Adverse childhood experiences, low self-esteem, and salient stimulus response in eating disorders.

BACKGROUND: Adverse childhood experiences (ACEs) are elevated in individuals with eating disorders (EDs), but how the neurobiology of EDs and ACEs interact is unclear. METHODS: Women 18-45 years old with anorexia nervosa (AN, n = 38), bulimia nervosa (BN, n = 32), or healthy controls (n = 60) were assessed for ACEs and ED behaviours and performed a taste-conditioning task during brain imaging. Mediation analyses tested relationships between ACE score, self-esteem, and ED behaviours. RESULTS: ACE scores were elevated in EDs and correlated positively with body mass index (p = 0.001), drive for thinness (p = 0.001), and body dissatisfaction (p = 0.032); low self-esteem mediated the relationship between ACEs and body dissatisfaction, drive for thinness, and bulimia severity. ACE scores correlated negatively (FDR-corrected) with unexpected, salient stimulus receipt in AN (substantia nigra) and BN (anterior cingulate, frontal and insular cortex, ventral striatum, and substantia nigra). When ACE scores were included in the model, unexpected stimulus receipt brain response was elevated in EDs in the anterior cingulate and ventral striatum. CONCLUSIONS: ACEs attenuate unexpected salient stimulus receipt response, which may be a biological marker for altered valence or hedonic tone perception in EDs. Low self-esteem mediates the relationships between ACEs and ED behaviours. Adverse childhood experiences should be assessed in biological studies, and their effects targeted in treatment.

Brain reward response in adolescents and young adults with anorexia nervosa is moderated by changes in body weight and sweetness perception.

OBJECTIVE: Anorexia nervosa (AN) is a severe psychiatric illness with complex etiology. Recently, we found elevated striatal brain response to sweet taste stimuli in adolescents and young adults with AN. Here, we tested the hypothesis that nutritional rehabilitation normalizes prediction error activation, a measure for dopamine-related reward circuit response, to salient caloric taste stimuli in AN. METHODS: A total of 28 individuals with AN (age = 16 ± 2 years; body mass index [BMI] = 16 ± 1) who previously underwent brain imaging while performing a taste prediction error task using sucrose as salient caloric stimulus, participated in a second brain imaging scan (BMI = 18 ± 1) after intensive specialized eating disorder treatment (41 ± 15 days). A total of 31 healthy controls (age = 16 ± 3 years; BMI = 21 ± 2) were also studied on two occasions. RESULTS: At baseline, individuals with AN demonstrated an elevated salience response in bilateral caudate head and nucleus accumbens, and right ventral striatum. At the second scan, elevated response was only found in the right nucleus accumbens. A moderator analysis indicated that greater increase in BMI and greater decrease in sweetness perception predicted lesser prediction error response at the second scan in AN. CONCLUSION: Consistent with the previously reported monetary stimulus-response, elevated taste prediction error response in AN was largely absent after weight restoration. This study indicates that changes in BMI and sweet taste perception are independent moderators of change of brain salience response in adolescents and young adults with AN. The study points toward dynamic changes in the brain reward circuitry in AN and highlights the importance of nutrition and weight restoration in that process. PUBLIC SIGNIFICANCE STATEMENT: AN is a severe psychiatric illness. Biological factors that integrate neurobiology and behavior could become important targets to improve treatment outcome. This study highlights the importance of weight normalization and taste perception the normalization of brain function, and food type or taste-specific interventions could help in the recovery process. Furthermore, the study suggests that food-related and nonfood-related reward processing adapts to illness state in AN.

I know I am not out of control, but I just cannot shake the feeling: exploring feeling out of control in eating disorders.

PURPOSE: Individuals with anorexia (AN) or bulimia nervosa (BN) often present with fear of loss of control in the context of eating. It is unclear whether this fear of loss of control, which has been associated with fear of failure and a sense of not being in charge of one's own life in eating disorders, can be distinguished from self-perceived maintained control over food intake in AN. Further, anxious traits are elevated across eating disorders and could contribute to this fear of loss of control. METHODS: We recruited 113 adult women: restricting type AN (n = 26), BN (n = 28), and healthy controls (CW, n = 59). Participants completed the Eating Expectancies Inventory (EEI), which assesses learned expectations on the effects of eating, including whether Eating Leads to Feeling out of Control, and the Trait Food Craving Questionnaire (FCQ-T), which measures food craving and the ability to withstand those cravings, including self-perceived Lack of Control Over Eating. RESULTS: Eating Leads to Feeling out of Control was elevated in AN and BN compared to CW. Lack of Control Over Eating was similar between AN and CW but elevated in BN. Intolerance of uncertainty correlated with those measures in CW only. CONCLUSION: Individuals with restricting-type AN experience feeling out of control when eating while maintaining self-perceived control over eating. The EEI's eating leads to feeling out of control is associated with negative self-improvement expectations. Targeting self-improvement through more functional strategies could be an important aspect in psychotherapy in AN and reduce the perceived need to restrict food intake. LEVEL OF EVIDENCE: Level III, Evidence obtained from well-designed cohort or case-control analytic studies.

Eye blink and reward prediction error response in anorexia nervosa.

BACKGROUND: Functional brain imaging has been used to study brain reward function and behavioral traits in anorexia nervosa (AN). Here we tested whether eye blink relates to behavior and brain imaging response as a method that is less costly and more accessible. METHOD: We recruited 26 women with AN and 50 healthy matched controls. All underwent a reward-learning prediction error task during functional magnetic resonance imaging. In addition, eye blink was measured for spontaneous blink rate, baseline blink amplitude, and startle response to an auditory stimulus. RESULTS: Baseline blink rate, amplitude and startle response were similar between groups. In AN, there were significant positive correlations between spontaneous blink rate and bulimia symptoms, and baseline blink amplitude and prediction error response in right-sided caudate, insula, and nucleus accumbens. Correlations between eye blink measures and body dissatisfaction or harm avoidance were no longer significant after multiple comparison adjustments. DISCUSSION: This study provides evidence that measures of eye blink response can be related to brain prediction error response and eating disorder behavior in AN. The catecholamine dopamine contributes to both eye blink and prediction error response providing indirect evidence that it could be a neurobiological correlate that contributes to behaviors relevant to AN.

Cortical thickness patterns as state biomarker of anorexia nervosa.

OBJECTIVE: Only few studies have investigated cortical thickness in anorexia nervosa (AN), and it is unclear whether patterns of altered cortical thickness can be identified as biomarkers for AN. METHOD: Cortical thickness was measured in 19 adult women with restricting-type AN, 24 individuals recovered from restricting-type AN (REC-AN) and 24 healthy controls. Those individuals with current or recovered from AN had previously shown altered regional cortical volumes across orbitofrontal cortex and insula. A linear relevance vector machine-learning algorithm estimated patterns of regional thickness across 24 subdivisions of those regions. RESULTS: Region-based analysis showed higher cortical thickness in AN and REC-AN, compared to controls, in the right medial orbital (olfactory) sulcus, and greater cortical thickness for short insular gyri in REC-AN versus controls bilaterally. The machine-learning algorithm identified a pattern of relatively higher right orbital, right insular and left middle frontal cortical thickness, but lower left orbital, right middle and inferior frontal, and bilateral superior frontal cortical thickness specific to AN versus controls (74% specificity and 74% sensitivity, χ2 p < .004); predicted probabilities differed significantly between AN and controls (p < .023). No pattern significantly distinguished the REC-AN group from controls. CONCLUSIONS: Higher cortical thickness in medial orbitofrontal cortex and insula probably contributes to higher gray matter volume in AN in those regions. The machine-learning algorithm identified a mixed pattern of mostly higher orbital and insular, but relatively lower superior frontal cortical thickness in individuals with current AN. These novel results suggest that regional cortical thickness patterns could be state markers for AN.

The partial dopamine D2 receptor agonist aripiprazole is associated with weight gain in adolescent anorexia nervosa.

OBJECTIVE: Finding medication to support treatment of anorexia nervosa has been difficult. Neuroscience-based approaches may help in this effort. Recent brain imaging studies in adults and adolescents with anorexia nervosa suggest that dopamine-related reward circuits are hypersensitive and could provide a treatment target. METHODS: Here, we present a retrospective chart review of 106 adolescents with anorexia nervosa some of whom were treated with the dopamine D2 receptor partial agonist aripiprazole during treatment in a specialized eating disorder program. RESULTS: The results show that aripiprazole treatment was associated with greater increase in body mass index (BMI) during treatment. DISCUSSION: The use of dopamine receptor agonists may support treatment success in anorexia nervosa and should be further investigated.

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

BACKGROUND: Previous 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. METHODS: Women recovered from restricting-type anorexia nervosa and healthy control women underwent fMRI during application of a prediction error taste reward learning paradigm. RESULTS: Twenty-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. LIMITATIONS: This was a cross-sectional study, and the sample size was modest. CONCLUSION: Anorexia 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.

Extremes of eating are associated with reduced neural taste discrimination.

OBJECTIVE: Eating disorders are severe psychiatric disorders of unknown etiology. Understanding how neuronal function affects food choices could help personalize treatment based on brain function. Here we wanted to determine whether disordered eating behavior is associated with alterations in the primary taste cortex's ability to classify taste stimuli, which could interfere with taste reward processing. METHOD: One-hundred and six women, 27 healthy comparison (age 26.15 ± 6.95 years), 21 with restricting-type anorexia nervosa (AN; age 23.10 ± 6.14 years), 19 recovered from restricting-type AN (recovered AN; age 26.95 ± 5.31 years), 20 with bulimia nervosa (BN; age 25.15 ± 5.31 years), and 19 with obesity (age 28.16 ± 8.13 years), received sucrose, control solution or no taste stimulation during functional magnetic resonance brain imaging. Multivariate Bayesian pattern analysis (decoding) and cross-validation tested taste classification accuracy (adjusted for comorbidity, medication use, taste perception, interoception, and brain activation volume). RESULTS: For sucrose versus control solution, classification accuracy differed (F = 2.53, P < 0.041). Post hoc tests indicated higher classification accuracy in healthy comparison compared to women with AN (P < 0.016) or obesity (P < 0.027), and in recovered AN as compared to AN (P < 0.016) or obesity (P < 0.047) groups. Taste stimulation resulted in sparse insula voxel activation across all groups. DISCUSSION: Reduced classification accuracy across stimuli in women with AN or obesity could indicate low brain encoding discrimination of stimulus quality, which could contribute to altered reward activation and eating drive that is not adjusted to nutritional needs. This deficit appears to normalize with recovery from AN, but adjusting food flavor intensity could aid in the treatment of individuals with AN or obesity. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2016; 49:603-612).

Reduced salience and default mode network activity in women with anorexia nervosa.

BACKGROUND: The neurobiology of anorexia nervosa is poorly understood. Neuronal networks contributing to action selection, self-regulation and interoception could contribute to pathologic eating and body perception in people with anorexia nervosa. We tested the hypothesis that the salience network (SN) and default mode network (DMN) would show decreased intrinsic activity in women with anorexia nervosa and those who had recovered from the disease compared to controls. The basal ganglia (BGN) and sensorimotor networks (SMN) were also investigated. METHODS: Between January 2008 and January 2012, women with restricting-type anorexia nervosa, women who recovered from the disease and healthy control women completed functional magnetic resonance imaging during a conditioned stimulus task. Network activity was studied using independent component analysis. RESULTS: We studied 20 women with anorexia nervosa, 24 recovered women and 24 controls. Salience network activity in the anterior cingulate cortex was reduced in women with anorexia nervosa (p = 0.030; all results false-discovery rate- corrected) and recovered women (p = 0.039) compared to controls. Default mode network activity in the precuneus was reduced in women with anorexia compared to controls (p = 0.023). Sensorimotor network activity in the supplementary motor area (SMA; p = 0.008), and the left (p = 0.028) and right (p = 0.002) postcentral gyrus was reduced in women with anorexia compared to controls; SMN activity in the SMA (p = 0.019) and the right postcentral gyrus (p = 0.008) was reduced in women with anorexia compared to recovered women. There were no group differences in the BGN. LIMITATIONS: Differences between patient and control populations (e.g., depression, anxiety, medication) are potential confounds, but were included as covariates. CONCLUSION: Reduced SN activity in women with anorexia nervosa and recovered women could be a trait-related biomarker or illness remnant, altering the drive to approach food. The alterations in the DMN and SMN observed only in women with anorexia nervosa suggest state-dependent abnormalities that could be related to altered interoception and body image in these women when they are underweight but that remit following recovery.

Neural Response to Expecting a Caloric Sweet Taste Stimulus Predicts Body Mass Index Longitudinally Among Young Adult Women With Anorexia Nervosa.

BACKGROUND: Anorexia nervosa (AN) is an often-chronic illness, and we lack biomarkers to predict long-term outcome. Recent neuroimaging studies using caloric taste stimuli suggest that paradigms that have tested conditioned neural responses to expectation or salient stimulus receipt may underpin behaviors. However, whether activation of those neural circuits can predict long-term outcome has not been studied. METHODS: We followed women treated for AN (n = 35, mean age [SD] = 23 [7] years) and tested whether functional imaging brain response during a taste conditioning paradigm could predict posttreatment body mass index (BMI). We anticipated greater neural activity relative to caloric stimulus expectation and that dopamine-related receipt conditions would predict lower posttreatment BMI, indicating fear-associated arousal. RESULTS: Follow-up occurred at mean (SD) = 1648 (1216) days after imaging. Stimulus expectation in orbitofrontal and striatal regions and BMI and BMI change at follow-up were negatively correlated, and these correlations remained significant for the right superior orbitofrontal cortex and BMI change after multiple comparison correction (r = -0.484, p = .003). This relationship remained significant after including time between brain scanning and follow-up in the model. Reward prediction error response did not predict long-term BMI. CONCLUSIONS: The orbitofrontal cortex is involved in learning and conditioning, and these data implicate this region in learned caloric stimulus expectation and long-term prediction of weight outcomes in AN. Thus, conditioned elevated brain response to the anticipation of receiving a caloric stimulus may drive food avoidance, suggesting that breaking such associations is central for long-term recovery from AN.

White matter integrity is reduced in bulimia nervosa.

OBJECTIVE: To investigate brain white matter (WM) functionality in bulimia nervosa (BN) in relation to anxiety. METHOD: Twenty-one control women (CW, mean age 27 ± 7 years) and 20 BN women (mean age 25 ± 5 years) underwent brain diffusion tensor imaging to measure fractional anisotropy (FA; an indication of WM axon integrity) and the apparent diffusion coefficient (ADC; reflecting WM cell damage). RESULTS: FA was decreased in BN in the bilateral corona radiata extending into the posterior limb of the internal capsule, the corpus callosum, the right sub-insular WM, and right fornix. In CW but not BN, trait anxiety correlated negatively with fornix, corpus callosum, and left corona radiata FA. ADC was increased in BN compared with CW in the bilateral corona radiata, corpus callosum, inferior fronto-occipital, and uncinate fasciculus. Alterations in BN WM functionality were not due to structural brain alterations. DISCUSSION: WM integrity is disturbed in BN, especially in the corona radiata, which has been associated with taste and brain reward processing. Whether this is a premorbid condition or an effect from the illness is yet uncertain. The relationships between WM FA and trait anxiety in CW but not BN may suggest that altered WM functionality contributes to high anxious traits in BN.

Trait anxiety is associated with amygdala expectation and caloric taste receipt response across eating disorders.

Anxious traits are elevated in eating disorders (EDs), are considered risk factors for ED development, and trait anxiety has been linked to ED psychopathology. How trait anxiety relates to ED neurobiology is not well understood. In this study 197 individuals across the ED spectrum (anorexia nervosa n = 91; other specified EDs n = 34; bulimia nervosa n = 56; binge ED n = 16), and 120 healthy controls were assessed for anxious traits and learned to expect and receive caloric or neutral taste stimuli during brain imaging. Amygdala sucrose expectation response differed across groups (Wilk's lambda = 0.945, p = 0.023), and was higher on the left in anorexia nervosa compared to healthy controls (p = 0.002). Expected sucrose receipt response across taste reward regions was not different between groups. In the ED sample, trait anxiety negatively moderated the relationship between amygdala expectation and right dorsal (p = 0.0062) and ventral (p = 0.0046) anterior insula receipt response. A subgroup analysis showed similar results for anorexia nervosa, and partially in bulimia nervosa. Across EDs, appetitive motivation correlated positively with bilateral orbitofrontal cortex, caudate head, and ventral striatal sucrose receipt response (r = 0.215 to 0.179, p = 0.002 to 0.012). Across the study sample, trait anxiety showed an inverted-U-shaped relationship with right (r = 0.147, p = 0.034) and left (r = 0.162, p = 0.016) amygdala expectation response. Amygdala sucrose expectation response is elevated in anorexia nervosa, correlates with sucrose receipt response, and this relationship is negatively moderated by trait anxiety across EDs. Trait anxiety may have an important role in how expectation drives taste stimulus receipt brain response and perhaps food approach in individuals with EDs.

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.

Associations between aerobic exercise and dopamine-related reward-processing: Informing a model of human exercise engagement.

Endurance or aerobic exercise has many physical and mental health benefits, but less is known about the specific impact that cardiovascular activity may have on dopamine-associated brain circuits involved in reward processing and mood regulation in humans. Understanding such effects will help to explain individual differences in both exercise uptake and maintenance. This study evaluated neural response to a classical taste-conditioning reward prediction error task with the use of functional magnetic resonance imaging, along with data on self-reported aerobic exercise among healthy young adult females (N = 111). Results indicated positive associations between reported aerobic exercise and regional brain response that remained significant after multiple comparison correction for the right medial orbital frontal cortex response to unexpected sucrose receipt (r = 0.315, p = .0008). The medial orbitofrontal cortex is implicated in reward and outcome value computation and the results suggest that aerobic exercise may strengthen this circuitry, or reciprocally, higher orbitofrontal cortical activity may reinforce exercise behavior. The findings aid in developing a model of how exercise engagement can modify reward-circuit function and could be used therapeutically in conditions associated with altered brain salience response.

Persistence, Reward Dependence, and Sensitivity to Reward Are Associated With Unexpected Salience Response in Girls but Not in Adult Women: Implications for Psychiatric Vulnerabilities.

BACKGROUND: Adolescence is a critical period for the development of not only personality but also psychopathology. These processes may be specific to sex, and brain reward circuits may have a role. Here, we studied how reward processing and temperament associations differ across adolescent and adult females. METHODS: A total of 29 adolescent girls and 41 adult women completed temperament assessments and performed a classical taste conditioning paradigm during brain imaging. Data were analyzed for the dopamine-related prediction error response. In addition, unexpected stimulus receipt or omission and expected receipt response were also analyzed. Heat maps identified cortical-subcortical brain response associations. RESULTS: Adolescents showed stronger prediction error and unexpected receipt and omission responses (partial η2 = 0.063 to 0.166; p = .001 to .043) in insula, orbitofrontal cortex (OFC), and striatum than adults. Expected stimulus receipt response was similar between groups. In adolescents versus adults, persistence was more strongly positively related to prediction error (OFC, insula, striatum; Fisher's z = 1.704 to 3.008; p = .001 to .044) and unexpected stimulus receipt (OFC, insula; Fisher's z = 1.843 to 2.051; p = .014 to .033) and negatively with omission (OFC, insula, striatum; Fisher's z = -1.905 to -3.069; p = .001 to .028). Reward sensitivity and reward dependence correlated more positively with unexpected stimulus receipt and more negatively with stimulus omission response in adolescents. Adolescents showed significant correlations between the striatum and FC for unexpected stimulus receipt and omission that correlated with persistence but were absent in adults. CONCLUSIONS: Associations between temperamental traits and brain reward response may provide neurotypical markers that contribute to developing adaptive or maladaptive behavior patterns when transitioning from adolescence to adulthood.

Anticipatory and consummatory pleasure in eating disorders.

BACKGROUND: Recent research suggests that anhedonia, or the inability to experience pleasure, is elevated in individuals with eating disorders (EDs). However, past literature has only studied anhedonia in EDs as a unidimensional construct rather than separately examining anticipatory (i.e., prediction of pleasure for a future event) and consummatory (i.e., enjoyment of a present event) pleasure. Given that these subcomponents of pleasure have distinct neurobiological correlates, studying pleasure as a multifaceted construct may yield important insights into the underlying mechanisms of binge eating or food restriction. METHODS: A sample of 124 women with anorexia nervosa, bulimia nervosa, or other specified feeding or eating disorder and 84 control women (CW) completed self-report measures of anticipatory pleasure, consummatory pleasure, ED symptoms, depression, harm avoidance, and anxiety. RESULTS: Individuals with EDs endorsed significantly lower anticipatory pleasure than CW, but there were no significant group differences in consummatory pleasure. Further, there were no significant differences in self-reported pleasure among ED diagnostic groups. Within the ED sample, anticipatory pleasure but not consummatory pleasure was positively related to binge eating frequency and significantly negatively correlated with cognitive ED symptoms, state and trait anxiety, and harm avoidance. Both anticipatory and consummatory pleasure was negatively associated with depression. CONCLUSION: The results of the current study suggest that lower pleasure across the ED spectrum may be due to deficits in anticipatory, but not consummatory, pleasure. Future research should continue to explore the behavioral, affective, and neural correlates of anticipatory pleasure in EDs to characterize better how it relates to the onset and maintenance of binge eating and other eating disorder pathology.

Anhedonia, or the inability to experience pleasure, has been observed in individuals with eating disorders. Neuroscience research suggests that pleasure may be separated into two distinct components: anticipatory pleasure (how much someone predicts they will enjoy a future experience) and consummatory pleasure (how much someone enjoys a present experience). In the current study, individuals with eating disorders and healthy controls completed questionnaires assessing anticipatory and consummatory pleasure, binge eating, other eating disorder behaviors, depression, anxiety, and constructs associated with reward and punishment sensitivity. The sample with eating disorders reported significantly lower anticipatory but not consummatory pleasure than the control sample. Within the eating disorder sample, greater anticipatory pleasure was also related to higher binge eating frequency but lower depression, anxiety, and weight and shape concerns. These results suggest that anticipatory pleasure may be particularly important in future research on the etiology and treatment of eating disorders.

Brain Structure in Acutely Underweight and Partially Weight-Restored Individuals With Anorexia Nervosa: A Coordinated Analysis by the ENIGMA Eating Disorders Working Group.

BACKGROUND: The pattern of structural brain abnormalities in anorexia nervosa (AN) is still not well understood. While several studies report substantial deficits in gray matter volume and cortical thickness in acutely underweight patients, others find no differences, or even increases in patients compared with healthy control subjects. Recent weight regain before scanning may explain some of this heterogeneity. To clarify the extent, magnitude, and dependencies of gray matter changes in AN, we conducted a prospective, coordinated meta-analysis of multicenter neuroimaging data. METHODS: We analyzed T1-weighted structural magnetic resonance imaging scans assessed with standardized methods from 685 female patients with AN and 963 female healthy control subjects across 22 sites worldwide. In addition to a case-control comparison, we conducted a 3-group analysis comparing healthy control subjects with acutely underweight AN patients (n = 466) and partially weight-restored patients in treatment (n = 251). RESULTS: In AN, reductions in cortical thickness, subcortical volumes, and, to a lesser extent, cortical surface area were sizable (Cohen's d up to 0.95), widespread, and colocalized with hub regions. Highlighting the effects of undernutrition, these deficits were associated with lower body mass index in the AN sample and were less pronounced in partially weight-restored patients. CONCLUSIONS: The effect sizes observed for cortical thickness deficits in acute AN are the largest of any psychiatric disorder investigated in the ENIGMA (Enhancing Neuro Imaging Genetics through Meta Analysis) Consortium to date. These results confirm the importance of considering weight loss and renutrition in biomedical research on AN and underscore the importance of treatment engagement to prevent potentially long-lasting structural brain changes in this population.

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 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.