This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Anorexia nervosa (AN) is a serious behavioral disorder whose core features are a refusal to maintain body weight at 85% of that expected, loss of menses for 3 or more months, and fear of fatness or of weight gain. AN affects 0.5 - 1.0% of females, and carries a mortality for those hospitalized with the disorder of 5 - 18%, among the highest of psychiatric illnesses. While etiologies have been proposed, there is currently no clear pathogenetic understanding of AN, and multiple pathological processes are likely to be at work. There are clear brain changes associated with AN that may contribute to the maintenance of AN and which are not well understood at this time. This study aims specifically to understand the changes in brain structure and function underlying AN and their relationship to the clinical syndrome of AN. Both structural and functional brain abnormalities occur in AN. Increased CSF volume, sulcal widening and loss of both gray and white matter have been reported in acutely ill patients, and there is some evidence that gray matter loss persists even after weight restoration. Functional magnetic resonance imaging (fMRI) studies have demonstrated increased activation in the anterior cingulate cortexes (ACCs) and in the amygdalas of AN patients compared with controls when subjects were shown pictures of high- and low-calorie drinks. The authors suggest that since overactivation of amygdala is associated with exposure to threat-cues in phobic states, their findings represent calorie phobia. This may be the case, but the psychopathology of AN is different from that of phobia in that the self-starvation in AN is extremely rewarding. The functional neuroanatomy of the reward of self-starvation in AN remains to be elucidated. We propose to use fMRI to study the functional neuroanatomy of fear and reward in patients with AN and in healthy controls by using an emotional Stroop interference task to activate brain areas associated both with fear (e.g., amygdala) and reward (e.g., nucleus accumbens, dorsolateral prefrontal cortex). We further propose to examine white matter organization using diffusion tensor imaging (DTI), both in the acutely starved state of AN, and after refeeding. Finally, we propose to replicate studies demonstrating reduced gray and white matter volumes in acute AN, and demonstrate that those changes partially reverse with refeeding. Elucidating the mechanisms of fear of fatness and reward of starvation that make treating AN so challenging can be a first step to tailoring specific therapies targeted to reducing these components of AN.
Showing the most recent 10 out of 1014 publications
