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 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 fimbriafornix, fronto-occipital fasciculus, as well as posterior cingulum WM. In the AN group, Harm Avoidance was predicted by left (F=5.8, Beta=−0.54, p<0.03) and right (F=6.0, Beta=−0.55, p<0.03) fimbria-fornix FA. 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.

Objective-To test whether women 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 women completed the study: 33 control women (CW, mean age 19.7 years) and 31 AN (mean age 19.6 years). Participants completed diagnostic exams, questionnaires for eating disorder severity and personality, as well as the Sensitivity to Punishment/Sensitivity to Reward Questionnaire (SPSRQ).Results-AN scored higher than CW on SPSRQ sensitivity to punishment (p<0.00001) and sensitivity to reward (p=0.005). AN women without anxiety or depression continued to have increased SPSRQ scores compared to CW.Conclusion-This is the first study comparing the SPSRQ in AN and CW. Results suggest that reward and punishment sensitivity are increased in AN and could be potential trait markers. It is possible that harm-avoidant, anxious behaviors in AN are related to this heightened sensitivity.Anorexia Nervosa (AN) is a severe, often persistent mental illness with the highest mortality rate among all the psychiatric disorders (1). AN is characterized by intense fear of gaining weight, food restriction and weight loss, body image distortion, and amenorrhea (2). Central to AN is the ego-syntonic nature of weight loss, as well as the high rate of treatment resistance and drop out (3). The underlying pathophysiology of AN is unknown.AN is frequently associated with co-morbid anxiety disorders that often predate the emergence of eating disorder (ED) pathology (4). Individuals with AN are consistently characterized as highly perfectionistic and controlling (5) and show temperament traits such as high harm avoidance (HA; shy, fearful, worrying behavior, tendency to avoid perceived punishment), and lower novelty seeking (NS; the desire to explore and approach potential rewards) (4,(6)(7)(8)(9). These characteristics raise the question whether such behaviors in AN are primary or adaptive in order to tolerate and handle the ups and downs of failures and Corresponding Author Guido K.W. Frank, MD, Assistant Professor, Departments of Psychiatry and Neuroscience, Director, Developmental Brain Research Program, University of Colorado Denver, The Children's Hospital, Gary Pavilion A036/B-130, 13123 East 16th Avenue, Aurora, CO 80045, Tel.: 720-777-1909, Guido.Frank@ucdenver.edu. NIH Public Access Author ManuscriptInt J Eat Disord. Author manuscript; available in PMC 2012 May 1. NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript accomplishments in daily life. While speculative, AN individuals may have heightened emotional or physiological sensitivity to experiences that are associated with reward or punishment, and that the eating disorder and associated behaviors may in some way serve to mitigate these responses by the sense of control received. We hypothesized that individuals with AN might be overly sensitive to the saliency of punishing or rewarding stimuli, and they may act to minimize exposure ...

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 to 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. Conclusion-ElevatedIU 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.

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.

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Animal models of human disease play a central role in modern biomedical science. Developing animal models for human mental illness presents unique practical and philosophical challenges. In this article we argue that (1) existing animal models of psychiatric disease are not valid, (2) attempts to model syndromes are undermined by current nosology, (3) models of symptoms are rife with circular logic and anthropomorphism, (4) any model must make unjustified assumptions about subjective experience, and (5) any model deemed valid would be inherently unethical, for if an animal adequately models human subjective experience, then there is no morally relevant difference between that animal and a human.

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