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.

Background/ObjectivesWhat drives overconsumption of food is poorly understood. Alterations in brain structure and function could contribute to increased food seeking. Recently brain orbitofrontal cortex volume has been implicated in dysregulated eating but little is know how brain structure relates to function.Subjects/MethodsWe examined obese (n=18, age=28.7.4±8.3 years) and healthy control women (n=24, age=27.4±6.3 years) using a multimodal brain imaging approach. We applied magnetic resonance and diffusion tensor imaging to study brain gray and white matter volume as well as white matter integrity, and tested whether orbitofrontal cortex volume predicts brain reward circuitry activation in a taste reinforcement-learning paradigm that has been associated with dopamine function.ResultsObese individuals displayed lower gray and associated white matter volumes (p<.05 family wise error (FWE)-small volume corrected) compared to controls in the orbitofrontal cortex, striatum, and insula. White matter integrity was reduced in obese individuals in fiber tracts including the external capsule, corona radiata, sagittal stratum, and the uncinate, inferior fronto-occipital, and inferior longitudinal fasciculi. Gray matter volume of the gyrus rectus at the medial edge of the orbitofrontal cortex predicted functional taste reward-learning response in frontal cortex, insula, basal ganglia, amygdala, hypothalamus and anterior cingulate cortex in control but not obese individuals.ConclusionsThis study indicates a strong association between medial orbitofrontal cortex volume and taste reinforcement-learning activation in the brain in control but not in obese women. Lower brain volumes in the orbitofrontal cortex and other brain regions associated with taste reward function as well as lower integrity of connecting pathways in obesity may support a more widespread disruption of reward pathways. The medial orbitofrontal cortex is an important structure in the termination of food intake and disturbances in this and related structures could contribute to overconsumption of food in obesity.

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 ...

Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (P<0.05, corrected for comorbidity, medication and multiple comparisons). Functionally, in controls the hypothalamus drove ventral striatal activity, but in anorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive–emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction.

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.