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.

Localized brain volume and white matter integrity alterations in adolescent anorexia nervosa.

OBJECTIVE: The neurobiological underpinnings of anorexia nervosa (AN) are poorly understood. In this study, we tested whether brain gray matter (GM) and white matter (WM) in adolescents with AN would show alterations comparable to those in adults. METHOD: We used magnetic resonance imaging to study GM and WM volume, and diffusion tensor imaging to assess fractional anisotropy for WM integrity in 19 adolescents with AN and 22 controls. RESULTS: Individuals with AN showed greater left orbitofrontal, right insular, and bilateral temporal cortex GM, as well as temporal lobe WM volumes compared to controls. WM integrity in adolescents with AN was lower (lower fractional anisotropy) in fornix, posterior frontal, and parietal areas, but higher in anterior frontal, orbitofrontal, and temporal lobes. In individuals with AN, orbitofrontal GM volume correlated negatively with sweet taste pleasantness. An additional comparison of this study cohort with adult individuals with AN and healthy controls supported greater orbitofrontal cortex and insula volumes in AN across age groups. CONCLUSIONS: This study indicates larger orbitofrontal and insular GM volumes, as well as lower fornix WM integrity in adolescents with AN, similar to adults. The pattern of larger anteroventral GM and WM volume as well as WM integrity, but lower WM integrity in posterior frontal and parietal regions may indicate that developmental factors such as GM pruning and WM growth could contribute to brain alterations in AN. The negative correlation between taste pleasantness and orbitofrontal cortex volume in individuals with AN could contribute to food avoidance in this disorder.

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.

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.

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.

Altered implicit category learning in anorexia nervosa.

OBJECTIVE: Recent research has identified specific cognitive deficits in patients with anorexia nervosa (AN), including impairment in executive functioning and attention. Another such cognitive process, implicit category learning has been less studied in AN. This study examined whether implicit category learning is impaired in AN. METHOD: Twenty-one women diagnosed with AN and 19 control women (CW) were administered an implicit category learning task in which they were asked to categorize simple perceptual stimuli (Gabor patches) into one of two categories. Category membership was based on a linear integration (i.e., an implicit task) of two stimulus dimensions (orientation and spatial frequency of the stimulus). RESULTS: AN individuals were less accurate on implicit category learning relative to age-matched CW. Model-based analyses indicated that, even when AN individuals used the appropriate (i.e., implicit) strategy they were still impaired relative to CW who also used the same strategy. In addition, task performance in AN patients was worse the higher they were in self-reported novelty seeking and the lower they were in sensitivity to punishment. CONCLUSIONS: These results indicate that AN patients have implicit category learning deficits, and given this type of learning is thought to be mediated by striatal dopamine pathways, AN patients may have deficits in these neural systems. The finding of significant correlations with novelty seeking and sensitivity to punishment suggests that feedback sensitivity is related to implicit learning in AN.

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.