High-fat taste challenge reveals altered striatal response in women recovered from bulimia nervosa: A pilot study

Objectives. Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) tend to have disordered thinking and eating behaviours in regards to fat containing foods. This is the first study to investigate neuronal pathways that may contribute to altered fat consumption in eating disordered patients. Methods. We used functional magnetic resonance imaging (fMRI) to compare responses to a high-fat cream stimulus, water, and a non-caloric viscous stimulus (CMC) to control for response to viscosity in individuals recovered from AN (N = 15), BN (N = 14) and a healthy control sample (CW, N = 18). Results. An interaction analysis (ANOVAR) comparing the three groups (AN, BN, CW) and the three conditions (cream, CMC, water) revealed significant differences in the left anterior ventral striatum (AVS). A post hoc analysis displayed a higher magnitude of response for the contrast cream/water in BN compared to AN or CW and for the contrast CMC/water in BN compared to AN. Conclusions. BN showed an exaggerated AVS response for the cream/water contrast in comparison to AN or CW. Moreover, BN showed an exaggerated AVS response for the CMC/water contrast in comparison to AN. These findings support the possibility that BN have an altered hedonic and/or motivational drive to consume fats.     

Taste reactivity deficit in anorexia nervosa

Aim: Anorexia nervosa is a complex psychiatric disorder posing a rapidly increasing burden on modern societies. Our purpose was to clarify perceptual‐motivational aspects of gustatory disturbances in the disease. Methods: A taste reactivity test, with the use of all five primary qualities in two concentrations, was performed in restrictive‐type anorexic patients, and their hedonic evaluations were compared to those of age‐matched healthy control subjects. Results: The patients gave significantly lower pleasantness scores for pleasant taste stimuli compared with controls. The differences were the greatest for the lower concentration sucrose, umami and sodium chloride. Ratings given for the aversive taste stimuli were similar in both experimental groups. Conclusion: Our findings contribute to a better understanding of complex symptoms of anorexia nervosa, and may also help to develop more effective cognitive‐behavioral therapies.     

Interhemispheric functional connectivity in anorexia and bulimia nervosa

The functional interplay between hemispheres is fundamental for behavioral, cognitive, and emotional control. Anorexia nervosa (AN) and bulimia nervosa (BN) have been largely studied with brain magnetic resonance imaging (MRI) in relation to the functional mechanisms of high‐level processing, but not in terms of possible inter‐hemispheric functional connectivity anomalies. Using resting‐state functional MRI (fMRI), voxel‐mirrored homotopic connectivity (VMHC) and regional inter‐hemispheric spectral coherence (IHSC) were studied in 15 AN and 13 BN patients and 16 healthy controls (HC). Using T1‐weighted and diffusion tensor imaging MRI scans, regional VMHC values were correlated with the left‐right asymmetry of corresponding homotopic gray matter volumes and with the white matter callosal fractional anisotropy (FA). Compared to HC, AN patients exhibited reduced VMHC in cerebellum, insula, and precuneus, while BN patients showed reduced VMHC in dorso‐lateral prefrontal and orbito‐frontal cortices. The regional IHSC analysis highlighted that the inter‐hemispheric functional connectivity was higher in the ‘Slow‐5’ band in all regions except the insula. No group differences in left–right structural asymmetries and in VMHC vs. callosal FA correlations were significant in the comparisons between cohorts. These anomalies, not explained by structural changes, indicate that AN and BN, at least in their acute phase, are associated with a loss of inter‐hemispheric connectivity in regions implicated in self‐referential, cognitive control and reward processing. These findings may thus gather novel functional markers to explore aberrant features of these eating disorders.     

Bulimia nervosa and abnormal cardiac repolarization

OBJECTIVE: Eating disorders (ED) are thought to be risk factors for sudden death, and arrhythmias are one of the major causes of sudden death in ED patients. Late potentials (LPs) are a predictor of arrhythmias and can be measured using signal-averaged electrocardiography (SAECG). We examined arryhthmogenicity by LPs in ED patients. METHODS: We performed SAECG on 48 female ED patients [21 with anorexia nervosa (AN) and 27 with bulimia nervosa (BN)] and on 20 healthy women. An LP was judged positive if two or more of the following criteria were fulfilled: QRS duration >120 ms, root-mean-square voltage <20 microV, and a high-frequency, low-amplitude duration >38 ms. We compared the occurrence of LPs among subgroups. RESULTS: Compared with the controls, BN patients with a history of AN had significantly more SAECG abnormalities. CONCLUSIONS: BN patients with a history of AN may be prone to ventricular arrhythmias.     

Assessment of ego state in anorexia nervosa and bulimia nervosa.

To clarify the effects of ego states on anorexia nervosa (AN) and bulimia nervosa (BN), the questionnaire of the Tokyo University Egogram (TEG) with critical parent, nurturing parent, adult, free child and adapted child scales was administered to 32 female AN patients aged 14 to 32 years (mean age 20 years) and 49 female BN patients aged 14 to 33 years (mean age 23 years). The scores on the critical parent and adapted child scales for AN were significantly lower than those for BN. A multiple logistic regression analysis including all of the TEG scales, age, duration of illness and education showed that the adapted child scale significantly discriminated between AN and BN. The adaptive ego state is suggested for differentiating between the two disorders.     

Normal brain tissue volumes after long-term recovery in anorexia and bulimia nervosa.

BACKGROUND: Individuals who are ill with anorexia (AN) and bulimia nervosa (BN) often have increased cerebrospinal fluid (CSF) volumes and decreased total gray and white matter volumes. It is unclear whether such disturbances persist after recovery from an eating disorder. METHODS: Magnetic resonance imaging was performed on 40 women who were long-term recovered (>1 year no binging, purging, or restricting behaviors, normal weight, and menstrual cycles, not on medication) from restricting or binge/purging type AN or BN and 31 healthy control women (CW). Voxel-based morphometry (VBM) was used for data analysis. RESULTS: Recovered AN and BN subgroups were similar to CW in terms of cerebrospinal fluid (CSF) volume as well as total or regional gray or white matter volume. CONCLUSIONS: These findings suggest that structural brain abnormalities are reversible in individuals with eating disorders after long-term recovery.     

Exploring the neurocognitive signature of poor set-shifting in anorexia and bulimia nervosa

Poor set-shifting has been implicated as a risk marker, maintenance factor and candidate endophenotype of eating disorders (ED). This study aimed to add clarity to the cognitive profile of set-shifting by examining the trait across ED subtypes, assessing whether it is a state or trait marker, and whether it runs in families. A battery of neuropsychological tasks was administered to 270 women with current anorexia (AN) and bulimia nervosa (BN), women recovered from AN, unaffected sisters of AN and BN probands, and healthy control women. Set-shifting was examined using both individual task scores and a composite variable (poor/intact/superior shifting) calculated from four neuropsychological tasks. Poor set-shifting was found at a higher rate in those with an ED particularly binge/purging subtypes. Some evidence for poor set-shifting was also present in those recovered from AN and in unaffected sisters of AN and BN. Clinically, poor set-shifting was associated with a longer duration of illness and more severe ED rituals but not body mass index. In sum, poor set-shifting is a transdiagnostic feature related to aspects of the illness but not to malnutrition. In part it is a familial trait, and is likely involved in the maintenance of the illness.     

Prediction error and somatosensory insula activation in women recovered from anorexia nervosa

BackgroundPrevious research in patients with anorexia nervosa showed heightened brain response during a taste reward conditioning task and heightened sensitivity to rewarding and punishing stimuli. Here we tested the hypothesis that individuals recovered from anorexia nervosa would also experience greater brain activation during this task as well as higher sensitivity to salient stimuli than controls.MethodsWomen recovered from restricting-type anorexia nervosa and healthy control women underwent fMRI during application of a prediction error taste reward learning paradigm.ResultsTwenty-four women recovered from anorexia nervosa (mean age 30.3 ± 8.1 yr) and 24 control women (mean age 27.4 ± 6.3 yr) took part in this study. The recovered anorexia nervosa group showed greater left posterior insula activation for the prediction error model analysis than the control group (family-wise error– and small volume–corrected p < 0.05). A group × condition analysis found greater posterior insula response in women recovered from anorexia nervosa than controls for unexpected stimulus omission, but not for unexpected receipt. Sensitivity to punishment was elevated in women recovered from anorexia nervosa.LimitationsThis was a cross-sectional study, and the sample size was modest.ConclusionAnorexia nervosa after recovery is associated with heightened prediction error–related brain response in the posterior insula as well as greater response to unexpected reward stimulus omission. This finding, together with behaviourally increased sensitivity to punishment, could indicate that individuals recovered from anorexia nervosa are particularly responsive to punishment. The posterior insula processes somatosensory stimuli, including unexpected bodily states, and greater response could indicate altered perception or integration of unexpected or maybe unwanted bodily feelings. Whether those findings develop during the ill state or whether they are biological traits requires further study.     

Impaired Set-Shifting Ability in Patients with Eating Disorders, Which Is Not Moderated by Their Catechol-O-Methyltransferase Val158Met Genotype

The aim of this study was to examine the set-shifting ability in women with both anorexia nervosa (AN) and bulimia nervosa (BN) and to investigate whether it is contributed by the catechol-O-methyltransferase (COMT) Val158Met genotype. A total of 102 Korean participants-40 women with lifetime AN, 28 women with lifetime BN, and 34 healthy women of comparable age and intelligence quotient- were examined. A neuropsychological battery of tests was applied and blood samples were obtained for COMT Val158Met genotyping. Set-shifting impairments Trail Making Test (TMT, Part B) were found in patients with AN and BN, respectively. Furthermore, the eating disorders were also linked to deficits in attentional mechanisms (TMT, Part A) and motor skills (Finger Tapping Test). Finally, set-shifting and its link to eating disorders were not moderated by COMT Val158Met genotype.     

Reward processing in anorexia nervosa

Individuals with anorexia nervosa (AN) demonstrate a relentless engagement in behaviors aimed to reduce their weight, which leads to severe underweight status, and occasionally death. Neurobiological abnormalities, as a consequence of starvation are controversial: evidence, however, demonstrates abnormalities in the reward system of patients, and recovered individuals. Despite this, a unifying explanation for reward abnormalities observed in AN and their relevance to symptoms of the illness, remains incompletely understood. Theories explaining reward dysfunction have conventionally focused on anhedonia, describing that patients have an impaired ability to experience reward or pleasure. We review taste reward literature and propose that patients' reduced responses to conventional taste-reward tasks may reflect a fear of weight gain associated with the caloric nature of the tasks, rather than an impaired ability to experience reward. Consistent with this, we propose that patients are capable of 'liking' hedonic taste stimuli (e.g., identifying them), however, they do not 'want' or feel motivated for the stimuli in the same way that healthy controls report. Recent brain imaging data on more complex reward processing tasks provide insights into fronto-striatal neural circuit dysfunction related to altered reward processing in AN that challenges the relevance of anhedonia in explaining reward dysfunction in AN. In this way, altered activity of the anterior cingulate cortex and striatum could explain patients' pathological engagement in behaviors they consider rewarding (e.g., self-starvation) that are otherwise aversive or punishing, to those without the eating disorder. Such evidence for altered patterns of brain activity associated with reward processing tasks in patients and recovered individuals may provide important information about mechanisms underlying symptoms of AN, their future investigation, and the development of treatment approaches.     

Amygdala hyperreactivity in restrictive anorexia nervosa

Functional imaging studies had often investigated heterogeneous samples of anorexia nervosa (AN) patients with varying paradigms and methodologies that had resulted in divergent results. The present study aimed to examine these issues by studying a well-defined sample of restrictive AN patients with a disorder-specific paradigm which had been used previously. Subjects showed increased blood oxygen level dependent responses of the cingulate, frontal, insular and parietal cortices. Group comparisons demonstrated increased activity of the right amygdala in the sample of restrictive AN patients. Our results are in support of other recently published functional imaging studies and point to a pivotal role of the right amygdala in AN. Signals of the midcingulum were reduced in comparison to healthy controls. The constellation of increased activity of the amygdala and decreased activity of the cingulate cortex likely represents parts of a negative feedback loop of emotional processing. Disgust ratings correlated with the amygdala signal negatively, which points to the complex role of this structure within eating disorders.     

Lower body weight is associated with less negative emotions in sad autobiographical memories of patients with anorexia nervosa

Food restriction and weight-loss have been proposed to represent pathogenic mechanisms of emotion regulation in anorexia nervosa (AN). However, there is a lack of studies empirically examining this hypothesis. Therefore, the present study compared 25 women with AN and 25 healthy control women (HC) regarding spontaneous emotional processing of autobiographic memories. Participants' idiographic memories of sad autobiographic events were analyzed using computerized, quantitative text analysis as an unobtrusive approach of nonreactive assessment. Compared to HC, AN patients retrieved more negative but a comparable number of positive emotions. Moreover, the lesser the body weight in AN patients, the lesser negative emotions they retrieved, irrespective of current levels of depressive symptoms and duration of illness. No such association was found in HC. These preliminary findings are in line with models of AN proposing that food restriction and weight-loss may be negatively reinforced by the alleviation of aversive emotional responses.     

Functional neuroanatomy of body shape perception in healthy and eating-disordered women.

BACKGROUND: Abnormalities in perception and evaluation of body shape are a hallmark of eating disorders. METHODS: Brain responses to line drawings of underweight, normal weight, and overweight female bodies were measured with functional magnetic resonance imaging in 9 women with bulimia nervosa, 13 with anorexia nervosa, and 18 healthy women. Participants rated the stimuli for fear and disgust. RESULTS: In the three groups, the lateral fusiform gyrus, inferior parietal cortex, and lateral prefrontal cortex were activated in response to body shapes compared with the control condition (drawings of houses). The responses in the lateral fusiform gyrus and in the parietal cortex were less strong in patients with eating disorders compared with healthy control subjects. Patients with eating disorders rated the body shapes in all weight categories as more aversive than did healthy women. In the group with eating disorders, the aversion ratings correlated positively with activity in the right medial apical prefrontal cortex. CONCLUSIONS: Processing of female body shapes engages a distributed neural network, parts of which are underactive in women with eating disorders. The considerable variability in subjective emotional reaction to body shapes in patients with eating disorders is associated with differential activity in the prefrontal cortex.     

Reduced 5-HT2A receptor binding after recovery from anorexia nervosa.

BACKGROUND: Several lines of evidence suggest that a disturbance of serotonin neuronal pathways may contribute to the pathogenesis of anorexia nervosa (AN). This study applied positron emission tomography (PET) to investigate the brain serotonin 2A (5HT2A) receptor, which could contribute to disturbances of appetite and behavior in AN. METHODS: To avoid the confounding effects of malnutrition, we studied 16 women recovered from AN (REC AN, >1 year normal weight, regular menstrual cycles, no bingeing or purging) compared with 23 healthy control women (CW) using [18F]altanserin, a specific 5-HT2A receptor antagonist on PET imaging. RESULTS: REC AN women had significantly reduced [18F]altanserin binding relative to CW in mesial temporal (amygdala and hippocampus), as well as cingulate cortical regions. In a subset of subjects (11 CW and 16 REC AN), statistical parametric mapping (SPM) confirmed reduced mesial temporal cortex 5HT2A receptor binding and, in addition, showed reduced occipital and parietal cortex binding. CONCLUSIONS: This study extends research suggesting that altered 5-HT neuronal system activity persists after recovery from AN and may be related to disturbances of mesial temporal lobe function. Altered 5-HT neurotransmission after recovery also supports the possibility that this may be a trait-related disturbance that contributes to the pathophysiology of AN.     

A cross-sectional and follow-up functional MRI study with a working memory task in adolescent anorexia nervosa

Structural and functional brain abnormalities have been described in anorexia nervosa (AN). The objective of this study was to examine whether there is abnormal regional brain activation during a working memory task not associated with any emotional stimuli in adolescent patients with anorexia and to detect possible changes after weight recovery. Fourteen children and adolescents (age range 11–18 years) consecutively admitted with DSM-IV diagnosis of AN and fourteen control subjects of similar age were assessed by means of psychopathological scales and functional magnetic resonance imaging (fMRI) during a working memory task. After seven months of treatment and weight recovery, nine AN patients were reassessed. Before treatment, the AN group showed significantly higher activation than controls in temporal and parietal areas and especially in the temporal superior gyrus during performance of the cognitive task. Control subjects did not show greater activation than AN patients in any region. A negative correlation was found between brain activation and body mass index and a positive correlation between activation and depressive symptomatology. At follow-up after weight recovery, AN patients showed a decrease in brain activation in these areas and did not present differences with respect to controls. These results show that adolescent AN patients showed hyperactivation in the parietal and especially the temporal lobe during a working memory task, suggesting that they must make an additional effort to perform at normal levels. This activation correlated with clinical variables. In these young patients, differences with respect to controls disappeared after weight recovery.     

Anorexia nervosa and obesity are associated with opposite brain reward response

Anorexia nervosa (AN) is a severe psychiatric disorder associated with food avoidance and malnutrition. In this study, we wanted to test whether we would find brain reward alterations in AN, compared with individuals with normal or increased body weight. We studied 21 underweight, restricting-type AN (age M 22.5, SD 5.8 years), 19 obese (age M 27.1, SD 6.7 years), and 23 healthy control women (age M 24.8, SD 5.6 years), using blood oxygen level-dependent functional magnetic resonance brain imaging together with a reward-conditioning task. This paradigm involves learning the association between conditioned visual stimuli and unconditioned taste stimuli, as well as the unexpected violation of those learned associations. The task has been associated with activation of brain dopamine reward circuits, and it allows the comparison of actual brain response with expected brain activation based on established neuronal models. A group-by-task condition analysis (family-wise-error-corrected P<0.05) indicated that the orbitofrontal cortex differentiated all three groups. The dopamine model reward-learning signal distinguished groups in the anteroventral striatum, insula, and prefrontal cortex (P<0.001, 25 voxel cluster threshold), with brain responses that were greater in the AN group, but lesser in the obese group, compared with controls. These results suggest that brain reward circuits are more responsive to food stimuli in AN, but less responsive in obese women. The mechanism for this association is uncertain, but these brain reward response patterns could be biomarkers for the respective weight state.     

Role of the ventral striatum in developing anorexia nervosa

Functional imaging data in adult patients with anorexia nervosa (AN) support a dysfunctional signal in the ventral striatum as neural signature of AN. In the present study, development of this signal was investigated with the prediction that a characteristic pattern of ventral–striatal signalling will be shown in response to cues associated with food restriction that reflects the evolvement of starvation dependence over time. The signal was assessed in adolescent patients with AN, whose duration of illness was about five times shorter relative to the adult sample. During functional magnetic resonance imaging subjects were required to estimate weights of body images (underweight, normal weight, overweight) and to process each stimulus in a self-referring way. Relative to age-matched, young healthy controls, underweight stimuli were already associated with greater activity of the ventral striatum, and processing of normal-weight stimuli elicited already reduced signalling. Subjective preferences showed exactly the same pattern of results. Relative to adult AN, the present data reveal a developing dysfunctional signal that, if untreated, will essentially contribute to the maintenance of AN. We discuss putative mechanisms that may play a crucial role in the development of AN, and also deduce new hypotheses about the involvement of the midbrain dopamine system, of which illness-related alterations may contribute to the development of AN.     

Gyrification brain abnormalities as predictors of outcome in anorexia nervosa

Gyrification brain abnormalities are considered a marker of early deviations from normal developmental trajectories and a putative predictor of poor outcome in psychiatric disorders. The aim of this study was to explore cortical folding morphology in patients with anorexia nervosa (AN). A MRI brain study was conducted on 38 patients with AN, 20 fully recovered patients, and 38 healthy women. Local gyrification was measured with procedures implemented in FreeSurfer. Vertex‐wise comparisons were carried out to compare: (1) AN patients and healthy women; (2) patients with a full remission at a 3‐year longitudinal follow‐up assessment and patients who did not recover. AN patients exhibited significantly lower gyrification when compared with healthy controls. Patients with a poor 3‐year outcome had significantly lower baseline gyrification when compared to both healthy women and patients with full recovery at follow‐up, even after controlling for the effects of duration of illness and gray matter volume. No significant correlation has been found between gyrification, body mass index, amount of weight loss, onset age, and duration of illness. Brain gyrification significantly predicted outcome at follow‐up even after controlling for the effects of duration of illness and other clinical prognostic factors. Although the role of starvation in determining our findings cannot be excluded, our study showed that brain gyrification might be a predictor of outcome in AN. Further studies are needed to understand if brain gyrification abnormalities are indices of early neurodevelopmental alterations, the consequence of starvation, or the interaction between both factors. Hum Brain Mapp 36:5113–5122, 2015. © 2015 Wiley Periodicals, Inc.     

Altered immunoreactive levels of G proteins in peripheral mononuclear cells of patients with anorexia nervosa and bulimia nervosa

Alterations of cellular G proteins have been implicated in the pathophysiology of some psychiatric disorders. So far, no study assessed G protein function in anorexia nervosa (AN) and bulimia nervosa (BN). Therefore, we measured immunoreactive levels of G(alpha s), G(alpha i), G(alpha q/11) and G(beta) protein subunits in mononuclear leukocytes of 71 drug-free women, including 25 subjects with AN, 26 individuals with BN and 20 healthy controls. As compared to healthy women, anorexic patients exhibited significantly increased levels of G(alpha i) and G(beta) proteins, while bulimic patients had significantly increased levels of G(alpha s), G(alpha i) and G(beta) proteins. Immunoreactive levels of peripheral G protein subunits were not significantly correlated with demographic or nutritional parameters. These findings, although obtained in peripheral blood cells, may suggest a derangement of G protein-mediated signal transduction in the pathophysiology of eating disorders.     

Personality disorders in anorexia nervosa and bulimia nervosa

Two self-report questionnaires (MCMI and BSI) designed to measure personality disorder (PD) according to DSM-III (R) criteria were administered to patients with a diagnosis of anorexia nervosa (AN) (n = 19), bulimia nervosa (BN) (n = 16), or both diagnoses (AN + BN) (n = 9), both before and after treatment for the eating disorder. The main finding was that self-reported Personality Disorder (PD) diagnoses are not stable enduring characteristics among this group of eating disorder patients. A high rate of PD diagnoses occurred in all patient groups at admission (93%) and at discharge (79%). Both MCMI and BSI scales were subject to significant change following treatment. A high prevalence of borderline personality disorder was found in patients with BN. Changes in depression and self-esteem scores correlated most strongly with changes in schizoid, schizotypal, histrionic and narcissistic scales. Assessment of PD using self-report measures should be interpreted with caution in acutely symptomatic patients with eating disorders.