Acute Anorexia Nervosa Research Articles

Anorexia Nervosa: A Single Region of Interest for Self-Referent Processing of Pictures of Body Images?

Back to table of contents Previous article Next article Letter to the EditorFull AccessAnorexia Nervosa: A Single Region of Interest for Self-Referent Processing of Pictures of Body Images?Charlotte Keating, B.B.N.Sc., (P.G.Dip.Psych.)Charlotte KeatingSearch for more papers by this author, B.B.N.Sc., (P.G.Dip.Psych.)Published Online:1 May 2010https://doi.org/10.1176/appi.ajp.2010.09121712AboutSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail To the Editor: I read with interest the study by Anne-Katharina Fladung, Ph.D., et al. (1), published in the February 2010 issue of the Journal, and wish to seek further interpretation of some of the outcomes.Patients with acute anorexia nervosa had an increase in ventral striatal activation in response to underweight female body images (versus normal weight) and showed preference for underweight images, whereas in healthy comparison subjects, ventral striatal activation was shown in response to normal weight female body images where these participants preferred normal relative to underweight images. Within groups, the difference (magnitude) between stimuli sets was significantly smaller in healthy women, interpreted as a "qualitative difference." To elaborate on this finding, perhaps women with anorexia nervosa are selectively biased toward processing normal weight images aversively and underweight images as rewarding, whereas healthy women may perceive underweight images aversively but normal weight images as at least preferable (within context). How can a similar pattern of striatal activation occur in both groups? Perhaps knowing participants' experience of aversion toward normal versus underweight body images might inform the interpretation regarding the difference in magnitude.When asked to judge the weight of the female body image, there were no between-group differences suggesting that perception of weight was independent of body mass index (or other anorexia nervosa factors). Examining which brain regions enable women with anorexia nervosa to appropriately perceive the weight of a female body image relative to which regions are involved when they are asked to imagine themselves to have the same body type depicted in the image (e.g., self-referent questioning in the feel task) might reveal important regions involved in dysmorphic self-assessments.A strength of the overall task is that it inherently taps disorder-specific constructs. Statistical analyses were "constrained to the bilateral ventral striatum," which was the region of interest. It may seem logically inconsistent that complex cognitive processing of visual stimuli in conjunction with highly thought-provoking self-referent questions would occur (or be postulated) within this single region of interest.Data (voxel clusters) were not available outside the region of interest. However, an absence of activity in cognitive cortices (at reduced significance thresholds) may warrant speculation. Is this abnormal? Does ventral striatal activation overcompensate for more executive regions? Absent activity is compared with a study (2) conversely showing frontal and parietal activation upon processing of wins and losses in a gambling task. Dr. Fladung et al. (1) highlighted that task differences in uncertainty and reward-linked value may account for disparate results between studies, but perhaps overlooked patients were already recovered (2).Relative to the previous study (2), Dr. Fladung et al. stated that the absence of differential ventral striatal activation toward disease nonrelated rewards but the presence of differential activation toward disease-related stimuli (in the current study) is consistent with theories of starvation dependence in patients. Given that the current study investigated patients experiencing acute anorexia nervosa whereas the previous study investigated recovered individuals (2)—without knowing whether brain activation in response to starvation-dependent-linked stimuli dissipates or persists—the conclusion remains speculative.Melbourne, AustraliaThe author reports no financial relationships with commercial interests.References1 Fladung A-K , Grön G , Grammer K , Herrnberger B , Schilly E , Grasteit S , Wolf RC , Walter H , von Wietersheim J : A neural signature of anorexia nervosa in the ventral striatal reward system. Am J Psychiatry 2009; 167:206–212 Google Scholar2 Wagner A , Aizenstein H , Venkatraman VK , Fudge J , May JC , Mazurkewicz L , Frank GK , Bailer UF , Fischer L , Nguyen V , Varter C , Putnam K , Kaye WH : Altered reward processing in women recovered from anorexia nervosa. Am J Psychiatry 2007; 164:1842–1849 Link, Google Scholar FiguresReferencesCited byDetailsCited ByAttachment Insecurity Predicts Punishment Sensitivity in Anorexia NervosaJournal of Nervous & Mental Disease, Vol. 204, No. 10, Vol. 8 Volume 167Issue 5 May 2010Pages 601-602 Metrics PDF download History Accepted 1 March 2010 Published online 1 May 2010 Published in print 1 May 2010

Psychopathology in underweight and weight-recovered females with anorexia nervosa

To compare general and eating disorder-specific psychopathology in patients with acute anorexia nervosa (acAN), weight-recovered patients (recAN) and healthy control women (HCW). One hundred anorexia nervosa patients (66 acAN and 34 recAN) and 88 HCW were included in our study. Psychopathology was assessed by self-report questionnaires [Symptom Check List 90 Revised (SCL-90-R), Eating Disorder Inventory-2 (EDI- 2)] as well as by interview [Structured Interview of Anorexia Nervosa and Bulimic Syndromes (SIAB-EX)] and compared using multivariate analysis of variance. Plasma leptin levels were determined using enzyme linked immunosorbent assay. Mean comparisons indicated highly significant differences between acAN and recAN subjects on all psychopatholgy variables, except for perfectionism. RecAN subjects did not differ from HCW. Partial weight recovery was associated with decreasing levels of psychopathology. Correlational analyses suggested strong negative associations between leptin levels and psychopathology. Prolonged malnutrition, as indicated by suppressed plasma leptin levels, is strongly related to eating disorder-specific as well as general psychopathological symptoms. Weight recovery is associated with the absence of psychopathology. These data emphasize the interaction between somatic and psychological variables.

A Neural Signature of Anorexia Nervosa in the Ventral Striatal Reward System

Animal studies assessing mechanisms of self-starvation under conditions of stress and diet suggest a pivotal role for the mesolimbic reward system in the maintenance of core symptoms in anorexia nervosa, which is corroborated by initial empirical evidence in human studies. The authors examined activity in the ventral striatal system in response to disease-specific stimuli in women with acute anorexia nervosa. Participants were 14 women with acute anorexia nervosa and 14 matched healthy comparison women who underwent functional magnetic resonance imaging (fMRI) during evaluation of visual stimuli depicting a female body with underweight, normal weight, and overweight canonical whole-body features according to standardized body mass indices. Participants were required to process each stimulus in a self-referring way. Ratings for each weight category were used as the control task. Behaviorally, women with anorexia nervosa provided significantly higher positive ratings in response to underweight stimuli than in response to normal-weight stimuli, while healthy comparison women showed greater preference for normal-weight stimuli relative to underweight stimuli. Functionally, ventral striatal activity demonstrated a highly significant group-by-stimulus interaction for underweight and normal-weight stimuli. In women with anorexia nervosa, activation was higher during processing of underweight stimuli compared with normal-weight stimuli. The reverse pattern was observed in healthy comparison women. These findings are consistent with predictions in animal studies of the pivotal role of the human reward system in anorexia nervosa and thus support theories of starvation dependence in maintenance of the disorder.

The role of leptin and cortisol in hyperactivity in patients with acute and weight-recovered anorexia nervosa

Introduction In food-restricted rats, leptin as well as corticotropin releasing factor attenuate semistarvation-induced hyperactivity (SIH). Results from studies in patients with anorexia nervosa (AN) showed an association between excessive physical activity (PA) and leptin. One recent report suggests a role for cortisol in PA. In this study, we assessed the relationships between PA and both, cortisol and leptin levels at the same time in patients with acute anorexia nervosa (acAN) in comparison to recovered patients (recAN). Methods Plasma leptin, plasma cortisol, body mass index (BMI), and expert-ratings of qualities of PA were assessed in 36 acAN patients, 27 recAN patients and 44 healthy control woman (HCW). Regression analyses were used to predict PA using BMI, leptin and cortisol levels as predictor variables. Results Leptin levels but not cortisol significantly contributed to the prediction of PA in acAN. In recAN PA was not elevated and not related to endocrine parameters but correlated positively with core eating disorder symptoms. Conclusions Our work lends support to the proposed inverse association between peripheral leptin levels and excessive physical activity in AN. This relationship is specific to the state of semistarvation. The role of additional mediators remains to be clarified.

Leptin and its associations with measures of psychopathology in patients with anorexia nervosa

Apart from energy homeostasis leptin has been shown to be involved in a number of neuronal networks. The aim of this study was to investigate how the residual variance of leptin levels, after controlling for BMI, is linked to eating-disorder-specific psychopathology and sexual desire in patients with anorexia nervosa (AN) compared to healthy controls. The sample included 57 subjects with acute AN and 77 healthy controls. Psychopathology was determined by EDI-2 and SCL-90-R and sexual problems were rated according to the Structured Interview of Anorexia Nervosa and Bulimic Syndromes (SIAB-EX). Plasma leptin was assessed by ELISA. Patients with a high drive for thinness had lower leptin levels at a given BMI and low leptin levels were associated with sexual problems, i.e. the absence of sexual desire and intimate relationships. Our results are in accordance with recent animal experiments linking low leptin levels with decreased sexual interest irrespective of body weight.

S100B in underweight and weight-recovered patients with anorexia nervosa

Anorexia nervosa (AN) commonly arises during adolescence, leading to interruptions of somatic and psychological development as well as to cortical atrophy and reductions of brain volume. While most brain changes shift towards normal with weight restoration, it is not certain whether they are related to the loss of brain cells, neuropil or merely due to fluid shifts. We measured S100B serum concentrations and psychometric characteristics in 34 patients with acute AN, 19 weight-recovered patients and 35 healthy control women (HCW). Plasma tryptophan and leptin levels were determined as markers for malnutrition and neuroendocrine adaptation to semi-starvation. Peripheral S100B concentrations of acute and former AN patients were not elevated and not statistically different from HCW. BMI, peripheral leptin levels and measures of psychopathology as well as executive cognitive functioning did not correlate with S100B. Plasma tryptophan was positively related to S100B. Our results are in line with our previous findings showing unaltered GFAP and NSE plasma levels in patients with acute AN. Together they do not support hypotheses comprising the degeneration of glial or neuronal cells to explain common signs of brain atrophy in patients with acute AN.

Glial and neuronal damage markers in patients with anorexia nervosa

Anorexia nervosa (AN) commonly arises during adolescence leading to interruptions of somatic and psychological development as well as to atrophic brain changes. It remains unclear whether these brain changes are related to the loss of neurons, glia, neuropil or merely due to fluid shifts. We determined leptin levels and two brain-derived damage markers: glial fibrillary acidic protein (GFAP) and neuron-specific enolase (NSE) of 43 acute AN patients and 50 healthy control woman (HCW). Peripheral GFAP and NSE concentrations of AN patients were not elevated and not different from HCW. Subjects with particularly low leptin concentration, indicating severe malnutrition, did not show abnormal values either. During weight recovery the marker proteins remained unchanged. Our preliminary results are in line with neuroimaging studies supporting the reversibility of brain changes in AN and do not substantiate hypotheses relying on the extensive damage of brain cells as an explanation for cerebral atrophy in AN.

Recovery from Anorexia Nervosa is Associated with Increased Fat Metabolism

Previous studies have reported that persons with acute Anorexia Nervosa (AN) have a higher respiratory quotient (RQ) and lower resting energy expenditure (REE), and those in recovery from AN ≤ 1 year have a higher percent truncal fat mass (%TFM), compared to control (C) persons. However, these metabolic and body composition factors have not been studied together in adults recovered from AN ≥ 2 years (R). Therefore, we measured RQ and REE (using indirect calorimetry) and body composition (using dual energy x‐ray absorptiometry) in adults R ≥ 2 years from AN to determine if previously reported differences exist in longer‐term recovery. RQ was lower in the R (n=17) compared to C (n=20) group (0.84 ± 0.05 v. 0.90 ± 0.05, respectively, p ≤ 0.005), even when adjusted for percent total fat mass (%FM) and antecedent food quotient. REE, adjusted for body composition, did not differ between the R and C group (1270 ± 166 kcal/day v. 1324 ± 128 kcal/day, respectively, p=0.4). Age, BMI and FM were comparable for both groups and, despite differences in fat oxidation, no difference in %FM (30 ± 7 v. 31 ± 7, p=0.5) or %TFM controlling for total FM (27 ± 9.8 v. 30 ± 8.8 respectively, p=0.8) existed.In conclusion, adults in recovery from AN ≥ 2 years appear to oxidize more fat than C adults, but this does not have an effect on overall metabolism or body composition.

The role of leptin in anorexia nervosa: clinical implications

Leptin is a hormone with pleiotropic functions affecting several tissues. Because leptin has a crucial role in the adaptation of an organism to semi-starvation, anorexia nervosa (AN) serves as a model disorder to elucidate the functional implications of hypoleptinaemia; vice versa, several symptoms in patients with this eating disorder are related to the low leptin levels, which are characteristic of acute AN. Weight gain in AN patients can induce relative hyperleptinaemia in comparison to controls matched for body mass index; circulating leptin concentrations in AN patients thus transverse from subnormal to supranormal levels within a few weeks. We review findings on leptin secretion in AN and focus on implications, particularly for the hypothalamus-pituitary-gonadal axis, bone mineral density and physical hyperactivity. Undoubtedly, the elucidation of leptin's function as a trigger of diverse neuroendocrine adaptations to a restricted energy intake has substantially advanced our knowledge of the pathogenesis of distinct symptoms of AN, including amenorrhoea that represents one of the four diagnostic criteria. The fact that hypoleptinaemia can induce hyperactivity in a rat model for AN has led to a series of studies in AN patients, which support the notion that application of leptin to severely hyperactive patients might prove beneficial.

Antidepressants for anorexia nervosa

Anorexia Nervosa (AN) is an illness characterised by extreme concern about body weight and shape, severe self-imposed weight loss, and endocrine dysfunction. In spite of its high mortality, morbidity and chronicity, there are few intervention studies on the subject. The aim of this review was to evaluate the efficacy and acceptability of antidepressant drugs in the treatment of acute AN. The strategy comprised of database searches of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, MEDLINE (1966 to April 28th, 2005), EMBASE (1980 to week 36, 2004), PsycINFO (1969 to August week 5, 2004), handsearching the International Journal of Eating Disorders and searching the reference lists of all papers selected. Personal letters were sent to researchers in the field requesting information on unpublished or in-progress trials. All randomised controlled trials of antidepressant treatment for AN patients, as defined by the Diagnostic and Statistical Manual, fourth edition (DSM-IV) or similar international criteria, were selected. Quality ratings were made giving consideration to the strong relationship between allocation concealment and potential for bias in the results; studies meeting criteria A and B were included. Trials were excluded if non-completion rates were above 50%. The standardised mean difference and relative risk were used for continuous data and dichotomous data comparisons, respectively. Whenever possible, analyses were performed according to intention-to-treat principles. Heterogeneity was tested with the I-squared statistic. Weight change was the primary outcome. Secondary outcomes were severity of eating disorder, depression and anxiety symptoms, and global clinical state. Acceptability of treatment was evaluated by considering non-completion rates. Only seven studies were included. Major methodological limitations such as small trial size and large confidence intervals decreased the power of the studies to detect differences between treatments, and meta-analysis of data was not possible for the majority of outcomes. Four placebo-controlled trials did not find evidence that antidepressants improved weight gain, eating disorder or associated psychopathology. Isolated findings, favouring amineptine and nortriptyline, emerged from the antidepressant versus antidepressant comparisons, but cannot be conceived as evidence of efficacy of a specific drug or class of antidepressant in light of the findings from the placebo comparisons. Non-completion rates were similar between the compared groups. A lack of quality information precludes us from drawing definite conclusions or recommendations on the use of antidepressants in acute AN. Future studies testing safer and more tolerable antidepressants in larger, well designed trials are needed to provide guidance for clinical practice.

Physical Activity and Restlessness Correlate with Leptin Levels in Patients with Adolescent Anorexia Nervosa

In food-restricted rats, leptin suppresses semistarvation-induced hyperactivity (SIH) and decreases exploratory behavior. Leptin ameliorates anxiety-related movement in ob/ob mice. In this study, we assessed the relationship between leptin and qualities of physical activity and restlessness in acute anorexia nervosa (AN). Serum leptin, body mass index (BMI), % body fat, and self- and expert-ratings of qualities of physical activity and restlessness were assessed in 26 inpatients with acute AN. Accelerometry was also performed. Regression analyses were used to predict activity and restlessness using BMI, % body fat, and leptin levels as predictor variables. Leptin levels significantly contributed to the prediction of all measures of activity and restlessness. This is the first study linking hypoleptinemia in AN patients to subjective and objective measures of higher physical activity and motor and inner restlessness. Leptin may directly or indirectly (or both) influence behaviors and cognitions contributing to hyperactivity and motor restlessness.

Linear and non‐linear heart rate variability measures in chronic and acute phase of anorexia nervosa

Previous results on heart rate variability (HRV) analysis in anorexia nervosa (AN) include some apparently conflicting data. In order to find out the reason for different results and to improve understanding of autonomic control in AN we compare HRV in acute and chronic AN. Spectral powers, fractal scaling exponent and sample entropy were computed from 24 h RR series derived from Holter ECG recordings in 17 anorexic patients, nine chronic and eight healthy women. We found that all linear and non-linear HRV measures change in different direction in acute and chronic AN. Acute AN is characterized by decreased HR and increased HRV. In chronic AN, HR is increased, HRV reduced and the difference between awake and sleeping values is high. HRV measures are associated with body mass index only in chronic AN. As HRV measures are significantly different between acute and chronic AN, we propose that HRV analysis might provide additional data in clinical practice.

Is Impaired Set-Shifting an Endophenotype of Anorexia Nervosa?

Set-shifting difficulties have been reported in subjects with anorexia nervosa and appear to persist after recovery; therefore, they may be endophenotypic traits. The goals of this study were to investigate whether set-shifting difficulties are familial by examining discordant sister-pairs in comparison with healthy unrelated women and to replicate, with a broader battery, the lack of influence of an acute illness state on neuropsychological performance. Forty-seven pairs of sisters discordant for anorexia nervosa and 47 healthy unrelated women who were comparable in age and IQ completed neuropsychological tasks selected to assess set-shifting ability. Analyses of variance with standard errors that are robust against correlations within family clusters were used to compare the groups. Results were adjusted for obsessive-compulsive, anxiety, and depression symptoms. Subjects with acute (N=24) and fully remitted (N=23) anorexia nervosa were compared to assess state versus trait effects. Sisters with and without anorexia nervosa took significantly longer than unrelated healthy women to shift their cognitive set (CatBat task) and demonstrated greater perceptual rigidity (Haptic Illusion task) but did not differ significantly from each other. Women with anorexia nervosa were slower than other groups on Trail Making tasks. Women who had fully recovered from anorexia nervosa made significantly fewer errors than those with acute anorexia nervosa on the Trail Making alphabet task, but these subgroups did not differ on other measures. Both affected and unaffected sisters had more set-shifting difficulties than unrelated healthy women. This finding, together with the replicated finding that set-shifting difficulties persist after recovery, suggests that set-shifting difficulties are trait characteristics and may inform the search for the endophenotype in anorexia nervosa.

Improved Eating-Disorder Treatments on Horizon

Improved Eating-Disorder Treatments on Horizon

Cognitive remediation therapy as an intervention for acute anorexia nervosa: a case report

The aim of this case report is to illustrate how cognitive remediation therapy (CRT) can be used as part of the treatment programme in acute anorexia nervosa (AN) to stimulate mental activities and improve thinking skills and information-processing systems when other therapies, for example cognitive behavioural therapy (CBT), may be too complex and intense for the patient to engage in. Furthermore, we hypothesize that CRT may be an effective tool in improving flexibility of thinking in AN, as previous neuropsychological findings have proved that rigidity is one of the maintaining factors in AN. Copyright © 2005 John Wiley & Sons, Ltd and Eating Disorders Association.

Which Psychotherapy for Acute Anorexia Nervosa

Studies of psychotherapy in acute anorexia nervosa are difficult to conduct because many patients are reluctant to engage in psychotherapy and dropout rates are high. These researchers conducted a controlled study of three types of manual-based psychotherapy in 56 female outpatients with anorexia nervosa (age range, 17–40; mean baseline BMI, …

Pharmacologic treatment of anorexia nervosa: Where do we go from here?

Anorexia nervosa (AN) is a serious mental disorder, characterized by severely low weight and cognitive distortions about body shape and weight. AN is generally associated with a range of psychological symptoms, including depression, anxiety, obsessions, and rituals. The current study summarized findings from randomized controlled trials (RCT) using pharmacologic treatments in patients with AN. We conducted a review of literature using Medline. Several classes of pharmacologic agents have been studied in small samples of patients with acute AN without finding clear benefit to eating, weight, body shape concerns, or associated psychopathology. Studies have been limited by small sample sizes, as well as by research design with most studies adding medication to comprehensive hospital-based treatment programs. Future directions for pharmacologic treatment research in AN should include outpatient trials, rigorous study of atypical antipsychotic medication, and assessment of medication effect for relapse prevention in weight-restored patients.

The contribution of anxiety and food restriction on physical activity levels in acute anorexia nervosa.

Excessive exercise is present in 40%-80% of anorexia nervosa (AN) patients. Hyperactivity often plays a role in developing and maintaining AN and represents an obstacle to weight gain in refeeding. Interconnections among caloric restriction, psychopathology, and physical activity in humans with AN are poorly investigated. Physical activity and food restriction during the last 3 months and status of body image/slimness ideal were assessed by the Structured Interview of Anorexia and Bulimia Nervosa (SIAB) in 30 adolescent patients with acute AN at admission to inpatient treatment. Anxiety, depression, and obsessive-compulsiveness were assessed with the Symptom Check-List-90-Revised (SCL-90-R). A regression model based on the independent variables body mass index, food reduction, body image/slimness ideal, anxiety, depression, and obsessive-compulsiveness was calculated to determine the relevant prediction variables of physical activity. The regression model explained 64% (R(2) = .64, p = .000) of the variance of physical activity. Only food restriction (p = .006) and anxiety (p = .004) contributed significantly to the variance. Our results indicate that anxiety symptoms and food restriction synergistically contribute to increased levels of physical activity in the acute phase of AN.

Elevated Physical Activity and Low Leptin Levels Co-occur in Patients with Anorexia Nervosa

Low leptin levels are an endocrinological hallmark of acute anorexia nervosa (AN); a subthreshold leptin secretion in adipocytes as a consequence of a reduced energy intake is presumed to be the major trigger of the adaptation of an organism to semistarvation. The aim of the current study is to define symptoms of AN that are potentially linked to low leptin levels. For this purpose, quantitative somatic and psychopathological variables were obtained in 61 inpatients with acute AN (study group 1) upon referral for inpatient treatment, and they were concomitantly blood sampled to allow determination of serum leptin levels. Correlations between these variables and logarithmic transformed (lg10) leptin levels were descriptively assessed. Apart from the well-known correlations between leptin levels and anthropometric measurements, the strongest correlation was observed between lg10 serum leptin levels and expert ratings of motor restlessness (r = -0.476; nominal P = 0.003) upon use of visual analog scales. We thus generated the hypothesis that physical activity levels in AN patients are related to serum leptin levels. This hypothesis was tested in an independent study group of 27 adolescent inpatients (study group 2) who were also assessed upon referral. Physical activity levels, which, in this study group, were assessed with the activity module of the expert rating form of the Structured Inventory for Anorexic and Bulimic Syndromes, were significantly correlated with lg10 leptin levels (r = -0.51; one-sided P = 0.006). A regression model based on the independent variables body mass index and lg10 leptin levels explained 37% of the variance of physical activity (R(2) = 0.37; P = 0.003); only the lg10 leptin levels contributed significantly to the variance (P = 0.003). Our results suggest that, similar to semistarvation-induced hyperactivity in rats, hypoleptinemia in patients with AN may be one important factor underlying the excessive physical activity.

Perceptions of family relationships in adolescents with anorexia nervosa and their unaffected sisters.

The family relationships of patients with anorexia nervosa (AN) have been extensively studied over recent years. However, using case-control designs with unrelated controls is subject to various cultural and familial biases. Studying subjective differential perceptions of family relationships in sister-pairs discordant for the disorder may overcome some of these limitations. The aim of the present study was therefore, to investigate subjective perceptions of family environments in a clinically ill sample of female adolescent patients with acute AN and in their healthy sisters using the Subjective Family Image Test. We found significantly lower perceived individual autonomy and higher perceived cohesion in patients compared with their sisters but no difference in perceived emotional connectedness. Lower perceived individual autonomy of the ill children resulted mainly from their relationships with mothers but also in part from their relationships with fathers. This observed pattern might contribute to the maintenance of the disorder and should be addressed in individual and family interventions.