample. The aim of this study was to investigate sex steroid hormone levels via hair-based assessments in acutely underweight AN in comparison with healthy, age-matched, female control participants. Additionally, we compared progesterone and DHEA hair levels longitudinally during inpatient treatment in AN. Collected hair samples were analyzed using liquid chromatography-mass spectrometry (LC-MS/MS) to determine a monthly hormone level of progesterone and DHEA. Our results indicate that DHEA hair hormone levels were similar across groups but progesterone was suppressed in underweight AN compared with healthy controls. In the longitudinal design, no significant change in hair hormone levels during partial weight restoration in patients with AN was observed. Our findings suggest that hair analysis can be used to detect suppressed progesterone levels in severe AN, and that progesterone does not increase during short-term weight restoration.

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.

Associations between pituitary-thyroid hormones and depressive symptoms in individuals with anorexia nervosa before and after weight-recovery

BackgroundThere is sound evidence that the hypothalamic-pituitary-thyroid axis plays a role in mood regulation. Alterations in this axis, particularly low triiodothyronine syndrome, are a common neuroendocrine adaptation to semi-starvation in patients with anorexia nervosa (AN), who also frequently suffer from co-existing depressive symptoms. We therefore aimed to investigate the associations between pituitary-thyroid function and psychopathology, in particular depressive symptoms, at different stages of AN using a combined cross-sectional and longitudinal study design. MethodsPituitary-thyroid status (FT3, free triiodothyronine; FT4, free thyroxine; conversion ratio FT3/FT4; TSH, thyroid-stimulating hormone) was assessed in 77 young acutely underweight females with AN (acAN) and in 55 long-term weight-recovered individuals with former AN (recAN) in a cross-sectional comparison to 122 healthy controls (HC). Further, pituitary-thyroid status of 48 acAN was reassessed after short-term weight-restoration. We performed correlation analyses of pituitary-thyroid parameters with self-reported measures of psychopathology. ResultsAcAN showed significantly lower FT3, FT4, FT3/FT4 ratio, and TSH levels compared to HC. Pituitary-thyroid alterations were partly reversed after short-term weight-restoration. RecAN still had lower FT3 concentrations than HC. Lower FT3 concentrations and FT3/FT4 ratios were associated with more severe depressive symptoms in acAN, occurring prominently in cases of manifest low triiodothyronine syndrome. Longitudinally increasing FT3/FT4 ratios (change scores) were inversely correlated with depressive and general psychiatric symptoms after short-term weight-restoration. ConclusionsOur results suggest a potential modulation of the severity of depressive symptoms by temporarily decreased FT3 concentrations and inhibited thyroid hormone conversion (FT3/FT4 ratios) in acutely underweight AN. Associations between conversion ratios FT3/FT4 and psychopathology seem to persist across short-term weight-restoration. The findings of our study might have relevant clinical implications, ranging from thyroid monitoring to experimental low-dose thyroid hormone supplementation in certain patients with AN showing severe psychiatric impairment and overt thyroid hormone alterations.

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.

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.

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.

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.

White matter microstructural differences in underweight adolescents with anorexia nervosa and a preliminary longitudinal investigation of change following short-term weight restoration

Anorexia nervosa (AN) affects approximately 2.9% of females and has the highest mortality rate among all psychiatric disorders. Despite several advances, the neurobiology of this disorder is still not well understood. Several studies have reported abnormalities in the white matter, but it is not know if these are disease-related or secondary to undernutrition. This study aimed to further our understanding of white matter pathology using diffusion-weighted imaging in underweight adolescents with AN, and to examine changes occurring after short-term weight restoration. Analyses were conducted on diffusion-weighted imaging from 24 female adolescents with AN and 17 age- and gender-matched healthy controls (HC), aged 14-19years. Groups were compared on fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) using tract-based spatial statistics analysis and DTI measures were correlated with eating disorder examination questionnaire (EDE-Q) subscales and body mass index (BMI). Preliminary repeated-measure analyses were also conducted on eight participants after short-term weight restoration (median 41days). Widespread increases in MD of up to 9% were found in underweight AN relative to HC, particularly in the corpus callosum. This was associated with both increased AD and RD, suggestive of dys- or de-myelination. There were no significant group differences in FA, and no significant correlations between DTI measures, BMI or EDE-Q subscale score. Weight restoration therapy significantly reduced MD, to levels significantly lower than HC, but did not consistently alter FA across individuals. White matter microstructure is significantly altered in female adolescents with AN, with preliminary longitudinal data suggesting that it may be reversible with short-term weight restoration. Level III: evidence obtained from well-designed cohort or case-control analytic studies.

Multi-omics data integration in anorexia nervosa patients before and after weight regain: A microbiome-metabolomics investigation

We have recently reported specific fecal metabolomic changes in acute and short-term weight restored patients with anorexia nervosa (AN). In this study we explored the association between those metabolomic changes and patients' gut microbiome composition. The gut microbiome of AN women was sequenced in both the underweight phase (n=21) and after short-term weight restoration (n=16) and compared to that of 20 healthy women. According to a multi-omics approach, microbiome data were correlated with 49 relevant fecal metabolites previously characterized in our participants by an untargeted metabolomic procedure. Compared to healthy women, AN patients 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 phylum, class, order, family and genus levels. These changes were observed in both the underweight and weight-restored condition. Moreover, the relationships among the 49 previously selected fecal metabolites and bacteria genera showed structures of different complexity among the 3 groups. In particular, a quarter of those relationships showed a divergent direction in the acutely ill patients with respect to the weight-restored ones or normal controls. Finally, in acutely ill patients 70% of those correlations showed a negative sign suggesting a prevalent metabolites consummation by gut microbiome. These data confirm a profound perturbation in the gut microbiome composition of AN patients. Moreover, for the first time, they provide the evidence that in AN gut bacteria are connected with several fecal metabolites in a different way from normal controls and with divergent directions in the acute phase with respect to the weight-restored phase.

Body Composition in Adolescents and Young Adults with Anorexia Nervosa: A Clinical Review.

Anorexia nervosa is a serious health condition characterized by a significant low body weight and alteration in body composition components. In the current paper, we aim to summarize the available literature concerning changes in body fat, lean, and bone masses, during anorexia nervosa and after complete weight restoration. Data were summarized using a narrative approach based on clinical expertise in the interpretation of the available evidence base in the literature. The available data revealed three main findings. Firstly, anorexia nervosa causes a significant reduction in body fat mass, however it is completely restored after short-term weight normalization but with a central adiposity phenotype that does not seem to negatively influence treatment outcomes and appears to normalize after 1 year of normal weight maintenance. Secondly, anorexia nervosa causes a significant reduction in bone mineral density, but weight restoration is associated first (≈12 months) with stabilization of bone mineral density, followed by improvements (after ≈16 months); and finally, with complete normalization (after ≈30 months) after normal-weight maintenance. Thirdly, during anorexia nervosa loss of lean and skeletal body mass occurring in particular from the extremities rather than the central regions has been consistently reported, especially in patients with a Body Mass Index (BMI) ≤ 16.5 Kg/m2 however short-term weight restoration is associated with complete normalization. Anorexia nervosa adversely affects body composition, however this medical complication seems to be reversible through the main treatment strategy of body weight restoration followed by normal weight maintenance, and this should be openly discussed with patients.

Metabolomics signatures of acutely ill and short-term weight recovered women with anorexia nervosa.

Although metabolomics studies are recently spreading and have allowed the characterization of putative biomarkers in many diseases, they are relatively scanty in anorexia nervosa (AN). In this explorative study we analyzed the fecal metabolomics profiles of women with AN in the underweight phase (n = 24) and after short-term weight restoration (n = 16) and compared them with 20 healthy women. An untargeted metabolomic procedure allowed the characterization of 224 metabolites involved in energy, lipid, and amino acid metabolism. A partial least square discriminant analysis identified 14 metabolites with a variable importance in projection score >1.5 that clearly differentiated underweight from weight-restored patients from healthy women. Compared with healthy women, fecal concentrations of valeric acid and 3-methyl,2-ketobutyric acid were increased in both underweight and weight-restored patients; fecal concentrations of propionic acid, stearic acid, linolenic acid, methyl-galactoside, coprosterol, cycloserine, and lauric acid were increased while fecal levels of xylose, fucose, and rhamnose were decreased in underweight patients and normalized after weight-restoration; fecal concentrations of piperine, phenylalanine, butyric acid, and meso-erythritol-1 were decreased while fecal levels of hydroxystearic acid were increased in weight-restored but normal in underweight AN patients. All these changes point to peculiar fecal metabolomics profiles of acute and short-term weight restored AN patients. The value of these changes to improve our understanding of the pathophysiology of AN and to characterize potential biomarker targets for developing new treatment strategies needs further studies to be clarified.

Rumination in anorexia nervosa: Cognitive-affective and neuroendocrinological aspects

Rumination about body weight/figure as well as food is common in patients with Anorexia Nervosa (AN) and may be a maintenance factor of the disorder. While rumination can generally be considered as a cognitive-affective process, food-related rumination may be driven primarily by a physiological response to undernutrition. In the current longitudinal study, we integrate ecological momentary assessment of rumination and affect and, as a biological marker of undernutrition, plasma leptin levels collected from 33 AN patients. At the very acute stage and again after short-term weight-restoration patients answered short questionnaires six times per day over two weeks. Analyses via hierarchical linear modelling confirmed that rumination is closely linked to affect in AN before and after weight-restoration. Rumination about food decreased during weight-restoration and was correlated with leptin levels. In contrast, rumination about body weight/figure was not linked to leptin, persisted after weight gain, and showed stronger connections with affect. This suggests that rumination about body weight/figure seems to be a cognitive-affective aspect of the disorder, but food-related rumination may need to be considered from a physiological perspective. It is possible that food-related ruminative thoughts reflect a physiological symptom induced by undernutrition, similar to well-described leptin-associated changes in physical activity.

Dynamic changes in white matter microstructure in anorexia nervosa: findings from a longitudinal study.

Gray matter (GM) 'pseudoatrophy' is well-documented in patients with anorexia nervosa (AN), but changes in white matter (WM) are less well understood. Here we investigated the dynamics of microstructural WM brain changes in AN patients during short-term weight restoration in a combined longitudinal and cross-sectional study design. Diffusion-weighted images were acquired in young AN patients before (acAN-Tp1, n = 56) and after (acAN-Tp2, n = 44) short-term weight restoration as well as in age-matched healthy controls (HC, n = 60). Images were processed using Tract-Based-Spatial-Statistics to compare fractional anisotropy (FA) across groups and timepoints. In the cross-sectional comparison, FA was significantly reduced in the callosal body in acAN-Tp1 compared with HC, while no differences were found between acAN-Tp2 and HC. In the longitudinal arm, FA increased with weight gain in acAN-Tp2 relative to acAN-Tp1 in large parts of the callosal body and the fornix, while it decreased in the right corticospinal tract. Our findings reveal that dynamic, bidirectional changes in WM microstructure in young underweight patients with AN can be reversed with brief weight restoration therapy. These results parallel those previously observed in GM and suggest that alterations in WM in non-chronic AN are also state-dependent and rapidly reversible with successful intervention.

Is hypercortisolism in anorexia nervosa detectable using hair samples?

Anorexia nervosa (AN) is a severe mental disorder accompanied by extensive metabolic and endocrine abnormalities. It has been associated with hypercortisolism using short-term measurement methods such as 24 h-urine, saliva, and blood. The aim of this study was to examine whether the proposed hypercortisolism in acutely underweight AN (acAN) is also reflected in a long-term measure: hair cortisol (HCC). To gain further insight, we compared hair cortisol to a well-established classical cortisol measure (24 h-urine; UCC) longitudinally in acAN.Hair samples were collected and analyzed using a LC-MS/MS-based method to provide a monthly cortisol value. We compared HCC in samples of 40 acAN with 40 pairwise age-matched healthy controls (HC) as well as 23 long-term recovered AN participants (recAN) with 23 pairwise age-matched HC (cross-sectional design). In the second part, UCC collected weekly during 14 weeks of weight-restoration therapy in 16 acAN was compared with the (time-corresponding) HCC using linear mixed models and bivariate correlations (longitudinal design).No group differences in HCC occurred comparing acAN and recAN to HC (cross-sectional study). The longitudinal analysis revealed a decrease of UCC but not HCC with weight gain. Furthermore, there was no overall significant association between UCC and HCC. Only in the last four weeks of weight-restoration therapy we found a significant moderate correlation between UCC and HCC.HCC did not reflect the expected hypercortisolism in acAN and did not decrease during short-term weight-restoration. Time-corresponding measurements of UCC and HCC were not consistently associated in our longitudinal analysis of acAN undergoing inpatient treatment. Given the drastic metabolic disturbances in acutely underweight AN our findings could be interpreted as disturbed cortisol incorporation or altered activity of 11-β-HSD-enzymes in the hair follicle.

Body composition in men with anorexia nervosa: Longitudinal study.

To compare body composition patterns before and after complete weight restoration in men with anorexia nervosa. Dual-energy X-ray absorptiometry (DXA) was used to measure body composition patterns in 10 men with anorexia nervosa before and after complete weight restoration, and in 10 healthy men matched to age and patients' post-treatment body mass index (BMI). Before weight restoration, men with anorexia nervosa displayed lower total body fat mass (FM) and lean mass (LBM) than those in the healthy comparison group, with a greater FM loss from the extremity than the trunk region. After short-term weight restoration, patients displayed complete normalization in total LBM and FM, but greater deposition of FM in the trunk region. Short-term weight restoration can normalize body composition patterns in men with anorexia nervosa, but results in a central adiposity phenotype. The clinical implication of this finding is unknown, but should be explored given the high levels of concern about central adiposity in anorexia nervosa.

Changes in lean and skeletal muscle body mass in adult females with anorexia nervosa before and after weight restoration

Data on the deficits in lean body mass (LBM) and total body skeletal muscle mass (SM) in anorexia nervosa (AN) is scarce and inconsistent. Furthermore, the usefulness of the reported body mass index (BMI) severity cut-off for AN has not been tested with respect to these important parameters. The study had two aims, namely to study LBM patterns and SM in adult females with AN before and after weight restoration, and to examine the clinical usefulness of the 16.5kg/m2 BMI cut-off for assessing the protein status in terms of LBM and SM in AN patients. Body composition was measured by dual-energy X-ray absorptiometry (DXA) before and after weight gain in 90 adult female inpatients with AN, and 90 controls matched by post-treatment BMI and age. Patients were stratified into two groups using BMI 16.5kg/m2 as a cut-off. Before weight restoration, patients in the BMI≤16.5kg/m2 subgroup (n=65) had lower LBM, SM and lean extremity mass percentage, but higher %LBM and lean trunk-to-extremity ratio on average than controls. However, those with BMI >16.5kg/m2 (n=25) displayed lower lean extremity mass percentage and higher %LBM, but no significant differences in LBM and SM with respect to controls. Moreover the time×subgroup interaction was significant in terms of LBM and SM, meaning that, changes occur in different manner over time in the two AN subgroups. However no differences were found between the two AN subgroups in either demographic or other eating disorder characteristics. After weight gain, normalization of LBM, %LBM, lean extremity mass percentage and SM was achieved across the entire AN sample, and the BMI≤16.5kg/m2 subgroup. The fat mass was the major determinant of gain in LBM; the higher the FM at baseline, the greater the increase in LBM. Our results suggest a BMI cut-off ≤16.5kg/m2 as a clinical threshold for determining AN severity. As short-term weight restoration is associated with a normalization in LBM and SM, it appears that biological regulation of weight gain remains intact in AN, i.e., unaffected by the severity of malnutrition. Changes in lean and skeletal muscle body mass in adult females with anorexia nervosa before and after weight restoration (ISRCTN168721194).