Jennifer O. Hagman

Alterations in Brain Structures Related to Taste Reward Circuitry in Ill and Recovered Anorexia Nervosa and in Bulimia Nervosa

OBJECTIVE The pathophysiology of anorexia nervosa remains obscure, but structural brain alterations could be functionally important biomarkers. The authors assessed taste pleasantness and reward sensitivity in relation to brain structure, which may be related to food avoidance commonly seen in eating disorders. METHOD The authors used structural MR imaging to study gray and white matter volumes in women with current restricting-type anorexia nervosa (N=19), women recovered from restricting-type anorexia nervosa (N=24), women with bulimia nervosa (N=19), and healthy comparison women (N=24). RESULTS All eating disorder groups exhibited increased gray matter volume of the medial orbitofrontal cortex (gyrus rectus). Manual tracing confirmed larger gyrus rectus volume, and volume predicted taste pleasantness ratings across all groups. Analyses also indicated other morphological differences between diagnostic categories. Antero-ventral insula gray matter volumes were increased on the right side in the anorexia nervosa and recovered anorexia nervosa groups and on the left side in the bulimia nervosa group relative to the healthy comparison group. Dorsal striatum volumes were reduced in the recovered anorexia nervosa and bulimia nervosa groups and predicted sensitivity to reward in all three eating disorder groups. The eating disorder groups also showed reduced white matter in right temporal and parietal areas relative to the healthy comparison group. The results held when a range of covariates, such as age, depression, anxiety, and medications, were controlled for. CONCLUSION Brain structure in the medial orbitofrontal cortex, insula, and striatum is altered in eating disorders and suggests altered brain circuitry that has been associated with taste pleasantness and reward value.

Heightened sensitivity to reward and punishment in anorexia nervosa

OBJECTIVE The objective of this study is to test whether females with anorexia nervosa (AN) have increased sensitivity to punishing or rewarding stimuli, behaviors that could drive high self-control and anxious, avoidant behaviors. METHOD Sixty-four females completed the study: 33 control females (CFs, mean age 19.7 years) and 31 females with AN (mean age 19.6 years). Participants completed diagnostic exams, questionnaires for eating disorder severity and personality, and the Sensitivity to Punishment/Sensitivity to Reward Questionnaire (SPSRQ). RESULTS Females with AN scored higher than CFs on SPSRQ sensitivity to punishment (p < 0.00001) and sensitivity to reward (p = 0.005). Females with AN without anxiety or depression continued to have increased SPSRQ scores compared to CFs. DISCUSSION This is the first study comparing the SPSRQ in females with AN and CFs. Results suggest that reward and punishment sensitivity are increased in females with AN and could be potential trait markers. It is possible that harm-avoidant, anxious behaviors in females with AN are related to this heightened sensitivity.

A Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Adolescents and Young Adults with Anorexia Nervosa: A Pilot Study.

OBJECTIVE The purpose of this double-blind, placebo-controlled exploratory pilot study was to evaluate the safety and efficacy of risperidone for the treatment of anorexia nervosa. METHOD Forty female subjects 12 to 21 years of age (mean, 16 years) with primary anorexia nervosa in an eating disorders program were randomized to receive risperidone (n = 18) or placebo (n = 22). Subjects completed the Eating Disorder Inventory 2, Color-A-Person Test, Body Image Software, and Multidimensional Anxiety Scale for Children at baseline and regular intervals. Weight, laboratory values, and electrocardiograms were monitored. Study medication was started at 0.5 mg daily and titrated upward weekly in 0.5-mg increments to a maximum dose of 4 mg until the subject reached a study endpoint. RESULTS The mean dose for the risperidone group was 2.5 mg and for the placebo group was 3 mg for a mean duration of 9 weeks. Subjects taking risperidone had a significant decrease on the Eating Disorder Inventory 2 Drive for Thinness subscale over the first 7 weeks (effect size, 0.88; p = .002), but this difference was not sustained to the end of the study (p = .13). The Eating Disorder Inventory 2 Interpersonal Distrust subscale decreased significantly more in subjects taking risperidone (effect size, 0.60; p = .03). Subjects taking risperidone had increased prolactin levels (week 7; p = .001). There were no significant differences between groups at baseline or the end of the study for the other rating scales, change in weight, or laboratory measurements. CONCLUSIONS This study does not demonstrate a benefit for the addition of risperidone in adolescents with anorexia nervosa during the weight-restoration phase of care. Clinical trial registration information-A Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Anorexia Nervosa, http://www.clinicaltrials.gov, NCT00140426.

Altered fimbria-fornix white matter integrity in anorexia nervosa predicts harm avoidance

The eating disorder anorexia nervosa (AN) is associated with high anxiety. The brain mechanisms that drive those behaviors are unknown. In this study we wanted to test whether brain white matter (WM) integrity is altered in AN, and related to heightened anxiety. Sixteen adult women with AN (mean age 24 ± 7 years) and 17 healthy control women (CW, mean age 25 ± 4 years) underwent diffusion tensor imaging (DTI) of the brain. The DTI brain images were used to calculate the fractional anisotropy (FA) of WM tracts, which is a measure for WM integrity. AN individuals compared to CW showed clusters of significantly reduced FA (p<0.05, corrected) in the bilateral fimbria-fornix and the fronto-occipital fasciculus, as well as the posterior cingulum WM. In the AN group, Harm Avoidance was predicted by FA in the left and right fimbria-fornix. Those findings were not due to WM volume deficits in AN. This study indicates that WM integrity is abnormal in AN in limbic and association pathways, which could contribute to disturbed feeding, emotion processing and body perception in AN. The prediction of Harm Avoidance in AN by fimbria-fornix WM integrity suggests that this pathway may be mechanistically involved in high anxiety in AN.

Heightened fear of uncertainty in anorexia and bulimia nervosa.

OBJECTIVE To test whether intolerance of uncertainty (IU) is related to eating disorder (ED) pathology. METHOD Thirty individuals with anorexia nervosa (AN), 19 with bulimia nervosa (BN), and 28 healthy control women (CW) completed the Intolerance of Uncertainty Scale (IUS). RESULTS AN and BN groups showed higher IU compared with CW. In AN and BN, Harm Avoidance and Depression scores were positively correlated with IU. In AN but not BN, IU was related positively to Drive for Thinness and Body Dissatisfaction. DISCUSSION Elevated IU is associated with AN and BN. Anxious traits may be inherent in EDs and IU could be a developmental factor contributing to anxiety, mood, and ED behavior in AN and BN.

Cognitive set-shifting in anorexia nervosa.

OBJECTIVE Adult anorexia nervosa (AN) is associated with inefficient cognitive flexibility and set-shifting. Whether such inefficiencies also characterize adolescent AN is an important area of research. METHOD Adolescents with AN and matched controls were administered a computerized task that required initial learning of an explicit rule using corrective feedback and learning of a new rule after a set number of trials. Adult patients with AN and controls were also examined. RESULTS Adolescents with AN did not differ from matched controls with respect to set-shifting cost (decrease in performance after rule change), whereas adults with AN had significantly greater set-shifting cost compared with controls. DISCUSSION This study suggests that set-shifting inefficiencies may not be a vulnerability factor for AN development in adolescents with AN, but might become an important aspect of the disorder at later age, and could point towards developmental neurobiologic brain changes that could affect AN at different ages.

Body size overestimation and its association with body mass index, body dissatisfaction, and drive for thinness in anorexia nervosa

BackgroundBody size overestimation is a fundamental feature in anorexia nervosa (AN). There have been inconclusive findings about the extent to which this feature distinguishes psychopathology and some authors have argued that overestimation may be a function of lower body mass index (BMI).MethodsWe examine body size estimation accuracy and body dissatisfaction in 74 females with AN and 11 age-matched female controls using two well-established psychophysical procedures.ResultsParticipants with AN overestimated their body size more and had greater body dissatisfaction than controls. Size accuracy was found to be independent of BMI and correlated with body dissatisfaction and drive for thinness in participants with AN.ConclusionsWe conclude that overestimation of body size in AN is related to the psychopathology associated with the disorder and is not due to any perceptual tendency for people with lower BMI to overestimate their body size. We discuss the implications of these findings for treatment of AN.

Response to Keating and Rossell.

To the Editor: The correlation between gyrus rectus volume and sweet taste pleasantness in the comparison group is striking as it supports the previous literature and is consistent with an important concept established by the works of Rolls, Kringelbach, and others (1). All eating disorder groups in our sample showed increased gyrus rectus volume relative to individuals in the comparison group, suggesting comparable pathophysiology. Groups were combined for that reason, and we did find a positive correlation between sweet taste pleasantness and volume in the eating disorder case subjects. In addition, within eating disorder subgroups, each individual group showed a positive correlation (anorexia nervosa, r50.120; bulimia nervosa, r50.287; recovered anorexia nervosa, r50.345) between sweet taste pleasantness and gyrus rectus volume, supporting the idea that analyzing the groups as a whole was valid. The correlation coefficients were modest. Despite a significant amount of research, we still know little about the connection between brain structure and function and these results are a step toward identifying target areas that could contribute to altered food intake. Taste pleasantness in individuals with eating disorder could be less well mapped (yet still positively) onto gyrus rectus neurons due to the altered volume, and this could interfere with correct value computation. It is important to view eating disorders as complex problems with a variety of factors that most likely contribute to development and then perpetuation of the illnesses. Expecting direct correlations between all those measures would be overly simplistic, and we believe that dissecting eating disorders by brain circuits that may contribute to the psychopathology will be more fruitful. Trait alterations seem to exist that cause heightened sensitivity to various (food- and nonfood-related) rewarding or punishing stimuli, contributing to a sense of instability across individuals with anorexia and bulimia nervosa (2, 3). This instability may contribute to heightened anxiety and intolerance of uncertainty (4). Additionally, as suggested in this study, there may be developmental factors such as altered brain volume in the orbitofrontal cortex that could interfere with the processing of value of food stimuli. We recently published a similarly designed study in adolescents with anorexia nervosa and found similarly larger gyrus rectus volumes, further supporting that this structure could be involved in the pathophys- iology of eating disorders (5). All eating disorder groups share an enlarged gyrus rectus, which could impair a healthy sensory satiety processing. In fact individuals with eating disorders share many similar behaviors but on different scales, and there is overlap in symptoms not only across subgroups but even depending on stage of recovery. For instance, individuals with bulimia nervosa are often able to restrict food intake in-between binge episodes. Furthermore, many individuals who meet criteria for one category of eating disorder will often shift into another eating disorder during the course of illness, which is consistent with a common vulnerability.