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.

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.

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.

Association of Brain Reward Response With Body Mass Index and Ventral Striatal-Hypothalamic Circuitry Among Young Women With Eating Disorders.

Importance: Eating disorders are severe psychiatric disorders; however, disease models that cross subtypes and integrate behavior and neurobiologic factors are lacking. Objective: To assess brain response during unexpected receipt or omission of a salient sweet stimulus across a large sample of individuals with eating disorders and healthy controls and test for evidence of whether this brain response is associated with the ventral striatal-hypothalamic circuitry, which has been associated with food intake control, and whether salient stimulus response and eating disorder related behaviors are associated. Design, Setting, and Participants: In this cross-sectional functional brain imaging study, young adults across the eating disorder spectrum were matched with healthy controls at a university brain imaging facility and eating disorder treatment program. During a sucrose taste classic conditioning paradigm, violations of learned associations between conditioned visual and unconditioned taste stimuli evoked the dopamine-related prediction error. Dynamic effective connectivity during expected sweet taste receipt was studied to investigate hierarchical brain activation between food intake relevant brain regions. The study was conducted from June 2014 to November 2019. Data were analyzed from December 2019 to February 2020. Main Outcomes and Measures: Prediction error brain reward response across insula and striatum; dynamic effective connectivity between hypothalamus and ventral striatum; and demographic and behavior variables and their correlations with prediction error brain response and connectivity edge coefficients. Results: Of 317 female participants (197 with eating disorders and 120 healthy controls), the mean (SD) age was 23.8 (5.6) years and mean (SD) body mass index was 20.8 (5.4). Prediction error response was elevated in participants with anorexia nervosa (Wilks λ, 0.843; P = .001) and in participants with eating disorders inversely correlated with body mass index (left nucleus accumbens: r = -0.291; 95% CI, -0.413 to -0.167; P < .001; right dorsal anterior insula: r = -0.228; 95% CI, -0.366 to -0.089; P = .001), eating disorder inventory-3 binge eating tendency (left nucleus accumbens: r = -0.207; 95% CI, -0.333 to -0.073; P = .004; right dorsal anterior insula: r = -0.220; 95% CI, -0.354 to -0.073; P = .002), and trait anxiety (left nucleus accumbens: r = -0.148; 95% CI, -0.288 to -0.003; P = .04; right dorsal anterior insula: r = -0.221; 95% CI, -0.357 to -0.076; P = .002). Ventral striatal to hypothalamus directed connectivity was positively correlated with ventral striatal prediction error in eating disorders (r = 0.189; 95% CI, 0.045-0.324; P = .01) and negatively correlated with feeling out of control after eating (right side: r = -0.328; 95% CI, -0.480 to -0.164; P < .001; left side: r = -0.297; 95% CI, -0.439 to -0.142; P = .001). Conclusions and Relevance: The results of this cross-sectional imaging study support that body mass index modulates prediction error and food intake control circuitry in the brain. Once altered, this circuitry may reinforce eating disorder behaviors when paired with behavioral traits associated with overeating or undereating.