Weight-restored Anorexia Nervosa Patients Research Articles

T-wave morphology among medically treated patients with Anorexia Nervosa

Anorexia nervosa (AN) has the highest rate of mortality of any psychiatric disorder, and cardiovascular complications occur in up to 80% of patients with AN and account for up to 30% of mortality. A controversy exists as to whether patients with AN are prone to develop electrocardiographic abnormalities related to repolarization.We aim to study previously unexplored T wave morphology markers in medically-treated patients with AN. Fifty-eight patients with AN (32 with restricting type and 26 with binge-eating/purging type) and 82 healthy controls were included in the study. ECGs were conducted under strict conditions and total cosine R-to-T (TCRT) and T-wave morphology dispersion (TMD) were computed according to accepted standards for a random beat and for an averaged beat. Forty-six AN patients were hospitalized (79.3%) during the study for a mean duration of 1.5 ± 1.1 months. AN patients had comparable QTc, TCRT, mean TMD, TMDpre, TMDpost and TCRTc values to those of healthy adults. Flattened T wave occurred slightly more often among AN patients than in controls (1.57 ± 1.23 leads affected compared with 1.11 ± 0.80 leads, respectively, p = 0.017). QTc, TCRT and TMD parameters' values were unaffected by the clinical type of AN.In conclusion, weight-restored AN patients are characterized by T wave flattening, but normal other T wave morphology parameters, which seemingly reflects an overall low risk of repolarization-associated ventricular arrhythmias. Long-term follow-up studies should be conducted to evaluate the prognostic significance of these novel repolarization markers in untreated patients or early in the refeeding phase.

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.

Increased lipid and lipoprotein concentrations in anorexia nervosa: A systematic review and meta-analysis.

Alterations in blood lipid concentrations in anorexia nervosa (AN) have been reported; however, the extent, mechanism, and normalization with weight restoration remain unknown. We conducted a systematic review and a meta-analysis to evaluate changes in lipid concentrations in acutely-ill AN patients compared with healthy controls (HC) and to examine the effect of partial weight restoration. A systematic literature review and meta-analysis (PROSPERO: CRD42017078014) were conducted for original peer-reviewed articles. Forty-eight studies were eligible for review; 33 for meta-analyses calculating mean differences (MD). Total cholesterol (MD = 22.7 mg/dL, 95% CI = 12.5, 33.0), high-density lipoprotein (HDL; MD = 3.4 mg/dL, CI = 0.3, 7.0), low-density lipoprotein (LDL; MD = 12.2 mg/dL, CI = 4.4, 20.1), triglycerides (TG; MD = 8.1 mg/dL, CI = 1.7, 14.5), and apolipoprotein B (Apo B; MD = 11.8 mg/dL, CI = 2.3, 21.2) were significantly higher in acutely-ill AN than HC. Partially weight-restored AN patients had higher total cholesterol (MD = 14.8 mg/dL, CI = 2.1, 27.5) and LDL (MD = 16.1 mg/dL, CI = 2.3, 30.0). Pre- versus post-weight restoration differences in lipid concentrations did not differ significantly. We report aggregate evidence for elevated lipid concentrations in acutely-ill AN patients compared with HC, some of which persist after partial weight restoration. This could signal an underlying adaptation or dysregulation not fully reversed by weight restoration. Although concentrations differed between AN and HC, most lipid concentrations remained within the reference range and meta-analyses were limited by the number of available studies.

Ghrelin response to hedonic eating in underweight and short-term weight restored patients with anorexia nervosa

IntroductionRecently, anorexia nervosa (AN) has been conceptualized as a reward-related disorder, and brain imaging studies have shown functional and structural abnormalities in areas of the brain involved in reward processes in both acute and recovered AN patients. However, the role of endogenous biochemical mediators, such as Ghrelin, in the modulation of reward processes has been poorly investigated in this eating disorder.ObjectivesHedonic eating, that is the consumption of food exclusively for pleasure and not to maintain energy homeostasis, is a useful paradigm to investigate the physiology of food-related reward.AimsWe assessed the Ghrelin response to food-related reward in symptomatic AN women in order to further explore the modulation of reward processes in this severe and debilitating disorder.MethodsPlasma levels of Ghrelin were measured in 7 underweight and 7 recently weight-restored satiated AN patients before and after the ingestion of a favorite (hedonic eating) and non-favorite (non-hedonic eating) food. Ghrelin responses were compared it that of previously studied healthy controls.ResultsWe found that in satiated underweight patients with AN plasma Ghrelin levels progressively decreased after the exposure and the consumption of both the favorite and non-favorite food whereas in satiated weight-restored AN patients and satiated healthy controls plasma Ghrelin concentrations significantly increased after the exposure to the favorite food and after eating it, but decreased after the non-favorite food.ConclusionsThese results suggest a derangement in the Ghrelin modulation of food-related pleasurable and rewarding feelings, which might sustain the reduced motivation toward food intake of acute AN patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Ghrelin response to hedonic eating in underweight and short-term weight restored patients with anorexia nervosa

Recently, anorexia nervosa (AN) has been conceptualized as a reward-related disorder, and alterations in brain reward processes have been documented in both acute and recovered AN patients. However, the role of endogenous biochemical mediators, such as ghrelin, in the modulation of reward processes has been poorly investigated in this eating disorder. Hedonic eating, that is the consumption of food exclusively for pleasure and not to maintain energy homeostasis, is a useful paradigm to investigate the physiology of food-related reward. Therefore, we assessed the response of peripheral ghrelin to hedonic eating in 7 underweight and 7 recently weight-restored AN patients and compared it to that of previously studied healthy controls. We found that in satiated underweight patients with AN plasma ghrelin levels progressively decreased after the exposure and the consumption of both the favorite and unfavorite food whereas in satiated weight-restored AN patients and satiated healthy controls plasma ghrelin concentrations significantly increased after the exposure to the favorite food and after eating it, but decreased after the unfavorite food. These results suggest a derangement in the ghrelin modulation of food-related pleasurable and rewarding feelings, which might sustain the reduced motivation toward food intake of acute AN patients.

Verbal Versus Figural Fluency Tests in Currently Ill and Weight Restored Anorexia Nervosa Patients.

Fluency tests allow domain-specific assessment of verbal and non-verbal executive functions (EF) comparison and also enable utilizing of both quantitative and qualitative scoring methods. Thirty-five currently ill anorexia nervosa patients (PANs), 33 weight-restored patients (WRAN) and 47 healthy controls (HCs) were administered the word fluency test and the five-point test. Results show that WRANs tended to perseverate more than HCs in the verbal-fluency test. In addition, PANs produced significantly less correct figures and perseverated more than HCs and WRANs; HCs used more strategy methods than PANs and WRANs. Additionally, a positive correlation was found in the HC group between the total number of words in the verbal phonemic test and the number of designs produced and the number of correct designs. No such correlations were found in both anorexia groups. In conclusion, there is a differentiation between verbal and non-verbal EF in PANs and WRANs, showing a deficiency in the non-verbal domain. These findings may contribute to our understanding of the cognitive nature of the disorder.

Deranged endocannabinoid responses to hedonic eating in underweight and recently weight-restored patients with anorexia nervosa

A dysregulation of reward mechanisms was suggested in the pathophysiology of anorexia nervosa (AN), but the role of the endogenous mediators of reward has been poorly investigated. Endocannabinoids, including anandamide and 2-arachidonoylglycerol, and the endocannabinoid-related compounds oleoylethanolamide and palmitoylethanolamide modulate food-related and unrelated reward. Hedonic eating, which is the consumption of food just for pleasure and not homeostatic need, is a suitable paradigm to explore food-related reward. We investigated responses of endocannabinoids and endocannabinoid-related compounds to hedonic eating in AN. Peripheral concentrations of anandamide, 2-arachidonoylglycerol, oleoylethanolamide, and palmitoylethanolamide were measured in 7 underweight and 7 weight-restored AN patients after eating favorite and nonfavorite foods in the condition of no homeostatic needs, and these measurements were compared with those of previously studied healthy control subjects. 1) In healthy controls, plasma 2-arachidonoylglycerol concentrations decreased after both types of meals but were significantly higher in hedonic eating; in underweight AN patients, 2-arachidonoylglycerol concentrations did not show specific time patterns after eating either favorite or nonfavorite foods, whereas in weight-restored patients, 2-arachidonoylglycerol concentrations showed similar increases with both types of meals. 2) Anandamide plasma concentrations exhibited no differences in their response patterns to hedonic eating in the groups. 3) Compared with 2-arachidonoylglycerol, palmitoylethanolamide concentrations exhibited an opposite response pattern to hedonic eating in healthy controls; this pattern was partially preserved in underweight AN patients but not in weight-restored ones. 4) Like palmitoylethanolamide, oleoylethanolamide plasma concentrations tended to be higher in nonhedonic eating than in hedonic eating in healthy controls; moreover, no difference between healthy subjects and AN patients was observed for food-intake-induced changes in oleoylethanolamide concentrations. These data confirm that endocannabinoids and endocannabinoid-related compounds are involved in food-related reward and suggest a dysregulation of their physiology in AN. This trial was registered at ISRCTN.org as ISRCTN64683774.

Employing executive functions of perceptual and memory abilities in underweight and weight-restored anorexia nervosa patients.

Executive functions (EF) have been widely investigated in anorexia nervosa (AN) revealing difficulties in various aspects. We aimed at testing the effects of EF on stimuli perception and its representations in memory. Thirty AN underweight patients, 30 weight-restored AN patients, and 44 control participants, were recruited. Various EF were assessed using the Rey-Osterrieth Complex Figure Test, analyzed with the Boston Qualitative Scoring System. No differences were found in visuo-constructional measures in either AN groups compared to controls on the copy and memory stages. However, both groups performed significantly worse than controls on most EF variables in the copy stage, while in the immediate and delayed memory stages the difference was less substantial. Difficulties in EF among AN patients, current and weight restored, are more pronounced in the perceptual module and less so when employed through memory retrieval. The pattern, which is apparent after weight gain, suggests that there is no ameliorative effect on these difficulties.

The sorting test of the D‐KEFS in current and weight restored anorexia nervosa patients

Efforts have been made to characterize executive functions (EF) in anorexia nervosa (AN) both in the acute stage of the illness and after weight gain, yet many questions remain. The question of verbal versus visuo-perceptual stimuli in this regard has not been adequately addressed. The aim of this study is to further examine EF in women with past and present AN and to compare their performances in verbal and visual modalities with women who have never suffered from an eating disorder. Thirty-five underweight AN patients, 33 weight-restored patients symptom-free for at least 2 years, and 48 healthy female controls completed the Delis-Kaplan Executive Function System Sorting Test, so as to evaluate their EF. No differences were observed between the scores of women with current and past AN. Both groups scored lower than controls on most test variables. However, while in the visuo-perceptual domain the performance of the AN groups was worse than that of controls, in the verbal domain they performed similarly to them. Women with a past or present diagnosis of AN show difficulties in visuo-perceptual EF, whereas verbal EF seem to be preserved. There may be a dissociation between verbal and visuo-perceptual EF that persists after weight restoration.

Grey matter abnormalities within cortico-limbic-striatal circuits in acute and weight-restored anorexia nervosa patients

Functional disturbances within cortico-striatal control systems have been implicated in the psychobiology (i.e. impaired cognitive-behavioral flexibility, perfectionist personality) of anorexia nervosa. The aim of the present study was to investigate the morphometry of brain regions within cortico-striatal networks in acute anorexia nervosa (AN) as well as long-term weight-restored anorexia nervosa (AN-WR) patients. A total of 39 participants: 12 AN, 13 AN-WR patients, and 14 healthy controls (HC) underwent high-resolution, T1-weighted magnetic resonance imaging (MRI), a cognitive-behavioral flexibility task, and a psychometric assessment. Group differences in local grey matter volume (GMV) were analyzed using whole brain voxel-based morphometry (VBM) and brain-atlas based automatic volumetry computation (IBASPM). Individual differences in total GMV were considered as a covariate in all analyses. In the regional brain morphometry, AN patients, as compared to HC, showed decreased GMVs (VBM and volumetry) in the anterior cingulate cortex (ACC), the supplementary motor area (SMA), and in subcortical regions (amygdala, putamen: VBM only). AN-WR compared to HC showed decreased GMV (VBM and volumetry) in the ACC and SMA, whereas GMV of the subcortical region showed no differences. The findings of the study suggest that structural abnormalities of the ACC and SMA were independent of the disease stage, whereas subcortical limbic-striatal changes were state dependent.

Agouti-related protein in patients with acute and weight-restored anorexia nervosa

An imbalance in appetite-regulating neuropeptides of the central nervous system has been associated with anorexia nervosa (AN), but the mechanisms of action are poorly understood. Agouti-related protein (AGRP), an orexigenic mediator of the hypothalamus, increases food intake and decreases energy expenditure in times of negative energy balance. The aim of the present study was to investigate AGRP in acute and fully weight-restored patients with AN, as well as during weight gain. Plasma AGRP and leptin levels were assessed using an enzyme-linked immunosorbent assay kit in a total of 175 female participants, including 75 patients with acute AN, 37 weight-restored AN patients and 63 healthy controls. Of the patients with acute AN, 33 were reassessed after partial weight gain. In weight-restored AN patients plasma AGRP levels were similar to those in healthy controls, whereas in patients with acute AN, AGRP was elevated. AGRP was inversely correlated with indicators of undernutrition such as body mass index and plasma leptin. In addition, AGRP levels normalized during weight gain of longitudinally assessed AN patients. Our results underline the significance of undernutrition and hypoleptinemia for the interpretation of peripheral AGRP concentrations. This provides support for the hypothesis that abnormal AGRP plasma levels in AN patients reflect undernutrition, rather than disease-specific traits.

Evidence-based pharmacotherapy of eating disorders

The objective was to review scientific evidence for efficacy and safety of pharmacotherapy in adults or children with an eating disorder (ED). We conducted a computer search for all randomized controlled trials (RCTs) published between 1960 and May 2010 for treatment of anorexia nervosa (AN), bulimia nervosa (BN) or binge-eating disorder (BED). For drugs for which no RCT was found, open trials or case reports were retrieved. Clinically relevant RCTs in the treatment of AN have used atypical antipsychotics, selective serotonin reuptake inhibitors (SSRIs), and zinc supplementation. Olanzapine demonstrated an adjunctive effect for in-patient treatment of underweight AN patients, and fluoxetine helped prevent relapse in weight-restored AN patients in 1/2 studies. For treatment of BN, controlled studies have used SSRIs, other antidepressants, and mood stabilizers. In 9/11 studies, pharmacotherapy yielded a statistically significant although moderate reduction in binge/purge frequency, and some additional benefits. For BED, RCTs have been conducted using SSRIs and one serotonin norepinephrine reuptake inhibitor (SNRI), mood stabilizers, and anti-obesity medications. In 11/12 studies, there was a statistically significant albeit limited effect of medication. Meta-analyses on efficacy of pharmacotherapy for BN and BED support moderate effect sizes for medication, but generally low recovery rates. Treatment resistance is an inherent feature of AN, where treatment should focus on renourishment plus psychotherapy. For BN and BED, combined treatment with pharmacotherapy and cognitive behaviour therapy has been more effective than either alone. Data on the long-term efficacy of pharmacotherapy for EDs are scarce. Short- and long-term pharmacotherapy of EDs still remains a challenge for the clinician.

Memory performance in acute and weight-restored anorexia nervosa patients

Anorexia nervosa (AN), at the stage of starvation and emaciation, is characterized by abnormalities in cognitive function, including memory performance. It is unclear whether memory impairment persists or is reversible following weight restoration, and whether memory function differs between AN subtypes. The aim of the present study was to investigate general memory performance in currently ill and fully weight-restored patients of different AN subtypes. Memory performance was assessed using the Wechsler Memory Scale-Revised (WMS-R) in a total of 99 participants, including 34 restricting-type AN patients (AN-RESTR), 19 binge-eating/purging-type AN patients (AN-PURGE), 16 weight-restored AN patients (AN-W-R) and 30 healthy controls (CONTROL). Cognitive evaluation included a battery of standardized neuropsychological tasks for validating the findings on memory function. Deficits were found with respect to immediate and delayed story recall in currently ill AN patients irrespective of AN subtype. These deficits persisted in weight-restored AN patients. Currently ill and weight-restored AN patients did not differ significantly from healthy controls with respect to working memory or other measures of neuropsychological functioning. The findings suggest that impaired memory performance is either a stable trait characteristic or a scar effect of chronic starvation that may play a role in the development and/or persistence of the disorder.

Set-shifting abilities, central coherence, and handedness in anorexia nervosa patients, their unaffected siblings and healthy controls: Exploring putative endophenotypes

Objective. There is consistent evidence that anorexia nervosa (AN) is associated with an impairment of set-shifting abilities and central coherence. No study to date investigated handedness in AN. Our aim was to study set-shifting abilities, central coherence, and handedness in subjects with lifetime AN, in a sample of unaffected sisters and in healthy controls, in order to explore their suitability as endophenotypes of AN. Methods. The Edinburgh Handedness Inventory and several neuropsychological tasks (Wisconsin Card Sorting Test, Trail Making Test, Rey-Osterrieth Complex Figure Test, Overlapping Figures Test, Object Assembly and Block Design) were administered to 153 subjects with lifetime AN, 28 unaffected sisters and 120 healthy controls. Results. AN subjects and their healthy sisters showed poorer performances on most tasks investigating set-shifting and central coherence. In addition, we did not find any differences between long-term recovered subjects, weight-restored AN patients and those in an acute phase of their illness. AN subjects were significantly more likely to be left-handed than healthy controls (OR=2.8, 95% C.I. 1.1–7.2). Conclusions. Set-shifting and central coherence seem to be promising cognitive endophenotypes that might help in the understanding of the pathogenetic processes involved in AN. Further studies on larger samples are needed to explore the generalizability and implications of our findings concerning handedness.

The slippery slope: prediction of successful weight maintenance in anorexia nervosa.

Previous research has found that many patients with anorexia nervosa (AN) are unable to maintain normal weight after weight restoration. The objective of this study was to identify variables that predicted successful weight maintenance among weight-restored AN patients. Ninety-three patients with AN treated at two sites (Toronto and New York) through in-patient or partial hospitalization achieved a minimally normal weight and were then randomly assigned to receive fluoxetine or placebo along with cognitive behavioral therapy (CBT) for 1 year. Clinical, demographic and psychometric variables were assessed after weight restoration prior to randomization and putative predictors of successful weight maintenance at 6 and 12 months were examined. The most powerful predictors of weight maintenance at 6 and 12 months following weight restoration were pre-randomization body mass index (BMI) and the rate of weight loss in the first 28 days following randomization. Higher BMI and lower rate of weight loss were associated with greater likelihood of maintaining a normal BMI at 6 and 12 months. An additional predictor of weight maintenance was site; patients in Toronto fared better than those in New York. This study found that the best predictors of weight maintenance in weight-restored AN patients over 6 and 12 months were the level of weight restoration at the conclusion of acute treatment and the avoidance of weight loss immediately following intensive treatment. These results suggest that outcome might be improved by achieving a higher BMI during structured treatment programs and on preventing weight loss immediately following discharge from such programs.

Bone density 11 years after anorexia nervosa onset in a controlled study of 39 cases.

To evaluate bone mineral density (BMD) and body composition 11 years after the onset of anorexia nervosa (AN). Thirty-nine AN subjects (36 females, 3 males), selected from a population-based sample, and 46 matched controls (COMP; 43 females, 3 males) were examined by using double-energy X-ray absorptiometry (DXA). Only 2 women still had AN. None of the men had AN. The females in the AN and COMP groups did not differ regarding BMD, nor was there a difference across female groups concerning body mass index (BMI). The female AN group had a significantly lower percentage of body fat. BMD among females in the AN group was related to lowest BMI ever. There was an inverse relationship between lumbar BMD and AN duration. Low BMD is not overrepresented among weight-restored AN patients at long-term follow-up compared with healthy women. However, the inverse relationship between BMD and AN duration may be indicative of a risk for osteopenia in patients with subchronic and chronic AN.